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Prolactin is a hormone best recognized for its roles in lactation and reproduction, although it has important immunomodulatory roles, particularly in the context of stress. Several mutations in the prolactin receptor gene have been identified in cattle that are associated with a short hair phenotype and improved thermotolerance in hot environments. Among these mutations, the SLICK1 allele is a single base pair deletion resulting in a frameshift mutation that introduces a premature stop codon, preventing transcription of 120 amino acids of the prolactin receptor intracellular tail. The shortened prolactin receptor tail lacks tyrosine residues that are docking sites for signal transducers and activators of transcription (STAT) molecules. The canonical pathway utilized by the prolactin receptor is JAK2/STAT5, although other STAT proteins such as STAT1 and STAT3 are also involved. It is unknown whether the presence of the SLICK1 allele could modify the functioning of JAK/STAT signaling pathways. To investigate prolactin receptor-associated signaling pathways in cattle carrying the SLICK1 allele, we performed immunohistochemistry in skin biopsies obtained from slick and non-slick heifers to evaluate the presence and abundance of phosphorylated (activated) STAT1, STAT3, and STAT5 in hair follicles and sweat glands. The presence of pSTAT3 was detected less often (P = 0.03) in hair follicles of slick (42.5% ± 10.7%; n=5) compared to non-slick heifers (79.5% ± 9.7%; n=6). No difference between genotypes was found for the presence of immunoreactivity for pSTAT1 (slick = 37.9% ± 11.3%; non-slick = 43.9% ± 10.3%; P = 0.70) or pSTAT5 (slick = 8.9% ± 7.1%; non-slick = 15% ± 6.5%; P = 0.52) in hair follicles. Additionally, presence of immunoreactivity for pSTAT1 (slick = 47.5% ± 21.8%; non-slick = 91.7% ± 25.2%; P = 0.24) and pSTAT3 (slick = 33.3% ± 24.3%; non-slick = 91.7% ± 24.3%; P = 0.16) in sweat glands did not differ between genotypes. Immunoreactivity for pSTAT5 was only detected in one slick sweat gland and zero non-slick sweat glands and therefore was not stat analyzed. When immunoreactive structures were detected, no difference was found regarding the proportion of cells positive for pSTAT1 (slick = 2.9% ± 2%; non-slick = 3.5% ± 1.9%; P = 0.84), pSTAT3 (slick = 6.4% ± 3.1%; non-slick = 8.7% ± 2.8%; P = 0.60), or pSTAT5 (slick = 0.5% ± 0.8%; non-slick = 1.5% ± 0.7%; P = 0.37) in hair follicles, or for pSTAT1 (slick = 11% ± 5.3%; non-slick = 12% ± 6.2%; P = 0.91) and pSTAT3 (slick = 18% ± 12.8%; non-slick = 16.7% ± 12.9%; P = 0.94) in sweat glands. Since prolactin signaling through its canonical receptor affects gene transcription, we investigated the global transcriptional response of skin explants from heifers carrying the SLICK1 allele and non-slick half-sisters after exposure to prolactin in vitro. Skin explants were subjected to RNA sequencing and the resulting data were analyzed using Ingenuity Pathway Analysis software. Bioinformatic analysis revealed that among the canonical signaling pathways identified in the expanded dataset were IL-17 signaling (P = 3.24e-3, z-score = 2.24), leukocyte extravagation signaling (P = 5.75e-4, z-score = 2.00), and wound healing signaling pathway (P = 2.29 e-3, z-score = 0.82). Upstream analysis identified differentially activated upstream regulators including TNF (P = 1.23 e-5, z-score = 3.38), IL-1β (P = 8.71e-3, z-score = 3.11), OSM (P = 1.49e-2, z-score = 2.73), IFNγ (P = 6.27e-3, z-score = 2.60), IL-17α (P = 6.69e-3, z-score = 2.40), IL-1R (P = 1.90e-5, z-score = 2.20), SHH (P = 5.24e-3, z-score = -2.18), and BMP4 (P = 4.12e-4, z-score = -2.18). Our results indicate that STAT3 is phosphorylated less often in the hair follicles of the skin of heifers carrying the SLICK1 allele. Additionally, the differential activation of immune-related genes and pathways could indicate differences in local immune regulation in the skin of SLICK1-carrier heifers.

No study on the relationship between hepatic steatosis and sex hormone levels in male patients with chronic hepatitis B (CHB) infection has been conducted.We aimed to investigate the association between serum sex hormones and hepatic steatosis among a cohort of males with CHB.In this cross-sectional study, 268 male patients with CHB were enrolled. All participants underwent anthropometric measurement, blood testing, and FibroScan test. Multiple logistic regression analysis was used to investigate the association of serum sex hormones with hepatic steatosis.We included 137 males with and 131 without hepatic steatosis in this study. Subjects with serum testosterone (T) levels in the highest tertile had an odds ratio (OR) (95% confidence interval [CI]) of 0.35 (0.18-0.70) (P for trend=0.003); those with serum prolactin (PRL) levels in the highest tertile had an OR (95%CI) of 0.21 (0.10-0.45) (P for trend0.001); and those with serum estradiol/testosterone (E2/T) in the highest tertile had an OR (95%CI) of 4.02 (1.97-8.20) (P for trend0.001) for hepatic steatosis.Lower serum total T and PRL levels and higher total E2/T are independently associated with presence of hepatic steatosis in male patients with CHB.

Aim: In this study, we aimed to investigate the effects of menopause on serum levels of cortisol, alpha-amylase, dopamine, and prolactin in women with periodontitis and healthy controls.Methods: The study included a total of 80 women. Patients were diagnosed according to the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions criteria. The clinical examination included plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment loss (AL) measurements. The systemic levels of cortisol, alpha-amylase,dopamine, and prolactin were measured biochemically. Data were analyzed statistically. Results: The mean participant age was 44.32±3.23 (range: 33–55) years. The mean PI was 0.98±0.10, GI 0.94±0.31, PD 2.59±0.23 mm, and AL 2.65±0.16 mm. While prolactin levels were statistically significantly lower in menopausal women (p0.05). Levels of cortisol, dopamine and prolactinwere found to be significantly high in women with periodontitis (p

BACKGROUND The impact of estrogen and testosterone on atherosclerotic cardiovascular disease is well known, but the role of the gonadotropins follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) to some extent remain less studied. OBJECTIVES To explore the angiogenic potential of gonadotropins on endothelial colony-forming cells (ECFCs). METHODS We examined the effects of various doses of gonadotropins on ECFCs obtained from cord blood by assessing colony number, proliferation, migration, and sprouting ability. Moreover, we studied thrombin generation in ECFCs exposed to gonadotropins by performing a thrombin generation assay. Finally, we determined the levels of circulating gonadotropins in 30 men, to exclude the effect of estrogen, with lower extremity arterial disease (LEAD), in comparison with age- and sex-matched controls. RESULTS Exposure to FSH, LH, or PRL resulted in an increase in ECFC migration but showed no effect on proliferation or ECFC commitment from cord blood mononuclear cells. Using a three-dimensional fibrin gel assay, we showed that ECFC sprouting was significantly enhanced by gonadotropins. Exposure to FSH also increased the thrombin generation of ECFCs exposed to FSH. Finally, FSH and LH levels in men with LEAD were higher than those in controls. CONCLUSION Gonadotropins increase ECFC-related angiogenesis and may be involved in thrombin generation in cardiovascular disease. Gonadotropins may act as biomarkers; moreover, we hypothesize that gonadotropin-blocking strategies may be a novel interesting therapeutic approach in atherosclerotic cardiovascular disease.

Background As the critical tissue of the central nervous system, the brain has been found to be involved in gonad development. Previous studies have suggested that gonadal fate may be affected by the brain. Identifying brain-specific molecular changes that occur during estrodiol-17β (E2) -induced feminization is crucial to our understanding of the molecular control of sex differentiation by the brains of fish. Results In this study, the differential transcriptomic responses of the Takifugu rubripes larvae brain were compared after E2 treatment for 55 days. Our results showed that 514 genes were differentially expressed between E2-treated-XX (E-XX) and Control-XX (C-XX) T. rubripes, while 362 genes were differentially expressed between E2-treated-XY (E-XY) and Control-XY (C-XY). For example, the expression of cyp19a1b, gnrh1 and pgr was significantly up-regulated, while st, sl, tshβ, prl and pit-1, which belong to the growth hormone/prolactin family, were significantly down-regulated after E2 treatment, in both sexes. The arntl1, bhlbe, nr1d2, per1b, per3, cry1, cipc and ciart genes, which are involved in the circadian rhythm, were also found to be altered. Differentially expressed genes (DEGs), which were identified between E-XX and C-XX, were significantly enriched in neuroactive ligand-receptor interaction, arachidonic acid metabolism, cytokine-cytokine receptor interaction and the calcium signaling pathway. The DEGs that were identified between E-XY and C-XY were significantly enriched in tyrosine metabolism, phenylalanine metabolism, arachidonic acid metabolism and linoleic acid metabolism. Conclusion A number of genes and pathways were identified in the brain of E2-treated T. rubripes larvae by RNA-seq. It provided the opportunity for further study on the possible involvement of networks in the brain-pituitary-gonadal axis in sex differentiation in T. rubripes.

Background: Postpartum fatigue is a common disorder worldwide and affects both physical and mental functioning. In breastfeeding women, Prolactin (PRL) is not only involved in immunoregulation, but also responsible for lactation. Prolactin levels in women with chronic fatigue are higher than normal, but a chronic fatigue state inhibits postpartum lactation in humans. Objectives: This paper explored the inhibition mechanism of lactation by postpartum fatigue in rats. Methods: Postpartum fatigue models were built by forcing mother rats to stand in water and divided into 3-hour, 9-hour and 15-hour per day fatigue groups according to the underwater time. Mother rats and their offspring were reunited in a dry cage for 90 minutes every 3 hours for feeding. The expression of PRL, PRL receptor (PRLR), Janus Kinase 2 (JAK 2), and Signal transducers and activators of transcription 5 (STAT5) mRNA were analyzed and the microstructure of mammary gland were observed under light and electron microscopy. Results: The expression of pituitary PRL mRNA and its downstream signaling pathway JAK2 and STAT5 mRNA were down-regulated in the severe postpartum fatigue rats. PRL mRNA responses were dose-related to duration of fatigue. The expression of PRLR mRNA increased. Postpartum fatigue led to functional degeneration of mammary gland. The breast lobules were shrunk and the number of alveoli were decreased. Few milk protein granules and fat droplets were observed in the cytoplasm under transmission electron microscope. Conclusion: Postpartum fatigue inhibits the lactation by down-regulating the expression of PRL and PRL-dependent signaling pathway in rats.

The present study was designed to estimate the active ingredients in the aqueous extract of fennel Foeniculum vulgare L. fruits and test the effects of different concentrations of the extract on serum estrogen and prolactin levels in female rats. The work was conducted to prepare the aqueous extract in the laboratory, while the secondary active substances in the extract were estimated using High-Performance Liquid Chromatography (HPLC) technology. The experiments were conducted in the animal house of the College of Science, Tikrit university,on a total of 12 adult albino virgin female rats divided into four groups, each having three rats.The aqueous extract of the fruit plant was administrated orally to animals at three concentrations (50%, 75%, and 100%) per day for 45 days. The fourth group was the control group that was left without treatment. Blood samples were obtained from the corner of the eye with a capillary tube and the serum was extracted to determine the hormone levels. The results showed that the aqueous extract of fennel fruits contains eleven active secondary metabolites, namely Eucalyptol, Terpinene, Anisole, Camphor, Anethole, Anisaldehyde, Apiole, a-pinene, Estragole, Fenchone, and Limonene, which seemed to played a role in regulating the levels of prolactin and estrogen hormones in rats treated with the extract. The results showed a direct relationship between the concentration of the fruit extract given to the animals and their serum levels of estrogen and prolactin. Increases in the levels of estrogen (44.56 ± 0.90 ng/ml) and prolactin (134.66 ± 0.80 ng/ml) were recorded using the concentration of 100% of the watery extract of Foeniculum vulgare L., as compared to the control group (126.33 ± 1.18; 6.37 ± 0.45 ng / ml, respectively). The results demonstrated the effective role of the aqueous extract of fennel fruits in stimulating estrogen and prolactin in female rats through their content of active compounds, which can be of great importance in stimulating the process of milk secretion in animals.

Prolactin and placental lactogens increase during pregnancy and are involved with many aspects of maternal metabolic adaptation to pregnancy, likely to impact on fetal growth. The aim of this study was to determine whether maternal plasma prolactin or placental lactogen concentrations at 20 weeks of gestation were associated with later birth of small-for-gestational-age babies (SGA). In a nested case–control study, prolactin and placental lactogen in plasma samples obtained at 20 weeks of gestation were compared between 40 women who gave birth to SGA babies and 40 women with uncomplicated pregnancies and size appropriate-for-gestation-age (AGA) babies. Samples were collected as part of the 'screening of pregnancy endpoints' (SCOPE) prospective cohort study. SGA was defined as birthweight s.d., P = 0.036 Student’s t-test) compared to control pregnancies carrying a male fetus. Despite the implications of these lactogenic hormones in maternal metabolism, single measurements of either prolactin or placental lactogen at 20 weeks of gestation are unlikely to be useful biomarkers for SGA pregnancies. Lay summary Early identification during pregnancy of small for gestational age (SGA) babies would enable interventions to lower risk of complications around birth (perinatal), but current detection rates of these at risk babies is low. Pregnancy hormones, prolactin and placental lactogen, are involved in metabolic changes that are required for the mother to support optimal growth and development of her offspring during pregnancy. The levels of these hormones may provide a measurable indicator (biomarker) to help identify these at risk pregnancies. Levels of these hormones were measured in samples from week 20 of gestation from women who went on to have SGA babies and control pregnancies where babies were born at a size appropriate for gestation age. Despite the implications of prolactin and placental lactogen in maternal metabolism, no significant differences were detected suggesting that single measures of either prolactin or placental lactogen at 20 weeks gestation are unlikely to be useful biomarker to help detect SGA pregnancies.

Introduction: Parvalbumin (PV)-positive cells are strategic elements of neuronal networks capable of influencing memory and learning processes. However, it is not known whether pituitary hormones may be related to PV expression in the hippocampus – a part of the limbic system with important functions in learning and memory. Objective: Since previous studies indicate that prolactin (PRL) plays a significant role in hippocampal-dependent learning and synaptic plasticity, we hypothesized that a rise in PRL levels can modify PV expression in the hippocampus. Methods: We employed biochemical, immunohistochemistry, and densitometry techniques – as well as a behavioural assay – in a hyperprolactinemia model using subcutaneous osmotic pumps in female mice. Results: PRL treatment via osmotic pump induced an increase in PRL receptor (PRLR) expression in most regions of the hippocampus analysed by Western blotting and immunohistochemistry methods. Fluorescent densitometry analysis revealed that PV expression decreases in the same layers in the hippocampus following PRL treatment, while double labelling immunostaining indicated close localization of PV and PRLR in PV-positive interneurons. In addition, we found that PRL induced a reduction in the β2/3 subunit of GABAA receptor (GABAAR) expression that was linearly correlated with the reduction in PV expression. This reduction in the β2/3 subunit of GABAAR expression was maintained in trained animals in which PRL treatment improved the learning of a spatial memory task. Conclusions: These data show, for the first time, that an increase in PRL level is associated with changes in key constituent elements of inhibitory circuits in the hippocampus and may be of relevance for the alterations in cognitive function reported in hyperprolactinemia.

Previous studies have demonstrated nonsteroidal antiinflammatory drug treatment in early lactation had a positive impact on whole-lactation milk production in older cows. The objective of this study was to evaluate proliferative, transcriptional, and epigenetic changes in the mammary gland that could explain increased production responses due to nonsteroidal antiinflammatory drug treatment. Sodium salicylate (SAL; 125 g/d) or water (CON) were administered via oral drench to multiparous Holstein cows (n = 8/treatment) once daily for 3 d beginning approximately 24 h after parturition, and mammary tissue was collected on d 1, 4, and 45 postpartum. Day 1 tissue was collected immediately preceding the initial drench, and d 4 tissue was collected 24 h following the final drench. Blood was collected twice weekly and analyzed for plasma glucose, insulin, β-hydroxybutyrate, free fatty acids, and prolactin. Cows were milked twice daily until d 7 of lactation, and thrice daily for the remainder of the study. Total RNA extracted from tissue was deep-sequenced and analyzed for differential gene expression using DESeq2. We detected no treatment effect on milk yield or plasma metabolites through 45 d of lactation; additionally, no change in mammary epithelial cell proliferation was detected when assessed by Ki67 labeling. Comparison of SAL versus CON revealed that only 16 of 18,286 genes were differentially expressed (false discovery rate

Background and Aim: Goats are widely distributed in southwest Algeria. The Saharan goat is perfectly adapted to the harsh conditions of arid areas, and it is characterized by resistance to long photoperiod and reduced metabolic needs, allowing the survival of its offspring by maintaining lactation. Several studies have demonstrated that parturition and lactation are critical periods that induce hormone, energy, and lipid status changes in mammals. However, the relationship between the blood biochemical parameters of parturition control and lactation functions in the Algerian Saharan goat has not been thoroughly documented. Therefore, this study assesses hormone and metabolite levels during parturition and early lactation in Saharan goats reared in arid areas. Materials and Methods: Experiments were performed on 14 multiparous female goats, and blood samples were collected during parturition, 4 days postpartum (D1PP-D4PP), and during the first 12 weeks of lactation (W1-W12) to analyze prolactin, cortisol, glucose (GLU), total proteins (TP), cholesterol (CHO), triglycerides (TGs), total lipids (TL), low-density lipoproteins (LDLs), high-density lipoproteins (HDLs), and very LDLs (VLDLs). Results: Statistical data analysis revealed a significant (p

Genistein is a soy isoflavone and shows various physiological activities, such as affinities for estrogen receptors (ERs) and inhibitory effects on the epidermal growth factor receptor (EGFR) pathway. A previous study reported that genistein downregulates milk production ability in mammary epithelial cells (MECs) while decreasing the phosphorylation of STAT5. The ER and EGFR pathways indirectly regulate STAT5. In this study, the repressing mechanism of genistein against the phosphorylation of STAT5 was investigated using a culture model of mouse MECs with milk production ability. The results revealed that genistein did not influence the behavior of ERa and ER beta, whereas genistein immediately repressed the phosphorylation of ERK1/2. However, the decrease in phosphorylated STAT5 occurred independent of the phosphorylation of EGFR. Genistein repressed new phosphorylation of STAT5 by prolactin without influencing the phosphorylation of JAK2. In conclusion, this study indicates that genistein directly inhibits the phosphorylation of STAT5 in lactating MECs.

As numerous studies of scientists show, the genotype for prolactin (PRL) and somatotropin (GH) genes of cows affects the milk productivity and the quality of their milk. In this regard, the purpose of this study was to study the milk productivity and qualitative composition of milk in Tatarstan-type cows with different genotypes of prolactin and somatotropin in the conditions of the Republic of Tatarstan. The analysis of the milk productivity of the first heifers of the Tatarstan type with different genotypes according to the loci of the prolactin and somatotropin genes showed that the highest indicators for milk yield, the amount of milk fat and protein had the genotypes PRL/AA, GH/LL and GH/LV compared with analogues of other genotypes.

Idiopathic condylar resorption (ICR) is an aggressive form of temporomandibular joint disease that most frequently presents in adolescent girls during the pubertal growth spurt. Although numerous studies have indicated that the etiopathogenesis of ICR may be related to estrogen deficiency, the decisive role of estrogens remains controversial, and other sex hormone disturbances have not yet been investigated in this regard. Therefore, the aim of this study was to ascertain the role of serum estrogen levels and also the roles of other sex hormones in the pathogenesis of ICR. Ninety-four ICR patients and 324 disc displacement (DD) patients, of both sexes, were enrolled. Information on menstruation and serum levels of follicle-stimulating hormone, luteinizing hormone, prolactin, 17β-estradiol (E2), testosterone, and progesterone were recorded and analyzed. The results showed that female ICR patients had normal puberty onset, within the average age range. Use of oral contraceptives and other menstruation-regulating pharmaceuticals was similar in the two groups. Of note, neither serum E2 levels nor those of the other sex hormones differed significantly between female ICR and DD patients. However, male ICR patients had significantly increased serum testosterone levels (P=0.002) and relatively higher E2 levels (P=0.095) compared to DD patients. This study found that reduced serum E2 did not contribute to ICR; instead, systemic testosterone disturbances were found to be related to ICR.

Breastfeeding is a hallmark of mammals. The determination of the role of neuropeptides in the neuroendocrine regulation of mammary gland functions and parental behavior in mammals and humans is a priority for understanding these vital processes. Since in lactating females the suckling stimulus induces burst secretion of prolactin, oxytocin, and thyrotropin-releasing hormone (TRH), here we investigate the possibility of the effect of TRH on prolactin-dependent lactogenesis and oxytocin-mediated milk ejection reflex, as well as on components of the maternal behavior. It was found that bilateral intranasal infusions of TRH to lactating female mice specifically facilitate suckling, but not eating or drinking, behavior. TRH increased the duration of suckling periods and the number of milk ejection reflexes in response to pups’ sucking, while simultaneously increasing the duration of intervals in between. Optical and electron microscopic studies revealed significant alterations in mammary alveolar epitheliocytes, indicating a TRH-induced increase in milk production in the mammary gland, as confirmed by a higher rate of weight gain in mouse pups and their better survival. The absence of changes in females’ thyroxine and triiodothyronine plasma levels, as determined by enzyme immunoassay, after chronic infusions of low-dose TRH attests to the invariability of the maternal thyroid status. We assume that TRH is implicated in coordinating the mechanisms of patterning the neuroendocrine milk ejection reflex, maternal behavior, and increased synthetic activity in the mouse mammary gland.

© 2021 American College of Medical Genetics and GenomicsPurpose: We aimed to investigate the molecular basis underlying a novel phenotype including hypopituitarism associated with primary ovarian insufficiency. Methods: We used next-generation sequencing to identify variants in all pedigrees. Expression of Rnpc3/RNPC3 was analyzed by in situ hybridization on murine/human embryonic sections. CRISPR/Cas9 was used to generate mice carrying the p.Leu483Phe pathogenic variant in the conserved murine Rnpc3 RRM2 domain. Results: We described 15 patients from 9 pedigrees with biallelic pathogenic variants in RNPC3, encoding a specific protein component of the minor spliceosome, which is associated with a hypopituitary phenotype, including severe growth hormone (GH) deficiency, hypoprolactinemia, variable thyrotropin (also known as thyroid-stimulating hormone) deficiency, and anterior pituitary hypoplasia. Primary ovarian insufficiency was diagnosed in 8 of 9 affected females, whereas males had normal gonadal function. In addition, 2 affected males displayed normal growth when off GH treatment despite severe biochemical GH deficiency. In both mouse and human embryos, Rnpc3/RNPC3 was expressed in the developing forebrain, including the hypothalamus and Rathke's pouch. Female Rnpc3 mutant mice displayed a reduction in pituitary GH content but with no reproductive impairment in young mice. Male mice exhibited no obvious phenotype. Conclusion: Our findings suggest novel insights into the role of RNPC3 in female-specific gonadal function and emphasize a critical role for the minor spliceosome in pituitary and ovarian development and function.

Purpose: To determine the effect of Bu-Shen-Zhu-Yun Decoction (BSZY-D) on the kisspeptin through JAK2/STAT5 signaling pathway in hyperprolactinemia (HPRL) infertility. Method: SD rats were treated with BSZY-D for cerebrospinal fluid (CSF) extraction. GT1-7 cells were subjected to different treatments. The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin of GT1-7 cells in different groups were detected by western blot, RT-qPCR and immunofluorescence. The expressions of CSN5 and GATA1 and other molecular features were checked by western blot, RT-PCR, co-immunoprecipitation and renilla luciferase activity. Results: The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin in the HPRL group were significantly decreased, and these changes could be reversed after BSZY-D treatment. In addition, the presence of PRLR deubiquitination was detected in the HPRL group, which could be reversed by shRNA-CSN5, suggesting that BSZY-D played a role through targeting CSN5. The binding level of GATA1 and CSN5 promoter in the HPRL group was significantly decreased, but elevated in the HPRL (BSZY-D/CSF) group (P < 0.05). Conclusion: BSZY-D improved the transcription activity of GATA1 and increased the binding of GATA1 and CSN5. BSZY-D was involved in the deubiquitination of PRLR, which contributes to alleviating the symptoms of HPRL infertility.

BACKGROUND: Carica papaya leaves (Carica papaya L) have been used empirically and traditionally as a galactogogue, but their mechanism as galactogogue is still unknown. AIM: This study aimed to analyze the effect of ethanol extract from papaya leaves on blood prolactin levels, prolactin receptor (prlr) gene expression, the number of breast alveoli and lobes of lactating rats. METHODS: This in vivo true experimental study with a post-test control group design was conducted on 24 rats with the same lactating period. They were divided into four groups consisting of six rats each. The control group was given daily standard food, whereas the three treatment groups were, respectively, given additionally ethanol extract of 0.95 mg, 1.9 mg, and 3.8 mg/200 g BW/day from day 1 to day 14 of lactation. On day 14, all of the rats were sacrificed, blood prolactin levels were measured by ELISA, prlr gene expressions were measured using RT-PCR, and numbers of breast alveoli and lobes were microscopically observed through staining histological specimens. A statistical analysis was carried out using one-way ANOVA, Tukey's test, Games–Howell test, and path analysis at 95% confidence level. RESULTS: Levels of blood prolactin levels, prlr gene expression, the number of breast alveoli, and lobes of all treatment rat groups were significantly above those of the control group (p < 0.05). The increases of all parameters were consistent; the most effective dose was 1.9 mg/200 g BW. CONCLUSION: The Carica papaya leaf ethanol extract had a galactogogue effect on lactating rats by increasing blood prolactin levels, prlr gene expression, and numbers number of breast alveoli and lobes.

Objective was to elucidate the effects of heat stress (HS) on embryo development during first 16 gestational days (GD) and circulating hormone concentrations on GD-16 in lactating Holstein cows. Cows in HS and control (CON) groups were exposed to temperature humidity index (THI) of ≥ 73 and P P P P P P

Background POU1F1 encodes both PIT-1α, which plays pivotal roles in pituitary development and GH, PRL and TSHB expression, and the alternatively spliced isoform PIT-1β, which contains an insertion of 26-amino acids (β-domain) in the transactivation domain of PIT-1α due to the use of an alternative splice acceptor at the end of the first intron. PIT-1β is expressed at much lower levels than PIT-1α and represses endogenous PIT-1α transcriptional activity. Although POU1F1 mutations lead to combined pituitary hormone deficiency (CPHD), no patients with β-domain mutations have been reported. Results Here, we report that a three-generation family exhibited different degrees of CPHD, including growth hormone deficiency with intrafamilial variability of prolactin/TSH insufficiency and unexpected prolactinoma occurrence. The CPHD was due to a novel POU1F1 heterozygous variant (c.143-69T>G) in intron 1 of PIT-1α (RefSeq number NM_000306) or as c.152T>G (p.Ile51Ser) in exon 2 of PIT-1β (NM_001122757). Gene splicing experiments showed that this mutation yielded the PIT-1β transcript without other transcripts. The lymphocyte PIT-1β mRNA expression was significantly higher in the patients with the heterozygous mutation than a control. A luciferase reporter assay revealed that the PIT-1β-Ile51Ser mutant repressed PIT-1α and abolished transactivation capacity for the rat prolactin promoter in GH3 pituitary cells. Conclusions We describe, for the first time, that the PIT-1β mutation can cause CPHD through a novel genetic mechanism, such as PIT-1β overexpression, and that POU1F1 mutation might be associated with a prolactinoma. Analysis of new patients and long-term follow-up are needed to clarify the characteristics of PIT-1β mutations.

A recent ethnobotanical study collected traditional knowledge on treatments and plants of tribes in Uige, Northern Angola, a region suffering from infant malnutrition and mortality. Aqueous extracts of twelve different plant species (leaves or stems) collected were prepared and subject of chemical profiling. The impact of twelve plant extracts on mammary epithelial cell differentiation was tested in vitro by dose-dependent treatment of HC11 cells. Leaf extracts of Carica papaya and Morinda lucida induced HC11 differentiation and elevated the mRNA expression of the milk protein β-casein, while the remaining ten inhibited the HC11 mammary differentiation.The majority of the plant extracts did not induce in vitro mammary epithelial cell differentiation assuming that the plants might rather exert their effects on prolactin levels or on other mechanism influencing the mammary gland health. Phenolic acids and flavonoids were identified as the predominant and potentially active chemical classes responsible for the observed lactogenic effects.

Изучена взаимосвязь аллельных вариантов генов пролактина и соматотропина с показателями молочной продуктивности коров черно-пестрой породы по 1 и 3 лактации. У первотелок, как и у полновозрастных животных, наиболее высокий удой (4642 и 6240 кг), количество молочного жира (174,1 и 215,0 кг) и молочного белка (149,0 и 182,5 кг) достигнуты в группе с генотипом PRL АА. По массовой доле жира и белка в молоке коровы с генотипом PRL ВВ достоверно превосходили животных с генотипом PRL АА на 0,12% (Р The interrelation of allelic variants of prolactin and somatotropin genes with indicators of milk productivity of black-and-white cows for the 1st and 3rd lactation was studied. The highest milk yield (4642 and 6240 kg) amount of milk fat (174.1 and 215.0 kg) and milk protein (149.0 and 182.5 kg) were in the group with the PRL AA genotype in first-calf heifers as well as in full-age animals. In terms of the mass fraction of fat and protein of milk, the cows with the PRL BB genotype significantly exceeded animals with the PRL AA genotype by 0.12% (P

Aim: to identify clinical and laboratory biomarkers that determine the nature of the course of myopic choroidal neovascularization (mCNV) and the response to anti-VEGF therapy in women.Material and methods. A prospective non-randomized study was conducted in 52 patients (52 eyes) with active mCNV, treated with ranibizumab intravitreally, 0.5mg. After 12months, the suppression of CNV activity, the number of injections and the fellow eye inclusion in the pathological process were taken into account. There were 2 groups: with a favorable clinical course (n = 31, age – 33,0 ± 5,1 years, anterior-posterior axis (APA) 28,5 ± 0,3 mm) and an unfavorable clinical course (n = 21, age – 34,0 ± 4,1 years, APA – 29,01 ± 0,1 mm). Structural retinal changes, choroid thickness, retinal blood flow, and heart rate were evaluated using OCT and OCTA protocols (Optovue XR Avanti, USA). Studies were conducted before the start of therapy and then one time per month. The concentration of sex and pituitary hormones (ELISA analyzer “Immunohem-2100”), lipoprotein A, Apo B/Apo A (Accent 200 Cormay, Poland), coagulogram data (Helena C-2, UK), and the concentration of highly sensitive C-reactive protein in blood serum before the start of antiangiogenic therapy were studied once.Results. In the first group, 1.4 ± 0.7 ranibizumab injections were administered to suppress the CNV activity. In the opposite group – 3.5 ± 2.1 injections, in 73.7 % of cases, relapses were diagnosed, in 3 cases – primary CNV in the fellow eye. Clinical and laboratory biomarkers of the unfavorable clinical course of mCNV were identified: extreme choroidal thinning, highly organized membranes of a large area, dome-shaped deformation of the posterior pole, excess of the reference values of lipoprotein A, fibrinogen and highly sensitive C-reactive protein by two or more times, an imbalance of sex and pituitary hormones (excess of the reference values of prolactin, follicle stimulating hormone, cortisol, progesterone concentration decrease), a predominant change in the menstrual-ovarian cycle according to the type of amenorrhea and opsomenorrhea.Conclusion. Myopic CNV biomarkers in women allow predicting the response to anti-VEGF therapy, the formation of relapses and the inclusion of the fellow eye in the pathological process.

We evaluated the efficacy of Tribulus terrestris in two different dosage regimes for the treatment of sexual dysfunction in pre and postmenopausal women and its effect on the vascular resistance of the clitoral artery using Power Doppler. A total of 104 women were randomly assigned to receive 94mg, three times/day (TT3) or 280mg once/day for 90 days (TT1). Evaluation was performed using FSFI and QS-F questionnaires, serum levels of prolactin, TSH, total testosterone and SHBG, and clitoral artery assessment with Power Doppler ultrasound. FSFI results demonstrated an improvement in all domains in both groups (P < 0.05) except for the "Satisfaction" in the TT3 premenopausal group. QS-F results showed a significant improvement in the mean total score in women of both reproductive phases, for both groups. Postmenopausal patients improved in all sexual domains, except for "orgasm" in the TT1 group. PI of the clitoral artery showed no difference in both reproductive phases, in both groups. We conclude that TTerrestris can be a safe alternative for the treatment of sexual dysfunction in pre and postmenopausal women as it is effective in reducing the symptoms with no side effects. Moreover, its use, increased total, free and bioavailable testosterone.

As a traditional veterinary medicine to promote lactation, Cui Nai Ling (CNL) can not only increase milk supply and promote health but also improve the overall physiological function and immunity of the animals. In order to further improve CNL’s effect on lactation, we have previously made a new CNL (NCNL) by adding Tetrapanacis Medulla and replacing Vaccariae Semen with fried Vaccariae Semen in CNL. We have demonstrated that the lactation-promoting effect of NCNL is better than that of CNL. However, the underlying mechanisms by which NCNL promotes lactation are unclear. In this study, we performed metabolomics, network pharmacology, and pharmacodynamic studies to explore the underlying mechanisms by which NCNL promotes lactation in rats with bromocriptine-induced hypogalactia. The results showed that NCNL significantly improved the loss of appetite in female adult rats and the weight loss of pups caused by the disorder of lactation. Biochemical analysis showed that NCNL could regulate the levels of PRL, T4, E2, Ca, UREA, GLU, ALT, AST, TCHO, and TG in serum. The pathological results showed that NCNL could promote lactation and increase the mammary gland index by improving breast acinar tissue morphology in rats with hypogalactia. Network pharmacology studies showed that NCNL promotes lactation through P13K-Akt, insulin resistance, and prolactin signaling pathways, among which the most frequently affected pathway was the P13K-Akt signaling pathway. Metabolomics studies showed that NCNL can significantly upregulate phenylalanine, tyrosine, and tryptophan biosynthesis and tyrosine metabolism pathways and downregulate cysteine and methionine metabolism pathways. NCNL can significantly increase the serum prolactin concentration, improve the glucose and lipid metabolism disorders, and regulate PI3K-Akt, insulin resistance, and prolactin pathways to affect the amino acids’ metabolism in the mammary gland and ultimately exert its therapeutic effect on bromocriptine-induced postpartum hypogalactia. These findings revealed the effect and application value of NCNL on animals with postpartum hypogalactia.

Prolactin (PRL) is a key hormone involved in canine mammary development and tumorigenesis. In this study, the influence of a single nucleotide polymorphism (SNP) in the PRL gene (rs23932236) on the clinicopathological parameters and survival of dogs with canine mammary tumors (CMTs) was investigated. A total of 206 female dogs with spontaneous mammary tumors were enrolled in this study and circulating blood cells were genotyped. This specific SNP was associated with larger size (>3 cm diameter) for malignant tumors ( P = .036), tumors with infiltrative/invasive growth pattern ( P = .010), vascular invasion ( P = .006), and lymph node metastasis ( P = .004). Carriers of the variant allele had a shorter overall survival compared to the wild-type population with an overall survival of 18.7 months and 22.7 months, respectively ( P = .004). These findings suggest that SNP rs23932236 of canine PRL gene may be used as an indicator for the development of clinically aggressive forms of CMTs.

Background Circulating prolactin concentration in rodents and humans is sexually dimorphic. Estrogens are a well-characterised stimulator of prolactin release. Circulating prolactin fluctuates throughout the menstrual/estrous cycle of females in response to estrogen levels, but remains continually low in males. We have previously identified androgens as an inhibitor of prolactin release through characterisation of males of a mouse line with a conditional pituitary androgen receptor knockout (PARKO) which have an increase in circulating prolactin, but unchanged lactotroph number. Objectives In the present study we aimed to specify the cell type that androgens act on to repress prolactin release. Materials and methods PARKO, lactotroph-specific, Pit1 lineage-specific and neural-specific conditional androgen receptor knockout male mice were investigated using prolactin ELISA, pituitary electron microscopy, immunohistochemistry and qRT-PCR. Results Lactotroph-specific, Pit1 lineage-specific and neural-specific conditional AR knockouts did not duplicate the high circulating prolactin seen in the PARKO line. Using electron microscopy to examine ultrastructure we showed that pituitary androgen receptor knockout male mice develop lactotrophs that resemble those seen in female mice. Castrated PARKO males have significantly reduced circulating prolactin compared to intact males. When expression of selected estrogen-regulated anterior pituitary genes were examined there were no differences in expression level between controls and knockouts. Discussion The cell type that androgens act on to repress prolactin release is not the lactotroph, cells in the Pit1-lineage, or the dopaminergic neurons in the hypothalamus. PARKO males develop a female-specific lactotroph ultrastructure that this is likely to contribute to the increase in circulating prolactin. Castrated PARKO males have significantly reduced circulating prolactin compared to intact males, which suggests that removal of both circulating estrogens and androgens reduces the stimulation of pituitary prolactin release. Conclusion Further investigation is needed into prolactin regulation by changes in androgen-estrogen balance, which is involved sexual dimorphism of development and diseases including hyperprolactinemia. This article is protected by copyright. All rights reserved.

The hormone prolactin acquires antiangiogenic and antivasopermeability properties after undergoing proteolytic cleavage to vasoinhibin, an endogenous prolactin fragment of 123 or more amino acids that inhibits the action of multiple proangiogenic factors. Preclinical and clinical evidence supports the therapeutic potential of vasoinhibin against angiogenesis-related diseases including diabetic retinopathy, peripartum cardiomyopathy, rheumatoid arthritis, and cancer. However, the use of vasoinhibin in the clinic has been limited by difficulties in its production. Here, we removed this barrier to using vasoinhibin as a therapeutic agent by showing that a short linear motif of just three residues (His46-Gly47-Arg48) (HGR) is the functional determinant of vasoinhibin. The HGR motif is conserved throughout evolution, its mutation led to vasoinhibin loss of function, and oligopeptides containing this sequence inhibited angiogenesis and vasopermeability with the same potency as whole vasoinhibin. Furthermore, the oral administration of an optimized cyclic retro-inverse vasoinhibin heptapeptide containing HGR inhibited melanoma tumor growth and vascularization in mice and exhibited equal or higher antiangiogenic potency than other antiangiogenic molecules currently used as anti-cancer drugs in the clinic. Finally, by unveiling the mechanism that obscures the HGR motif in prolactin, we anticipate the development of vasoinhibin-specific antibodies to solve the on-going challenge of measuring endogenous vasoinhibin levels for diagnostic and interventional purposes, the design of vasoinhibin antagonists for managing insufficient angiogenesis, and the identification of putative therapeutic proteins containing HGR.

Oxytocin receptor (OXTR) is involved in social behaviors, thermoregulation, and milk ejection, yet little is known about its role in breast cancer. To investigate the role of OXTR in mammary gland development and tumorigenesis, a transgenic mouse model of OXTR overexpression (++Oxtr) was used. Overexpression of OXTR-induced progressive mammary hyperplasia, unexpected milk production, and tumorigenesis in females. OXTR-induced mammary tumors showed ERBB2 upregulation and mixed histological subtypes with predomination of papillary and medullary carcinomas. OXTR overexpression led to an activation of prolactin (PRL)/p-STAT5 pathway and created a microenvironment that promotes mammary-specific tumorigenesis. PRL inhibitor bromocriptine (Br) could mitigate OXTR-driven mammary tumor growth. The study demonstrates Oxtr is an oncogene and a potential drug target for HER2-type breast cancer.

Prolactin has a rich mechanistic set of actions and signaling in order to elicit developmental effects in mammals. Historically, prolactin has been appreciated as an endocrine peptide hormone that is responsible for final, functional mammary gland development and lactation. Multiple signaling pathways impacted upon by the microenvironment contribute to cell function and differentiation. Endocrine, autocrine and paracrine signaling are now apparent in not only mammary development, but also in cancer, and involve multiple cell types including those of the immune system. Multiple ligands agonists are capable of binding to the prolactin receptor, potentially expanding receptor function. Prolactin has an important role not only in tumorigenesis of the breast, but also in a number of hormonally responsive cancers such as prostate, ovarian and endometrial cancer, as well as pancreatic and lung cancer. Although pituitary and extra-pituitary sources of prolactin such as the epithelium are important, stromal sourced prolactin is now also being recognized as an important factor in tumor progression, all of which potentially signal to multiple cell types in the tumor microenvironment. While prolactin has important roles in milk production including calcium and bone homeostasis, in the disease state it can also affect bone homeostasis. Prolactin also impacts metastatic cancer of the breast to modulate the bone microenvironment and promote bone damage. Prolactin has a fascinating contribution in both physiologic and pathologic settings of mammals.

Nasturtium is a plant in the family Trapaeolaceae cultivated in Europe, Asia, Africa, and America, which has numerous healing, antiseptic, and expectorant activities. It is the most important herbal medicine used for curing some diseases like diabetes, bronchitis, cardiovascular disorders, and urinary tract infections. There are many chemical constituents isolated from Nasturtium including polyphenols, glucosilonates and fatty acids. Many systems of the body like the reproductive system are affected by some herbal plants, which contain essential chemical active substances with biological properties. The present study was conducted to investigate the effect of hydroethanolic extract of Nasturtium on parameters of reproductive and sex hormones on male rats. Sixty mature male albino rats weighing 180-200 g were divided into three equal groups at random. The first group was kept as a monitor and consisted of 20 rats that were given distilled water daily for 30 days. The second group consisted of 20 rats, which were given hydroethanolic extract of Nasturtium flowers orally via a stomach tube at a dose of 250 mg/kg body weight (BW.), and the third group consisted of 20 rats, those were given hydro-alcoholic extract of Nasturtium leaves every day for four weeks. Blood samples were collected from all rats to estimate serum levels of luteinizing hormone (LH) and follicular stimulating hormone (FSH), testosterone and prolactin. The testicles, seminal vesicles and prostate glands were weighted and the sperms were collected from the epididymis to calculate the sperm count. The results showed decreased testosterone level in flower extract (1.10 ± 0.238) and leaves extract (0.89 ± 0.08) compared to the control group (3.75 ± 0.35). Also, LH decreased in flower extract (0.225 ± 0.025) and leave extract (0.103 ± 0.003) compared to the control group (0.105 ± 0.003). Meanwhile, serum FSH level in flower extract (0.60 ± 0.07)and leaves extract (0.45 ± 0.05) showed non-significant change compared with the control group (0.35 ± 0.029). The fast mobility of sperm indicated non-significant change compared with the control group. In conclusion, hydroethanolic extract of Nasturtium make attributed levels on sex hormones, which give negative effect on fertility despite of its chemical compounds.

Summary Parasitic diseases of sheep involving gastrointestinal nematodes (GIN) are one of the main problems that affect fl ock productivity, especially during the peripartum period. Around lambing, the ewes are immunosuppressed and the nematode faecal egg count (FEC) increases at four weeks before lambing, reaching a peak between the fourth and sixth week postpartum and subsequently decreasing towards weaning. Prolactin has been credited with a suppressive effect on immune system, along with other hormones that intervene in metabolism, such as leptin, which has an important role in the activation of other hormones. Cortisol has also been included; this is stimulated by any stressful event and inhibits the proliferation of T-cells and alters the function of immunoglobulins. Another related hormone is pepsinogen, which is considered a marker of the integrity of the abomasum mucosa, as well as the albumin concentration that increases in the presence of a GIN infection. The humoral and cellular immune response, as well as inflammatory reactions, are the main mechanisms of action against GIN. Lymphocytes direct the effector mechanisms in a Th2 cell response, including interleukins (IL-4, IL-5, IL-9, IL-10) and transforming growth factor beta (TGF-β) together with immunoglobulins (IgA, IgG, IgM and IgE), which prevent the invasion of pathogens. Eosinophils with a cytotoxic effect are indicators of a parasitic infection, with importance in the immune protection of infected individuals. The genetic selection of resistant individuals measured by FEC is dependent on the heritability (h2), which is moderately inheritable and highly repeatable. Effects that influence the resistance or susceptibility of sheep to GIN infections in the peripartum period are determined by the interaction of various factors, such as genotype or breed, nutrition, age, type of birth, season and production system, etc., which are studied in this review.

Milk is critical for the survival of all mammalian offspring, where its production by a mammary gland is also positively associated with its lactose concentration. A clearer understanding of the factors that regulate lactose synthesis stands to direct strategies for improving neonatal health while also highlighting opportunities to manipulate and improve milk production and composition. In this review we draw a cross-species comparison of the extra- and intramammary factors that regulate lactose synthesis, with a special focus on humans, dairy animals, and rodents. We outline the various factors known to influence lactose synthesis including diet, hormones, and substrate supply, as well as the intracellular molecular and genetic mechanisms. We also discuss the strengths and limitations of various in vivo and in vitro systems for the study of lactose synthesis, which remains an important research gap. Supplementary Information The online version contains supplementary material available at 10.1007/s10911-021-09491-6.

A gradual change in daylight length during the year affects the breeding season of Egyptian geese. So the application of optimal photoperiod is essential to improve the reproductive capacity of the animal. This study was conducted to assess the changes in behaviour, circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and reproductive traits during the season of breeding in Geese. Eighty female geese at age 12 months with an average body weight of 2800 ± 200 g were selected and observed from 1st January to June. A total of 80 female Egyptian geese at age 12 months with an average body weight 2800 ± 200 g were distributed randomly into four groups (20 geese for each group), 5 replicates groups were made comprising 4 birds each. Our results showed a significant increase in feeding, locomotion, body care, and alert behaviour during laying period, with more walking, flaying and swimming, sun rays help bird for more preening to self-grooming enrichment by a pool of water help bird for swimming. The highest FSH and LH levels were recorded during the period of laying, while their lowest levels were during the period of incubation. Egg number and hatchability increased in June compared to March, April, and May by an increase in daylight hours during the breeding season. It could be concluded that the increase in daylight length had a favorable effect on behaviour, gonadotropins, egg number, and hatchability during spring (March- beginning of June, where there is an increase in daylight length) in geese.

Prolactin is an adenohypophyseal hormone of vertebrates produced by the neuroendocrine signaling of the hypothalamus. It plays important role in different vertebrate species and referred to as “The Parental Hormone” or “The Hormone of Maternity”. In birds the role of Prolactin is limited as the parental hormone but the behavioral functions like the regulation of season-al reproduction, combating stress of predators, nest building abilities and regulations of migratory cycle are diversified. The classical role of Prolactin in different birds’ species like pigeons and doves is secretion of crop sac “milk” after hatching of eggs and regulation of migration in different type of mi-grants. Reports have suggested that acute and chronic stressors and ener-getic constraints depress prolactin levels disrupting the parental effort in nest building, mate selection, incubation and crop milk production. Although prolactin is diverse in its function but acts through the same receptors throughout the vertebrate series. However, this review establishes that pro-lactin plays an intense role in regulating breeding behaviours and migration in birds along with the interactions of other hormones. Prolactin helps the birds to carry out wide range of behaviour and become evolutionarily suc-cessful.

Aquatic ecosystems often receive a wide spectrum of pollutants introduced directly or indirectly. The herbicide atrazine, an endocrine disrupting chemical (EDC), frequently contaminates potable wat...

A supply of hormone-producing cells from stem/progenitor cells is critical to sustain the endocrine activity of the pituitary gland. In the adenohypophysis composing the anterior and intermediate lobe (AL and IL, respectively), stem/progenitor cells expressing sex-determining region Y-box 2 (SOX2) and S100β are located in the marginal cell layer (MCL) facing Rathke's cleft (primary niche) and the parenchyma of the AL (secondary niche). Our previous studies using mice and rats indicated that the tetraspanin superfamily CD9 and CD81 are expressed in S100β/SOX2-positive cells of primary and secondary niches (named CD9/CD81/S100β/SOX2-positive cell), and the cells located in the AL-side niches exhibit plasticity and multipotency. However, it is unclear whether CD9/CD81/S100β/SOX2-positive cells in the IL-side primary niche are stem/progenitor cells for the AL or IL. Here, we successfully isolated pure CD9/CD81/S100β/SOX2-positive cells from the IL-side primary niche. They had a higher level of S100β and SOX2 mRNA and a greater pituisphere forming capacity than those of CD9/CD81/S100β/SOX2-positive cells isolated from the AL. They also had capacity to differentiate into all types of adenohypophyseal hormone-producing cells, concomitantly with the loss of CD9 expression. Loss of CD9 and CD81 function in CD9/CD81/S100β/SOX2-positive cells by siRNA treatment impaired prolactin cell differentiation. Consistently, in the pituitary gland of CD9/CD81 double knockout mice, dysgenesis of the MCL and a lower population of prolactin cells were observed. These results suggest that the CD9/CD81/S100β/SOX2-positive cells in the MCL of the IL-side are potential suppliers of adult core stem cells in the AL.

Egg rejection is the most effective and widespread defense used by host species to counteract the extreme fitness costs frequently imposed by obligate avian brood parasites. Yet, the proximate mechanisms underlying between- and within-individual variation in host responses remain poorly explored. Emerging evidence suggests that egg rejection is dependent on individual physiological states, and draws attention to the role of hormones as mediators of flexible antiparasitic responses. In this perspective article, I outline recent advances in our understanding of the proximate factors that mediate egg rejection. I also point out some areas where knowledge remains still lacking, especially those related to the development and maintenance of effective cognitive functions, the potential role of oxidative stress, immunological state, and developmental stressors. I propose new hypotheses that stimulate future research on behavioral host responses toward brood parasitism.

BACKGROUND/OBJECTIVES Premenstrual syndrome (PMS) is a disorder characterized by repeated emotional, behavioral, and physical symptoms before menstruation, and the exact cause and mechanism are uncertain. Hyperprolactinemia interferes with the normal production of estrogen and progesterone, leading to PMS symptoms. Thus, we judged that the inhibition of prolactin hypersecretion could mitigate PMS symptoms. MATERIALS/METHODS Hordeum vulgare L. extract (HVE), Chrysanthemum zawadskii var. latilobum extract (CZE), and Lomens-P0 the mixture of these extracts were tested in subsequent experiments. The effect of extracts on prolactin secretion at the in vitro level was measured in GH3 cells. Nitric oxide and pro-inflammatory mediator expression were measured in RAW 264.7 cells to confirm the anti-inflammatory effect. Also, the hyperprolactinemic Institute for Cancer Research (ICR) mice model was used to measure extract effects on prolactin and hormone secretion and uterine inflammation. RESULTS Anti-inflammatory effects of and prolactin secretion suppress by HVE and CZE were confirmed through in vitro experiments (P < 0.05). Treatment with Lomens-P0 inhibited prolactin secretion (P < 0.05) and restored normal sex hormone secretion in the hyperprolactinemia mice model. In addition, extracts significantly inhibited the expression of pro-inflammatory biomarkers, including interleukin-1β, and -6, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 (P < 0.01). We used high-performance liquid chromatography analyses to identify tricin and chlorogenic acid as the respective components of HVE and CZE that inhibit prolactin secretion. The Lomens-P0, which includes tricin and chlorogenic acid, is expected to be effective in improving PMS symptoms in the human body. CONCLUSIONS The Lomens-P0 suppressed the prolactin secretion in hyperprolactinemia mice, normalized the sex hormone imbalance, and significantly suppressed the expression of inflammatory markers in uterine tissue. This study suggests that Lomens-P0 may have the potential to prevent or remedy materials to PMS symptoms.

Mithun (Bos frontalis) is a unique domestic free-range bovine species available in North Eastern hilly (NEH) regions of India and is reared for its protein rich meat. Mithun suffers severe non-cyclical population fluctuations; however, it is not yet declared as endangered species. Mithun follows some sort of seasonality based on the calving trend and semen production, although it is a perennial breeder. However, there is need to study the rhythmic changes of endocrine profiles to understand the hormone flow pattern in mithun to select the suitable time for blood collection to assess the exact endocrine profiles and to select the suitable time for natural breeding or semen collection by artificial methods for further research, conservation and propagation of its germplasm. Therefore, the present study was designed to evaluate the reproductive as well as metabolic endocrinological profiles in 24:00 h in intact adult mithun bulls during different seasons (winter, spring, summer and autumn) to know the rhythmic changes and flow pattern of the endocrinological profiles to improve its reproductive efficiency. Experimental mithun bulls (n = 6; age: 5-6 years; body condition score: 5-6 out of 10, classified as good) were selected for the study. Endocrinological profiles, follicle stimulating hormone (FSH), luteinizing hormone/interstitial cell stimulating hormone (LH/ICSH), testosterone, cortisol, thyroxine (T4), insulin like growth factor-1 (IGF-1), prolactin and melatonin (MT) were estimated at 04:00 h interval for one whole day in four seasons. The analysis was completed in two different ways as different times of collection (08:00, 12:00, 16:00, 20:00, 24:00 and 04:00 h) and day (08:00 to 16:00 h)night time (20:00 to 04:00 h) collections. Repeated measures ANOVA analysis revealed that the bulls in winter and spring had significantly (p 0.05) higher FSH, LH, testosterone, T4, IGF-1 and MT than those in summer whereas the bulls in summer had significantly higher cortisol and prolactin than those in winter and spring seasons. Similarly FSH, LH, testosterone, T4, IGF-1 and MT were significantly (p 0.05) higher in night than in day time collections whereas cortisol and prolactin were significantly (p 0.05) higher in day than in night time collections in different seasons. Correlation analysis revealed that FSH, LH, testosterone, T4, IGF-1 and MT had significant (p 0.05) positive correlation with each other whereas these had significant (p 0.05) negative correlation with cortisol and prolactin. The study concludes that season and time of blood collection had significant effect on the endocrinological profiles in mithun bulls. Estimation of FSH, LH, testosterone, T4, IGF-1 and MT during night time and cortisol and prolactin during day time was more appropriate to get correct value of the endocrinological profiles. Spring and winter have significantly greater beneficial effects than summer on reproduction and artificial breeding programs in mithun species in the semi-intensive management in the present location.

Currently, most researchers believe that circannual fluctuations in the functioning of the human body relate not so much to fluctuations in melatonin levels as to changes in the ambient temperature. The goal of this work was to study the seasonal dynamics of melatonin, prolactin, sex hormones, and adrenal hormones in healthy people by a meta-analysis of publications and, based on its outcome, to draw a conclusion on the influence of the photoperiod and air temperature on seasonal changes in the functioning of the organism of modern humans. Using Review Manager 5.3, we carried out a meta-analysis of 31 panel and 12 cross-sectional studies devoted to the seasonal dynamics of circulating hormones. We found that the level of circulating norepinephrine and aldosterone increases in winter compared to summer, which, along with the previously established winter increase in the activity of thyroid hormones, corroborates the significant effect of circannual air temperature fluctuations on the hormonal status of modern humans. However, since a number of studies have shown the seasonal dynamics of melatonin, while our meta-analysis revealed a significant increase in the diurnal average prolactin level in women of reproductive age in spring compared to fall, the influence of the photoperiod on our contemporaries cannot be ruled out completely. Hormonal changes, in turn, can cause seasonal changes in physiological parameters and reproductive functions, as well as affect the development and exacerbation of certain pathologies.

Prolactin (PRL) is a versatile hormone that exerts more than 300 functions in vertebrates, mainly associated with physiological effects in adult animals. Although the process that regulates early development is poorly understood, evidence suggests a role of PRL in the early embryonic development regarding pluripotency and nervous system development. Thus, PRL could be a crucial regulator in oocyte preimplantation and maturation as well as during diapause, a reversible state of blastocyst development arrest that shares metabolic, transcriptomic, and proteomic similarities with pluripotent stem cells in the naïve state. Thus, we analyzed the role of the hormone during those processes, which involve the regulation of its receptor and several signaling cascades (Jak/Mapk, Jak/Stat, and PI3k/Akt), resulting in either a plethora of physiological actions or their dysregulation, a factor in developmental disorders. Finally, we propose models to improve the knowledge on PRL function during early development.

In the present study, we investigated the effect of the synthetic analog of prostaglandin F2α (PGF2α)—cloprostenol—on cultured steroidogenic luteal cells of selected felid species over a 2-day culture period. The changes induced by cloprostenol were measured based on progesterone concentration and mRNA expression analysis of selected genes. Cloprostenol significantly reduced concentration of progesterone in cell culture medium of small luteal cells isolated from domestic cat corpora lutea (CL) at the development/maintenance stage (P < 0.05), but did not influence progesterone production in cultured cells from the regression stage. A decrease or complete silencing of progesterone production was also measured in cultured luteal cells of African lion (formation stage) and Javan leopard (development/maintenance stage). Gene-expression analysis by real-time PCR revealed that treatment with cloprostenol did not have an influence on expression of selected genes coding for enzymes of steroidogenesis (StAR, HSD3B, CYP11A1) or prostaglandin synthesis (PTGS2, PGES), nor did it effect hormone receptors (AR, ESR1, PGR, PTGER2), an antioxidative enzyme (SOD1) or factors of cell apoptosis (FAS, CASP3, TNFRSF1B, BCL2) over the studied period. Significant changes were measured only for expressions of luteinizing hormone (P < 0.05), prolactin (P < 0.05) and PGF2α receptors (P < 0.005) (LHCGR, PRLR, and PTGFR). The obtained results confirm that PGF2α/cloprostenol is a luteolytic agent in CL of felids and its impact on progesterone production depends on the developmental stage of the CL. Cloprostenol short-term treatment on luteal cells was associated only with functional but not structural changes related to luteal regression.Summary sentenceIn cultured luteal cells of felids, cloprostenol can cause functional regression by reducing progesterone secretion and down-regulating expression of luteinizing hormone receptor, prolactin receptor, and prostaglandin F2α receptor.

Tudor staphylococcal nuclease (Tudor-SN) participates in milk synthesis and cell proliferation in response to prolactin (PRL) and plays a regulatory role on mTOR phosphorylation. However, the complicated molecular mechanism of Tudor-SN regulating milk protein synthesis and cell proliferation still remains to be illustrated. In present study, we observed that the proteins level of phosphorylated Tudor-SN and phosphorylated STAT5 were simultaneously enhanced upon PRL treatment in bovine mammary epithelial cells (BMECs). Tudor-SN overexpression and knockdown experiment showed that Tudor-SN positively regulated the synthesis of milk protein, cell proliferation and the phosphorylation of STAT5, which was dependent on Tudor-SN phosphorylation. STAT5 knockdown experiment showed that Tudor-SN stimulated mTOR pathway through regulating STAT5 activation, which was required for PRL to activate the mTOR pathway. Thus, these results demonstrate the primary mechanism of Tudor-SN coordinating with STAT5 to regulate milk protein synthesis and cell proliferation under stimulation of PRL in BMECs, which may provide some new perspectives for increasing milk production.

Background: Testosterone (T) and estradiol (E2) play a critical role in male sexual function being essential for modulating libido and erectile function. We hypothesized that an imbalance of T/E2 ratio may be an important factor leading to the development of low sexual desire in ageing men. Objective: To evaluate the relationship between imbalance of T/E2 ratio and low sexual desire in ageing men. Patients and Methods: This study was conducted on 50 low sexual desire old men and 40 healthy control men (mean age 59.8 years & range 55-69 years). These men were subjected to history taking, clinical examination, sexual desire score of IIEF and SDI-2 as well as estimation of serum sex hormones (total T, free T, E2, prolactin, and SBHG) using ELISA method. Results: The sexual desire score of IIEF and SDI-2 were significantly lower in patients compared with the controls. The levels of TT, E2, TT/E2, FT and FT/E2 were significantly lower among study group compared with the controls. On the other hand, there were significant positive correlations between FT and FT/E2 ratio and both sexual desire score of IIEF and SDI-2. SHBG, E2, TT/E2 showed poor AUCs (AUC = 0.651, 0.626, 0.685 respectively). FT/E2 showed fair AUC (AUC = 0.727). Serum FT showed good AUC (AUC = 0.882), TT, combined T/E2 and FT and combined TT and E2 showed excellent AUC (AUC = 0.900, 0.903, 0.958 respectively). Conclusion: Although older men with low sexual desire had significantly lower total and free T, our study failed to show significant correlations between total T, E2 or TT/E2 ratio and sexual desire score of IIEF and SDI-2. However, true androgen deficiency (FT) and true T/E2 imbalance (FT/E2 ratio) may have a role in discrimination between low and normal sexual desire in older men.

Holstein heifers (n = 45) were subjected to treatments according to a 2 × 2 factorial design where the main effects were the photoperiod treatments during the second isometric (ISO, 52-61 wk of age) and the second allometric (ALLO, 62 wk of age to 8 wk before calving) periods of mammary gland development. During the ISO period, heifers were subjected to either a short-day photoperiod (SDP; 8 h light, 16 h dark; n = 22) or a long-day photoperiod (LDP; 16 h light, 8 h dark; n = 23). During the ALLO period, the photoperiodic treatments were either maintained (SDP:SDP, n = 11; LDP:LDP, n = 11) or switched (SDP:LDP, n = 11; LDP:SDP, n = 12). The treatments ended 8 wk before calving. All animals were then subjected to about 16 h of light per day. Serum prolactin (PRL) concentration during the ISO period was greater in heifers exposed to LDP than in those exposed to SDP. For the first 20 wk of the ALLO period, heifers exposed to LDP had greater serum concentration of PRL than those exposed to SDP. On the other hand, previous exposure to LDP during the ISO period reduced the concentration of PRL compared with those exposed to SDP during that period. During the second 20 wk of the ALLO period, PRL concentration remained greater in the serum of heifers then exposed to LDP than SDP, but serum PRL was greater in heifers exposed to LDP during the ISO period. During the last weeks before calving, when all animals were exposed to LDP, previous exposure to LDP during the ALLO period reduced serum PRL. Early-lactation milk (wk 1-5) and energy-corrected milk (wk 2-6) production were higher in the heifers exposed to SDP than in those exposed to LDP during ALLO. Photoperiod had no effect on milk production after that period. In conclusion, the results do not support to the hypothesis that photoperiod affects mammary gland development during the second allometric phase. However, they confirm that a short-day photoperiod in late gestation enhances milk production in the following lactation in primiparous heifers. Using serum PRL as an indicator of the photoperiodic response, we can conclude that responsiveness to the photoperiodic signal is still conditioned by a previous photoperiod several months after it ends.

What is the gene expression pattern of prolactin receptor (PRLR) in human pre-implantation embryos and what are its functions during the embryonic development and adhesion process?A total of 405 discarded human vitrified oocytes and embryos donated for research by consenting couples were used in this study. The oocytes and embryos were used to analyse PRLR expression and to evaluate the influence of prolactin (PRL) supplementation in the embryo culture medium on embryo developmental competence and viability. The rates of blastocyst development and adhesion, outgrowth area, cytoskeletal reorganization and nascent adhesion formation were compared between groups.PRLR expression increased significantly after embryo compaction (P0.0001) and blastulation (P0.0001). Supplementation of the embryo culture medium with PRL did not improve the developmental rate and morphological grade. In contrast, blastocyst outgrowth was significantly increased in embryos cultured with PRL (P = 0.0004). Phosphorylation of JAK2, downstream of the prolactin receptor family, was markedly higher in the PRL-treated embryos than in embryos cultured without PRL. Furthermore, the expression of mRNAs encoding ezrin-radixin-moesin proteins and epithelial-mesenchymal transition-related genes was stimulated by the activation of PRL-JAK2 signalling. The PRL-treated embryos had higher mRNA expression of integrins than non-treated embryos, and transcriptional repression of cadherin 1 was observed after PRL treatment. More nascent adherent cells expressed focal adhesion kinase and paxillin in PRL-treated embryos than in non-treated embryos.Human embryos express PRLR at the morula and blastocyst stages, and PRLR signalling stimulates blastocyst adhesion by promoting integrin-based focal adhesions and cytoskeletal organization during trophoblast outgrowth.