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Ovariectomy (OVX) causes a depletion of circulating estradiol (E2) and influences hypothalamic kisspeptin neurons, which govern gonadotropin-releasing hormone (GnRH) release and ultimately gonadotropin secretion. In this study, we examined the changes induced by OVX on the anterior pituitary gland in female rats. OVX significantly increased the mRNA expression of gonadotropin α, luteinizing hormone (LH) β, and follicle-stimulating hormone (FSH) β subunits within the pituitary gland compared with control (sham-operated) rats, and this was completely suppressed by E2 supplementation. High-dose dihydrotestosterone supplementation also prevented the OVX-induced increase in the expression of the three gonadotropin subunits. GnRH receptor mRNA expression within the pituitary was significantly increased in OVX rats, and this increase was completely inhibited by E2 supplementation. The mRNA expression of the receptors for adenylate cyclase-activating polypeptide and kisspeptin was unchanged by OVX. Although the mRNA levels of inhibin α, βA, and βB subunits within the pituitary gland were not modulated by OVX, follistatin gene expression within the pituitary gland was increased by OVX, and this increase was completely inhibited by E2 supplementation after OVX. In experiments using a pituitary gonadotroph cell model (LβT2 cells), follistatin itself did not modulate the mRNA expression of gonadotropin LHβ and FSHβ subunits, and the GnRH-induced increase in the expression of these genes was slightly inhibited in the presence of follistatin. Our current observations suggest that OVX induces several characteristic changes in the pituitary gland of rats. [ABSTRACT FROM AUTHOR]

Hyperandrogenism causes dysfunction of the hypothalamic–pituitary–gonadal (HPG) axis in reproductive women. In this study, we examined the effects of dihydrotestosterone (DHT) on characteristic changes in rat anterior pituitary gland samples. DHT was administered to ovary-intact 6-week postnatal female rats for 7 days, after which the anterior pituitary glands were examined and compared with those in control rats. Estrous cyclicity was not drastically disrupted by DHT treatment. Common gonadotropin α subunit (Cga), luteinizing hormone β subunit (Lhb), and follicle-stimulating hormone (FSH) β subunit (Fshb) gene expression levels were not modulated by DHT treatment, while prolactin (Prl) gene expression was significantly repressed by DHT. Gonadotropin-releasing hormone (GnRH) receptor (Gnrh-r) gene expression was significantly inhibited by DHT, whereas pituitary adenylate cyclase-activating polypeptide (PACAP) receptor (Pca1-r) gene expression was increased by DHT. Gene expression levels of the receptors encoded by thyrotropin-releasing hormone (Trh-r) and kisspeptin (Kiss1-r) genes were unchanged. Expression of inhibin α subunit (Inha) and activin βA subunits (Actba) within the pituitary was inhibited by DHT treatment, while activin B subunit (Actbb) and follistatin (Fst) gene expression was unchanged by DHT. In mouse pituitary gonadotroph LβT2 cells, DHT did not modulate the gene expression of Gnrh-r, but it inhibited the expression of Inha and Actba subunits within the LβT2 cells. In rat prolactin-producing GH3 cells, DHT did not modulate prolactin gene expression, but it increased Pac1-r gene expression. The present observations suggest that DHT directly or indirectly affects the anterior pituitary gland and induces characteristic changes in hormone-producing cells. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the general characteristics, menstruation status, and fertility outcomes of patients with hypogonadotropic hypogonadism (HH). Methods: We evaluated 16 patients with HH who visited our institution between April 2012 and March 2016 with a complaint of amenorrhea. Results: Four (25%) patients had primary amenorrhea and the remaining 12 (75%) cases had secondary amenorrhea. Among the patients with primary amenorrhea, weight loss was considered to be the underlying cause in one (25%) patient, whereas the remaining three (75%) cases were idiopathic HH. Among HH cases with secondary amenorrhea, six (50%) developed amenorrhea following weight loss, whereas the remaining six cases were of unknown etiology. Among the 16 patients with HH, we observed the sporadic restart of the menstrual cycle in four (25%) women during follow‐up. Infertility treatment was administered to nine patients with HH who wished to become pregnant. Clomiphene citrate was effective in four patients with secondary amenorrhea and induced follicular development. Seven of nine patients with HH (77.8%) became pregnant following infertility treatment. In some cases of HH, the serum levels of gonadotropin increased sporadically during follow‐up, regardless of the recovery of menstruation. We followed one patient with HH for more than 20 years. Although her gonadotropin levels were generally low and sometimes fluctuated without spontaneous menstruation, they increased dramatically to menopausal levels at 50 years of age. However, they again decreased to hypogonadotropic levels. Conclusion: As the pathophysiology varied widely among patients, the etiologic factors underlying HH might also vary. [ABSTRACT FROM AUTHOR]

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Purpose: Relaxin‐3 is a hypothalamic neuropeptide that belongs to the insulin superfamily. We examined whether relaxin‐3 could affect hypothalamic Kiss‐1, gonadotropin‐releasing hormone (GnRH), and pituitary gonadotropin subunit gene expression. Methods: Mouse hypothalamic cell models, mHypoA‐50 (originated from the hypothalamic anteroventral periventricular region), mHypoA‐55 (originated from arcuate nucleus), and GT1‐7, and the mouse pituitary gonadotroph LβT2 were used. Expression of Kiss‐1, GnRH, and luteinizing hormone (LH)/follicle‐stimulating hormone (FSH) β‐subunits was determined after stimulation with relaxin‐3. Results: RXFP3, a principle relaxin‐3 receptor, was expressed in these cell models. In mHypoA‐50 cells, relaxin‐3 did not exert a significant effect on Kiss‐1 expression. In contrast, the Kiss‐1 gene in mHypoA‐55 was significantly increased by 1 nmol/L relaxin‐3. These cells also express GnRH mRNA, and its expression was significantly stimulated by relaxin‐3. In GT1‐7 cells, relaxin‐3 significantly upregulated Kiss‐1 expression; however, GnRH mRNA expression in GT1‐7 cells was not altered. In primary cultures of fetal rat neuronal cells, 100 nmol/L relaxin‐3 significantly increased GnRH expression. In pituitary gonadotroph LβT2, both LHβ‐ and FSHβ‐subunit were significantly increased by 1 nmol/L relaxin‐3. Conclusions: Our findings suggest that relaxin‐3 exerts its effect by modulating the expression of Kiss‐1, GnRH, and gonadotropin subunits, all of which are part of the hypothalamic‐pituitary‐gonadal axis. [ABSTRACT FROM AUTHOR]

Purpose Accumulating evidence indicates that hypothalamic kisspeptin plays a pivotal role in the regulation of the hypothalamic-pituitary-gonadal ( HPG) axis. In this study, the direct action of the gamma-aminobutyric acid ( GABA)A receptor agonist on kisspeptin-expressing neuronal cells was examined. Methods A hypothalamic cell model of rat hypothalamic cell line R8 ( rHypoE8) cells and primary cultures of neuronal cells from fetal rat brains were stimulated with a potent and selective GABAA receptor agonist, muscimol, to determine the expression of the Ki SS-1 gene. Results Stimulation of the rHypoE8 cells with muscimol significantly increased the level of Ki SS-1 messenger (m) RNA expression. The ability of muscimol to increase the level of Ki SS-1 mRNA also was observed in the primary cultures of the neuronal cells from the fetal rat brains. The muscimol-induced increase in Ki SS-1 mRNA expression was completely inhibited in the presence of the GABAA receptor antagonist. Although muscimol increased the expression of Ki SS-1, the natural compound, GABA, failed to induce the expression of Ki SS-1 in the rHypoE8 cells. Muscimol did not modulate gonadotropin-releasing hormone expression in either the rHypoE8 cells or the primary cultures of the fetal rat brains. Conclusions This study's observations suggest that the activation of the GABAA receptor modulates the HPG axis by increasing kisspeptin expression in the hypothalamic neurons. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association between semen characteristics and outcomes of intrauterine insemination (IUI)., Methods: This retrospective analysis examined 1380 IUI procedures involving 421 couples. The association of clinical pregnancy with pre- and post-wash sperm characteristics was assessed., Results: Pre- and post-wash sperm characteristics did not differ between IUI cycles that resulted in pregnancy and those that did not. When the motility of pre-wash sperm was below the normal range (<42%) established by the World Health Organization (WHO), the pregnancy rate was significantly lower. In the IUI cycles when post-wash sperm motility was below the WHO standard, pregnancy was not achieved. The frequency of improvement in post-wash sperm motility in repeated IUI cycles appeared to correlate with the success of future IUI cycles. At the fourth IUI cycle, pregnancy was not achieved unless the post-wash sperm motility was normal in at least two of three attempts. When post-wash sperm concentration was below the normal range, the woman's age did not affect the IUI outcomes., Conclusions: Sperm motility above the lower limit of the WHO criteria in post-wash semen samples is an important factor in IUI outcomes., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Anti-Müllerian hormone (AMH) is primarily produced by ovarian granulosa cells and contributes to follicle development. AMH is also produced in other tissues, including the brain and pituitary; however, its roles in these tissues are not well understood. In this study, we examined the effect of AMH on pituitary gonadotrophs. We detected AMH and AMH receptor type 2 expression in LβT2 cells. In these cells, the expression of FSHβ- but not α- and LHβ-subunits increased significantly as the concentration of AMH increased. LβT2 cells expressed Kiss-1 and Kiss-1R. AMH stimulation resulted in decreases in both Kiss-1 and Kiss-1R. The siRNA-mediated knockdown of Kiss-1 in LβT2 cells did not alter the basal expression levels of α-, LHβ-, and FSHβ-subunits. In LβT2 cells overexpressing Kiss-1R, exogenous kisspeptin stimulation significantly increased the expression of all three gonadotropin subunits. However, kisspeptin-induced increases in these subunits were almost completely eliminated in the presence of AMH. In contrast, GnRH-induced increases in the three gonadotropin subunits were not modulated by AMH. Our observations suggested that AMH acts on pituitary gonadotrophs and induces FSHβ-subunit expression with concomitant decreases in Kiss-1 and Kiss-1R gene expression. Kisspeptin, but not GnRH-induced gonadotropin subunit expression, was inhibited by AMH, suggesting that it functions in association with the kisspeptin/Kiss-1R system in gonadotrophs.

Hypothalamic kisspeptin, encoded by the Kiss-1 gene, governs the hypothalamic-pituitary-gonadal axis by directly regulating the release of gonadotropin-releasing hormone. In this study, we examined the roles of activin, inhibin, and follistatin in the regulation of Kiss-1 gene expression using primary cultures of fetal rat neuronal cells, which express the Kiss-1 gene and kisspeptin. Stimulation with activin significantly increased Kiss-1 gene expression in these cultures by 2.02 ± 0.39-fold. In contrast, a significant decrease in Kiss-1 gene expression was observed with inhibin A and follistatin treatment. Inhibin B did not modulate Kiss-1 gene expression. Activin, inhibin, and follistatin were also expressed in fetal rat brain cultures and their expression was controlled by estradiol (E2). The inhibin α, βA, and βB subunits were upregulated by E2. Similarly, follistatin gene expression was significantly increased by E2 in these cells. Our results suggest the possibility that activin, inhibin, and follistatin expressed in the brain participate in the E2-induced feedback control of the hypothalamic-pituitary-gonadal axis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier B.V.)

Purpose: Accumulating evidence indicates that hypothalamic kisspeptin plays a pivotal role in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis. In this study, the direct action of the gamma-aminobutyric acid (GABA) A receptor agonist on kisspeptin-expressing neuronal cells was examined., Methods: A hypothalamic cell model of rat hypothalamic cell line R8 (rHypoE8) cells and primary cultures of neuronal cells from fetal rat brains were stimulated with a potent and selective GABA A receptor agonist, muscimol, to determine the expression of the KiSS-1 gene., Results: Stimulation of the rHypoE8 cells with muscimol significantly increased the level of KiSS-1 messenger (m)RNA expression. The ability of muscimol to increase the level of KiSS-1 mRNA also was observed in the primary cultures of the neuronal cells from the fetal rat brains. The muscimol-induced increase in KiSS-1 mRNA expression was completely inhibited in the presence of the GABA A receptor antagonist. Although muscimol increased the expression of KiSS-1, the natural compound, GABA, failed to induce the expression of KiSS-1 in the rHypoE8 cells. Muscimol did not modulate gonadotropin-releasing hormone expression in either the rHypoE8 cells or the primary cultures of the fetal rat brains., Conclusions: This study's observations suggest that the activation of the GABA A receptor modulates the HPG axis by increasing kisspeptin expression in the hypothalamic neurons., Competing Interests: The authors declare no conflict of interest. Human and Animal Rights: This study's protocol was approved by the committee of the Experimental Animal Center for Integrated Research at Shimane University, Izumo, Japan. All the institutional and national guidelines for the care and use of laboratory animals were followed. This article does not contain any study with human participants that has been performed by any of the authors.