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Introduction: Historically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatmentresistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors. Methods: Nationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes. Results: We analyzed 84 PAs, 69%in females and 31% in males (P<0.001), diagnosed at a mean age of 35.2±14.9 years, mostly through screening (60.7%). Median follow-up was 9 years (IQR:4-16). Prolactin-secreting PAs (PRLomas) (53.5%) and microadenomas (65.5%) were most common. Dopamine agonist treatment was first line for 16 macroPRLomas and 25 microPRLomas, 60.9% of them achieved PRL normalization. There was no significant association observed with tumor size, sex, treatment duration or MEN1 PV. The risk of progression from micro-PA to invasive macro-PA was 7.2% (4/55), after 8 years (IQR:4-13), all of them were microPRLomas. Kaplan-Meier estimation curve showed significantly higher progression probability in microPRLomas than in other microadenomas subtypes (P=0.017) or microNFPAs (P=0.032). No differences were found between sex, age, or germline MEN1 PV. Conclusion: MEN1-related micro-PAs have a low risk of progressing to invasive macro-PAs, regardless of sex, age at diagnosis, or MEN1 germline PV. The risk is higher for microPRLomas over the long term. Therefore, long-term surveillance with reduced frequency, rather than intensive short-term monitoring, may be appropriate for patients with MEN1-related PAs. [ABSTRACT FROM AUTHOR]

Pituitary adenomas (PAs) are the third most common brain tumors in adults right after meningiomas and gliomas. Taking into account their hormonal activity in vivo, they can be divided in functioning PAs, which secrete hormones, and nonfunctioning pituitary adenomas (NFPAs), which are not associated with increased hormone secretion. We present the case of a man diagnosed with pituitary apoplexy. A transsphenoidal surgery was performed with subtotal removal of the mass. Pituitary hormones were measured before and after the procedure on several occasions, showing always normal PRL values, so he was diagnosed with a clinically NFPA. Two years later, the patient noticed a visual deficit. A new magnetic resonance imaging study was performed, showing adenomatous recurrence, and the patient underwent a new surgery. After this, hormonal evaluation revealed high levels of PRL on several occasions. After treatment with cabergoline was started, PRL levels normalized, the visual deficit improved, and there was a slight adenoma reduction. This case report represents an exception to the paradigm that in the presence of a macroadenoma and normal PRL levels (avoiding the “hook effect”), a prolactinoma can be discarded. Moreover, it stresses the importance of comprehensive, regular, and lifelong surveillance of patients with NFPAs and the close monitoring of serum PRL.

Pituitary adenomas (PAs) are the third most common brain tumors in adults right after meningiomas and gliomas. Taking into account their hormonal activity in vivo, they can be divided in functioning PAs, which secrete hormones, and nonfunctioning pituitary adenomas (NFPAs), which are not associated with increased hormone secretion. We present the case of a man diagnosed with pituitary apoplexy. A transsphenoidal surgery was performed with subtotal removal of the mass. Pituitary hormones were measured before and after the procedure on several occasions, showing always normal PRL values, so he was diagnosed with a clinically NFPA. Two years later, the patient noticed a visual deficit. A new magnetic resonance imaging study was performed, showing adenomatous recurrence, and the patient underwent a new surgery. After this, hormonal evaluation revealed high levels of PRL on several occasions. After treatment with cabergoline was started, PRL levels normalized, the visual deficit improved, and there was a slight adenoma reduction. This case report represents an exception to the paradigm that in the presence of a macroadenoma and normal PRL levels (avoiding the "hook effect"), a prolactinoma can be discarded. Moreover, it stresses the importance of comprehensive, regular, and lifelong surveillance of patients with NFPAs and the close monitoring of serum PRL. [ABSTRACT FROM AUTHOR]

Antipsychotic medications are essential for managing severe mental illnesses like schizophrenia, which impacts about 1% of the global population. Despite efficacy, in some cases, they can induce hyperprolactinemia, affecting roughly half of the patients. The prevalence of this condition varies with the specific medication used. Although prolactinomas are rare among schizophrenia patients, treating them with dopamine agonists poses conflicts with antipsychotic medication, necessitating careful monitoring and adjustments. The aim of this study was to explore the presence of brain tumors, prolactinomas, and other structural brain changes in schizophrenia patients treated with second-generation antipsychotics using cerebral computed tomography (CT) scans. We conducted a cross-sectional study involving 152 hospitalized patients diagnosed between 1 January 2020 and 31 March 2024. Evaluations included cerebral CT scans, prolactin level assessments, and the monitoring of side effects. Patients, with an average age of 42.79 years and an illness duration of 17.89 years, predominantly received olanzapine (46.05%) and risperidone (36.84%). Side effects, reported by 61.78% of patients, included tremors, dizziness, and weight gain. Abnormal prolactin levels were observed in 53.95% of patients, more prevalent in females on risperidone and in both genders on olanzapine. No prolactinomas were detected on CT scans. Managing hyperprolactinemia in schizophrenia patients undergoing antipsychotic therapy is essential to prevent long-term complications and to ensure treatment compliance. [ABSTRACT FROM AUTHOR]

Objective Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune cells. Design and Methods Five surgically resected prolactinomas (PRLomas) from 3 cabergoline (CBG)-treated patients and 2 treatment-naive patients were analyzed by using single-cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape. Results Six major cell populations, namely tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%), were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components such as perforin and the granzymes GZMB, GNLY, and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from the CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in the CBG-treated samples. Conclusions Our scRNA-seq studies revealed key differences in the transcriptomic features of CBG-treated and CBG-untreated PRLomas in both tumor and microenvironment cellular constituents, and for the first time, describe the previously unknown activation of CD8+ T cells following CBG treatment, which may play a role in the tumoricidal actions of CBG. [ABSTRACT FROM AUTHOR]

IntroductionHistorically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatment-resistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors.MethodsNationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes.ResultsWe analyzed 84 PAs, 69%in females and 31% in males (P

Serum prolactin (PRL) levels exhibit a gradual rise both in male and female rats from birth to adulthood, with females consistently displaying higher levels compared to age-matched males. This pattern has traditionally been attributed to the development and maturation of endocrine and neuroendocrine networks responsible for regulating PRL synthesis and secretion. However, the effect of dopamine (DA), which acts as an inhibitory factor on lactotroph function, also increases from birth to puberty, particularly in females. Nonetheless, the secretion of PRL remains higher in females compared to males. On the other hand, the observed sex differences in serum PRL levels during early postnatal development cannot be attributed to the influence of estradiol (E2). While serum E2 levels gradually increase after birth, only after 45 days of life do the disparities in E2 levels between females and males become evident. These observations collectively suggest that neither the maturation of hypothalamic DA regulation nor the rise in E2 levels can account for the progressive and sustained elevation in serum PRL levels and the observed sexual dimorphism during postnatal development. This review highlights the importance of recent discoveries in animal models that shed light on inhibitory mechanisms in the control of PRL secretion within the pituitary gland itself, that is intrapituitary mechanisms, with a specific emphasis on the role of transforming growth factor β1 and activins in PRL secretion. [ABSTRACT FROM AUTHOR]

IntroductionUsually, prolactinomas are treated with dopamine agonists (DA). Surgery is considered an option when the patient cannot bear or does not respond positively to DA therapy.AimThis study aims to determine the early and late outcomes of surgery, with particular emphasis on developing prognostic factors for surgical treatment and analyzing risk factors affecting the recurrence of hyperprolactinemia and prolactinoma.Material and methodsThis retrospective study was conducted at the Feofaniya Clinical Hospital of the State Administration of Affairs (Kyiv, Ukraine), evaluating 109 patients' records from 2009 to 2019. The main patients' inclusion criteria were: serum prolactin (PRL) level of more than 100 ng/ml, presence of pituitary adenoma (PA) on MRI, histologically approved PA by microscopy. According to the size of the prolactin-secreting PA (PSPAs) the selected 109 patients were divided into two groups: micro- (≤10 mm, n = 75) and macroadenoma group (10–40 mm, n = 34).Results1 month after the operation, PRL levels decreased by 87% (p

Abstract Background The optimal therapeutic approach for cystic prolactinomas remains unclear. This study aimed to evaluate the remission rates of prolactinoma patients after surgical treatment and the risk factors affecting postoperative remission in cystic prolactinoma patients. Methods The clinical data were retrospectively compiled from 141 patients with prolactinomas (including 41 cases of cystic prolactinomas, 21 cases of solid microprolactinomas and 79 cases of solid macroprolactinomas) who underwent transsphenoidal surgery (TSS) between April 2013 and October 2021 at the First Affiliated Hospital of Sun Yat-sen University. Results Early postoperative remission was achieved in 65.83% (n = 27/41) of cystic prolactinomas, 80.95% (n = 17/21) of solid microprolactinomas and 40.51% (n = 32/79) of solid macroprolactinomas. The mean length of follow up in all patients was 43.95 ± 2.33 months (range: 6-105 months). The follow-up remission rates were 58.54%, 71.43% and 44.30% in cystic, solid micro- and solid macroprolactinomas, respectively. For cystic prolactinomas, the early postoperative remission rates in the patients with preoperative dopamine agonists (DA) treatment were significantly higher than those without preoperative DA treatment (p = 0.033), but the difference in the follow-up remission rates between these two groups was not significant (p = 0.209). Multivariate stepwise logistic regression analysis indicated that tumor size and preoperative prolactin (PRL) levels

Male patients with prolactinomas usually present with typical hyperprolactinemia symptoms, including sexual dysfunction and infertility. However, clinical factors related to sexual dysfunction and surgical outcomes in these patients remain unclear. This study aimed to investigate the outcomes of male patients with prolactinomas after transsphenoidal surgery and the risk factors affecting sexual dysfunction. This study was conducted on 58 male patients who underwent transsphenoidal surgery for prolactinomas between May 2014 and December 2020 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. We evaluated the sexual function of patients before and after surgery through International Index of Erectile Function-5 scores, libido, and frequency of morning erection. Of the 58 patients, 48 (82.8%) patients had sexual intercourse preoperatively. Among those 48 patients, 41 (85.4%) patients presented with erectile dysfunction. The preoperative International Index of Erectile Function-5 scores in patients with macroprolactinomas were significantly higher than those in patients with giant prolactinomas (17.63 ± 0.91 vs 13.28 ± 1.43; P = 0.01). Postoperatively, the incidence of erectile dysfunction was 47.9%, which was significantly lower than that preoperatively (85.4%; P = 0.01). Twenty-eight (68.3%) patients demonstrated an improvement in erectile dysfunction. Tumor size and invasiveness were significantly correlated with the improvement of erectile dysfunction. Preoperative testosterone

Background: The optimal therapeutic approach for cystic prolactinomas remains unclear. This study aimed to evaluate the remission rates of prolactinoma patients after surgical treatment and the risk factors affecting postoperative remission in cystic prolactinoma patients. Methods: The clinical data were retrospectively compiled from 141 patients with prolactinomas (including 41 cases of cystic prolactinomas, 21 cases of solid microprolactinomas and 79 cases of solid macroprolactinomas) who underwent transsphenoidal surgery (TSS) between April 2013 and October 2021 at the First Affiliated Hospital of Sun Yat-sen University. Results: Early postoperative remission was achieved in 65.83% (n = 27/41) of cystic prolactinomas, 80.95% (n = 17/21) of solid microprolactinomas and 40.51% (n = 32/79) of solid macroprolactinomas. The mean length of follow up in all patients was 43.95 ± 2.33 months (range: 6-105 months). The follow-up remission rates were 58.54%, 71.43% and 44.30% in cystic, solid micro- and solid macroprolactinomas, respectively. For cystic prolactinomas, the early postoperative remission rates in the patients with preoperative dopamine agonists (DA) treatment were significantly higher than those without preoperative DA treatment (p = 0.033), but the difference in the follow-up remission rates between these two groups was not significant (p = 0.209). Multivariate stepwise logistic regression analysis indicated that tumor size and preoperative prolactin (PRL) levels < 200 ng/ml were independent predictors for early postoperative remission in cystic prolactinomas. Conclusion: For cystic prolactinomas, tumor size and preoperative PRL levels were independent predictors of early postoperative remission. Preoperative DA therapy combined with TSS may be more beneficial to cystic prolactinoma patients. [ABSTRACT FROM AUTHOR]

The hypothalamic neuroendocrine catecholamine dopamine regulates the lactotroph function, including prolactin (PRL) secretion, proliferation, and apoptosis. The treatment of PRL-secreting tumors, formerly known as prolactinomas, has relied mainly on this physiological characteristic, making dopamine agonists the first therapeutic alternative. Nevertheless, the group of patients that do not respond to this treatment has few therapeutical options. Prolactin is another physiological regulator of lactotroph function, acting as an autocrine/paracrine factor that controls PRL secretion and cellular turnover, inducing apoptosis and decreasing proliferation. Furthermore, the signaling pathways related to these effects, mainly JAK/STAT and PI3K/Akt, and MAPK, have been extensively studied in prolactinomas and other tumors as therapeutic targets. In the present work, the relationship between PRL pathophysiology and prolactinoma development is explored, aiming to comprehend the value of PRL and PRLR-associated pathways as exploratory fields alternative to dopamine-related approaches, which are worth physiological characteristics that might be impaired and can be potentially restored or upregulated to provide more options to the patients. [ABSTRACT FROM AUTHOR]

Prolactinomas have been reported to impair cognition in broad aspects. However, few studies investigated the influence of prolactinomas on cognitive flexibility never mentioning the underlying neural and electrophysiological mechanism. We recorded scalp electroencephalography (EEG) in a colour-shape switching task. Patients with prolactinomas showed longer reaction time in switch trials and larger switch costs relative to healthy controls (HCs). Compared to HCs who showed stronger frontal theta activity in switch trials, the generally weak frontal theta activity in patients implied that they could not afford the executive control to configure task sets. Meanwhile, machine-learning based classification revealed that patients manifested non-selective brain patterns in response to different task types (colour vs. shape task) and different task states (switch vs. repeat state), which collectively suggested the cognitive dysfunction in preparation for a changing environment. Compared to HCs who showed stronger frontoparietal synchronization in switch trials, this enhanced frontoparietal connectivity was disrupted among patients with severe prolactinomas. This finding implicated greater hyperprolactinemia was linked to a larger decrease in cognitive performance. Taken together, the present study highlighted frontal theta power, and frontoparietal connectivity at theta band as the electrophysiological markers of the impaired cognitive flexibility and task control in patients with prolactinomas. [ABSTRACT FROM AUTHOR]

Abstract Background Recently, a hotspot mutation in prolactinoma was observed in splicing factor 3b subunit 1 (SF3B1 R625H ), but its functional effects and underlying molecular mechanisms remain largely unexplored. Methods Using the CRISPR/Cas9 genome editing system and rat pituitary GH3 cells, we generated heterozygous Sf3b1 R625H mutant cells. Sanger and whole-genome sequencing were conducted to verify the introduction of this mutation. Transcriptome analysis was performed in SF3B1-wild-type versus mutant human prolactinoma samples and GH3 cells. RT-PCR and minigene reporter assays were conducted to verify aberrant splicing. The functional consequences of SF3B1 R625H were evaluated in vitro and in vivo. Critical makers of epithelial-mesenchymal transition and key components were detected using western blot, immunohistochemistry, and immunofluorescence. Suppressing proteins was achieved using siRNA. Results Transcriptomic analysis of prolactinomas and heterozygous mutant cells revealed that the SF3B1 R625H allele led to different alterations in splicing properties, affecting different genes in different species. SF3B1R625H promoted aberrant splicing and DLG1 suppression in both rat cells and human tumors. In addition, SF3B1R625H and knocking down DLG1 promoted cell migration, invasion, and epithelial-mesenchymal transition through PI3K/Akt pathway. Conclusions Our findings elucidate a mechanism through which mutant SF3B1 promotes tumor progression and may provide a potent molecular therapeutic target for prolactinomas with the SF3B1 R625H mutation.

The hypothalamic neuroendocrine catecholamine dopamine regulates the lactotroph function, including prolactin (PRL) secretion, proliferation, and apoptosis. The treatment of PRL-secreting tumors, formerly known as prolactinomas, has relied mainly on this physiological characteristic, making dopamine agonists the first therapeutic alternative. Nevertheless, the group of patients that do not respond to this treatment has few therapeutical options. Prolactin is another physiological regulator of lactotroph function, acting as an autocrine/paracrine factor that controls PRL secretion and cellular turnover, inducing apoptosis and decreasing proliferation. Furthermore, the signaling pathways related to these effects, mainly JAK/STAT and PI3K/Akt, and MAPK, have been extensively studied in prolactinomas and other tumors as therapeutic targets. In the present work, the relationship between PRL pathophysiology and prolactinoma development is explored, aiming to comprehend the value of PRL and PRLR-associated pathways as exploratory fields alternative to dopamine-related approaches, which are worth physiological characteristics that might be impaired and can be potentially restored or upregulated to provide more options to the patients.

PurposeThree dopamine agonists [bromocriptine, cabergoline, and quinagolide (CV)] have been used for hyperprolactinemia treatment for decades. Several studies have reviewed the efficacy and safety of bromocriptine and cabergoline. However, no systematic review or meta-analysis has discussed the efficacy and safety of CV in hyperprolactinemia and prolactinoma treatment.MethodsFive medical databases (PubMed, Web of Science, Embase, Scopus, and Cochrane Library) were searched up to 9 May 2022 to identify studies related to CV and hyperprolactinemia. A meta-analysis was implemented by using a forest plot, funnel plot, sensitivity analysis, meta-regression, and Egger’s test via software R 4.0 and STATA 12.ResultsA total of 1,211 studies were retrieved from the five medical databases, and 33 studies consisting of 827 patients were finally included in the analysis. The pooled proportions of patients with prolactin concentration normalization and tumor reduction (>50%) under CV treatment were 69% and 20%, respectively, with 95% confidence intervals of 61%–76% and 15%–28%, respectively. The pooled proportion of adverse effects was 13%, with a 95% confidence interval of 11%–16%.ConclusionOur study showed that CV is not less effective than cabergoline and bromocriptine in treating hyperprolactinemia, and the side effects were not significant. Hence, this drug could be considered an alternative first-line or rescue treatment in treating hyperprolactinemia in the future.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022347750.

Abstract Background Prolactinoma is a functional pituitary adenoma that secretes excessive prolactin. Dopamine agonists (DAs) such as bromocriptine (BRC) are the first-line treatment for prolactinomas, but the resistance rate is increasing year by year, creating a clinical challenge. Therefore, it is urgent to explore the molecular mechanism of bromocriptine resistance in prolactinomas. Activation of the P38 MAPK pathway affects multidrug resistance in tumours. Our previous studies have demonstrated that inhibiting MAPK14 can suppress the occurrence of prolactinoma, but the role of MAPK11/12/13/14 (p38 MAPK) signalling in dopamine agonist-resistant prolactinomas is still unclear. Methods A prolactinoma rat model was established to determine the effect of bromocriptine on MAPK11/12/13/14 signalling. DA-resistant GH3 cells and DA-sensitive MMQ cells were used, and the role of MAPK11/12/13/14 in bromocriptine-resistant prolactinomas was preliminarily verified by western blot, RT-qPCR, ELISA, flow cytometry and CCK-8 experiments. The effects of MAPK11 or MAPK14 on bromocriptine-resistant prolactinomas were further verified by siRNA transfection experiments. Results Bromocriptine was used to treat rat prolactinoma by upregulating DRD2 expression and downregulating the expression level of MAPK11/12/13/14 in vivo experiments. The in vitro experiments showed that GH3 cells are resistant to bromocriptine and that MMQ cells are sensitive to bromocriptine. Bromocriptine could significantly reduce the expression of MAPK12 and MAPK13 in GH3 cells and MMQ cells. Bromocriptine could significantly reduce the expression of MAPK11, MAPK14, NF-κB p65 and Bcl2 in MMQ but had no effect on MAPK11, MAPK14, NF-κB p65 and Bcl2 in GH3 cells. In addition, knockdown of MAPK11 and MAPK14 in GH3 cells by siRNA transfection reversed the resistance of GH3 cells to bromocriptine, and haloperidol (HAL) blocked the inhibitory effect of bromocriptine on MAPK14, MAPK11, and PRL in MMQ cells. Our findings show that MAPK11 and MAPK14 proteins are involved in bromocriptine resistance in prolactinomas. Conclusion Bromocriptine reduces the expression of MAPK11/12/13/14 in prolactinomas, and MAPK11 and MAPK14 are involved in bromocriptine resistance in prolactinomas by regulating apoptosis. Reducing the expression of MAPK11 or MAPK14 can reverse bromocriptine resistance in prolactinomas.

Objective: Cabergoline is a potent dopamine receptor agonist commonly used in the treatment of hyperprolactinemia. However, there are scarce data on the imaging characteristics of prolactinomas that could predict the response to treatment. The present study prospectively evaluated the effectiveness of cabergoline in the reduction of tumor volume and serum prolactin levels in treatment-naive cases of prolactinomas besides evaluating the imaging features of tumors on T2-weighted magnetic resonance imaging that could potentially predict the response to treatment. Methods: The present study evaluated 83 prolactinomas (52 micro- and 31 macroprolactinomas) for a 24-month period. The T2-weighted signal characteristics of prolactinomas were evaluated at the start of treatment in addition to the estimation of tumor volumes and prolactin levels. T2-weighted signal characteristics of tumors allowed the categorization of tumors into homogeneous and heterogeneous groups. Patients were started on cabergoline therapy, and thereafter, serial magnetic resonance imagings were performed at 4-, 8-, 12-, 18-, and 24-month intervals to monitor the changes in tumor volume and prolactin levels. Results: A total of 30 (27 micro- and 3 macroadenomas) patients showed complete disappearance of tumor at 24 months. More than a 75% reduction in tumor volume was noted in 82.7% of microadenomas and 78.6% of macroadenomas. More than a 75% reduction in prolactin levels was seen in 88.5% of microadenomas and 77.9% of macroadenomas at 24 months. After 1 year of treatment with cabergoline, 68.6% (35/51) showed normalization of prolactin levels and 64.7% (33/51) showed more than 50% reduction in tumor volume in the homogeneous group. In comparison, only 28.12% (9/32) showed normalization of prolactin levels and 31.25% (11/32) showed >50% tumor volume reduction among the heterogeneous group. Heterogeneous prolactinomas had more number of macroadenomas and were significantly larger and more secreting compared to homogeneous tumors at baseline (all P < .05) Conclusion: Cabergoline administered for 12-24 months induced a significant tumor volume reduction with amelioration of clinical symptoms of prolactin excess and normalization of serum prolactin levels. T2-weighted homogeneous tumors had a more favorable outcome in comparison to the heterogeneous tumors. [ABSTRACT FROM AUTHOR]

Pituitary neuroendocrine tumors (PitNET) are commonly benign tumors accounting for 10-25% of intracranial tumors. Prolactin-secreting adenomas represent the most predominant type of all PitNET and for this subtype of tumors, the medical therapy relies on the use of dopamine agonists (DAs). DAs yield an excellent therapeutic response in reducing tumor size and hormonal secretion targeting the dopamine receptor type 2 (D2DR) whose higher expression in prolactin-secreting adenomas compared to other PitNET is now well established. Moreover, although DAs therapy does not represent the first-line therapy for other PitNET, off-label use of DAs is considered in PitNET expressing D2DR. Nevertheless, DAs primary or secondary resistance, occurring in a subset of patients, may involve several molecular mechanisms, presently not fully elucidated. Dopamine receptors (DRs) expression is a prerequisite for a proper DA function in PitNET and several molecular events may negatively modify DR membrane expression, through the DRs down-regulation and intracellular trafficking, and DR signal transduction pathway. The current mini-review will summarise the presently known molecular events that underpin the unsuccessful therapy with DAs.

Background: Recently, a hotspot mutation in prolactinoma was observed in splicing factor 3b subunit 1 (SF3B1R625H), but its functional effects and underlying molecular mechanisms remain largely unexplored. Methods: Using the CRISPR/Cas9 genome editing system and rat pituitary GH3 cells, we generated heterozygous Sf3b1R625H mutant cells. Sanger and whole-genome sequencing were conducted to verify the introduction of this mutation. Transcriptome analysis was performed in SF3B1-wild-type versus mutant human prolactinoma samples and GH3 cells. RT-PCR and minigene reporter assays were conducted to verify aberrant splicing. The functional consequences of SF3B1R625H were evaluated in vitro and in vivo. Critical makers of epithelial-mesenchymal transition and key components were detected using western blot, immunohistochemistry, and immunofluorescence. Suppressing proteins was achieved using siRNA. Results: Transcriptomic analysis of prolactinomas and heterozygous mutant cells revealed that the SF3B1R625H allele led to different alterations in splicing properties, affecting different genes in different species. SF3B1R625H promoted aberrant splicing and DLG1 suppression in both rat cells and human tumors. In addition, SF3B1R625H and knocking down DLG1 promoted cell migration, invasion, and epithelial-mesenchymal transition through PI3K/Akt pathway. Conclusions: Our findings elucidate a mechanism through which mutant SF3B1 promotes tumor progression and may provide a potent molecular therapeutic target for prolactinomas with the SF3B1R625H mutation. [ABSTRACT FROM AUTHOR]

Pituitary neuroendocrine tumors (PitNET) are commonly benign tumors accounting for 10-25% of intracranial tumors. Prolactin-secreting adenomas represent the most predominant type of all PitNET and for this subtype of tumors, the medical therapy relies on the use of dopamine agonists (DAs). DAs yield an excellent therapeutic response in reducing tumor size and hormonal secretion targeting the dopamine receptor type 2 (D2DR) whose higher expression in prolactin-secreting adenomas compared to other PitNET is now well established. Moreover, although DAs therapy does not represent the first-line therapy for other PitNET, off-label use of DAs is considered in PitNET expressing D2DR. Nevertheless, DAs primary or secondary resistance, occurring in a subset of patients, may involve several molecular mechanisms, presently not fully elucidated. Dopamine receptors (DRs) expression is a prerequisite for a proper DA function in PitNET and several molecular events may negatively modify DR membrane expression, through the DRs down-regulation and intracellular trafficking, and DR signal transduction pathway. The current mini-review will summarise the presently known molecular events that underpin the unsuccessful therapy with DAs. [ABSTRACT FROM AUTHOR]

Background: Prolactinoma is a functional pituitary adenoma that secretes excessive prolactin. Dopamine agonists (DAs) such as bromocriptine (BRC) are the first-line treatment for prolactinomas, but the resistance rate is increasing year by year, creating a clinical challenge. Therefore, it is urgent to explore the molecular mechanism of bromocriptine resistance in prolactinomas. Activation of the P38 MAPK pathway affects multidrug resistance in tumours. Our previous studies have demonstrated that inhibiting MAPK14 can suppress the occurrence of prolactinoma, but the role of MAPK11/12/13/14 (p38 MAPK) signalling in dopamine agonist-resistant prolactinomas is still unclear. Methods: A prolactinoma rat model was established to determine the effect of bromocriptine on MAPK11/12/13/14 signalling. DA-resistant GH3 cells and DA-sensitive MMQ cells were used, and the role of MAPK11/12/13/14 in bromocriptine-resistant prolactinomas was preliminarily verified by western blot, RT-qPCR, ELISA, flow cytometry and CCK-8 experiments. The effects of MAPK11 or MAPK14 on bromocriptine-resistant prolactinomas were further verified by siRNA transfection experiments. Results: Bromocriptine was used to treat rat prolactinoma by upregulating DRD2 expression and downregulating the expression level of MAPK11/12/13/14 in vivo experiments. The in vitro experiments showed that GH3 cells are resistant to bromocriptine and that MMQ cells are sensitive to bromocriptine. Bromocriptine could significantly reduce the expression of MAPK12 and MAPK13 in GH3 cells and MMQ cells. Bromocriptine could significantly reduce the expression of MAPK11, MAPK14, NF-κB p65 and Bcl2 in MMQ but had no effect on MAPK11, MAPK14, NF-κB p65 and Bcl2 in GH3 cells. In addition, knockdown of MAPK11 and MAPK14 in GH3 cells by siRNA transfection reversed the resistance of GH3 cells to bromocriptine, and haloperidol (HAL) blocked the inhibitory effect of bromocriptine on MAPK14, MAPK11, and PRL in MMQ cells. Our findings show that MAPK11 and MAPK14 proteins are involved in bromocriptine resistance in prolactinomas. Conclusion: Bromocriptine reduces the expression of MAPK11/12/13/14 in prolactinomas, and MAPK11 and MAPK14 are involved in bromocriptine resistance in prolactinomas by regulating apoptosis. Reducing the expression of MAPK11 or MAPK14 can reverse bromocriptine resistance in prolactinomas. [ABSTRACT FROM AUTHOR]

Instruction: The current study reports a woman with pituitary adenoma and frontal convexity meningioma that was detected accidentally. To the best of our knowledge, this case is considered as a rare clinical scenario. Case Presentation: A 37 years old woman suffering from amenorrhea and galactorrhea had her detail investigation showed hyperprolactinemia. The patient was diagnosed with a prolactinoma, and a frontal convexity meningioma was discovered on magnetic resonance imaging (MRI). The prolactinoma controlled with Bromocriptine therapy, while the meningioma monitored through medical observation. After two months of pharmaceutical medication, her symptoms improved with the decrease in serum prolactin. Conclusion: Thanks to sophisticated MRI techniques, meningioma and prolactinoma were incidentally detected. It should be noted that co-morbidity of prolactinoma and meningioma is very rare. The mechanism of the association between these two familiar types of intracranial tumors has not yet been clarified, which indicates the need for further studies to offer possible targeted treatment for patients.

Prolactinomas are the most frequently observed pituitary adenomas (PAs), and 5%–18% tumors were resistant to the dopamine agonists (DAs). MicroRNAs (miRNAs) dysfunction play a key role in tumorigenesis. Agilent miRNA and an expression chip were used for six prolactinomas and three normal pituitary specimens. Differentially expressed genes were confirmed by RT-qPCR. The level of DDR1 and SAT1 was determined with tissue micro-array (TMA) and western blot. A MMQ cell line was used for functional experiments. We have identified 5-miRNA and 12 target gene signatures of prolactinomas through gene ontology analysis. miRNA-199a-5p was selected for experiments that integrated the results from prolactinomas specimens and a rat prolactinoma model induced by 17-b-estradiol. Tumors with low miRNA-199a-5p had a significantly invasive behavior and a higher tumor volume (p

Prolactinomas have been reported for the failure of cognitive functions. However, the electrophysiological mechanisms of attention processing in prolactinomas remain unclear. In a visual mission, we monitored the scalp electroencephalography (EEG) of the participants. Compared with the healthy controls (HCs), larger frontoparietal theta and alpha coherence were found in the patients, especially in the right-lateralized hemisphere, which indicated a deficit in attention processing. Moreover, the frontoparietal coherence was positively correlated with altered prolactin (PRL) levels, implying the significance of PRL for adaptive brain compensation in prolactinomas. Taken together, this research showed the variations in attention processing between the HCs and prolactinomas. The coherence between frontal and parietal regions may be one of the possible electrophysiological biomarkers for detecting deficient attention processing in prolactinomas.

Prolactinomas have been reported for the failure of cognitive functions. However, the electrophysiological mechanisms of attention processing in prolactinomas remain unclear. In a visual mission, we monitored the scalp electroencephalography (EEG) of the participants. Compared with the healthy controls (HCs), larger frontoparietal theta and alpha coherence were found in the patients, especially in the right-lateralized hemisphere, which indicated a deficit in attention processing. Moreover, the frontoparietal coherence was positively correlated with altered prolactin (PRL) levels, implying the significance of PRL for adaptive brain compensation in prolactinomas. Taken together, this research showed the variations in attention processing between the HCs and prolactinomas. The coherence between frontal and parietal regions may be one of the possible electrophysiological biomarkers for detecting deficient attention processing in prolactinomas. [ABSTRACT FROM AUTHOR]

Prolactinoma is the most common cause of pituitary tumours. Current medical guidelines recommend dopamine agonists (cabergoline or bromocriptine) as the initial therapy for prolactinoma. However, surgical removal can also be considered in selected cases, such as patients with macroadenomas with local complications (bleeding or optic chiasm pressure) or those not responding to medical treatment. The present retrospective study included patients with prolactinomas (n=43; female, 24; male, 19) who were primarily managed with medical (n=32) or surgical (n=11) treatment. Macroadenoma (n=29.67%) was commonly detected in both genders (female, 54%; male, 84%). Moreover, the mean pre-treatment prolactin levels were similar in both genders (female, 683.3 ± 1347 ng/mL; male, 685.4 ± 805 ng/mL; p=0.226). Surgically treated patients had a greater reduction in tumour size (27.7 ± 17.9 mm pre-treatment vs. 8.72 ± 14.2 mm post-treatment) than non-surgically treated ones (12.5 ± 7.5 mm pre-treatment vs. 4.1 ± 4.2 mm post-treatment; p=0.00). However, the decrease in prolactin levels was similar between the two patient groups (p=0.108). During the follow-up period (10.6 ± 7.0 years), the average cabergoline dose of the patients was 1.42 ± 1.47 mcg/week. Although a surgical approach was considered for selected cases of prolactinoma, the average dose used for medical treatment was highly inadequate for the patients in the present study. [ABSTRACT FROM AUTHOR]

Prolactinomas are the most frequently observed pituitary adenomas. Prolactinomas invasion is a key risk factor associated with operation results, and it is highly correlated with clinical prognosis. Nuclear receptor subfamily 2 group C member 2 (NR2C2) first cloned from testis is involved in the invasion and metastasis of several human tumors. In 46 patients with prolactinamas, the expression levels of CCNB1, Notch2, and NR2C2 was determined with tissue micro-array (TMA). The association between NR2C2 levels and clinical parameters was established with univariate analysis. The levels of Notch2 and CCNB1 were analyzed by RT-PCR and western blot techniques.The average methylation levels of the NR2C2 promoter were 0.505 and 0.825 in invasive prolactinomas (IPA) and non-IPA groups, respectively (p = 0.013). Univariate analysis also showed that there is a significant relationship between high NR2C2 expression and invasion (x2 = 7.043, p = 0.008), prolactin granules (x2 = 8.712, p = 0.003), and tumor size (x2 = 4.261, p = 0.039.) With the knockdown of NR2C2, cell proliferation was inhibited. Genes related to epithelial-mesenchymal transition (EMT) induced the apoptosis in MMQ cells. In addition, the level of Notch2 and CCNB1 were down-regulated with the knockdown of NR2C2. Moreover, miR-129-5p reduced mRNA levels of NR2C2, and they inhibited cell proliferation by inducing apoptosis levels of MMQ cells. Our findings proved NR2C2 played the important role in tumorigenesis tumor invasion of prolactinomas; moreover, NR2C2 is identified as a potential target.

Background: Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone agonists). Both estrogen and antiandrogens are reported to increase prolactin levels. The objective is to systematically review the evidence of the effects of antiandrogens on prolactin levels, hyperprolactinemia, and prolactinomas among transgender women on estrogen therapy. Methods: We searched PubMed, Embase, and PsycInfo up to May 2020. We included studies with at least 3 months follow-up that evaluated the effects of antiandrogens among transgender women and reported on prolactin levels, hyperprolactinemia, or image-confirmed prolactinomas. Two reviewers independently screened studies for eligibility, serially abstracted data, and independently assessed risk of bias and graded strength of evidence. Findings: We included 17 studies (16 publications): 8 prospective cohorts, 8 retrospective cohorts, and 1 cross-sectional study, each with a moderate to serious risk of bias. Among transgender women on estrogen, prolactin levels increased by over 100% with cyproterone acetate and by up to 45% with spironolactone. However, we were unable to isolate the effects of antiandrogens from estrogen therapy. We were unable to draw conclusions about effects of antiandrogens on hyperprolactinemia and prolactinomas. Interpretation: Prolactin levels may be increased in transgender women who are taking both estrogens and an antiandrogen. Future research is needed to determine the effects of different antiandrogens on prolactin levels separately from estrogen therapy. Ideally, future studies would be prospective, provide either a comparison of two different antiandrogens or compare combination of estrogen and antiandrogen therapy to estrogen alone, and control for possible confounders. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced 'lockdowns' are the new 'norm' as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions. The clinical care of patients with pituitary disorders typically involves a multidisciplinary team, working in concert to deliver timely, often complex, disease investigation and management, including pituitary surgery. COVID-19 has brought about major disruption to such services, limiting access to care and opportunities for testing (both laboratory and radiological), and dramatically reducing the ability to safely undertake transsphenoidal surgery. In the absence of clinical trials to guide management of patients with pituitary disease during the COVID-19 pandemic, herein the Professional Education Committee of the Pituitary Society proposes guidance for continued safe management and care of this population. [ABSTRACT FROM AUTHOR]

To study the effects of microRNA-374-5p (miR-374-5p) on the cell proliferation, apoptosis, and migration of rat pituitary tumor cell line MMQ, and to explore its mechanism. Metltods MMQc ells in the logarithmic growth phase were divided into groups A, B, C and D. MMQc ells in the group A were cultured in cell culture medium, and group B was added with miR-374- 5p mimic, group C with miR-374-5p inhibitor, and group D with miR-374-5p mimic and miR-374-5p inhibitor. After O, 24, 48 and 72 hours of treatment, microplate reader was used to detect the optical density value of each group at 490 nm (OD value meant the ability of cell proliferation in each group). After 72-hour treatment, cells were collected by centrifugation for Annexin V-FITC and PI staining. flow cytometry was used for detecting the percent of Annexin positive cells and PI positive cells which indicated the apoptosis level in each group. Meanwhile the mRNA levels of PTIG, E-cadherin, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), Ncadherin Snail, and Vimentin were measured by real-time PCR. We separately cotransfected the wild type (WT) pituitary tumor-transforming gene (PTIG) luciferase vector and mutant (mut) PTIG luciferase vector with microRNA-NC or miR- 374-Sp mimic into MMQ cells, which were named as NC-WT group, NC-mut group, WT group, and mut group, respectively. Dual luciferase reporter gene assay was used to measure the optical density value after 72-hour transfection. Results Compared with groups A and D, the cell proliferation decreased in the group B and increased in the group C at 24, 48 and 72 h (both P < 0. 05). The percentages of Annexin V-positive cells in the groups A, B, C, and D were 3. 7%± 1.4%, 17.6%±5. 3%, 3. 4%±1. 5%, and 4. 5%±1. 4%, respectively, the percentages of Pl-positive cells were 2.4%±0. 9%. 11. 2％士3.7%, 2. 5%±1. 2%, and 2. 7%±0. 9%, respectively; there was statistical difference between group B and groups A, C and D (all P < 0. 05). Compared with groups A and D, the mRN A levels of PTIG and Ncadherin of group B decreased and the mRN A level of E-cadherin increased (all P < 0. 05). The luciferase activities of the NC-WT group, NC-mut group, WT group, and mut group were 13. 2土2.6,15.3士3.2, 4. 7土1.6,and 14.3土3.5,respectively; there was statistical difference between the WT group and the other groups (all P < 0. 05). C onclusion In MMQ cells, miR-374-Sp can inhibit cell proliferation,induce the apoptosis and inh如t the migration-related genes, and furthermore, PTIG is the target gene of miR-374-Sp. [ABSTRACT FROM AUTHOR]

The dopaminergic treatment represents the primary treatment in prolactinomas, which are the most common pituitary adenomas and account for about 40% of all pituitary tumours with an annual incidence of six to ten cases per million population. The dopaminergic treatment includes ergot and non-ergot derivatives with high affinity for the dopamine receptors D1 or/and D2. Through the activation of the dopaminergic pathway on pituitary lactotrophs, the dopamine agonists inhibit the prolactin synthesis and secretion, therefore normalizing the prolactin levels and restoring eugonadism, but they also lead to tumour shrinkage. Treatment with dopamine agonists has been associated – apart from the common side effects such as gastrointestinal symptoms, dizziness and hypotension – with neuropsychiatric side effects such as impulse control disorders (e.g. pathological gambling, compulsive shopping, hypersexuality and binge eating) and also with behavioral changes from low mood, irritability and verbal aggressiveness up to psychotic and manic symptoms and paranoid delusions not only in patients with prolactinomas but also in patients with Parkinson’s disease and restless leg syndrome. They usually have de novo onset after initiation of the dopaminergic treatment and have been mainly reported in patients with Parkinson’s disease, who are being treated with higher doses of dopamine agonists. Moreover, dopamine and prolactin seem to play an essential role in the metabolic pathway. Patients with hyperprolactinemia tend to have increased body weight and an altered metabolic profile with hyperinsulinemia and increased prevalence of diabetes mellitus in comparison to healthy individuals and patients with non-functioning pituitary adenomas. Treatment with dopamine agonists in these patients in short-term studies seems to lead to weight loss and amelioration of the metabolic changes. Together these observations provide evidence that dopamine and prolactin have a crucial role both in the regard and metabolic system, findings that merit further investigation in long-term studies.

Impairment of cognitive functions has been reported in prolactinomas. However, the electrophysiological mechanisms of response activation and response inhibition in prolactinomas remain unclear. We recorded participants’ scalp electroencephalography (EEG) in a visual Go/Nogo task. Compared to the healthy controls (HCs), the patients demonstrated worse performance and their prolactin (PRL) levels negatively correlated with behavioral results. Meanwhile, patients’ P300 amplitudes in the Go and Nogo conditions were smaller than the HCs. The amplitudes of N200nogo in patients were smaller than the HCs as well. Lower frontal theta power was found in the patients than the HCs in both Go and Nogo conditions, which indicated a deficit in response activation and inhibition. Moreover, the PRL levels mediated the relationship between frontal theta power and behavior performance, implying that lower frontal theta power caused the dysfunction of response control by abnormally high PRL levels. Patients also showed lower occipital alpha power than the HCs, which suggested that the impaired response inhibition may arise from deficient attention control. Taken together, the present study revealed the neurocognitive discrepancies between prolactinomas and the HCs. The frontal theta oscillation was highlighted as the electrophysiological markers of the impaired response control in prolactinomas.

Objective To testify the expression of nuclear receptor subfamily 2 group C member 2 (NR2C2) in the prolactinomas, and analyze the relationship between NR2C2 and clinical features. MethodsImmunohistochemical staining and Western blotting were used to detect the expression of NR2C2 in 46 prolactinoma patients. The relationship between NR2C2 and clinical features was analyzed by follow-up data. RNA interference technique(RNAi) knocked down the NR2C2 level in MMQ cells, and cell viability was detected by cell proliferation assay. Flow cytometry was used to detect the apoptosis level by Annexin V/PI staining. ResultsThe patients were divided into invasive group and non-invasive group according to Knosp classification. The H-score of NR2C2 in the invasive group was 148.2±42.7, and 45.2±28.72 in the non-invasive group(P＜0.01). The level of NR2C2 was positively correlated with tumor size(r=0.327,P=0.039), and there was higher NR2C2 level in patients with loose granules than those in dense granules(P=0.003). Western blot experiments filtered the fragments Sh-B(23.4%) and Sh-C(34%) compared to NR2C2 protein level in control MMQ cell(P＜0.01). The cell viability of Sh-B group reduced 24.8%, 39.2% and 48.3%, and Sh-C group was 19.1%, 26.4% and 32.5% compared to control cell after 24 h, 48 h and 72 h transfection(all P＜0.05). After 24 h RNAi, Annexin V positive cells were （10.3±3.1）% in the Sh-B group and（8.5±2.3）% in Sh-C group, and PI positive cells were（7.3±2.1）% and （5.6±1.8）% separately（all P＜0.05). ConclusionNR2C2 is closely related to the tumorigenesis and development of prolactin adenoma. [ABSTRACT FROM AUTHOR]

Membrane progesterone receptors are known to mediate rapid nongenomic progesterone effects in different cell types. Recent evidence revealed that mPRα is highly expressed in the rat pituitary, being primarily localized in lactotrophs, acting as an intermediary of P4-inhibitory actions on prolactin secretion. The role of mPRs in prolactinoma development remains unclear. We hypothesize that mPR agonists represent a novel tool for hyperprolactinemia treatment. To this end, pituitary expression of mPRs was studied in three animal models of prolactinoma. Expression of mPRs and nuclear receptor was significantly decreased in tumoral pituitaries compared to normal ones. However, the relative proportion of mPRα and mPRβ was highly increased in prolactinomas. Interestingly, the selective mPR agonist (Org OD 02-0) significantly inhibited PRL release in both normal and tumoral pituitary explants, displaying a more pronounced effect in tumoral tissues. As P4 also regulates PRL secretion indirectly, by acting on dopaminergic neurons, we studied mPR involvement in this effect. We found that the hypothalamus has a high expression of mPRs. Interestingly, both P4 and OrgOD 02-0 increased dopamine release in hypothalamus explants. Moreover, in an in vivo treatment, that allows both, pituitary and hypothalamus actions, the mPR agonist strongly reduced the hyperprolactinemia in transgenic females carrying prolactinoma. Finally, we also found and interesting gender difference: males express higher levels of pituitary mPRα/β, a sex that does not develop prolactinoma in these mice models. Taken together, these findings suggest mPRs activation could represent a novel tool for hyperprolactinemic patients, especially those that present resistance to dopaminergic drugs. [ABSTRACT FROM AUTHOR]

Dopamine agonists such as bromocriptine and cabergoline are the predominant treatment drugs for prolactinoma by inhibiting prolactin secretion and shrinking tumor size. However, the pathways of either dopamine or its agonists that lead to the death of cells are incompletely understood and some are even conflicting conclusions. The main aim of this paper is to review the different pathways of dopamine and its agonists in prolactinomas to help to gain a better understanding of their functions and drug resistance mechanisms.

Introduction: Prolactinomas are the most common type of pituitary gland tumors that secrete overly prolactin. They account for approximately 60% of all hormone-secreting hypophysis tumors., Aim: This study aims to analyze gender differences in patients with prolactinomas who were operated on transsphenoidal surgery and conduct a single-center retrospective analysis of patient data., Material and Methods: This study evaluated the medical records of 109 patients (61 females and 48 males) from 2009 to 2019 at Feofaniya Clinical Hospital of the State Administration of Affairs in Kyiv, Ukraine. The primary criterion for including patients was a Serum Prolactin (PRL) level of over 100 ng/ml and the presence of a pituitary adenoma (PA) as observed on MRI. Additionally, the histological examination needed to confirm the presence of Prolactin-Secreting Pituitary Adenomas (PSPAs) without plurihormonal activity through both microscopy and immunohistochemical (IHC) staining., Results: Significant differences in preoperative PRL levels were not observed. However, males had significantly larger tumor sizes and prevalence of macroadenomas. In male patients, the preoperative PLR levels showed a weak negative correlation with age (r=-0.304, p < 0.036) and a positive correlation with tumor size (r=0.555, p < 0.001) and cavernous sinus invasion (r=0.339, p < 0.018). In females, preoperative PRL was significantly associated only with tumor size and Knosp grade., Conclusion: Prolactin-Secreting Pituitary Adenomas (PSPAs) are more common in women than men and are characterized by larger and more invasive tumors with high PRL levels at diagnosis. The PRL level and tumor size before surgery can predict early biochemical remission in both males and females with an accuracy of 58.3% and 68.8%, respectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Dopamine agonists such as bromocriptine and cabergoline are the predominant treatment drugs for prolactinoma by inhibiting prolactin secretion and shrinking tumor size. However, the pathways of either dopamine or its agonists that lead to the death of cells are incompletely understood and some are even conflicting conclusions. The main aim of this paper is to review the different pathways of dopamine and its agonists in prolactinomas to help to gain a better understanding of their functions and drug resistance mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: Lactotroph adenomas (LA) are the most frequently encountered pituitary tumors. Although more frequently observed in women, LAs in men were recently included in a more aggressive category regardless of histological grading, by the WHO. We aimed to perform a rigorous retrospective review of a single center’s pre-operative evaluation, patient characteristics and outcomes of male LAs patients requiring pituitary surgery.Methods: A retrospective review, over 11 years, of patients who underwent resection of a pituitary adenoma at a single center was conducted. Predictors of persistent disease in male LAs patients along with a comparison to predictors of silent corticotroph adenomas (SCAs) patients who also underwent surgery at the center was also conducted.Results: Thirty-one male patients with LAs were identified. When compared to SCAs patients, LAs male patients were younger (41 vs. 50 years of age, p = 0.01). Men with LAs had more invasive tumors (75% vs. 44.7% p = 0.02). More LAs in men had residual tumor after surgery than patients with SCA (92.6% vs. 42.1%, p < 0.001). Male patients with LAs and patients with SCA had similar rates of requiring additional surgery (28.9% vs. 24.1%, p = NS) and radiation therapy (18.4% vs. 19.4%, p = NS).Conclusions: High rates of DA resistance, invasive tumors and postoperative residual disease in male patients with LA who required surgery are shown. Surgery improved optic chiasm compression, PRL level and central hypogonadism but, not surprisingly, failed to normalize other pituitary hormones and/or eliminate need for DA therapy. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor alpha (PPARa) has been involved in the regulation of somatotroph tumour cells and may be targeted by different drugs, some of them are in current clinical use. The aim of this study was to investigate the expression of PPARa in additional phenotypes of pituitary adenomas (PA), the relationship between PPARa and its potential molecular partner aryl hydrocarbon receptor interacting protein (AIP) in these tumours, and the effects of PPARa agonists on lactotroph cells. Seventy-five human PA - 57 non-functioning (NFPA) and 18 prolactinomas (PRL-PA) - were characterised for PPARa and AIP expression by real time RT-PCR and/or immunohistochemistry (IHC), and the effects of fenofibrate and WY 14 643 on MMQ cells were studied in vitro. PPARa was expressed in a majority of PA. PPARa immunostaining was observed in 93.7% PRL-PA vs. 60.6% NFPA (p = 0.016), the opposite being found for AIP (83.3% in NFPA vs. 43.7% in PRL-PA, p = 0.003). PPARa expression was unrelated to gonadotroph differentiation in NFPA, but positively correlated with tumour volume in PRL-PA. Both drugs significantly reduced MMQ cell growth at high concentrations (100-200 µM). At the same time, despite modest stimulating effects on PRL secretion were observed, these were overcome by the reduction in cell number. In conclusion, PPARa is commonly expressed by PRL-PA and NFPA, regardless of AIP, and may represent a new target of PPARa agonists. [ABSTRACT FROM AUTHOR]