Increased Serum Prolactin Research Articles

Wheel Running During Pregnancy Alleviates Anxiety-and Depression-Like Behaviors During the Postpartum Period in Mice: The Roles of NLRP3 Neuroinflammasome Activation, Prolactin, and the Prolactin Receptor in the Hippocampus.

Despite the increase in the prevalence of postpartum depression among maternal disorder, its treatment outcomes remain suboptimal. Studies have shown that exercise can reduce postpartum depressive episodes in the mother, but the effects of exercise during pregnancy on maternal behavior and the potential mechanisms involved remain poorly understood. From the second day of pregnancy to the day of birth, dams exercised for 1h a day by running on a controlled wheel. The maternal behaviors of the dams were assessed on postpartum day 2 to postpartum day 8. Chronic restraint stress was applied from postpartum day 2 to day 12. Blood was collected on postpartum days 3 and 8, then subjected to ELISA to determine the serum concentration of prolactin. The weight of each dam and the food intake were recorded. Anxiety- and depression-like behavioral tests were conducted, and hippocampal neuroinflammation and prolactin receptor levels were measured. The dams exhibited elevated levels of anxiety and depression, decreased serum prolactin levels, decreased prolactin receptor expression, and activation of NLRP3-mediated neuroinflammation in the hippocampus following the induction of postpartum chronic restraint stress, which were reversed with controlled wheel running during pregnancy. Overall, the findings of this study revealed that the preventive effects of exercise during pregnancy on postpartum anxiety-and depression-like behaviors were accompanied by increased serum prolactin levels, hippocampal prolactin receptor expression and hippocampal NLRP3-mediated neuroinflammation.

Bmal1 regulates female reproduction in mice via the hypothalamic-pituitary-ovarian axis.

The hypothalamic-pituitary-gonadal axis (HPG) is the key neuroendocrine axis involved in reproductive regulation. Brain and muscle ARNT-like protein 1 (Bmal1) participates in regulating the metabolism of various endocrine hormones. However, the regulation of Bmal1 on HPG and female fertility is unclear. This study aims to explore the regulation of female reproduction by Bmal1 via the HPG axis in mice. Bmal1-knockout (Ko) mice were generated using the CRISPR/Cas9 technology. The structure, function, and estrous cycle of ovarian in Bmal1 Ko female mice were measured. The key genes and proteins of the HPG axis involved in regulating female reproduction were examined through transcriptome analysis and then verified by RT-PCR, immunohistochemistry, and western blot. Furthermore, the fertility of female mice was detected after intervening prolactin (PRL) and progesterone (Pg) in Bmal1 ko mice. The number of offspring and ovarian weight were significantly lower in Bmal1-Ko mice than in wild-type (Wt) mice. In Bmal1-Ko mice, ovarian cells were arranged loosely and irregularly, and the total number of follicles was significantly reduced. No corpus luteum was found in the ovaries. Vaginal smears revealed that Bmal1-Ko mice had an irregular estrus cycle. In Bmal1-Ko mice, Star expression was decreased, PRL and luteinizing hormone (LH) levels were increased, and dopamine (DA) and Pg levels were decreased. Inhibition of PRL partially recovered the estrous cycle, corpus luteum formation, and Star expression in the ovaries. Pg supplementation promoted embryo implantation in Bmal1-Ko female mice. Bmal1 Ko increases serum PRL levels in female mice likely by reducing DA levels, thus affecting luteal formation, resulting in decreased Star expression and Pg production, hindering female reproduction. Inhibition of PRL or restoration of Pg can partially restore reproductive capacity in female Bmal1-Ko mice. Thus, Bmal1 may regulate female reproduction via the HPG axis in mice, suggesting that Bmal1 is a potential target to treat female infertility.

Long-term proton pump inhibitors therapy and prevalence of hyperprolactinemia. a cross-sectional study in outpatient gastroenterology clinics

Objective: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. Method: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. And comprised patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for >3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. Results: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinemia and 70(42%) with hypreprolactinemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Pateints having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinemia. Conclusion: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management. Key Words: Proton pump inhibitors, Long-term therapy, Hyperprolactinemia, Omeprazole, Prolactin.

Prolactin level changes according to atypical antipsychotics use: a study based on Clinical Data Warehouse

IntroductionAntipsychotics are associated with increased serum prolactin. It depends on the type of the antipsychotics and gender. There are previous studies, but it is necessary to compare them including new drugs.ObjectivesAntipsychotic drugs are known as the major cause of non-neoplastic hyperprolactinemia. This study aimed to investigate the levels of serum prolactin elevation depending on the use of antipsychotic drugs in patients through the Clinical Data WarehouseMethodsOur study included 118 subjects who were all diagnosed according to ICD-10 for schizophrenia, schizotypal and delusional disorders, manic episodes, and bipolar affective disorders. All the subjects were taking one of risperidone, blonanserin, amisulpride, and olanzapine. They had prolactin blood tests collected retrospectively through CDW.Results Among the 118 subjects included in the analysis, the mean serum prolactin level was 65.1± 54.7ng/ml. Serum prolactin levels were significantly higher in subjects taking risperidone or amisulpride compared to blonanserin and olanzapine. The female subjects who took amisulpride or olanzapine had significantly higher prolactin levels, but there was no difference in prolactin levels between the sex in the subjects who took risperidone or blonanserin.ConclusionsThis study suggests the need for regular monitoring of serum prolactin levels in patients who are taking antipsychotics, especially in female patients. Further studies on the subjects with controlled confounding variables and larger sample groups are needed.Disclosure of InterestNone Declared

Determinants of Knowledge Sharing Behaviors: Developing and Testing an Integrated Theoretical Model

Hyperprolactinemia is a hypothalamic-pituitary disorder caused by increased serum prolactin levels from a variety of causes. Increased secretion of prolactin (PRL) in the blood can lead to a variety of somatic disorders, including menstrual abnormalities such as scanty or absent menstruation, as well as breast engorgement and infertility. If left untreated, this condition can progress and lead to recurrent miscarriage, embryonic arrest, osteoporotic fractures, and other complications. In recent years, the combination of traditional Chinese medicine and Western medicine has been used to effectively treat hyperprolactinemia. This review aims to provide a comprehensive overview of the treatment of hyperprolactinemia using both traditional and modern medicine, to improve diagnosis and treatment options for this condition.

Impact of high-fat diet and exposure to constant light on reproductive competence of female ICR mice.

Obesity and exposure to light at night are prevalent in modern society and associated with changes in physiology and behavior that can affect a female's ability to support offspring growth during pregnancy and lactation. A 2X3 factor study of ICR mice was conducted to determine the effect of diet [control (CON; 10% fat) or high fat (HF; 60% fat)] and exposure to regular 12 h light:dark cycles (LD) or continuous low (L5) or high (L100) lux of light on gestation length, birth litter size, milk composition and litter growth to lactation day 12. HF diet reduced birth litter size, but increased postnatal d 12 litter weight (P<0.05), whereas constant light tended to increase litter weight (P=0.07). Continuous light increased gestation length, altered dam feed intake, increased serum prolactin and increased final dam and mammary gland weight (P<0.05), while decreasing mammary ATP content and milk lactose (P<0.05). Correlation analysis indicated a positive relationship between final litter weight and mammary size, metabolic stores (e.g. maternal fat pad weight), kcal of feed intake, and gestation length (P<0.05). Although CON mice spent more time eating than HF dams, the calorically dense HF diet was related to greater rates of litter growth to peak lactation. Constant light circadian disrupting effects appear to be confounded by a potential long day photoperiod response exemplified by higher circulating levels of prolactin and increased body and mammary weight of females exposed to these conditions. Other model systems may be better to study the interacting effects of obesity and circadian disruption on reproductive competence.

#6286 NEPHROCALCINOSIS IN 3 GENERATIONS OF FEMALE PATIENTS DUE TO A PATHOGENIC MEN1 MUTATION

Abstract Background and Aims Multiple Endocrince Neoplasia type 1 (MEN1) syndrome, has an autosomal dominant transmission pattern, characterized by hyperparathyroidism, benign or malignant tumors in pancreas islets, pituitary tumors, thymic carcinomas, adrenal cortex adenomas and angio-fibromas of the skin. We are describing 2 cases of MEN1 with first and cardinal manifestations within the kidney. Method Medical records review, whole exome sequencing (WES), bioinformatics analysis by Ingenuity Pathway Analysis, QIAGEN Results Patient 1. A 28 year old female presented with horseshoe kidney, multiple pyelonephritis episodes, primary hyperparathyroidism, hypercalcemia, magnesiuria, reduced bone mass, and nephrocalcinosis. Her mother and grandmother suffered from hyperparathyroidism. WES analysis demonstrated a 12-base deletion between intron 9 and exon 10 in MEN1 gene (c.1351-3_1359delCAGGTGCGGCAG) with an apparent pathogenicity [1]. An accompanying alteration of CLDN16 gene (c.324+13C&amp;gt;G, rs369250510) was also detected. Till now this alteration is considered benign. Patient 2. A 48 year old female, with primary hyperparathyroidism in the last 15 years (the mother of Patient 1), with nephrocalcinosis since 1997 (calcium oxalate stones), preserved renal function, hypercalcemia, magnesiuria, reduced bone mass, hypertelorism with concurrent diplopia. In 2013, parathyroeidectomy resulted in stabilization of nephrocalcinosis. WES revealed the same pathogenic deletion as in her daughter. A research for epigastric pain revealed a cystic pancreatic mass, with accompanying increase in serum gastrin and chromogranin. A pituitary adenoma is manifested with a marginally increased serum prolactin. Her mother suffers from primary hyperparathyroidism with nephrocalcinosis. Conclusion In familial nephrocalcinosis/lithiasis/hyperparathyroidism genetic counselling and screening defines individualized treatment and may prevent extra renal disease manifestations.

Sex Differences in Serum Prolactin Levels in Children and Adolescents on Antipsychotics: A Systematic Review and Meta-Analysis.

Serum prolactin levels are influenced by sex, physical development and medications among other factors. Antipsychotics usually increase serum prolactin levels in both adults and younger patients, but no study has reviewed the potential association between sex and vulnerability for developing hyperprolactinemia among children and adolescents. Systematic review and meta-analysis of serum prolactin levels in children and adolescents on antipsychotic treatment for any psychiatric diagnosis to determine the effect of sex. A systematic search was performed in MEDLINE/PubMed/Web of Science and Cochrane databases for randomized controlled trials of antipsychotics in children and adolescents reporting serum prolactin levels by sex. Of 1278 identified records, seven studies were included, comparing different single antipsychotics to placebo (risperidone N=4; lurasidone N=1; olanzapine N=1; queriapine N=1). Both male and female children and adolescents on antipsychotics presented a significant increase in prolactin levels relative to subjects receiving a placebo. (Male: 16.53 with 95% CI: 6.15-26.92; Female: 26.97 with 95% CI: 9.18-44.75). The four studies using risperidone had similar findings (Male: 26.49 with 95% CI: 17.55-35.43; Female: 37.72 with 95% CI: 9.41-66.03). In the direct comparison between sexes, females showed greater increases in prolactin, but the differences were not statistically significant. Serum prolactin levels are increased in children and adolescents of both sexes on antipsychotics, with females showing a slightly greater increase than males. Further research is needed to clarify the influence of sex and pubertal status on prolactin levels in children and adolescents taking antipsychotics.

360 The Ability of an Enhanced Zeolite-Based Flow Agent to Mitigate the Effects of Ergot-Like Alkaloids Consumed by Beef Cattle

Abstract Aluminosilicate-based flow agents, like zeolites, may impact digestion of ergot-like alkaloids in the ruminant gut. Twenty-four steers (226 ± 27.6 kg) were used in a 21-d experiment to test the effects of an enhanced zeolite-based flow agent (KALLSIL, Kemin Industries, Des Moines, IA) on site of ergot-like alkaloid excretion, serum prolactin, rectal temperature, respiration rate, and nutrient digestibility. Treatments were control (E+) or enhanced zeolite inclusion (E+Z; 2 g/kg, DM basis). Steers were fed a TMR at 1.85% of BW (DM-basis). Tall-fescue seed was included in the diet at 11.14%, providing 465 µg of ergovaline/kg DM. Steers had no ORTS during the experiment. Rectal temperature and respiration rate were recorded daily at 0700 and 1200 h from steers housed tie stalls in a room kept at (18.5°C ± 0.33°C, 32.6% ± 2.19%). Serum was harvested from blood collected on d-1, 7, 14, and 21 to measure prolactin. On d-21 jugular catheters were placed to measure prolactin following the infusion of thyrotropin-releasing hormone (TRH; 1 µg/kg BW). Spot samples of feces and urine were collected every 8 h from d 17-20, with 2-hour advancement each day to determine digestibility, N balance, and recovery of ergot-like alkaloids. Digestion and N balance was not affected by treatment (P ≥ 0.16). Enhanced zeolite tended (P = 0.15) to increase recovery of ergovaline. Prolactin concentration decreased over time (P &amp;lt; 0.01), but was greater (P = 0.01) at each time point for E+Z steers. Following the infusion of TRH, prolactin tended (P = 0.11) to be greater for E+Z. Rectal temperatures and respiration rates were not affected (P ≥ 0.89) by E+Z. Results from this study indicate that enhanced zeolite inclusion tended to increase recovery of ergot-like alkaloids in feces and increased serum prolactin when offered to beef steers in a diet containing ergot-like alkaloids.

Influence of form of selenium supplementation and tall fescue endophyte toxicity on growth performance, serum parameters, and tissue masses of grazing beef steers.

To test the hypothesis that average daily gain (ADG) and clinical parameters of steers grazing novel non-toxic (NTE) or toxic KY-31 (TE) endophyte-infected tall fescue would be improved by ad libitum intake of vitamin‐mineral mixes (V-M) that contain 27 ppm Se as a 1:1 blend of SELPLEX:sodium selenite (MIX) vs. sodium selenite (ISe), 32 fescue-naïve beef steers partially depleted of Se were randomly assigned to ad libitum consumption ISe vs. MIX for 35 days and fed enough of a NTE/alfalfa/grain diet to achieve 0.57 kg BW gain/day. Then, within Se-form treatments, two steers were randomly assigned to each of four NTE (ISe = 316 ± 31 kg BW, MIX = 315 ± 22 kg BW) or TE (ISe = 316 ± 37 kg BW, MIX = 314 ± 39 kg BW) paddocks for 84 days and had ad libitum access to their respective V-M. The MIXED procedure of SAS was used to assess effects of day, Se-form (ISe, MIX) and endophyte (NTE, TE) treatments, and their interactions. Whole blood Se decreased (P < 0.01) 31% from days 0 to 84 and was 6.2% greater (P < 0.01) for MIX steers. Serum prolactin decreased (P < 0.01) 18% for NTE and 48% for TE steers from days 0 to 84 and was 17% greater (P = 0.01) for MIX vs. ISe for TE steers. Serum alkaline phosphatase activity decreased (P < 0.02) 27% from days 0 to 84 and was 15% greater (P < 0.02) for MIX steers. Serum urea nitrogen increased (P < 0.02) 8.2% from days 0 to 84 for TE but not NTE steers. Average daily gain was less (P < 0.01) for steers grazing TE (−0.18 kg/day) compared with NTE (0.09 kg/d). Although there was increased serum alkaline phosphatase activity and increased serum prolactin for TE + MIX steers compared with TE + ISe steers, MIX supplementation was unable to increase serum prolactin concentrations or ADG to the same levels as steers grazing NTE. Longer adaptation to MIX supplementation ad libitum may be necessary for maximal Se assimilation to restore serum prolactin levels in steers grazing TE.

Prolactin at moderately increased levels confers a neuroprotective effect in non-secreting pituitary macroadenomas.

Prolactin, a hormone synthesized by the anterior pituitary gland demonstrates promise as a neuroprotective agent, however, its role in humans and in vivo during injury is not fully understood. To investigate whether elevated levels of prolactin attenuate injury to the retinal nerve fiber layer (RNFL) following compression of the optic chiasm in patients with a prolactin secreting pituitary macroadenoma (i.e., prolactinoma). A retrospective cross-sectional study of all pituitary macroadenoma patients treated at a single institution between 2009 and 2019. Primary outcome measures included RNFL thickness, mean deviation, and prolactin levels for both prolactin-secreting and non-secreting pituitary macroadenoma patients. Sixty-six patients met inclusion criteria for this study (14 prolactin-secreting and 52 non-secreting macroadenoma patients). Of 52 non-secreting macroadenoma patients, 12 had moderate elevation of prolactin secondary to stalk effect. Patients with moderate elevation in prolactin demonstrated increased RNFL thickness compared to patients with normal prolactin levels (p < 0.01). Additionally, a significant positive relation between increasing levels of prolactin and RNFL thickness was identified in patients with moderate prolactin elevation (R = 0.51, p-value = 0.035). No significant difference was identified between prolactinoma patients and those with normal prolactin levels. Moderately increased serum prolactin is associated with increased RNFL thickness when compared to controls. These associations are lost when serum prolactin is < 30 ng/ml or elevated in prolactinomas. This suggests a neuroprotective effect of prolactin at moderately increased levels in preserving retinal function during optic chiasm compression.

Metformin attenuates the production and proliferative effects of prolactin induced by medroxyprogesterone acetate during fertility-sparing treatment for endometrial cancer

BackgroundProgestin is used for fertility-sparing treatment in cases of endometrial cancer (EC). Progestin can induce hyperprolactinemia by increasing pituitary secretion and endometrial decidualization. However, progestin induces prolactin (PRL) secretion, which stimulates cell proliferation and deleteriously affects treatment. To date, the detrimental effect of PRL, the secretion of which is induced by medroxyprogesterone acetate (MPA) during fertility-sparing treatment, has not yet been fully elucidated. Therefore, we aimed to assess the effects of PRL on EC cells during combined treatment with progestin and metformin.MethodsIn total, 71 patients with EC/endometrial atypical hyperplasia who underwent fertility-sparing treatment at our institution from 2009–2019 were enrolled. Serum PRL levels were determined using enzyme immunoassays; mRNA levels in endometrial tissues were determined using quantitative reverse-transcription PCR. To evaluate MPA-induced decidualization, cancer-associated stromal cells were enzymatically released from surgically removed specimens of six patients with EC. To examine PRL-induced cell proliferation, the EC cell lines Ishikawa, HEC1B, and HEC265 were used. In vitro cell proliferation was evaluated using the WST assay; protein levels of signaling molecules were determined using western blotting.ResultsMPA administration significantly increased serum PRL levels at 3 and 6 months and upregulated IGFBP-1 and PRL mRNA expression in tissues at 3 months of fertility-sparing treatment. Metformin significantly reduced MPA-induced IGFBP-1 and PRL mRNA expression during fertility-sparing treatment and significantly inhibited the upregulation of IGFBP-1 and PRL mRNA and PRL levels due to decidualization induced by MPA and cAMP treatment in primary cultured EC stromal cells. In vitro, PRL increased cell proliferation and ERK1/2 phosphorylation levels, whereas metformin attenuated these increases.ConclusionsMPA upregulated PRL levels in serum and endometrial tissues during fertility-sparing treatment. Metformin co-administration reduced PRL production and attenuated PRL-induced cell-proliferation activity. This study may provide valuable insights on the application of metformin to improve the outcomes of fertility-sparing treatment.

Phase 1b study of the novel first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in combination with pembrolizumab in patients with immune checkpoint inhibitor (ICI)-relapsed and refractory solid malignancies and dose escalation update.

2574 Background: LNS8801 is an oral, highly selective, small molecule agonist of the G protein-coupled estrogen receptor (GPER). LNS8801 normalizes c-Myc levels in cancer cells, inhibits proliferation, suppresses invasion, and enhances immune recognition. In preclinical models, LNS8801 has demonstrated increased activity with ICIs. In the first-in-human dose escalation study, LNS8801 was safe and tolerable alone and in combination with pembrolizumab in patients with metastatic solid tumors (NCT04130516). Methods: Patients who are relapsed and refractory (r/r) to PD-1/L1 ICIs and have measurable disease are enrolling in a Phase 1b cohort and receive LNS8801 (125 mg, QD, PO) and pembrolizumab (200 mg, Q3W, IV) (NCT04130516). The primary objective is safety and tolerability assessed according to NCI CTCAE v5.0. Secondary endpoints include pharmacokinetic, pharmacodynamics (eg., increase in serum prolactin over the initial 10 hours of dosing to assess GPER engagement), objective response rate and clinical benefit rate per RECIST v1.1. Results: Updates from the dose escalation portion of the study include long term benefit in a monotherapy patient with cutaneous melanoma on treatment for 2 years with RECIST stable, metabolically inactive disease by PET; a metastatic uveal melanoma patient on therapy for a year, and growing confidence in LNS8801’s favorable safety profile and predictive systemic biomarkers. As of 2/1/22, 13 ICI r/r patients were treated with LNS8801 and pembrolizumab, including those who entered the study directly after confirmed progression on ICIs. Cancer types include lung (3), colorectal, vaginal, nasopharyngeal, neuroendocrine, uterine, and pancreatic cancer, mesothelioma (2), and cutaneous and uveal melanoma. 46% of patients had AEs possibly related to study drugs (31% grades 1-2 and 31% grade 3), with colitis (15%) and fatigue (23%) appearing in more than 10% of patients. Of the 10 evaluable patients, 7 had stable disease (SD), with 4 patients demonstrating tumor regression. At the data cut-off, duration of treatment ranged from 0.7–7.5 months with 4 patients treated between 4.8 and 7.5 months and 4 patients continuing on treatment. All evaluated patients with SD had a prolactin response indicative of systemic target engagement. Conclusions: The combination of LNS8801 and pembrolizumab is tolerable without unanticipated toxicities and demonstrates encouraging anti-tumor activity in patients that are r/r to ICIs, including patients who enrolled immediately after confirmed progression on pembrolizumab alone. These data, as well as continued follow-up on patients with long-term benefit from dose escalation, support further development of LNS8801 as a cancer therapeutic. Clinical trial information: NCT04130516.

0398 Is Increased Serum Prolactin Associated with Excessive Daytime Sleepiness? A Proof-of-Concept Analysis

Abstract Introduction With this study we aimed to: 1) identify subjects with hyperprolactinemia in a clinical sample of patients; 2) compare the neurologic, psychiatric, and sleep conditions found in patients subgrouped by excessive daytime sleepiness (EDS) and hyperprolactinemia; 3) identify patients with hyperprolactinemia and EDS not supported by the presence of any other neurologic, psychiatric, or sleep disorder, or substance/medication use. Methods A retrospective chart review of inpatients was carried out in order to identify all patients in whom the prolactin (PRL) serum levels were determined. A total of 130 subjects were retrieved: 55 had increased levels of PRL while the remaining 75 participants had normal PRL levels. Results EDS was reported by 32 (58.2%) participants with increased PRL and 34 (45.3%) with normal PRL. Obstructive sleep apnea or other sleep or neurologic/psychiatric conditions could explain EDS in all participants with normal PRL. Among subjects with increased PRL, eight had no other neurologic/psychiatric or sleep disorder (or drug) potentially causing EDS; these participants, at polysomnography, had time in bed, sleep period time, and total sleep time longer than those with EDS associated to another condition. Conclusion These findings can be considered as a preliminary indication of a role of hyperprolactinemia in EDS and represent a basis for future controlled studies able to test in a reliable, objective, and methodologically more appropriate way this hypothesis. Support (If Any) This study was partially supported by a fund from the Italian Ministry of Health “Ricerca Corrente” (RC n. 2764026) (Drs. Cosentino, Aricò, Lanuzza, Lanza, Tripodi, and Ferri)

Glutamine Supplementation Attenuates Bisphenol A-Induced Testicular Toxicity in Rats.

The induction of testicular toxicity by bisphenol A (BPA) may involve oxidative stress. Glutamine (Gln) is a rate limiter for the synthesis of glutathione (GSH), which inhibits oxidative stress. This study assessed the potential of BPA to preserve testicular structure and function in BPA-treated albino rats. Thirty-two adult male albino rats (210-250 g) were randomly allocated to 4 (A-D) of 8 rats per group with the approval of the Research Ethics Committee. Groups B-D were orally treated with Gln (20 mg/kg body weight), BPA (50 mg/kg body weight) and Gln (20 mg/kg body weight) + BPA (50 mg/kg body weight) daily for 65 days, respectively. Group A (control) was orally treated with normal saline (0.2 mL) daily for 65 days. At the termination of treatment, the rats were weighed and anaesthetized blood samples were collected and evaluated for gonadal hormones. The testes were weighed and evaluated for sperm parameters, oxidative stress markers and histology. The data were analysed using one-way analysis of variance and Bonferroni post hoc test. BPA caused a significant (P < 0.001) decrease in testis and body weights, sperm count, volume, motility and normal morphology when compared to the control. BPA significantly (P < 0.001) decreased serum testosterone, follicle-stimulating hormone, luteinising hormone, testicular catalase, superoxide dismutase, GSH and GSH peroxidase levels relative to control. Significantly (P < 0.001) increased serum prolactin, estradiol and testicular malondialdehyde levels occurred in BPA-treated rats relative to control. The testes of BPA-treated rats showed sloughing and coalescence of germ cells. However, Gln supplementation prevents BPA-induced testicular toxicity. Gln supplementation restored testis histology. Based on the observation in this study, Gln seems effective against BPA-induced testicular toxicity.

Prolactin signaling modulates stress-induced behavioral responses in a preclinical mouse model of migraine.

The aim of this study was to determine if prolactin signaling modulates stress-induced behavioral responses in a preclinical migraine model. Migraine is one of the most complex and prevalent disorders. The involvement of sex-selective hormones in migraine pathology is highly likely as migraine is more common in women and its frequency correlates with reproductive stages. Prolactin has been shown to be a worsening factor for migraine. Normally prolactin levels are low; however levels can surge during stress. Dopamine receptor agonists, which suppress pituitary prolactin release, are an effective migraine treatment in a subset of patients. Previously, we showed that administration of prolactin onto the dura mater induces female-specific behavioral responses, suggesting that prolactin may play a sex-specific role in migraine. The effects of prolactin signaling were assessed using a preclinical migraine model we published recently in which behavioral sensitization is induced by repeated stress. Plasma prolactin levels were assessed in naïve and stressed CD-1 mice (n=3-5/group) and transgenic mice with conditional deletion of the Prlr in Nav1.8-positive sensory neurons (Prlr conditional knock-out [CKO]; n=3/group). To assess the contribution of prolactin release during stress, naïve or stressed male and female CD-1 mice were treated with the prolactin release inhibitor bromocriptine (2mg/kg; n=7-12/group) or vehicle for 5days (8-12/group) and tested for facial hypersensitivity following stress. Additionally, the contribution of ovarian hormones in regulating the prolactin-induced responses was assessed in ovariectomized female CD-1 mice (n=6-10/group). Furthermore, the contribution of Prlr activation on Nav1.8-positive sensory neurons was assessed. Naïve or stressed male and female Prlr CKO mice and their control littermates were tested for facial hypersensitivity (n=8-9/group). Immunohistochemistry was used to confirm loss of Prlr in Nav1.8-positive neurons in Prlr CKO mice. The total sample size is n=245; the full analysis sample size is n=221. Stress significantly increased prolactin levels in vehicle-treated female mice (39.70±2.77; p<0.0001). Bromocriptine significantly reduced serum prolactin levels in stressed female mice compared to vehicle-treated mice (-44.85±3.1; p<0.0001). Additionally, no difference was detected between female stressed mice that received bromocriptine compared to naïve mice treated with bromocriptine (-0.70±2.9; p=0.995). Stress also significantly increased serum prolactin levels in male mice, although to a much smaller extent than in females (0.61±0.08; p<0.001). Bromocriptine significantly reduced serum prolactin levels in stressed males compared to those treated with vehicle (-0.49±0.08; p=0.002). Furthermore, bromocriptine attenuated stress-induced behavioral responses in female mice compared to those treated with vehicle (maximum effect observed on day 4 post stress [0.21±0.08; p=0.03]). Bromocriptine did not attenuate stress-induced behavior in males at any timepoint compared to those treated with vehicle. Moreover, loss of ovarian hormones did not affect the ability of bromocriptine to attenuate stress responses compared to vehicle-treated ovariectomy mice that were stressed (maximum effect observed on day 4 post stress [0.29±0.078; p=0.013]). Similar to CD-1 mice, stress increased serum prolactin levels in both Prlr CKO female mice (27.74±9.96; p=0.047) and control littermates (28.68±9.9; p=0.041) compared to their naïve counterparts. There was no significant increase in serum prolactin levels detected in male Prlr CKO mice or control littermates. Finally, conditional deletion of Prlr from Nav1.8-positive sensory neurons led to a female-specific attenuation of stress-induced behavioral responses (maximum effect observed on day 7 post stress [0.32±0.08; p=0.007]) compared to control littermates. These data demonstrate that prolactin plays a female-specific role in stress-induced behavioral responses in this preclinical migraine model through activation of Prlr on sensory neurons. They also support a role for prolactin in migraine mechanisms in females and suggest that modulation of prolactin signaling may be an effective therapeutic strategy in some cases.

Prolactin Level and Breastmilk Production among Mothers of Low-Birth-Weight Infants Admitted to Level II Neonatal Intensive Care Unit

Background. Kangaroo mother care (KMC) has been proven by several studies to promote breastfeeding, but many of the studies focus on the success of exclusive breastfeeding, and less on its galactogenic effects.&#x0D; Objective. We aim to determine the maternal serum prolactin levels and breastmilk volume of mothers who rendered KMC to their infants.&#x0D; Materials and Methods. This is a randomized controlled, open-labeled, interventional study in the Neonatal Intensive Care Unit of a tertiary government hospital. Infants weighing &lt; 2000 grams admitted in NICU Level II, together with medically stable mothers and no contraindication for breastfeeding were simultaneously enrolled. Primary outcome measures were maternal serum prolactin levels and expressed milk volume on day 3 and day 7 postpartum. Two-sample t-test was used to compare groups, and paired t-test to compare within groups. Tests were two-tailed, with a p-value of &lt; 0.05 considered statistically significant.&#x0D; Trial Registration. Australia-New Zealand Clinical Trial Registry ID ACTRN12614000218695&#x0D; Results. Fifty mother-infant dyads were equally allocated into KMC and control groups (p &lt; 0.001). There was significantly larger milk volume on the third day (29.6 ± 27.8 mL vs 16.3 ± 26.1 mL; p &lt; 0.001) and seventh post-partum day (72.4 ± 62.3 mL vs 47.3 ± 43.8 mL; p &lt; 0.000). There were increased serum prolactin levels compatible with post-partum state. The increase was more evident in the KMC (5244 ± 2702 mIU/L, on the 3rd postpartum day versus 4969 ± 2426 mIU/L, on the 7th postpartum day, p = 0.996) compared to control group (4129 ± 2485 mIU/L on the 3rd postpartum day versus 3705 ± 2731 mIU/L on the 7th postpartum day, p = 0.301).&#x0D; Conclusion. We noted a significantly larger milk volume in the KMC group. There was also a greater increase in the prolactin levels in the KMC group, but this did not reach statistical significance. Further studies should be done to determine mechanism of galactogenesis through KMC.

Increased Serum Prolactin and Excessive Daytime Sleepiness: An Attempt of Proof-of-Concept Study.

The objectives of this study were: (1) to identify subjects with hyperprolactinemia in a clinical sample of patients; (2) to compare the neurologic, psychiatric, and sleep conditions found in patients subgrouped by excessive daytime sleepiness (EDS) and hyperprolactinemia; and (3) to identify patients with hyperprolactinemia and EDS not supported by the presence of any other neurologic, psychiatric, or sleep disorder, or substance/medication use. A retrospective chart review of inpatients was carried out in order to identify all patients in whom the prolactin (PRL) serum levels were determined. A total of 130 subjects were retrieved: 55 had increased levels of PRL, while the remaining 75 participants had normal PRL levels. EDS was reported by 32 (58.2%) participants with increased PRL and 34 (45.3%) with normal PRL. Obstructive sleep apnea or other sleep or neurologic/psychiatric conditions could explain EDS in all participants with normal PRL. Among subjects with increased PRL, eight had no other neurologic/psychiatric or sleep disorder (or drug) potentially causing EDS; these participants, at polysomnography, had time in bed, sleep period time, and total sleep time longer than those with EDS associated to another condition. These findings can be considered as a preliminary indication of a role of hyperprolactinemia in EDS and represent a basis for future controlled studies able to test this hypothesis in a reliable, objective, and methodologically more appropriate way.

Aggressive prolactinoma (Review).

Aggressive prolactinoma (APRL) is a subgroup of aggressive pituitary tumors (accounting for 10% of all hypophyseal neoplasia) which are defined by: invasion based on radiological and/or histological features, a higher proliferation profile when compared to typical adenomas and rapidly developing resistance to standard medication/protocols in addition to an increased risk of early recurrence. This is a narrative review focusing on APRL in terms of both presentation and management. Upon admission, the suggestive features may include increased serum prolactin with a large tumor diameter (mainly >4 cm), male sex, early age at diagnosis (<20 years), and genetic predisposition [multiple endocrine neoplasia type 1 (MEN1), aryl hydrocarbon receptor interacting protein (AIP), succinate dehydrogenase (SDHx) gene mutations]. Potential prognostic factors are indicated by assessment of E-cadherin, matrix metalloproteinase (MMP)-9, and vascular endothelial growth factor (VEGF) status. Furthermore, during management, APRL may be associated with dopamine agonist (DA) resistance (described in 10-20% of all prolactinomas), post-hypophysectomy relapse, mitotic count >2, Ki-67 proliferation index ≥3%, the need for radiotherapy, lack of response in terms of controlling prolactin levels and tumor growth despite multimodal therapy. However, none of these as an isolated element serves as a surrogate of APRL diagnosis. A fourth-line therapy is necessary with temozolomide, an oral alkylating chemotherapeutic agent, that may induce tumor reduction and serum prolactin reduction in 75% of cases but only 8% have a normalization of prolactin levels. Controversies surrounding the duration of therapy still exist; also regarding the fifth-line therapy, post-temozolomide intervention. Recent data suggest alternatives such as somatostatin analogues (pasireotide), checkpoint inhibitors (ipilimumab, nivolumab), tyrosine kinase inhibitors (TKIs) (lapatinib), and mTOR inhibitors (everolimus). APRL represents a complex condition that is still challenging, and multimodal therapy is essential.

Increase in Thyrotropin Is Associated with an Increase in Serum Prolactin in Euthyroid Subjects and Patients with Subclinical Hypothyroidism.

Background: Prevalence and clinical significance of hyperprolactinemia in subclinical hypothyroidism have been reported in few studies. The upper limit of the normal range for TSH used to diagnose subclinical hypothyroidism is a matter of controversy. Some experts believe that the upper limit of the normal TSH range should be reduced from 4.2 to 2.5 mIU/L. Some evidence suggests a positive relationship between TSH > 2.5 mIU/L and cortisol as an indicator of metabolic stress. With this view prolactin as a stress hormone can be elevated in TSH >2.5 in comparison to TSH< 2.5. Hence the aim of this study was to evaluate the relationship between TSH and prolactin levels in the TSH range <10. Methods: This cross-sectional study was performed on apparently healthy subjects with TSH<10 mIU/L. Subjects with the age of 18 to 35 years were enrolled. The sera were analyzed for prolactin, FT3, FT4, TSH, TPO-Ab and Tg-Ab. Results: From the total number of 519 participants, in 65 subjects (12.5%) TSH was < 2.5. Seventy-nine subjects (15.2%) had TSH: 2.5-4.2 and 375 (72.3%) of the participants had TSH> 4.2 mIU/L. The mean age, weight and BMI of subjects in the three TSH groups were not significantly different. In the three TSH groups, the prevalence of hyperprolactinemia was zero, 3.8 and 30.7%, respectively. There was a positive and significant correlation between prolactin and TSH levels (r=0.613). Conclusion: Hyperprolactinemia is common in patients with subclinical hypothyroidism (30.7%) and there is a positive correlation between TSH and PRL in subjects with TSH<10 mIU/l.