Hyperprolactinemia (HPRL) is a common adverse reaction induced by antipsychotic therapy in patients with schizophrenia, which greatly undermines medication adherence and impairs physiological functions of multiple body systems. In this real-world study, we analyzed retrospective prolactin testing data to compare the incidence of HPRL between schizophrenia patients and patients with other psychiatric disorders, so as to identify clinical high-risk factors. Meanwhile, hormones including thyroid-stimulating hormone (TSH), free tetraiodothyronine (FT4), free triiodothyronine (FT3), tetraiodothyronine (T4), Triiodothyronine (T3), and estradiol that closely correlated with prolactin metabolism were also included in the analysis. The results indicated that female patients with schizophrenia had the highest risk of HPRL (19.31%, n = 2009), and women during the prime reproductive (25-40 years) showed the highest average prolactin concentration (1,389.22 ± 50.138 mIU/L, n = 966). Distinct antipsychotics usage rates were observed among different clinical subgroups. Risperidone, paliperidone and sulpiride showed an increasing trend with elevated PRL levels, whereas quetiapine and aripiprazole were more frequently prescribed in the low-risk HPRL group. Antipsychotics showed divergent dopamine D2/D3 and 5-HT2A receptor-binding affinities (Ki values), and we constructed a weighted multi-receptor affinity index that demonstrated a strong linear correlation with the PRL risk score (R[2] = 0.878). Additionally, the average incidence of extrapyramidal symptoms (EPS) increased with rising PRL levels (P = 2.24E-10). Further analysis of EPS risk revealed distinct safety profiles across antipsychotics, with aripiprazole-characterized by low HPRL liability-demonstrating a higher EPS risk. The severe HPRL group presented a tendency of decreased thyroid function (TSH, P = 0.0027; FT4, P = 0.000031; FT3, P = 0.0076; T4, P = 0.0025) and a significant reduction in estradiol levels (P = 0.000049). Based on homogeneous clinical real-world data, this study comprehensively evaluated multiple antipsychotic medications simultaneously. It provides empirical clinical evidence for individualized medication strategies in patients with comorbid HPRL and EPS, and offers real-world evidence for the clinical early risk recognition, and long-term medication decision-making among patients with multiple adverse reactions concurrently.

Feather elongation is sustained by continuous cell proliferation within the feather follicle; however, the molecular mechanisms responsible for feather growth termination remain poorly understood. In this study, we investigated molecular changes associated with feather growth termination by comparing two chicken wing feather types with contrasting growth characteristics: primary wing feathers and primary coverts. Histological and bromodeoxyuridine incorporation analyses demonstrated that primary wing feathers remained in an active growth phase, whereas primary coverts exhibited pulp regression, reduced cell proliferation, and characteristics of growth termination. Gene expression analyses showed that primary coverts exhibited reduced expression of prolactin receptor (PRLR), type 2 iodothyronine deiodinase (DIO2), and insulin-like growth factor 2 (IGF2), together with marked induction of the thyroid hormone (TH)-inactivating enzyme type 3 iodothyronine deiodinase (DIO3). In contrast, primary wing feathers exhibited relatively higher expression of PRLR, DIO2, and IGF2 than primary coverts, while maintaining consistently low DIO3 expression. Reporter assays showed increased IGF2 promoter activity following triiodothyronine (T3) treatment in all three independent experiments, although the increase did not reach statistical significance. Thus, the reporter assay provides only tentative support for T3 responsiveness of the IGF2 promoter, consistent with our previous in vivo and primary-culture findings showing T3-dependent increases in IGF2 expression. These coordinated transcriptional changes are consistent with remodeling of local TH metabolism during the transition from active feather growth to growth termination. While local TH concentrations and direct deiodinase activities remain to be quantified, and the causal relationship between PRL/PRLR signaling and DIO3 induction remains unresolved, this study provides a molecular framework for understanding how local endocrine regulation translates systemic hormonal signals into feather type-specific growth responses during avian feather development.

Gynecomastia is a benign proliferation of male breast glandular tissue caused by an imbalance between estrogen and androgen activity. Spironolactone, a potassium-sparing diuretic commonly prescribed for edema and ascites in chronic liver disease, is a recognized cause of drug-induced gynecomastia because of its antiandrogenic effects. We report the case of a man in his 50s with chronic liver disease and type 2 diabetes mellitus who presented with bilateral breast swelling and mild tenderness of one month's duration. Clinical examination revealed bilateral soft glandular enlargement without nipple discharge, a hard mass, or axillary lymphadenopathy. Breast ultrasonography demonstrated diffuse fibroglandular proliferation with subareolar thickening consistent with bilateral gynecomastia. Laboratory investigations showed mildly reduced serum testosterone with relative estrogen predominance, while prolactin, luteinizing hormone, follicle-stimulating hormone, and thyroid function tests were within normal limits. Chronic liver disease likely contributed to hormonal imbalance through impaired estrogen metabolism and altered sex hormone regulation, thereby increasing susceptibility to spironolactone-induced gynecomastia. Spironolactone therapy was discontinued, and conservative management with clinical monitoring was advised. The patient showed gradual symptomatic improvement during follow-up. This case highlights the importance of recognizing medication-induced endocrine adverse effects, particularly in patients with chronic systemic illnesses such as hepatic dysfunction.

Peripartum cardiomyopathy (PPCM) is a rare yet potentially life-threatening form of heart failure that occurs during late pregnancy or within the months following delivery. Bromocriptine, which suppresses prolactin secretion, has emerged as a promising adjunctive therapy for PPCM; however, the optimal timing of its initiation remains uncertain. We describe two patients with PPCM who received bromocriptine at different stages of the disease course. The first patient was a 30-year-old woman who presented 33 days after delivery with cardiogenic shock, a left ventricular ejection fraction (LVEF) of 12%, and a left ventricular thrombus. Despite treatment with intra-aortic balloon pumping, venoarterial extracorporeal membrane oxygenation, anticoagulation, and guideline-directed medical therapy, recovery of left ventricular function plateaued. Bromocriptine was initiated on hospital day 44, after which LVEF increased from 38% to 53% within seven days and subsequently recovered to 60%. The second patient was a 35-year-old woman who developed acute heart failure nine days after delivery with an LVEF of 28%. Because left ventricular function remained markedly impaired despite standard heart failure therapy, bromocriptine was initiated on hospital day seven. Her LVEF improved to 39% by hospital day 15 and ultimately recovered to 61%. These cases demonstrate a temporal association between bromocriptine initiation and subsequent improvement in left ventricular systolic function at different stages of the clinical course of PPCM.

Gastrointestinal disorders are increasingly common among young adults, particularly medical students exposed to chronic stress and irregular dietary habits. Proton pump inhibitors (PPIs) are widely prescribed for the management of gastroesophageal reflux disease (GERD), gastritis, and related acid-peptic disorders. However, prolonged PPI therapy has been associated with impaired iron absorption and may contribute to iron deficiency anemia (IDA). We report the case of 26-year-old female, unmarried, postgraduate medical student with iron deficiency anaemia and galactorrhea. The patient presented to gastroenterology clinic with a complaint of mild non-colicky epigastric pain, nausea, fatigue and shortness of breath. Comprehensive evaluation included complete blood count with peripheral smear, iron profile study, stool routine and stool for occult blood, serum IgA anti TTG, viral markers, upper gastro intestinal endoscopy (UGIE) & biopsy, H. Pylori ammonia breath test, gastric emptying scintigraphy, USG abdomen and pelvis, and serum prolactin levels. Based on the clinical, laboratory, and radiological findings, a diagnosis of iron deficiency anemia secondary to long-term PPI use and domperidone-induced galactorrhea was established. The patient was treated with intravenous ferric carboxymaltose (1500 mg), advised discontinuation of PPI-domperidone therapy, and initiated on a low-FODMAP diet. Significant clinical and hematological improvement was observed on follow-up, along with resolution of galactorrhea. Although PPIs remain highly effective and generally safe agents for acid suppression, concerns regarding their long-term adverse effects are increasing. Iron deficiency anemia resulting from chronic PPI use and concurrent domperidone-induced galactorrhea occurring in the same patient is rarely reported. This case underscores the importance of meticulous history taking, appropriate diagnostic evaluation, and rational test utilization in identifying uncommon medication-related adverse effects. Clinicians should consider prolonged PPI use as a potential contributing factor when evaluating unexplained iron deficiency anemia, particularly in young individuals receiving long-term therapy.

This study evaluated the response of milk production and endocrine profile to a switch from short-day photoperiod (SDPP) with natural light to long-day photoperiod (LDPP) with white light-emitting diode (WLED) or induction lighting (IL) in lactating dairy cows. Nine Holstein cows (198 ± 10.0 days in milk) were initially exposed to SDPP of 10:14 h light-dark cycle (10L:14D) with natural light (SDPP period), followed by a long-day photoperiod (LDPP; 16L:8D) using either WLED (443 nm peak, LDPP-W, n = 5) or IL (IL; 529 nm peak, LDPP-I, n = 4). Each period comprised a 1-week adaptation and a 2-week sampling period. Milk yield decreased after switching to LDPP-W (p < 0.05) but remained unchanged with LDPP-I. The slope of milk yield over the entire trial period (from the beginning of SDPP to the end of LDPP period) differed depending on lighting type (p = 0.05), being negative in the LDPP-W and positive in the LDPP-I. Plasma prolactin concentration in the light period increased after switching to LDPP-I but not to LDPP-W. These results indicate that LDPP using IL is likely more effective in promoting milk yield than WLED, potentially due to enhanced prolactin secretion.

Women during lactation undergo significant bone loss and metabolic changes. However, the underlying mechanisms in the brain remain unclear. Herein, we found that prolactin receptor (PRLR)[+] neurons in the hypothalamus control lactation physiology and metabolism in mice. Prolactin induces tyrosine hydroxylase (Th) expression in PRLR[+] dopaminergic neurons of the arcuate nucleus (ARC). Interestingly, neuropeptide Y (NPY) expression was elevated to alter energy demand and nociceptive threshold during lactation. Knocking down either PRLR or NPY in the ARC significantly reduced food demand and nociceptive threshold. Importantly, in addition, prolactin also induces Th expression in the hypothalamic paraventricular nucleus (PVN) to increase sympathetic outflow to mobilize Ca[2+] in bone. Importantly, brain-derived osteoanabolic hormone communication network factor 3 (CCN3) is downstream of PRLR signaling in the dopaminergic neurons. Thus, hypothalamic PRLR[+] neurons identified in the current study regulate bone and fat metabolism, nociceptive threshold, and energy demand in mice during lactation.

The NR4A nuclear receptor family (NR4A1, NR4A2, and NR4A3) comprises stimulus-responsive orphan nuclear receptors expressed in endocrine tissues, including the anterior pituitary gland. However, their functional roles in lactotrophs remain poorly understood. Because prolactin (PRL) secretion varies markedly across reproductive states, it provides a useful physiological model for investigating gene expression changes associated with distinct secretory conditions. In this study, we examined the expression patterns of the three Nr4a genes in the rat pituitary under physiological and pharmacological conditions associated with altered PRL secretion and evaluated the contribution of each NR4A family member to PRL secretion. Pituitary Nr4a gene expression increased in parallel with elevated PRL secretion during pregnancy and lactation. In contrast, Nr4a expression declined after weaning as PRL secretion decreased, and the nocturnal increase in Nr4a expression observed during early pseudopregnancy was absent after mid-pregnancy. Pseudopregnancy was also associated with an overnight increase in PRL secretion accompanied by increased pituitary Nr4a expression. These coordinated changes in PRL secretion and Nr4a expression were suppressed by dopaminergic inhibition in vivo and in primary pituitary cultures, whereas oxytocin transiently enhanced PRL secretion and Nr4a expression. Importantly, knockdown of Nr4a2, but not Nr4a1 or Nr4a3, significantly reduced PRL secretion without affecting Prl mRNA expression. These findings demonstrate that NR4A family members are associated with physiological PRL secretory states and identify NR4A2 as a selective regulator of PRL secretion at the level of hormone release rather than transcription.

Reproductive failure is an increasing concern for polar bear (Ursus maritimus) populations. Although hormone monitoring has improved understanding of reproductive function, serum-based assessments have been underutilized. This study evaluated the use of multiplex immunoassays to characterize key hormones in females. Serum samples (n = 103; 2-8 per bear) were collected from 25 females and used to characterize follicle stimulating hormone (FSH), growth hormone (GH), leptin, luteinizing hormone (LH), and prolactin (PRL) using commercial panels. Assay validation confirmed biologically meaningful profiles parallelism, acceptable spike-and-recovery (range: 91.6-99.8%), and analyte stability across four freeze-thaw cycles (<15% difference). Age groups were defined as juvenile (0-5.0 y), young adult (5.1-12.0 y), adult (12.1-20.0 y), and senior (>20.0 y). Juveniles were excluded from analyses except where age group was evaluated. Seasons were classified based on northern hemisphere astronomical seasons. FSH was frequently below the assay's minimum detectable limit (MDL), indicating that although assay specificity was confirmed, the sensitivity was insufficient to reliably quantify physiological concentrations in this species. Detectable values (range: 7.8 to 22.4 ng/mL) were mostly restricted to the breeding season, with no samples above the MDL from May through November. GH concentrations differed significantly by season (P = 0.001), with the greatest model-adjusted mean during winter (4.29 ± 2.0 ng/mL) and lowest during summer (0.59 ± 0.28 ng/mL). Leptin concentrations differed by age group (P = 0.001), with the greatest model-adjusted mean in seniors (1.69 ± 0.50 ng/mL) and lowest in young adults (0.58 ± 0.42 ng/mL). LH also varied by age (P = 0.0002), with seniors showing the greatest model-adjusted mean (0.65 ± 0.18 ng/mL) and immature bears, the lowest (0.16 ± 0.04 ng/mL). PRL model-adjusted mean peaked in winter (38.05 ± 9.71 ng/mL) and spring (36.38 ± 8.49 ng/mL; P = 0.0001) and age group (P = 0.04); however, post-hoc tests revealed no significant difference in pairwise comparisons among the age groups. These results demonstrate the applicability of multiplex technology for reproductive hormone monitoring in polar bears. Notably, this study provides the first comprehensive characterization of several key hormones in female polar bears.