A study on the correlations of PRL levels with anxiety, depression, sleep, and self-efficacy in patients with prolactinoma.

Purpose: The purpose of this study was to explore the factors influencing PRL levels in patients with prolactinoma and to investigate the correlations between anxiety, depression, sleep, self-efficacy, and PRL levels. Methods: This retrospective study included 176 patients with prolactinoma who received outpatient treatment at the Affiliated Hospital of Zunyi Medical University from May 2017 to August 2022. The general information questionnaire, Hospital Anxiety and Depression Scale (HADS), Athens Insomnia Scale (AIS), and General Self-Efficacy Scale (GSES) were used for data collection. A generalized estimating equation (GEE) model was used to analyze the factors influencing PRL levels in patients with prolactinoma. GEE single-effect analysis was used to compare PRL levels at different time points between anxiety group and nonanxiety group, between insomnia group and normal group, and between low, medium, and high self-efficacy groups. Results: The median baseline PRL level and the PRL levels at 1, 3, 6, and 12 months of follow-up were 268.50 ng/ml, 122.25 ng/ml, 21.20 ng/ml, 19.65 ng/ml, and 16.10 ng/ml, respectively. Among patients with prolactinoma, 59.10% had anxiety (HADS-A score = 7.35 ± 3.34) and 28.98% had depression (HADS-D score = 5.23 ± 3.87), 9.10% had sleep disorders (AIS score = 6.10 ± 4.31) and 54.55% had low self-efficacy (GSES score = 2.13 ± 0.83). Educational level, tumor size, number of visits, sleep quality, anxiety level, and self-efficacy level were found to be factors influencing PRL levels in patients with prolactinoma (P<0.05). Higher PRL levels were observed in the anxiety group compared to the non-anxiety group (P<0.001), in the insomnia group compared to the normal group (P<0.05), and in the low self-efficacy group compared to the medium and high self-efficacy groups (P<0.05). Conclusion: PRL levels in patients with prolactinoma are related to education level, tumor size, number of visits, anxiety, self-efficacy, and sleep but not depression. PRL levels were higher in patients with anxiety, low self-efficacy, and sleep disorders.

Behavioural and physiological responses to stressors in sheep with temperament classified by genotype or phenotype.

The single nucleotide polymorphism (SNP) rs107856856, located in the tryptophan hydroxylase-2 gene, is associated with the behavioural phenotype for sheep temperament measured at weaning. Here, we tested the association between that SNP and physiological and behavioural responses to stressors in adult sheep. Two groups of adult sheep, one with genotype A/A (calm genotype) and the other with G/G (nervous genotype) in rs107856856, were selected from 160 sheep and were exposed, twice, to an open-field arena and an isolation box test (IBT). During each repeat, the behaviour and physiological responses (cortisol, prolactin, dehydroepiandrosterone [DHEA], brain derived neurotrophic factor [BDNF], characteristics of the response of body temperature, and oxidative stress) were measured. The behavioural and physiological responses of the sheep were compared between genotypes and also between groups classified on their phenotype as assessed by their initial isolation box score ("low responders" and "high responders"). The SNP rs107856856 had some effects on the behavioural phenotype (IBT score) but no effects on the physiological response to stress (cortisol, prolactin, DHEA, BDNF, oxidative stress or changes in body temperature) in the adult sheep, probably because the sheep were exposed, and therefore had adapted, to human contact during their life.

Analyses of mRNA Expression Levels of Pituitary Hormones, Their Hypothalamic Regulating Factors, and Receptors Involved in Metamorphosis with Special Reference to the Summer and Winter Seasons.

Bullfrog (Rana catesbeiana) larvae inhabiting the main island of Japan overwinter as preclimax animals, whereas the larvae that reached climax in summer complete metamorphosis. We analyzed the mRNA expression levels of the adenohypophyseal hormones, hypothalamic hormones, and their receptors that are involved in controlling metamorphosis in tadpoles at various developmental stages available in summer and winter in order to understand the hormonal mechanism regulating metamorphosis progression. Corticotropin-releasing factor (CRF) and thyrotropin ß-subunit (TSHß) mRNA expression was enhanced as they reached the climax stage in metamorphosing summer tadpoles, although type 2 CRF receptor (CRFR2) mRNA levels demonstrated a tendency of elevation, indicating the activation of the hypothalamo-hypophyseal axis for stimulating the release of thyroid hormone in summer. Arginine vasotocin (AVT) mRNA levels were elevated as metamorphosis progressed, but mRNA expression levels were not synchronized with those of proopiomelanocortin (POMC) and V1b-type AVT receptor (V1bR). The elevation of mRNA levels of prolactin (PRL) 1A and type 3 thyrotropin-releasing hormone receptor (TRHR3), but not of thyrotropin-releasing hormone (TRH) precursor mRNA levels, was noted in climactic tadpoles, indicating that PRL mRNA levels are not simply dependent on the expression levels of TRH precursor mRNA. In the preclimactic larvae captured in winter, which are in metamorphic stasis, mRNA levels of pituitary hormones, hypothalamic factors, and their receptors remained low or at levels similar to those of the larvae captured in summer. These results indicate the relationship between the mRNA expression of metamorphosis-related factors and the seasonal progression/stasis of metamorphosis.

How to pause fertility.

Prolactin suppresses the ovarian cycles of lactating mice by directly repressing the activity of a cell population known as kisspeptin neurons.

Dopamine D2 receptor antagonist counteracts hyperglycemia and insulin resistance in diet-induced obese male mice.

Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.

Treatment of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM).

Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.

Diagnosis of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM).

Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correctcause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Societyof Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.

IMPACT OF METFORMIN ON OSTEOPROTEGERIN LEVELS IN POLYCYSTIC OVARIAN WOMEN.

Metformin is an important agent in the treatment of polycystic ovary syndrome (PCOS) treatment. Osteoblast express osteoprotegerin (OPG) which has integral effects on bone metabolism nexus. This cross-sectional research sought to identify the impact of metformin therapy on serum level osteoblast express osteoprotegerin and prolactin in women with polycystic ovary syndrome. Methods: 30 patients with PCOS and 30 controls. The current study revealed that prolactin levels were increased in PCOS group compared to control group which is highly significant. While after treatment with metformin prolactin level was reduced significantly in than before treatment. Osteoprotegerin concentrations were considerably dropped in the PCOS group contrasted with the control group. Conversely, serum osteoprotegerin in metformin-treated group were higher compared to PCOS group. Osteoblast express osteoprotegerin level increased after 3 months of treatment with metformin in women with polycystic ovary syndrome.

Role of prolactin in the protective effect of amisulpride against 1,2-Diacetylbenzene's neurotoxicity.

Exposure to organic solvents is associated with various health problems, including neurodegenerative diseases. Among these solvents, 1,2-diethylbenzene is notable for its ability to produce a toxic metabolite, 1,2-Diacetylbenzene (DAB), which can cause memory impairment. Prolactin (PRL) is theorized to protect the central nervous system. Certain antipsychotic drugs, known for increasing PRL secretion, have shown to improve cognitive performance in psychotic Alzheimer's patients. Among these, amisulpride stands out for its high efficacy, limited side effects, and high selectivity for dopamine D2 receptors. In our study, we explored the potential of amisulpride to inhibit DAB-induced neurotoxicity via PRL activation. Our results show that amisulpride enhances the PRL/JAK/STAT, PI3K/AKT, and BDNF/ERK/CREB pathways, playing critical roles in PRL's neuroprotection pathways and memory formation. Additionally, amisulpride inhibited DAB-triggered NLRP3 inflammasome activation and apoptosis. Collectively, these findings suggest that amisulpride may be a promising therapeutic intervention for DAB-induced neurotoxicity, partly through activating the PRL pathway.

Macroprolactin over time: Is there any point in rechecking it in people with a persistently elevated serum prolactin?

OBJECTIVE AND DESIGN: Macroprolactinemia may influence the interpretation of serum prolactin levels-a recognised phenomenon since 1981. The degree of macroprolactinaemia over time is less well described. We determined how macroprolactin status (based on polyethylene glycol (PEG) precipitation) varied by analysing serial measurements in hyperprolactinaemic individuals over a period of 9 years. PATIENTS AND MEASUREMENTS: Results from 1810 individuals were included. All serum total prolactin results (measured using Roche Cobas 8000 analyser) were extracted from the laboratory information system for the period 1 January 2012 to 1 April 2021, along with relevant patient demographic/test data. Samples with a macroprolactin screening test performed (on samples with prolactin > 700 miu/L) were included in the main analysis. RESULTS: During the study period, 2782 macroprolactin checks were performed (12.5% of all prolactin tests) in 1810 individuals (599 males/2183 females, median-age: 35, interquartile range: 25-47, range: 16-93 years). Multiple macroprolactin checks were carried out on 465 patients (1437 measurements) with 94 patients (141 measurements) screening positive (<60% recovery). Only 19 patients (18 female) had at least one result above and one below the 60% screening cut-off, with 10 of these patients having results close to the 60% cut-off; in 9 patients, results were clearly different between repeat samples. In seven cases, the adjusted monomeric prolactin showed a potentially clinically significant difference. CONCLUSIONS: In this study, only 19/465 patients appeared to change macroprolactin status based on a 60% PEG recovery cut-off. The majority of these 19 patients were on antipsychotic/antidepressant medication(s) or had a prolactinoma; in only 7 did monomeric prolactin change significantly. This suggests that once macroprolactin status has been determined, clinical decision making is rarely affected by repeating it.

Levodopa attenuates the feed intake reduction caused by ergot alkaloids in cattle.

Consumption of ergot alkaloids from endophyte-infected tall fescue results in losses to the livestock industry in many countries and a means to mitigate these losses is needed. The objective of this study was to evaluate intra-abomasal infusion of the dopamine precursor, levodopa (L-DOPA), on dopamine metabolism, feed intake, and serum metabolites of steers exposed to ergot alkaloids. Twelve Holstein steers (344.9 ±â€…9.48 kg) fitted with ruminal cannula were housed with a cycle of heat challenge during the daytime (32 °C) and thermoneutral at night (25 °C). The steers received a basal diet of alfalfa cubes containing equal amounts of tall fescue seed composed of a mixture of endophyte-free (E-) or endophyte-infected tall fescue seeds (E+) equivalent to 15 µg ergovaline/kg body weight (BW) for 9 d followed by intra-abomasal infusion of water (L-DOPA-) or levodopa (L-DOPA+; 2 mg/kg BW) for an additional 9 d. Afterward, the steers were pair-fed for 5 d to conduct a glucose tolerance test. The E+ treatment decreased (P = 0.005) prolactin by approximately 50%. However, prolactin increased (P = 0.050) with L-DOPA+. Steers receiving E+ decreased (P < 0.001) dry matter intake (DMI); however, when supplemented with L-DOPA+ the decrease in DMI was less severe (L-DOPA × E, P = 0.003). Also, L-DOPA+ infusion increased eating duration (L-DOPA × E, P = 0.012) when steers were receiving E+. The number of meals, meal duration, and intake rate were not affected (P > 0.05) by E+ or L-DOPA+. The L-DOPA+ infusion increased (P < 0.05) free L-DOPA, free dopamine, total L-DOPA, and total dopamine. Conversely, free epinephrine and free norepinephrine decreased (P < 0.05) with L-DOPA+. Total epinephrine and total norepinephrine were not affected (P > 0.05) by L-DOPA+. Ergot alkaloids did not affect (P > 0.05) circulating free or total L-DOPA, dopamine, or epinephrine. However, free and total norepinephrine decreased (P = 0.046) with E+. Glucose clearance rates at 15 to 30 min after glucose infusion increased with L-DOPA+ (P < 0.001), but not with E+ (P = 0.280). Administration of L-DOPA as an agonist therapy to treat fescue toxicosis provided a moderate increase in DMI and eating time and increased plasma glucose clearance for cattle dosed with E+ seed.

Fescue has become the dominant cool-season perennial grass in the southeastern region of the United States and is also found in other countries. Endophytes from a plant­fungus symbiotic relationship produce toxic alkaloids that have caused significant annual economic losses to the livestock industry. Treatments to alleviate this toxicosis are still demanded. This study evaluates the infusion of the dopamine precursor, levodopa (L-DOPA), to mitigate the toxicosis caused by ergot alkaloids. When L-DOPA was infused, eating duration increased and the decrease in feed intake caused by ergot alkaloids was less severe. Additionally, circulating dopamine and glucose clearance increased with L-DOPA. These results suggest that L-DOPA has the potential to aid in the mitigation of the toxicosis caused by ergot alkaloids.

Effect of melatonin on reproductive function in propylthiouracil induced hypothyroidism in adult male rats.

OBJECTIVE: Thyroid hormones are essential for regulating metabolism, reproduction, and growth. Hypothyroidism is connected with lower sperm count and motility, leading to male infertility. Oxidative stress is likely to be linked to this interaction. Melatonin, being known as an oxidative scavenger, may offer a feasible treatment method for reproductive dysfunction accompanying hypothyroidism in adult male rats. The purpose of this investigation was to determine the mechanism by which melatonin treatment affected spermatogenic and steroidogenic function in an experimental model-induced hypothyroidism in adult male rats. MATERIALS AND METHODS: Twenty-one male albino adult rats weighing between 150 and 210 g were used in this experiment. Rats were split into three groups and studied for 11 weeks. The control euthyroid group, in which rats received 0.9% Sodium Chloride (NaCl) solution by intraperitoneal injection [solvent for 6-propyl 2-thouracil (PTU)], 6 days/week for 8 weeks; the PTU-induced hypothyroid group, in which chemical thyroidectomy was induced by intraperitoneal injection of PTU at a dose of 10 mg/kg body weight, 6 days/week for 8 weeks; and the melatonin-treated hypothyroid group, which received 3 mg/kg melatonin intraperitoneally daily for 21 days plasma free Triiodothyronine (T3), free Thyroxin (T4), thyroid stimulating hormone (TSH), free testosterone, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and prolactin were measured. Also, semen analysis, testicular tissue malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) were accessed. RESULTS: The results indicated that melatonin significantly increased sperm viability and motility compared to the untreated PTU-induced hypothyroid group (p<0.001). Testicular MDA and TNF-α showed a significant decrease in the melatonin-treated hypothyroid group compared with the PTU-induced hypothyroid group (p<0.05). In addition, plasma testosterone levels were significantly increased, accompanied by a significant reduction of plasma prolactin levels compared to the untreated hypothyroid group (p<0.05 for both). CONCLUSIONS: Based on the study findings, melatonin could mitigate gonadal dysfunction induced by hypothyroidism by improving several components of semen analysis, such as sperm motility and sperm viability, as well as by enhancing testosterone production focusing on oxidative and inflammatory stress as the underlying mechanisms.

The association of reproductive hormones, thyroid function, and vitamin levels with premature ejaculation: A prospective case-control study.

PURPOSE: To investigate whether serum hormone (testosterone, prolactin, gonadotropins, and thyroid hormones) and vitamin (vitamin B12, folic acid, and vitamin D) levels are associated with premature ejaculation (PE). MATERIALS AND METHODS: This prospective case-control study included 126 patients with PE (lifelong PE [LPE] in 94 and acquired PE [APE] in 32) who presented to the urology outpatient clinic between April 2016 and January 2023 and 92 healthy men as a control group. The diagnosis of PE was based on the criteria defined by the International Society for Sexual Medicine. Serum total testosterone (TT), free and bioavailable testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, thyroid-stimulating hormone, free triiodothyronine, thyroxine (fT4), vitamin B12, folic acid, and vitamin D levels were measured. RESULTS: Serum TT, fT4, and vitamin D levels were significantly higher in patients with PE than in the control group (p=0.022, p=0.002, and p=0.044, respectively). However, the serum vitamin B12 level was significantly lower in the PE group (p=0.021). In the multivariate logistic regression analysis, only vitamin B12 was found to be an independent risk factor for PE, with an estimated odds ratio of 0.997 (95% confidence interval 0.994-0.999, p=0.036). CONCLUSIONS: This study demonstrated that lower vitamin B12 levels are associated with the presence of PE. Therefore, we believe that it would be beneficial to consider vitamin B12 levels in the evaluation of patients with PE.

Reconsideration of Surgical Indication for Prolactin-producing Pituitary Tumor Focusing on Visual Impairment.

Prolactin-producing pituitary tumor (PRLoma) is the most prevalent functional pituitary tumor. If the tumor becomes large, vision can be impaired. In contrast to other pituitary tumors, cabergoline (CAB) is extremely effective for PRLoma and has become the first-line treatment. In this study, we examined our experience with the pharmacological and surgical management of PRLomas with visual impairment (VI) to determine whether VI could be a surgical indication. Further, we discussed the function of surgery in situations where the gold standard of PRLoma treatment was CAB administration. Of the 159 patients with PRLomas (age, 13-77 [mean = 36.3] years; men, 29; women, 130) at Tokyo Women's Medical University Hospital from 2009 to 2021, 18 (age, 15-67 [mean = 35.8] years; men, 12; woman, 6) had VI (subjectively, 12; objectively, 6). They started CAB treatment immediately (maximum dose: 0.5 to 6 mg/week; average: 2.17 mg/week). VI improved in 16 patients (88.9%) but did not improve in 2 (11.1%) requiring surgeries. One of the two patients had a parenchymal tumor resistant to CAB, and the other had a cystic tumor due to intratumoral bleeding. Consequently, CAB is the first-line treatment for PRLomas with VI because of its significantly high rate of improvement. However, close and rigorous surveillance is necessary for cases resistant to CAB, and the correct decision is required regarding surgical interventions at proper timing and appropriate surgical approaches considering the purpose of surgery.

Sleep promotes T-cell migration towards CCL19 via growth hormone and prolactin signaling in humans.

Sleep strongly supports the formation of adaptive immunity, e.g., after vaccination. However, the underlying mechanisms remain largely obscure. Here we show in healthy humans that sleep compared to nocturnal wakefulness specifically promotes the migration of various T-cell subsets towards the chemokine CCL19, which is essential for lymph-node homing and, thus, for the initiation and maintenance of adaptive immune responses. Migration towards the inflammatory chemokine CCL5 remained unaffected. Incubating the cells with plasma from sleeping participants likewise increased CCL19-directed migration, an effect that was dependent on growth hormone and prolactin signaling. These findings show that sleep selectively promotes the lymph node homing potential of T cells by increasing hormonal release, and thus reveal a causal mechanism underlying the supporting effect of sleep on adaptive immunity in humans.

Case report: Complete restoration of the HPA axis function in Cushing's disease with drug treatment.

This report describes a rare case of a 20-year-old man with an ACTH- and prolactin-secreting invasive pituitary macroadenoma causing hyperprolactinemia and Cushing's disease. He was later found to have an AIP mutation. Treatment with cabergoline (1.5 mg weekly) normalized prolactin concentrations and induced a major shrinkage of the adenoma. Not only was urinary free cortisol normalized for more than 14 years, but also the treatment induced normal hypothalamo-pituitary-adrenal (HPA) axis function as illustrated by the reappearance of a normal cortisol/ACTH circadian rhythm, cortisol suppression to dexamethasone, and disappearance of the excessive and aberrant responses to CRH and desmopressin, respectively. This case is the first description of complete restoration of the physiological characteristics of the HPA axis by a medication during the treatment of Cushing's disease. Although exceptional, it illustrates that drugs targeting the pituitary adenoma can bring true complete remission of Cushing's disease.