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General and Comparative Endocrinology Aug 2024Prolactin is involved in regulating various physiological activities of vertebrates and is one of the most momentous pituitary hormones. However, not enough attention is... (Review)
Review
Prolactin is involved in regulating various physiological activities of vertebrates and is one of the most momentous pituitary hormones. However, not enough attention is currently paid to prolactin, especially in teleost. This paper aims to gather, organize, and analyze recent studies on the regulation and functions of prolactin. By comparing with other animal groups, it highlights the significant role of prolactin in fish reproduction, immunity, growth, and osmotic pressure regulation, as well as the upstream and downstream factors that may be involved in the regulation of prolactin functions were introduced to provide a theoretical basis for the in-depth study and potential practical application of prolactin.
Topics: Animals; Prolactin; Fishes; Reproduction
PubMed: 38657738
DOI: 10.1016/j.ygcen.2024.114530 -
Journal of Biomolecular Structure &... Apr 2024This study delves into the functional and structural implications of non-synonymous single nucleotide polymorphisms (nsSNPs) within the Prolactin Receptor (PRLR) gene....
Comprehensive analysis of prolactin receptor (PRLR) gene nonsynonymous single nucleotide polymorphisms (nsSNPs) reveals multifaceted impact on protein structure, function, and interactions.
This study delves into the functional and structural implications of non-synonymous single nucleotide polymorphisms (nsSNPs) within the Prolactin Receptor (PRLR) gene. Thirteen deleterious nsSNPs were identified through bioinformatics tools, with SIFT predicting 168 out of 395 nsSNPs as detrimental, exhibiting tolerance index (TI) scores ranging from 0 to 0.05. Polyphen2 assigned likelihood scores >0.99 to all 13 nsSNPs, indicating high probability of harm, while Panther scores classified most nsSNPs as 'probably damaging', with specific mutations like W218R scoring 0.74, suggesting a higher impact. Stability analysis using DDG I-Mutant and DDG Mupro consistently predicted decreased stability for all mutations, with CUPSAT indicating mutations like V125G and W218R significantly decreasing stability. Structural analysis through DynaMut predicted destabilization for all mutations except L196I and L292H. MutPred2 highlighted structural alterations for all nsSNPs except L196I, L293V, R315W, and S353N. Domain analysis revealed key mutations within essential functional domains, with five nsSNPs located within Fibronectin type-III domains. Bayesian analysis through ConSurf identified 9 critical residues, with 11 nsSNPs exhibiting notably high conservation. STRING analysis unveiled a complex interaction network, indicating involvement in vital biological processes like lactation. Molecular dynamics (MD) simulations, spanning 100 nanoseconds, elucidated structural dynamics induced by detrimental missense SNPs. Post-translational modification (PTM) analysis identified specific mutations, such as R351, involved in methylation, while S353 was implicated in phosphorylation and glycosylation. These findings offer comprehensive insights into the molecular and phenotypic effects of deleterious nsSNPs in the PRLR gene, crucial for selective breeding.Communicated by Ramaswamy H. Sarma.
PubMed: 38656135
DOI: 10.1080/07391102.2024.2335295 -
Biomedicine & Pharmacotherapy =... May 2024Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting...
Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting as a dopamine D2 receptor antagonist and possessing anti-inflammatory properties, exhibits limited ability to penetrate the blood brain barrier (BBB). This weak penetration hampers its inhibitory effect on prolactin release in the pituitary gland, consequently leading to hyperprolactinemia. In order to enhance the central nervous system efficacy of sulpiride and reduce serum prolactin levels, we covalently linked sulpiride to VPALR derived from the nuclear DNA repair protein ku70. In vivo study on depressive mice using intraperitoneal injection of VPALR-SUL demonstrated a significant increase in struggle time and total distance compared to those treated with only sulpiride while also reducing serum prolactin concentration. The pharmacokinetic study results showed that VPALR-SUL prolonged half-life and increased bioavailability. In conclusion, VPALR-SUL exhibited potential for enhancing sulpiride transport across the BBB, augmenting its antidepressant effects, and reducing serum prolactin levels. This study laid a foundation for improving sulpiride delivery and developing novel antidepressants.
Topics: Animals; Prolactin; Sulpiride; Antidepressive Agents; Mice; Male; Cell-Penetrating Peptides; Depression; Blood-Brain Barrier; Biological Availability
PubMed: 38642503
DOI: 10.1016/j.biopha.2024.116610 -
PloS One 2024Obesity 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,...
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.
Topics: Humans; Mice; Male; Rats; Animals; Insulin Resistance; Mice, Obese; Dopamine D2 Receptor Antagonists; Prolactin; Receptors, Prolactin; Diabetes Mellitus, Type 2; Sulpiride; Obesity; Diet, High-Fat; Hyperglycemia; Hypertrophy; Insulin
PubMed: 38635745
DOI: 10.1371/journal.pone.0301496 -
Best Practice & Research. Clinical... May 2024Somatotroph (GH) adenomas/PitNETs typically arise from adenohypophysis and are biochemically active, leading to acromegaly and gigantism. More rarely, they present with... (Review)
Review
Somatotroph (GH) adenomas/PitNETs typically arise from adenohypophysis and are biochemically active, leading to acromegaly and gigantism. More rarely, they present with ectopic origin and do not present overt biochemical or clinical features (silent variants). Histopathological examination should consider the clinical and radiological background, and include multiple steps assessing tumor morphology, pituitary transcription factors (PTFs), hormone secretion, proliferation markers, granulation, and somatostatin receptors (STRs), aimed at depicting as better as possible tumor origin (in case of non-functioning and/or metastatic tumor), and clinical behavior, including response to treatment. GH-secreting tumors are part of the Pit-1 family tumors and can secrete GH only (pure somatotrophs) or co-secrete prolactin (mixed tumors; in this case, various histological subtypes have been identified). Each subtype presents unique radiological, biochemical, and clinical characteristic. Therefore, the integration of biochemical, clinical, radiological, and histopathological elements is fundamental for proper diagnosis and management of pituitary adenomas/PitNETs, to be performed in referral Centers. In more recent times, the importance of genetic and epigenetic evaluation in the characterization of pituitary tumors (i.e., early identification of aggressive variants) has been outlined by some large studies, with the intention of improving targeted treatments.
Topics: Humans; Growth Hormone-Secreting Pituitary Adenoma; Adenoma; Pituitary Neoplasms
PubMed: 38614953
DOI: 10.1016/j.beem.2024.101894 -
Zoological Science Feb 2024Bullfrog () larvae inhabiting the main island of Japan overwinter as preclimax animals, whereas the larvae that reached climax in summer complete metamorphosis. We...
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 () 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 β-subunit (TSHβ) 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.
Topics: Animals; Seasons; Pituitary Hormones; Prolactin; Japan; Larva
PubMed: 38587515
DOI: 10.2108/zs230080 -
Journal of Neuroendocrinology Apr 2024The conserved and multifaceted functions of prolactin (PRL) are coordinated through varied distribution and expression of its cell-surface receptor (PRLR) across a range... (Review)
Review
The conserved and multifaceted functions of prolactin (PRL) are coordinated through varied distribution and expression of its cell-surface receptor (PRLR) across a range of tissues and physiological states. The resultant heterogeneous expression of PRLR mRNA and protein across different organs and cell types supports a wide range of PRL-regulated processes including reproduction, lactation, development, and homeostasis. Genetic variation within the PRLR gene also accounts for several phenotypes impacting agricultural production and human pathology. The goal of this review is to highlight the many elements that control differential expression of the PRLR across tissues, and the various phenotypes that exist across species due to variation in the PRLR gene.
PubMed: 38586906
DOI: 10.1111/jne.13385 -
Endocrine Apr 2024Men with macroprolactinoma can present persistent hypogonadism despite normoprolactinemia achieved with clinical and/or neurosurgical treatment. Usually, testosterone...
BACKGROUND
Men with macroprolactinoma can present persistent hypogonadism despite normoprolactinemia achieved with clinical and/or neurosurgical treatment. Usually, testosterone replacement therapy is indicated. Nevertheless, although off-label, clomiphene citrate (CC), a selective estrogen receptor modulator, has also been used, mainly when fertility is an issue. The aim of this study is to evaluate the effectiveness of CC in recovering the gonadal axis in men with macroprolactinoma, with or without hyperprolactinemia, and evaluate its safety as a long-term therapy.
METHODS
This is a retrospective study including 10 men with macroprolactinoma on cabergoline treatment and persistent hypogonadism. All patients received initially 50 mg/d of CC.
RESULTS
The median age at diagnosis of prolactinomas was 34 (range, 26-60) years old. All patients were treated with cabergoline at a median maximum dose of 2 (1-7) mg/week, with a median time of treatment of 8.5 (2-15) years. Prolactin was still above the normal range when CC was introduced only in two patients. The mean duration of CC therapy was 3.2 (±2.8) years. Prolactin levels maintained stable (p = 0.252) and testosterone increased (p = 0.027) significantly on CC therapy. Tumor size remained stable. Eight patients (80%) maintained testosterone above 300 ng/dL and were classified as responders. Three responders succeeded in using a lower dose of CC and one of them completed withdrawal CC and maintained eugonadism. There were no side effects or safety concerns reported.
CONCLUSION
CC should be seen as a safe treatment option for men with macroprolactinoma and persistent hypogonadism.
PubMed: 38578401
DOI: 10.1007/s12020-024-03817-0 -
Breastfeeding Medicine : the Official... Apr 2024: Migraine attacks are common in women of reproductive age. Although attacks are often less severe and less frequent during pregnancy, they regularly reoccur shortly...
: Migraine attacks are common in women of reproductive age. Although attacks are often less severe and less frequent during pregnancy, they regularly reoccur shortly after delivery. When first-line analgesic treatment is insufficient, triptans may be used for acute treatment of migraine attacks. Milk levels of occasional triptan use have shown to be low, and no adverse effects in breastfed infants have been reported. However, the available knowledge on the safety of triptans during breastfeeding is still limited. Four (inter)national pharmacovigilance databases were searched for breastfeeding related adverse drug reactions of triptans. These included the Dutch Pregnancy Drug Register and three databases of spontaneous reports (Netherlands Pharmacovigilance Centre Lareb, the European Medicines Agency [EudraVigilance], and the World Health Organization [VigiBase]). A total of 26 reports on 27 breastfeeding related adverse drug reactions were identified (one report involved two separate adverse drug reactions). These involve three main complaints: painful breasts and/or nipples, painful milk ejection reflex, and a decrease in milk production. The hypothesized pharmacological mechanism relates to the serotonin-receptor agonistic properties of triptans. These may lead to vasoconstriction in the breasts and nipples, including the vasculature surrounding the milk ducts and alveoli, and may also influence the hormonal function and levels of prolactin. The reported adverse drug reactions do not negatively impact the overall compatibility of triptans with breastfeeding. However, breastfeeding women may experience them as unsettling. Awareness of these potential adverse drug reactions is essential and should be weighed against the potential adverse effects of (untreated) symptoms of migraine attacks.
PubMed: 38563407
DOI: 10.1089/bfm.2024.0022