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Nature Reviews. Endocrinology Dec 2023Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone... (Review)
Review
Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone secretion from endocrine organs. However, the evolutionary biology of pituitary hormones and their receptors provides evidence for a broad range of functions in vertebrate physiology. Over the past decade, we and others have discovered that thyroid-stimulating hormone, follicle-stimulating hormone, adrenocorticotropic hormone, prolactin, oxytocin and arginine vasopressin act directly on somatic organs, including bone, adipose tissue and liver. New evidence also indicates that pituitary hormone receptors are expressed in brain regions, nuclei and subnuclei. These studies have prompted us to attribute the pathophysiology of certain human diseases, including osteoporosis, obesity and neurodegeneration, at least in part, to changes in pituitary hormone levels. This new information has identified actionable therapeutic targets for drug discovery.
Topics: Humans; Pituitary Hormones; Pituitary Gland; Prolactin; Adipose Tissue; Brain
PubMed: 37715028
DOI: 10.1038/s41574-023-00894-5 -
Journal of Ovarian Research Nov 2023The prolactin receptor gene (PRLR) may contribute to polycystic ovarian syndrome (PCOS) since it plays important roles in physiological ovarian functions. PRLR-knockout...
The prolactin receptor gene (PRLR) may contribute to polycystic ovarian syndrome (PCOS) since it plays important roles in physiological ovarian functions. PRLR-knockout mice have irregular cycles and subfertility and variants in or around the PRLR gene were associated in humans with female testosterone levels and recurrent miscarriage. We tested 40 variants in the PRLR gene in 212 Italian families phenotyped by type 2 diabetes (T2D) and PCOS and found two intronic PRLR-variants (rs13436213 and rs1604428) significantly linked to and/or associated with the risk of PCOS. This is the first study to report PRLR as a novel risk gene in PCOS. Functional studies are needed to confirm these results.
Topics: Humans; Female; Animals; Mice; Polycystic Ovary Syndrome; Receptors, Prolactin; Prolactin; Diabetes Mellitus, Type 2; Infertility; Hyperandrogenism
PubMed: 37993904
DOI: 10.1186/s13048-023-01280-5 -
International Journal of Molecular... Sep 2023Prolactin (PRL) and growth hormone (GH) are peptide hormones that bind to the class 1 cytokine receptor superfamily, a highly conserved cell surface class of receptors.... (Review)
Review
Prolactin (PRL) and growth hormone (GH) are peptide hormones that bind to the class 1 cytokine receptor superfamily, a highly conserved cell surface class of receptors. Both hormones control their own secretion via a negative autocrine loop in their own mammosomatotroph, lactotroph or somatotroph. In this regard, GH and PRL are regulated by similar signaling pathways involving cell growth and hormone secretion. Thus, GH and PRL dysregulation and pituitary neuroendocrine tumor (PitNET) development may have common pathogenic pathways. Based on cell linage, lactotroph and somatotroph PitNETs come from pituitary-specific POU-class homeodomain transcription factor (Pit-1). Mammosomatotroph and plurihormonal PitNETs are a unique subtype of PitNETs that arise from a single-cell population of Pit-1 lineage. In contrast, mixed somatotroph-lactotroph PitNETs are composed of two distinct cell populations: somatotrophs and lactotrophs. Morphologic features that distinguish indolent PitNETs from locally aggressive ones are still unidentified, and no single prognostic parameter can predict tumor aggressiveness or treatment response. In this review, we aim to explore the latest research on lactotroph and somatotroph PitNETs, the molecular mechanisms involved in PRL and GH axis regulation and the signaling pathways involved in their aggressiveness, particularly focused on mammosomatotroph and mixed subtypes. Finally, we summarize epidemiological, clinical, and radiological features of these exceptional tumors. We aim to shed light, from basic to clinical settings, on new perspectives and scientific gaps in this field.
PubMed: 37762304
DOI: 10.3390/ijms241814002 -
Langenbeck's Archives of Surgery Aug 2023In esthetic surgery, the use of silicone implants is a topic of hot discussion.
INTRODUCTION
In esthetic surgery, the use of silicone implants is a topic of hot discussion.
MATERIAL AND METHODS
An analysis of 119 esthetic surgical interventions on the mammary gland was performed. A study of the immune and endocrine parameters after mammoplasty was carried out.
RESULTS
The phenomenon of an increase in the levels of autoantibodies to the TSH receptor was revealed. The phenomenon of pre-operative growth of prolactin and TSH levels has been confirmed. An increase in thyroid autoimmunity after silicone mammoplasty is interpreted as a result of a silicone adjuvant action. An increase in the incidence of ASIA syndrome in patients who underwent breast surgery was registered. However, it was observed in both patients with silicone and non-silicone breast surgeries and therefore could not be solely explained by the use of silicone. Within 12 months following silicone mammoplasty, the patients with an increase of anti-TSH receptor autoimmunity nevertheless did not show any clinical and laboratory signs of overt thyroid disease, thus staying in a pre-nosological state. PRACTICAL RECOMMENDATIONS: Based on these results, we recommend the following for esthetic surgery: (a) all patients planned for silicone implant surgery should be examined for autoantibodies to the TSH receptor and (b) patients who have undergone breast endoprosthesis, starting 6 months after the operation, need long-term follow-up for thyroid status with mandatory testing for the level of these autoantibodies.
Topics: Humans; Autoimmunity; Silicones; Breast Implants; Thyroid Gland; Autoantibodies
PubMed: 37581699
DOI: 10.1007/s00423-023-03030-z -
Journal of Chemical Information and... Sep 2023Homodimeric class 1 cytokine receptors include the erythropoietin (EPOR), thrombopoietin (TPOR), granulocyte colony-stimulating factor 3 (CSF3R), growth hormone (GHR),...
Homodimeric class 1 cytokine receptors include the erythropoietin (EPOR), thrombopoietin (TPOR), granulocyte colony-stimulating factor 3 (CSF3R), growth hormone (GHR), and prolactin receptors (PRLR). These cell-surface single-pass transmembrane (TM) glycoproteins regulate cell growth, proliferation, and differentiation and induce oncogenesis. An active TM signaling complex consists of a receptor homodimer, one or two ligands bound to the receptor extracellular domains, and two molecules of Janus Kinase 2 (JAK2) constitutively associated with the receptor intracellular domains. Although crystal structures of soluble extracellular domains with ligands have been obtained for all of the receptors except TPOR, little is known about the structure and dynamics of the complete TM complexes that activate the downstream JAK-STAT signaling pathway. Three-dimensional models of five human receptor complexes with cytokines and JAK2 were generated here by using AlphaFold Multimer. Given the large size of the complexes (from 3220 to 4074 residues), the modeling required a stepwise assembly from smaller parts, with selection and validation of the models through comparisons with published experimental data. The modeling of active and inactive complexes supports a general activation mechanism that involves ligand binding to a monomeric receptor followed by receptor dimerization and rotational movement of the receptor TM α-helices, causing proximity, dimerization, and activation of associated JAK2 subunits. The binding mode of two eltrombopag molecules to the TM α-helices of the active TPOR dimer was proposed. The models also help elucidate the molecular basis of oncogenic mutations that may involve a noncanonical activation route. Models equilibrated in explicit lipids of the plasma membrane are publicly available.
Topics: Humans; Receptors, Cytokine; Cytokines; Janus Kinase 2; Ligands; Signal Transduction
PubMed: 37694948
DOI: 10.1021/acs.jcim.3c00926 -
Journal of the American Academy of... Sep 2023Antipsychotic-induced hyperprolactinemia is common in children and adolescents, but this quotidian presence in our clinics should neither reassure us nor make us...
Antipsychotic-induced hyperprolactinemia is common in children and adolescents, but this quotidian presence in our clinics should neither reassure us nor make us complacent. The report by Koch and colleagues stands out against the landscape of trials describing the adverse effects of psychotropic medications in youth. It goes beyond the typical examination of adverse effects in most clinical trials. The authors followed children and adolescents aged 4 to 17 years who were dopamine-serotonin receptor antagonist naive (≤1-week exposure) or free, and serially evaluated not only serum prolactin concentrations but medication concentrations and side effects for 12 weeks after participants began aripiprazole, olanzapine, quetiapine, or risperidone. This report provides insights into the temporal course of adverse effects, examines differential tolerability among dopamine-serotonin receptor antagonists, links specific adverse effects-galactorrhea, decreased libido, and erectile dysfunction-with prolactin concentrations in youth, and focuses on the clinical aspects of hyperprolactinemia and related adverse effects in children and adolescents.
Topics: Male; Female; Adolescent; Child; Humans; Antipsychotic Agents; Hyperprolactinemia; Prolactin; Dopamine; Risperidone; Aripiprazole
PubMed: 37172820
DOI: 10.1016/j.jaac.2023.05.003 -
Frontiers in Immunology 2024The development of B cells into antibody-secreting plasma cells is central to the adaptive immune system as they induce protective and specific antibody responses... (Review)
Review
The development of B cells into antibody-secreting plasma cells is central to the adaptive immune system as they induce protective and specific antibody responses against invading pathogens. Various studies have shown that, during this process, hormones can play important roles in the lymphopoiesis, activation, proliferation, and differentiation of B cells, and depending on the signal given by the receptor of each hormone, they can have a positive or negative effect. In autoimmune diseases, hormonal deregulation has been reported to be related to the survival, activation and/or differentiation of autoreactive clones of B cells, thus promoting the development of autoimmunity. Clinical manifestations of autoimmune diseases have been associated with estrogens, prolactin (PRL), and growth hormone (GH) levels. However, androgens, such as testosterone and progesterone (P4), could have a protective effect. The objective of this review is to highlight the links between different hormones and the immune response mediated by B cells in the etiopathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). The data collected provide insights into the role of hormones in the cellular, molecular and/or epigenetic mechanisms that modulate the B-cell response in health and disease.
Topics: Humans; B-Lymphocytes; Autoimmunity; Animals; Hormones; Autoimmune Diseases; Cell Differentiation; Lupus Erythematosus, Systemic
PubMed: 38680484
DOI: 10.3389/fimmu.2024.1385501 -
Biomedicines Aug 2023Obesity has been identified as a serious health concern in domestic cats. Feline mammary cancer (FMC) is also a concern, as it is highly prevalent and aggressive.... (Review)
Review
Obesity has been identified as a serious health concern in domestic cats. Feline mammary cancer (FMC) is also a concern, as it is highly prevalent and aggressive. Considering the identified connection between obesity and breast cancer, it is worthwhile to investigate the potential obesity-cancer relationship in FMC. This review investigated the association between adipokines and other obesity-associated molecules and FMC, with the aim of identifying gaps in the current literature for future research. Based on the reports to date, it was found that tissue concentrations of leptin, serum concentrations of leptin receptor, serum amyloid A, and estrogen correlate positively with FMC, and serum concentrations of leptin correlate negatively with FMC. The roles of adiponectin and prolactin in FMC development were also investigated, but the reports are either lacking or insufficient to suggest an association. Numerous research gaps were identified and could be used as opportunities for future research. These include the need for studies on additional cohorts to confirm the association of leptin/leptin receptor and serum amyloid A with FMC, and to address the role of adiponectin and prolactin in FMC. It is also important to investigate the genetic determinants of FMC, evaluate the use of molecular-targeted therapies in FMC, and exploit the enrichment of the triple-negative immunophenotype in FMC to address current clinical needs for both human triple-negative breast cancer and FMC. Finally, mechanistic studies with any of the molecules reviewed are scarce and are important to generate hypotheses and ultimately advance our knowledge and the outcome of FMC.
PubMed: 37626804
DOI: 10.3390/biomedicines11082309 -
Cells Sep 2023Prolactin-inducible protein (PIP), also referred to as gross cystic disease fluid protein 15 (GCDFP-15), has been a trending topic in recent years due to its potential... (Review)
Review
Prolactin-inducible protein (PIP), also referred to as gross cystic disease fluid protein 15 (GCDFP-15), has been a trending topic in recent years due to its potential role as a specific marker in breast cancer. PIP binds to aquaporin-5 (AQP5), CD4, actin, fibrinogen, β-tubulin, serum albumin, hydroxyapatite, zinc α2-glycoprotein, and the Fc fragment of IgGs, and the expression of PIP has been demonstrated to be modulated by various cytokines, including IL4/13, IL1, and IL6. PIP gene expression has been extensively studied due to its captivating nature. It is influenced by various factors, with androgens, progesterone, glucocorticosteroids, prolactin, and growth hormone enhancing its expression while estrogens suppress it. The regulatory mechanisms involve important proteins such as STAT5A, STAT5B, Runx2, and androgen receptor, which collaborate to enhance PIP gene transcription and protein production. The expression level of PIP in breast cancer is dependent on the tumor stage and subtype. Higher expression is observed in early-stage tumors of the luminal A subtype, while lower expression is associated with luminal B, basal-like, and triple-negative subtypes, which have a poorer prognosis. PIP expression is also correlated with apocrine differentiation, hormone receptor positivity, and longer metastasis-free survival. PIP plays a role in supporting the immune system's antitumor response during the early stages of breast cancer development. However, as cancer progresses, the protective role of PIP may become less effective or diminished. In this work, we summarized the clinical significance of the PIP molecule in breast cancer and its potential role as a new candidate for cell-based therapies.
PubMed: 37759471
DOI: 10.3390/cells12182252 -
Animal Biotechnology Nov 2023A total of 266 records of buffalo raised in two experimental herds in Egypt were assessed to detect prolactin () and prolactin receptor () genes' polymorphism using...
A total of 266 records of buffalo raised in two experimental herds in Egypt were assessed to detect prolactin () and prolactin receptor () genes' polymorphism using PCR-Single Strand Conformational Polymorphism (SSCP) and PCR-Restricted Fragment Length Polymorphism (RFLP) techniques as well as to investigate their association with calf birth weight (BW), weaning weight (WW), lactation period (LP), total milk yield (TMY), stillbirth, calving ease (CE), gestation length (GL), postpartum interval to pregnancy (PPIP), calving interval (CI), and age at first calving (AFC). Predicted breeding values were estimated and used in the association with detected genotypes. A monomorphic pattern of the studied 156 bp segment was recorded and absence of its polymorphism in buffalo was corroborated. We also determined polymorphism of reflected in three loci: 2, 4, and 9. Significant differences among 9 genotypes (AA, AB, and BB) were displayed for all studied traits as well as among 2 genotypes, except for CE, while 4 genotypes significantly differed only in BW, WW, TMY, stillbirth, GL, and AFC. In practice, strong associations among genotypes of the gene and the traits of interest candidate this gene to be selective in Egyptian buffalo breeding for improving both productive and reproductive traits.
Topics: Pregnancy; Female; Animals; Prolactin; Receptors, Prolactin; Buffaloes; Egypt; Stillbirth; Genotype
PubMed: 35148254
DOI: 10.1080/10495398.2022.2028160