Search Results (131)

Prolactin (PRL) is a hormone synthesized by lactotrophs in the anterior pituitary gland. It is also produced by extrapituitary glands such as the prostate and breast, where it promotes growth. Notably, PRL also contributes to cancer development in these glands. PRL is known to stimulate cancer cell migration, suggesting its possible involvement in metastasis, for which cell migration is a critical step. However, the role and mechanisms by which PRL induces cancer cell migration are not yet fully understood. One well-studied mechanism involves its receptor, the prolactin receptor (PRLR). After PRL binds to its receptor, PRLR dimerizes and induces transphosphorylation of Janus kinase 2 (JAK2), which subsequently phosphorylates p21-activated kinase 1 (PAK1), leading to increased cell migration. Although the PRL-JAK2-PAK1 pathway in cancer cell migration has been investigated, the molecular mechanism remains incompletely understood. Additionally, other PRL-activated pathways are implicated in migration, but their roles remain debated. This narrative review examines and discusses the main findings on the involvement of PRL in the migration of cancerous and non-cancerous cells, as well as the molecular mechanisms involved. We conclude that PRL promotes the migration of both cancerous and non-cancerous cell lines and should, therefore, be taken into account in future cancer research. Full article

Intense broodiness restricts egg production in Zhedong White Geese, with prolactin (PRL) being a key regulator. This study aimed to elucidate the role of PRL gene alternative splice variants in regulating broodiness in Zhedong White Geese. A total of 20 Zhedong White Geese at 400 days of age were selected and divided into two groups of 10 based on their physiological states: the laying period and the brooding period. Through bioinformatics and molecular biology approaches, PRL-L and PRL-S were identified and characterized. The results showed that PRL-S lacked a signal peptide and the first 57 amino acids at the N-terminus, leading to the disappearance of its first α-helix structure. Functional validation demonstrated that the recombinant PRL-S protein, prepared using a prokaryotic expression system, possessed physiological activity, including receptor binding and the activation of downstream signaling pathways. Furthermore, Real-time PCR and Western blot analyses revealed that the expression of both splice variants in the hypothalamic–pituitary–ovarian axis exhibited significant spatiotemporal specificity and was closely associated with reproductive states. This study revealed the molecular characteristics, in vitro functional activity, and expression patterns of PRL-S, providing new insights into the regulatory mechanisms of PRL. Full article

The global push to eliminate antibiotic growth promoters in poultry has accelerated the demand for effective natural alternatives. β-Glucans—branched polysaccharides derived from Saccharomyces cerevisiae cell walls—enhance immunity and gut health; however, their mechanistic effect on the somatotropic axis and meat quality in broilers remains unresolved. Herein, the hypothesis that dietary β-glucan modulates somatotropic signaling to improve growth performance and breast muscle quality was tested with 240 one-day-old Ross 308 chicks allocated to three groups—untreated control, 250 mg β-glucan/kg feed, and 1 g β-glucan/kg feed—and reared for 35 d. Growth performance, plasma growth hormone (GH) and prolactin (PRL), somatotropic axis gene expression in liver and breast muscle, and postmortem meat quality were assessed. β-Glucan supplementation significantly elevated final body weight, breast muscle weight, and plasma GH and PRL, and upregulated hepatic IGF-1 and muscle GH receptor mRNA at 35 d, and hepatic GH receptor mRNA at 17 d. Muscle pH was higher and relative drip loss lower in supplemented birds 72 h postmortem. These results support the hypothesis and identify 1 g β-glucan/kg feed as an effective dose for improving growth and meat quality through somatotropic axis modulation—a novel mechanistic demonstration in broiler chickens. Full article

This study investigated the association of polymorphisms in four genes with growth traits in two Japanese quail lines: a high-growth-rate selected line (HGR) and a control line (CL). It utilized 21 generations of divergent selection to identify potential selection signatures, comparing allele frequency shifts between the high-growth and unselected base populations. Growth Hormone (GH), Prolactin (PRL), Bone Morphogenetic Protein Receptor Type-1B (BMPR-1B), and Vasoactive Intestinal Peptide Receptor 1 (VIPR-1) genes were genotyped using PCR-RFLP. While the PRL gene was monomorphic, the GH, BMPR-1B, and VIPR-1 loci were polymorphic. Association analysis demonstrated that these variants significantly influenced body weight. In the HGR line, the homozygous genotypes (BB) of GH and BMPR-1B were significantly correlated with increased body weight at various ages. The AA genotype of VIPR-1 correlated with growth, while the BB genotype reduced body weight. An in silico analysis suggested that GH and VIPR-1 variants were functionally disadvantageous. The BMPR-1B variant was tolerated, indicating its potential as a genetic marker. Significant additive effects were estimated for the associated SNPs, thereby highlighting their heritable potential. These findings suggest that GH, BMPR-1B, and VIPR-1 polymorphisms are valuable for marker-assisted selection to improve growth performance within Japanese quail breeding programs. Full article

The molecular coordination between the central nervous system and peripheral organs is fundamental to euryhalinity. This study elucidates the distinct adaptive strategies of the brain and gills in the four-finger threadfin (Eleutheronema tetradactylum), an aquaculture species of growing importance, during long-term (30-day) acclimation to low salinity (5 versus 25 control). A profound dichotomy in tissue-specific plasticity was uncovered: while the brain maintained remarkable transcriptional stability with only 10 differentially expressed genes (DEGs), the gills underwent extensive remodeling with 702 DEGs. Gill DEGs were functionally enriched in ion transport and metabolic remodeling, highlighted by the significant upregulation of the Na⁺-Cl⁻ cotransporter (slc12a10) and the prolactin receptor (prlr), coupled with a profound downregulation (log₂FC = −5.97) of aquaporin-1 (aqp1). This indicates a concerted strategy to enhance ion uptake while minimizing water permeability. In contrast, the brain’s subtle response was dominated by the upregulation of key neuroendocrine hormones, including growth hormone (gh), prolactin (prl), and pro-opiomelanocortin (pomc). This suggests a top-down regulatory cascade. Integrative pathway analysis identified the PI3K-Akt and JAK-STAT signaling pathways as the primary conduits linking central hormonal signals to peripheral physiological adjustments. These results demonstrate that the euryhalinity of E. tetradactylum is achieved through a highly efficient strategy: a transcriptionally stable brain provides precise endocrine commands that orchestrate robust peripheral remodeling in the gills. This study deciphers the molecular basis of the brain–gill axis in osmoregulation and provides a rich repository of candidate genes for the genetic improvement of low salinity tolerance in aquaculture. Full article

Background/Objectives: Pregnancy is associated with increased renal secretory clearance of drugs mediated by organic anion transporters (OATs) and organic cation transporter 2 (OCT2). Circulating concentrations of pregnancy-related hormones (PRHs) increase with gestational age, providing a plausible mechanism for renal OAT and OCT2 regulation. Methods: Using primary human proximal tubular epithelial cells (PTECs), we quantified the effects of PRHs, at trimester-specific concentrations, on the mRNA expression of renal drug transporters (apical and basal) and metabolizing enzymes (DMETs), as well as endocytic receptors. PTECs from three female, premenopausal donors were cultured in an optimized Transwell system that maintains measurable OAT activity. PTECs were then exposed for 72 h to trimester-matched PRH cocktails at physiologic (1×) or supraphysiologic (10×) concentrations, with medium replaced every 24 h. DMET and endocytic receptor mRNA were quantified by RT-qPCR, and uptake activities of OAT1/2/3, OCT2, OAT4, and OCTN1 were measured with selective substrates or substrate–inhibitor pairs. Results: At 1× PRHs, renal DMET and endocytic receptor mRNA expression was unchanged across trimester-related PRH concentration except for consistent downregulation of PEPT2. Uptake activity for all measured transporters was unchanged. At 10× PRHs, selective changes in mRNA expression of transporters were observed (e.g., induction of OAT1), but these changes did not translate into changes in activity. Conclusions: Our data argue against PRHs as the main driver of the increase in OAT-mediated drug secretion during pregnancy. Alternative mechanisms (e.g., flow-dependent mechanotransduction and untested hormones [e.g., prolactin, hCG]) should be evaluated to explain gestation-dependent changes in renal secretory clearance of drugs. Full article

Approximately 40% of women start pregnancy with overweight or obesity, and around 70% retain weight in the postpartum period (PP). Obesity is related to low-grade systemic inflammation, primarily driven by the secretome of white adipose tissue (WAT), which includes dysfunctional adipocytes and immune cells that infiltrate WAT, releasing pro-inflammatory signals into the circulation. In women with obesity, the mammary gland undergoes structural and endocrine changes, such as reduced prolactin secretion, fewer mammary gland branches, and a higher abundance of adipocytes in mammary fat pad, which have not been studied under this condition. Maternal obesity during lactation also alters the composition of breast milk, promoting pro-inflammatory characteristics. The endocannabinoid system (ECS) is hyperactive in obesity, contributing to metabolic inflammation. Its primary receptors, cannabinoids 1 and 2, are expressed in the mammary gland and implicated in inflammation and weight gain. Endocannabinoids (ECs), the main ECS ligands, are typically not released into the bloodstream; however, their increased levels in obesity suggest upregulation in peripheral tissues. ECs are also present in breast milk, where their higher concentrations in women with obesity may influence infant food intake. Full article

Sexual size dimorphism (SSD) refers to the phenomenon where males and females of the same species exhibit differences in overall or partial body size, and it is widespread among mammals, birds, reptiles, and fish. Notably, this dimorphism is significantly influenced by the sexually dimorphic secretion of growth hormone (gh), a key pituitary-derived growth regulator. Commonly, the secretion of gh is positively regulated by glucagon family members such as growth hormone-releasing hormone (ghrh) and adenylate cyclase-activating polypeptide 1 (adcyap1). To explore the stimulators for pituitary hormones (especially gh) in the teleost, we performed genome-wide identification and functional characterization of the glucagon family on Chinese tongue sole (Cynoglossus semilaevis) that exhibits typical female-biased sexual size dimorphism. Four members of adcyap1/vasoactive intestinal polypeptide(vip)/ghrh family and ten members of their receptor family were identified. Expression pattern analysis revealed high expression of adenylate cyclase-activating polypeptide 1b (adcyap1b) and its receptors in the brain. Moreover, two alternative splice variants for the adcyap1b gene were discovered, resulting from the skipping of exon 4. Following the acquisition of the two eukaryotic recombinant protein splice variants (ADCYAP1b_tv1 and ADCYAP_tv2) from HEK 293T cells, incubation experiments were conducted using C. semilaevis pituitary cell line. The results demonstrated that both variants promoted the expression of gh, pro-opiomelanocortin (pomc), and corticoliberin (crh), but ADCYAP1b_tv1 had a significantly stronger effect and uniquely stimulated prolactin (prl) and somatolactin (sl). This study demonstrates a functional divergence between the two ADCYAP1b splice variants in teleosts, with ADCYAP1b_tv1 acting as a more potent and versatile pituitary hormone stimulator. Further research on their receptor-binding affinity and downstream signaling pathways would be valuable for exploring the mechanism underlying sexual size dimorphism. Full article

Spotty liver disease (SLD), primarily caused by Campylobacter hepaticus and (less frequently) by Campylobacter bilis, significantly impacts commercial layer hens by causing liver lesions, reducing egg production, and increasing mortality, meaning it can result in serious economic losses for farmers. This study explored the relationship between infection, liver dysfunction, and reproduction, aiming to identify host genetic markers for tracking SLD progression. Hens were orally inoculated with the C. hepaticus strain NSW44L and monitored over a seven-day period. Pathogen colonisation was quantified using qPCR across the liver, bile, caeca, spleen, and ovarian follicles, while liver lesions were scored and hepatic transcriptomes analysed using RNA-seq. C. hepaticus was detected in the liver, caeca, and spleen from one day post-inoculation (dpi) (1.44–1.68 log₁₀ CFU/mL), appeared in bile by the third dpi (3.64 log₁₀ CFU/mL), and reached the follicles by the fourth dpi (3.25 log₁₀ CFU/mL). The highest bacterial loads were found in bile on days six and seven (up to 7.18 CFU/mL). Liver lesions were first observed on the fourth dpi, reaching their peak at the sixth and seventh dpi. Gene expression analysis in liver tissue revealed a notable downregulation of yolk-precursor and metabolic genes, such as prolactin receptor (PRLR), 7-dehydrocholesterol reductase (DHCR7), and malic enzyme 1 (ME1). In contrast, from days three to seven post-infection, there was significant upregulation of avidin (AVD), a biotin-binding protein, and versican (VCAN), which is linked to tissue remodelling and inflammation. These findings correlate with the disease’s progression from initial liver infection to widespread bacterial presence, suggesting value as host biomarkers for effective SLD monitoring and the development of targeted therapies. Full article

The intensification of global climate warming exacerbates the issue of heat stress in dairy cows, making the SLICK mutation in the prolactin receptor (PRLR) gene a critical target for enhancing heat tolerance in these animals. This study aims to investigate the effects of CRISPR/Cas9-mediated editing of the PRLR gene on the biological characteristics of bovine fibroblasts and early embryonic development following somatic cell nuclear transfer (SCNT). Using the CRISPR/Cas9 system, we targeted and edited a 20 bp–150 bp region within exon nine of the PRLR gene. After conducting off-target predictions and activity screenings, we identified optimal guide RNA (sgRNA) sequences and established stable transgenic cell lines. Transcriptome sequencing was performed on edited cells to identify key genes and validate their expression profiles. Edited cells were utilized as donor cells for SCNT, during which we assessed oocyte levels of reactive oxygen species (ROS), glutathione (GSH), and mitochondrial function to analyze embryonic developmental performance. We constructed a cellular stress resistance network aimed at mitigating damage transmission while maintaining embryonic developmental homeostasis. This research provides technical support and theoretical reference for genetic editing breeding programs aimed at improving heat tolerance in dairy cattle. Full article

Gut microbiota have a significant impact neurotransmitters, short-chain fatty acids (SCFAs), immune signaling molecules, and gut hormones. These signaling molecules interact with receptors on the gut wall, immune cells, or the enteric nervous system (ENS), and reach the central nervous system (CNS) via the Vagus nerve (VN). SCFAs interact with G protein-coupled receptors (GPCRs), Toll-like receptors (TLRs), and proliferator-activated receptors (PPARs), influencing inflammatory reactions, gut motility, nutrient absorption, hormone secretion, neurochemical signaling, and brain functions. Olfactory receptor OR51E1 influences blood pressure, vascular reactivity, and arterial stiffness. Activation of the brainstem nucleus tractus solitarius (NTS) by glucagon-like peptide 1 (GLP-1) influences mood, cognition, and gastrointestinal motility. Prolactin-releasing peptide (PrRP) binds to its receptor (PrRPR), suppressing food intake, and regulating stress, cardiovascular reactions, and circadian rhythms. In-depth studies on how gut microbiota control cognitive behavior, mood, and neuropsychiatric disorders are lacking. G protein receptor 119 (GPR119) suppresses appetite and may find an application in the treatment of type 2 diabetes and obesity. The binding of butyrate to nuclear factor kappa B (NF-κB) and proliferator-activated receptor γ (PPARγ) regulates the production of pro-and anti-inflammatory cytokines. This suppresses protein CD36, preventing the uptake of oxidized low-density lipoprotein (ox-LDL) and cardiovascular diseases (CVDs). This review focuses on a few prominent health conditions related to CVDs, i.e., metabolic syndrome (MetS), cancer, and brain functions. Information in this review is based on animal and preclinical studies published in repositories such as PubMed, the National Institutes of Health (NIH), NIH PubChem, ScienceDirect, MDPI, Frontiers, Cell Press, and the CAS Content Collection. Full article

Background: Dopamine agonists (DAs) are first-line therapy for prolactin-secreting pituitary adenomas; however, a small proportion of tumors are resistant. Previous reports suggested that reduced D2R mRNA expression might cause resistance. This study aimed to determine if resistant prolactinomas express D2R protein. We also explored a role of estrogen receptor alpha (ERα) expression in DA resistance. Methods: We retrospectively selected 15 tumor specimens from 13 total patients (8 controls from 8 patients, 7 from 5 resistant patients) with resected lactotroph cell-type tumors. We reviewed age at diagnosis, tumor size, initial prolactin level, medical treatment, and reason for surgery. Immunohistochemistry was performed for D2R, prolactin, and ERα protein expression. Results: D2R expression was positive in seven of eight controls vs. two of seven in resistant tumors (p = 0.02). ERα expression did not significantly correlate with DA resistance. The two D2R expressing resistant tumors were ERα negative and both derived from a pre-pubertal female, supporting prior reports suggesting ERα may modulate DA therapy response. Conclusions: Our study introduces a reproducible method for assessing D2R protein expression in prolactinomas using commercially available D2R antibodies. Our findings align with current evidence indicating that lack of D2R expression, previously indicated by decreased mRNA levels, is common in DA-resistant prolactinomas and provide a basis for discontinuation of DA therapy to avoid potential harm to these patients. Full article

Prolactin (PRL) and growth hormone (GH) originate from somatomammotropic cells and share regulatory mechanisms. Alpha₂-adrenergic receptor stimulation with clonidine is routinely used in diagnosing GH deficiency (GHD), yet its effect on PRL secretion remains unclear. This study aimed to assess the impact of clonidine-induced α₂-adrenergic receptor stimulation on PRL secretion and compare PRL dynamics between children with idiopathic short stature (ISS) and GHD. Forty-nine children with height < −2.0 SD (29 ISS, 20 GHD) underwent clonidine stimulation (0.15 mg/m² administered orally). Serum GH and PRL were measured at 0, 30, 60, 90, and 120 min. Groups did not differ in chronological age, bone age, height SDS, or BMI SDS. Both groups exhibited a significant decrease in PRL at 30, 60, and 90 min compared to baseline. In ISS, PRL concentrations increased from 60 min onward, returning near baseline at 120 min. In GHD, PRL remained suppressed throughout the test. GH and PRL concentrations correlated positively at 90 (r = 0.35, p < 0.05) and 120 min (r = 0.35, p < 0.05). Clonidine-induced alpha2-adrenergic stimulation suppresses PRL in both ISS and GHD, but recovery is observed only in ISS, suggesting a potential involvement of GH signaling in PRL regulation. Full article

Maternal behavior encompasses a range of biologically driven responses whose expression and duration vary across species. Maternal responses rely on robust adaptive changes in the female brain, enabling mothers to engage in caregiving, nourishing, and offspring protection. Morphological and functional changes in the maternal brain enhance sensitivity to offspring cues, eliciting maternal behaviors, rewarding responses, and social processing stimuli essential for parenting. Maternal behavior comprises a range of biological responses that extend beyond basic actions, reflecting a complex, evolutionarily shaped neurobiological adaptation. These behaviors can be broadly categorized into direct behaviors, which are explicitly aimed at the care of the offspring, and indirect behaviors that, overall, ensure the protection, nourishment, and survival of the newborn. The secretion of main neuropeptide hormones, such as oxytocin (OT), prolactin (PRL), and placental lactogens (PLs), during the peripartum period, is relevant for inducing and regulating maternal responses to offspring cues, including suckling behavior. Although PRL is primarily associated with reproductive and parental functions in vertebrates, it also modulates distinct neural functions during pregnancy that extend from lactogenesis to adult neurogenesis, neuroprotection, and neuroplasticity, all of which contribute to preparing the maternal brain for motherhood and parenting interactions. Parvocellular OT-containing neurons in the paraventricular nucleus (PVN) and in the anterior hypothalamic nucleus (AHN) project axon collaterals to the medial preoptic area, which, in turn, projects to the nucleus accumbens (NACC) and lateral habenula (lHb) via the retrorubral field (RRF) and the ventral tegmental area (VTA), which mediate the motivational aspects of maternal responses to offspring cues. The reshaping process of the brain and neural networks implicated in motherhood depends on several factors, such as up- and downregulation of neuronal gene expression of bioactive peptide hormones (i.e., OT, PRL, TIP-39, galanin, spexin, pituitary adenylate cyclase-activating polypeptide (PACAP), corticotropin-releasing hormone (CRH), peptide receptors, and transcription factors (i.e., c-fos and pSTAT)) in target neurons in hypothalamic nuclei, mesolimbic areas, the hippocampus, and the brainstem, which, overall, regulate the expression of maternal behavior to offspring cues, as shown in postpartum female rodents. In this review, we describe the modulatory neuropeptides, the neural networks underlying peptide transmission systems, and cell signaling involved in parenthood. We highlight the dysregulation of neuropeptide hormones and their receptors in the central nervous system in relation to psychiatric disorders. Full article

Prolactin (PRL) is a hormone primarily associated with lactation, but it plays various roles in both men and women. PRL belongs to the family of peptide hormones, including placental lactogen and growth hormone. Interestingly, PRL is a pleiotropic hormone affecting several physiological and pathological conditions, including fertility. Moreover, several pathophysiological roles have been associated with this hormone, including those of the immune system, autoimmune disorders, asthma, and ageing. Additionally, PRL receptors are ubiquitously expressed in tissues, including the mammary gland, gonads, liver, kidney, adrenal gland, brain, heart, lungs, pituitary gland, uterus, skeletal muscle, skin blood cells, and immune system. Therefore, in the present paper, we cover the potential role that PRL may play in asthma by promoting inflammation and modulating immune responses. The detection of its receptor in lung tissue suggests a direct role in airway smooth muscle contractility through activation of signaling pathways such as JAK2-STAT5, MAPK/ERK1/2, and PI3K/Akt, as well as influencing ionic currents that regulate cell contraction, proliferation, and survival. In this sense, this review aims to explore the potential involvement of PRL in asthma pathophysiology by examining its interactions with intracellular signaling pathways and its possible impact on airway smooth muscle contractility and immune modulation. Full article