Search Results (116)

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

Endometriosis is a disorder characterized by the presence of endometrial tissue outside the uterus, leading to dyspareunia, chronic pelvic pain, dysuria, and infertility. The latter has been related to implantation failure associated with alterations in decidualization, a process regulated by sex hormones such as progesterone. Membrane progesterone receptor β (mPRβ) exhibits a lower expression in endometriotic tissues than in normal endometrial ones. However, the role of mPRβ in decidualization is unknown. This work aimed to investigate whether mPRβ plays a role in the decidualization of endometrial stromal cells (ESCs) derived from women with and without endometriosis. The mPR agonist OrgOD-2 induced the gene expression of key decidualization markers (insulin-like growth factor binding protein 1, prolactin, transcription factor heart and neural crest derivatives-expressed transcript 2, and fork-head transcription factor) in healthy ESCs, eutopic (uterine cavity), and ectopic (outside of the uterine cavity) ESCs from women with endometriosis. Notably, the expression of the decidualization markers was lower in endometriotic cells than in healthy endometrial ones. An siRNA mediated knockdown of mPRβ reduced the expression of decidualization-associated genes in ESCs treated with a decidualization stimuli, regardless of whether cells were derived from healthy women or those with endometriosis. Our data suggest that progesterone, through mPRβ activation, regulates the decidualization process in endometrial stromal cells from women with and without endometriosis. Full article

Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene expression profile in the frontal cortex and hippocampus (HPC) that are relevant to social and attentional/cognitive schizophrenia-linked symptoms; on the other hand, RLA rats display phenotypic traits linked to increased anxiety and sensitivity to stress-induced depression-like behaviours. The present studies aimed to evaluate the enduring and potentially positive effects of neonatal handling-stimulation (NH) on the traits differentiating these two strains of rats. Methods: We evaluated the effects of NH on anxious behaviour, prepulse inhibition of startle (PPI), spatial working memory, and hormone responses to stress in adult rats of both strains. Furthermore, given the proposed involvement of neuronal/synaptic plasticity and neurotrophic factors in the development of anxiety, stress, depression, and schizophrenia-related symptoms, using Western blot (WB) we assessed the effects of NH on the content of brain-derived neurotrophic factor (BDNF), its trkB receptor and Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the prefrontal cortex (PFC), anterior cingulate cortex (ACg), ventral (vHPC), and dorsal (dHPC) hippocampus of adult rats from both strains. Results: NH increased novelty-induced exploration and reduced anxiety, particularly in RLA rats, attenuated the stress-induced increment in corticosterone and prolactin plasma levels, and improved PPI and spatial working memory in RHA rats. These effects correlated to long-lasting increases of BDNF and PSA-NCAM content in PFC, ACg, and vHPC. Conclusions: Collectively, these findings show enduring and distinct NH effects on neuroendocrine and behavioural and cognitive processes in both rat strains, which may be linked to neuroplastic and synaptic changes in the frontal cortex and/or hippocampus. Full article

Background/Objectives: Pituitary apoplexy (PA) is a rare medical emergency characterized by the sudden onset of symptoms resulting from hemorrhage and/or infarction within the pituitary gland. Precipitating factors include the use of dopamine agonists (DAs), whose main indication is the treatment of prolactin (PRL)-secreting pituitary neuroendocrine tumors (PitNETs), but which can also be considered in non-functioning PitNETs. Here we report a case of PA in a patient taking cabergoline for a non-functioning PitNET, followed by a review of the literature focusing on the cases of PA associated with the use of DAs. Methods: A review of the literature was performed, searching Pubmed for other clinical cases of PA associated with the use of DAs, from inception to March 2025. Results: We found 43 cases of PA associated with the use of DAs. All the patients had secreting tumors: 86% were classified as PRL-secreting PitNETs, 7% were classified as GH-secreting PitNETs, and 4.6% included a mixed PRL/GH-secreting PitNET and a TSH-secreting PitNET. By contrast, here we present a case of PA in a non-functioning PitNET during cabergoline therapy. Our patient was managed conservatively and endocrine function recovered spontaneously. In our case, cabergoline might have promoted PA, which is consistent with the reported efficacy of cabergoline in inducing tumor shrinkage of non-functioning PitNETs that express dopamine 2 receptors, including silent PIT1 and SF1 or NULL tumors. Conclusions: Our case confirms cabergoline efficacy in non-functioning PitNETs and sheds light on a possible complication of its use. Patients, particularly those with large tumors, should be closely monitored for this occurrence. Full article

Background: Prolactin receptor (PRLR) signaling affects breastfeeding and potentially breast cancer treatment response. Methods: The prognostic impact of 20 PRLR single nucleotide polymorphisms (SNPs) in relation to adjuvant treatment groups in patients with primary breast cancer (n = 1701, 2002–2016, Sweden) was evaluated. Genomic DNA was genotyped on Illumina OncoArray, and survival analyses with up to 15-year follow-up were performed. Interaction models, adjusted for potential confounders, were created with different adjuvant treatment modalities: chemotherapy, radiotherapy, tamoxifen, and aromatase inhibitors. Results: Five SNPs (rs7734558, rs6860397, rs2962101, rs7732013, and rs4703503) showed interactions with radiotherapy and were utilized to create seven combined genotypes: six unique and one ‘rare’. Patients carrying combined genotype AG/GG/TT/CC/TC or ‘rare’ combinations derived greater benefits from radiotherapy than other patient groups (both HR_adj ≤ 0.29, Bonferroni-adjusted P_int ≤ 0.039). Expression Quantitative Trait Loci (eQTL) analysis revealed that three PRLR SNPs were associated with decreased PRLR expression. To explore potential SNP-associated effects, gene expression and transcriptional networks were analyzed in the METABRIC cohort and indicated that PRLR-low tumors were associated with reduced DNA repair signaling and enhanced anti-tumoral immunity. Conclusions: PRLR merits further evaluation as a putative pharmacogenomic biomarker in relation to radiotherapy for breast cancer patients. Full article

Background: Prolactin (PRL) is a key reproductive hormone that regulates follicular development through endocrine and paracrine mechanisms. However, its specific role in porcine follicular development remains unclear. Methods: In the in vivo experiments, follicular fluid and tissue cells were obtained from small (1–2 mm), medium (3–4 mm), and large (5–6 mm) porcine follicles. PRL levels in follicular fluid were measured by ELISA. The expression levels of genes and proteins related to follicular development were assessed using quantitative real-time PCR (RT-qPCR) and Western blotting (WB). In the in vitro experiments, CCK-8, RT-qPCR, and WB were used to detect the effects of different concentrations (0, 30, and 300 ng/mL) of recombinant porcine prolactin (prPRL) on granulosa cell (GC) proliferation, steroid hormone synthesis, and angiogenesis, and transcriptome sequencing was performed. Results: The PRL concentration was significantly higher in large follicles compared to small and medium follicles. During follicular development, expression levels of PRL, PRL receptor (PRLR), proteolytic enzymes (CTSD, MMP2, MMP14, and BMP-1), and angiogenic factors (VEGFA and FGF-2) increased and then decreased. Moreover, prPRL promoted GC proliferation, increased the expression of PCNA and cyclin D1, upregulated steroidogenesis-related genes CYP11A1 and 3β-HSD, and significantly enhanced the expression of key angiogenic factors VEGFA and FGF-2. RNA-seq analysis identified 226 differentially expressed genes (DEGs), which were mainly enriched in signaling pathways such as the Hippo, JAK/STAT, and Rap1 pathways. Conclusions: PRL may regulate porcine follicle development by affecting cell proliferation and angiogenesis in GCs through the Hippo, JAK/STAT and Rap1 signaling pathways. Full article

Prolactin is a polypeptide hormone that plays a critical role in male reproduction. However, the underlying mechanisms of prolactin-regulated testosterone secretion and the roles of lncRNAs in this process remain unclear. We performed a comprehensive analysis of the testicular tissues of cashmere goats with different prolactin levels by means of RNA-sequencing. Then, we constructed a lncRNA–miRNA–mRNA interaction network by integrating previously submitted testicular mRNA sequencing data. We identified a novel lncRNA named lncRWDD3 and investigated its effects on testosterone synthesis in the Leydig cells of cashmere goat. The primary Leydig cells were used to explore the biological function of lncRWDD3/miR-1388-5p/NPY1R in vitro. This study found that 200 ng/mL of prolactin achieved the highest testosterone secretion in Leydig cells. LncRWDD3 or NPY1R overexpression promoted cAMP levels, testosterone secretion, and related gene expression, while lncRWDD3 or NPY1R interference had the opposite effect. It was found that lncRWDD3 acts on miR-1388-5p as a ceRNA, and neuropeptide Y receptor Y1 (NPY1R) was confirmed to be a target of chi-miR-1388-5p. Our research shows that prolactin regulates the testicular function of cashmere goats via the lncRNA–miRNA–mRNA ceRNA network, and lncRWDD3 acts as a ceRNA to activate NPY1R/cAMP signaling via the sponging of miR-1388-5p in order to govern testosterone synthesis in the Leydig cells of cashmere goats. Our results provide insights for future studies on the molecular mechanism of the prolactin regulation of testicular function in goats. Full article

Prolactin is a hormone for which actions on the central nervous system such as neurogenesis and neuroprotection have been described by acting on specific receptors. The presence of prolactin receptors in the brain, including the hippocampus, is well documented; however, it is unknown whether these receptors change with age and whether they are related to sex. For this reason, a study of the expression of prolactin receptors, in the short and long isoforms, in the hippocampus of male and female rats has been carried out by qPCR and in situ hybridization, with a densitometric analysis in the following life stages: prepubertal, postpubertal, young adult, adult, and old. The results revealed the greater expression of the long isoform than of the short isoform in males, but not in females, with significant differences between males and females and in the different life stages studied. With significant differences, the highest expression of both isoforms appeared in male rats in the postpubertal stage, and the lowest expression was observed in adult and old animals. In situ hybridization showed differences in the localization of PRLR mRNA expression in CA1, CA3, and DG depending on the age and sex of the rats. The results obtained suggest that hippocampal aging is related to a decrease in prolactin receptors, which helps to better understand brain aging. Full article

A study was designed to explore the possibility of using herbal supplementation to sustain growth performance during heat stress exposure in Kenguri sheep. This 60-day study was conducted on 24 Kenguri ewes (1–2 years old), randomly assigned to four treatment groups (n = 6 per group) as follows: KC (n = 6; Kenguri Control), KHS (n = 6; Kenguri Heat Stress), KCS (n = 6; Kenguri Control and herbal supplement), and KHSS (n = 6; Kenguri Heat Stress and herbal supplement). The herbal mixture of Ocimum sanctum (Tulsi), Emblica officinalis (Amla), Morinda citrifolia (Noni), Withania somnifera (Ashwagandha), and Phyllostachys edulis (Bamboo) was used in this study. The herbal supplement used in the present study was given to the KCS and KHSS groups’ animals in dry powder form at a dose of 0.8 g/Kg BW/Day. All variables were recorded fortnightly, and gene expression analysis was performed at the end of the experiment. The results indicated that the recorded temperature–humidity index (THI) provided thermal comfort for KC and KCS while inducing extremely severe heat stress to the KHS and KHSS groups. Heat stress did not alter the feed intake, while the herbal supplement during heat stress increased the feed intake from day 30 onwards. Furthermore, heat stress significantly (p < 0.001) increased the water intake, while the herbal supplement did not alter the heat stress-induced water intake. In addition, neither heat stress nor herbal supplements influenced the body weight and allometric measurements studied. Furthermore, heat stress significantly (p < 0.01) decreased the level of plasma tri-iodo-thyronine (T₃) and thyroxin (T₄) and had a non-significant effect on plasma growth hormone (GH), insulin-like growth factor-1 (IGF-1), while the herbal supplements significantly (p < 0.01) increased the levels of all these hormones studied. Likewise, in peripheral blood mononuclear cells (PBMCs) the expression patterns of growth hormone receptor (GHR), Insulin-like growth factor 1 (IGF1) and prolactin receptor (PRLR) were significantly (p < 0.001) downregulated during heat stress (0.25, 0.3, and 0.48-fold change, respectively). However, the herbal supplement significantly (p < 0.01) increased the heat stress-induced reduction in the expression pattern of these three genes (0.65, 0.61, and 0.61-fold change, respectively). Therefore, from this study, it could be concluded that although the herbal supplements did not bring positive changes in body weight and allometric measurements, it still had a beneficial impact on the endocrinology and genes governing growth performance in Kenguri ewes. Thus, the herbal feed additive used in the study shows promise for relieving heat stress in Kenguri ewes. Full article

During pregnancy, the maternal body adapts in several ways to create an optimal environment for embryonic growth. These changes include endocrine and metabolic shifts that can lead to insulin resistance and gestational diabetes mellitus (GDM), impacting both the mother and fetus in the short and long term. Fetal macrosomia, a condition where the fetus is significantly larger than average, is a primary concern associated with GDM. Although the underlying mechanism remains unclear, a pregnancy-induced proinflammatory state, combined with altered glucose homeostasis, plays a critical role. Several cytokines and hormones, such as interleukin 6 (IL-6), insulin growth factor 1 (IGF-1), prolactin (PRL), or progesterone, are essential for fetal growth, the control of the inflammatory response, and the regulation of lipid and carbohydrate metabolism to meet energy demands during pregnancy. However, although the role of these cytokines in metabolism and body growth during adulthood has been extensively studied, their implication in the pathophysiology of GDM and macrosomia is not well understood. Here, we review this pathophysiology and pose the hypothesis that an aberrant response to cytokine receptor activation, particularly involving the suppressor of cytokine signaling 2 (SOCS2), contributes to GDM and fetal macrosomia. This novel perspective suggests an unexplored mechanism by which SOCS2 dysregulation could impact pregnancy outcomes. Full article

Prolactin-releasing peptide (PrRP) has a regulatory role in both acute and chronic stress, suggesting its potential contribution to stress-related disorders such as depression. However, not all individuals with depression respond equally to stressors. We aimed to determine whether the PrRP system could underlie stress coping, an important aspect of depression. The forced swim test was used both as a stressor and as a method to assess coping strategy. Based on immobility time, active coping and passive coping subgroups were identified, and 10 brain regions were studied using qPCR to measure the mRNA expression levels of PrRP and its receptors (specific: GPR10; non-specific: NPFFR2). Passive coping animals spent more time in an immobile posture and exhibited altered mRNA expression levels in the medullary A1 region, the habenula, and the arcuate nucleus than control or active coping rats. Additionally, we identified corticotropin-releasing hormone and vesicular glutamate transporter 2 positive neurons in the A1 medullary region that contained Prrp, suggesting a modulatory role of PrRP in these excitatory neurons involved in stress regulation. Our findings reinforce the hypothesis that PrRP plays a role in stress coping, a process closely linked to depression. However its effect is brain region-specific. Full article

Prolactin (PRL) regulates its own secretion by short-loop feedback to tuberoinfundibular dopaminergic (TIDA) neurons. PRL-induced cellular mechanisms in the regulation of tyrosine hydroxylase (TH) are not completely understood. The objectives were to (1) examine PRL-induced, time-dependent hypothalamic changes in JAK2-STAT5B signaling, TH activity, TH phosphorylation state and Th mRNA levels, and (2) evaluate direct influences of PRLR-STAT5B signaling on Th promoter activity. Ovariectomized rats were administered ovine PRL. JAK2 and STAT5 phosphorylation in the mediobasal hypothalamus peaked at 15 and 30–60 min, respectively. TH Ser40 phosphorylation in the median eminence was increased between 2 and 72 h, correlating with increased dihydroxyphenylalanine (DOPA) accumulation. Th mRNA levels in TIDA neurons were unchanged up to 72 h but elevated by 7 days. PRL did not alter Th promoter activity in CAD cells, and STAT5B did not bind three putative Gamma Interferon Activation Sites (GAS) elements. We conclude that PRL initiates an integrated cascade of cellular mechanisms in TIDA neurons, including JAK2-STAT5B activation, TH Ser40 phosphorylation coupled to increased TH activity, followed by a delayed rise in Th gene expression. PRL-induced changes in Th gene expression are not the result of STAT5-mediated transactivation but likely result from enduring changes in TIDA neuronal activity. Full article

This study designed three sgRNAs (sgRNA139, sgRNA128, and sgRNA109) targeting the prolactin gene receptor (PRLR) in fetal cattle, utilized Cas9 to cleave endogenous DNA, and screened stable cell lines for somatic cell nuclear transfer experiments to investigate the impact of different editing sites on embryonic development. The results showed that sgRNA139 had the highest cleavage efficiency (Fcut = 0.65, Indels = 42.19%), while sgRNA109 had the lowest (Fcut = 0.45, Indels = 35.31%). No significant differences were observed in cell growth status after electroporation (p > 0.05), and the transfection efficiency exceeded 90% after five days of culture. In the evaluation of key embryonic development indicators, sgRNA109 significantly reduced the cleavage rate and blastocyst rate (p < 0.01), whereas sgRNA139 showed no significant effect on the cleavage rate (p > 0.05), but its blastocyst rate was slightly lower than that of the control group (p > 0.05). This study demonstrates that highly specific sgRNAs and stable edited cell lines used as donor cells can significantly regulate the later stages of embryonic development. This study not only provides new experimental evidence for the functional study of the PRLR but also lays an important theoretical foundation for the innovation of molecular breeding technologies in dairy cattle. Full article

Medicinal plants and natural compounds have been considered alternative therapeutic options for counteracting postmenopausal disorders thanks to their different concomitant effects, including antioxidant and anti-inflammatory properties and the regulation of hormone activity. It is important to highlight that the efficacy of medicinal plants and natural compounds increases when used in combination, thus making the development of herbal formulations rational. Therefore, the present study aimed to evaluate the phytochemical and pharmacological properties of an innovative formulation consisting of resveratrol and water extracts from Equisetum arvense, Crateagus curvisepala, Vitex agnus-castus, and Glycine max. The phenolic composition and radical scavenger properties were evaluated using chromatographic and colorimetric (ABTS) methods, whilst the limits of biocompatibility were assessed through allelopathy, the Artemia salina (brine shrimp) lethality test, and Daphnia magna cardiotoxicity assay. The protective effects were evaluated on C2C12 cell lines exposed to the pro-oxidant stimulus, which consisted of hydrogen peroxide. The gene expression of estrogen 1 (ESR1, also known as ERα) and prolactin (PRLR) receptors, interleukin 6 (IL-6), tumor necrosis factor α (TNFα), and receptor activator of nuclear factor kappa-Β ligand (RANKL) was measured. The results of the phytochemical analysis showed that the main phytochemicals were hydroxycinnamic and phenolic acids, in particular coumaric acid (7.53 µg/mL) and rosmarinic acid (6.91 µg/mL), respectively. This could explain the radical scavenger effect observed from the 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. According to the ecotoxicological models’ results, the formulation was revealed to be non-toxic, with a LC₅₀ value > 1 mg/mL. Therefore, a biocompatible concentration range (200–1000 µg/mL) was used in C2C12 cells, where the formulation blunted the hydrogen peroxide-induced upregulation of TNFα, IL-6, RANKL, ESR1, and PRLR. Overall, the results of this study corroborate the use of the formulation for facing the oxidative stress and inflammation, which forms the basis of the osteoclastogenic process. Full article

In our previous study, we found that changes in plasma prolactin (PRL) concentration were significantly associated with heat stress in dairy cows, and that PRL plays an important role in milk performance. Microarray sequencing revealed that thyrotropin releasing hormone (TRH) and prolactin receptor (PRLR), two genes important for PRL expression or function, may affect milk performance, reproduction, and heat stress response in dairy cattle. In this study, we further validated the genetic effects of the three genes in Chinese Holsteins. The potential variants within the three genes were first detected in 70 Chinese Holstein bulls and then screened in 1152 Chinese Holstein cows using the KASP (Kompetitive allele-specific PCR) method. In total, 42 variants were identified. Further, 13 SNPs were retained for KASP genotyping, including 8 in TRH, 3 in PRL, and 2 in PRLR. Using SNP-based association analyses, the multiple significant (p < 0.05) associations of these 13 SNPs with milk performance, reproduction, and heat stress response traits were found in the Holstein population. Furthermore, linkage disequilibrium analysis found a haplotype block in each of the TRH and PRL genes. Haplotype-based association analyses showed that haplotype blocks were also significantly (p < 0.05) associated with milk performance, reproduction, and heat stress response traits. Collectively, our results identified the genetic associations of TRH, PRL, and PRLR with milk performance, reproduction, and heat stress response traits in dairy cows, and found the important roles of SNP g.55888602A/C and g.55885455A/G in TRH in all traits, providing important molecular markers for genetic selection of high-yielding dairy cows. Full article