Prolactin promotes the recruitment of main olfactory bulb cells and enhances the behavioral exploration toward a socio-sexual stimulus in female mice.

Olfactory communication is triggered by pheromones that profoundly influence neuroendocrine responses to drive social interactions. Two principal olfactory systems process pheromones: the main and the vomeronasal or accessory system. Prolactin receptors are expressed in both systems suggesting a participation in the processing of olfactory information. We previously reported that prolactin participates in the sexual and olfactory bulb maturation of females. Therefore, we explored the expression of prolactin receptors within the olfactory bulb during sexual maturation and the direct responses of prolactin upon pheromonal exposure. Additionally, we assessed the behavioral response of adult females exposed to male sawdust after prolactin administration and the consequent activation of main and accessory olfactory bulb and their first central relays, the piriform cortex and the medial amygdala. Last, we investigated the intracellular pathway activated by prolactin within the olfactory bulb. Here, prolactin receptor expression remained constant during all maturation stages within the main olfactory bulb but decreased in adulthood in the accessory olfactory bulb. Behaviorally, females that received prolactin actively explored the male stimulus. An increased cFos activation in the amygdala and in the glomerular cells of the whole olfactory bulb was observed, but an augmented response in the mitral cells was only found within the main olfactory bulb after prolactin administration and the exposure to male stimulus. Interestingly, the ERK pathway was upregulated in the main olfactory bulb after exposure to a male stimulus. Overall, our results suggest that, in female mice, prolactin participates in the processing of chemosignals and behavioral responses by activating the main olfactory system and diminishing the classical vomeronasal response to pheromones.

Prolactin is an Endogenous Antioxidant Factor in Astrocytes That Limits Oxidative Stress-Induced Astrocytic Cell Death via the STAT3/NRF2 Signaling Pathway.

Oxidative stress-induced death of neurons and astrocytes contributes to the pathogenesis of numerous neurodegenerative diseases. While significant progress has been made in identifying neuroprotective molecules against neuronal oxidative damage, little is known about their counterparts for astrocytes. Prolactin (PRL), a hormone known to stimulate astroglial proliferation, viability, and cytokine expression, exhibits antioxidant effects in neurons. However, its role in protecting astrocytes from oxidative stress remains unexplored. Here, we investigated the effect of PRL against hydrogen peroxide (H2O2)-induced oxidative insult in primary cortical astrocyte cultures. Incubation of astrocytes with PRL led to increased enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX), resulting in higher total antioxidant capacity. Concomitantly, PRL prevented H2O2-induced cell death, reactive oxygen species accumulation, and protein and lipid oxidation. The protective effect of PRL upon H2O2-induced cell death can be explained by the activation of both signal transducer and activator of transcription 3 (STAT3) and NFE2 like bZIP transcription factor 2 (NRF2) transduction cascades. We demonstrated that PRL induced nuclear translocation and transcriptional upregulation of Nrf2, concurrently with the transcriptional upregulation of the NRF2-dependent genes heme oxygenase 1, Sod1, Sod2, and Gpx1. Pharmacological blockade of STAT3 suppressed PRL-induced transcriptional upregulation of Nrf2, Sod1 and Gpx1 mRNA, and SOD and GPX activities. Furthermore, genetic ablation of the PRL receptor increased astroglial susceptibility to H2O2-induced cell death and superoxide accumulation, while diminishing their intrinsic antioxidant capacity. Overall, these findings unveil PRL as a potent antioxidant hormone that protects astrocytes from oxidative insult, which may contribute to brain neuroprotection.

Effect of Hyperprolactinemia on Bone Metabolism: Focusing on Osteopenia/Osteoporosis.

Prolactin is a hormone secreted from lactotroph cells in the anterior pituitary gland to induce lactation after birth. Hyperprolactinemia unrelated to lactation is a common cause of amenorrhea in women of a childbearing age, and a consequent decrease in the gonadotropin-releasing hormone (GnRH) by a high prolactin level can result in decreased bone mineral density. Osteoporosis is a common skeletal disorder characterized by decreased bone mineral density (BMD) and quality, which results in decreased bone strength. In patients with hyperprolactinemia, changes in BMD can be induced indirectly by the inhibition of the GnRH-gonadal axis due to increased prolactin levels or by the direct action of prolactin on osteoblasts and, possibly, osteoclast cells. This review highlights the recent work on bone remodeling and discusses our knowledge of how prolactin modulates these interactions, with a brief literature review on the relationship between prolactin and bone metabolism and suggestions for new possibilities.

Post-warming culture of human vitrified blastocysts with prolactin improves trophoblast outgrowth.

BACKGROUND: Human embryos express the prolactin (PRL) receptor at the morula and blastocyst stages. Treatment with PRL from cleavage to the blastocyst stage improves blastocyst outgrowth on fibronectin-coated dishes. However, whether post-warming PRL treatment of blastocysts cultured without PRL could improve outgrowth competence remains unknown. Furthermore, the optimal time for post-warming PRL treatment remains to be ascertained. This study investigated the effects of PRL treatment during recovery culture on human blastocyst outgrowth and its related genes. METHODS: In total, 374 discarded vitrified blastocysts were randomly allocated to two groups, to be cultured with (n = 208) or without PRL (control; n = 166) for 120 min for recovery, and then plated on fibronectin-coated dishes. The expression level of PRL-interacting genes, blastocyst adhesion rate, outgrowth area, distance of trophoblast migration, and outgrowth degeneration were examined. RESULTS: The mRNA expression of ezrin, radixin, and moesin, which regulate cell adhesion and invasion by controlling actin reorganization during epithelial-to-mesenchymal transition (EMT), was stimulated by PRL treatment for 120 min. The expression of EMT-related genes, transforming growth factor ß1, snail1, and twist1 was also promoted following treatment with PRL for 120 min. PRL-treated blastocysts also exhibited augmented expression of cadherin 2 and transcriptional repression of cadherin 1. Higher mRNA expression of integrin-based focal adhesion-related genes, ITGA5 and ITGB1, was observed after treatment with PRL for 120 min than in the non- and shorter-treatment groups. PRL treatment for 120 min did not alter the rate of blastocyst adhesion to fibronectin-coated dishes 96 h after the outgrowth culture assay. However, multiple linear regression analysis revealed that the outgrowth area was significantly increased in PRL-treated blastocysts. The migration distance of trophoblast cells was significantly increased and degeneration rate was significantly decreased after PRL treatment. Furthermore, a more beneficial effect of PRL treatment on blastocyst outgrowth was observed when the blastocysts were vitrified on day 5 than when they were vitrified on day 6. CONCLUSIONS: Post-warming culture of human vitrified blastocysts with PRL for 120 min promoted trophoblast outgrowth in vitrified human blastocysts. Furthermore, PRL treatment may reduce outgrowth degeneration by increasing resistance to apoptosis during trophoblast migration.

Prolactin regulates RANKL expression via signal transducer and activator of transcription 5a signaling in mammary epithelial cells of dairy cows.

Receptor of activated nuclear factor kappa B ligand (RANKL) is regulated by prolactin in the mammary gland. However, the intrinsic molecular mechanism is not well understood. Herein, mammary epithelial cells (MECs) of dairy cows were isolated to characterize the molecular mechanism of prolactin in vitro. We demonstrated that prolactin stimulation increased the expression of RANKL in MECs. Moreover, the expression of RANKL induced by prolactin was inhibited by the prolactin receptor or signal transducer and activator of transcription 5A (STAT5a) knockdown. Furthermore, prolactin markedly increased RANKL-Luciferase reporter activity in MECs. We identified a putative gamma-interferon activated site (GAS) in the region between residues -883 to -239 bp of the RANKL promoter. Subsequently, we found that the mutated GAS sequence failed to respond to prolactin stimulation. In addition, STAT5a knockdown markedly decreased prolactin-stimulated RANKL promoter activity. Western blot results revealed that RANKL overexpression markedly decreased the STAT5a phosphorylation level in MECs. These findings indicate that prolactin could regulate RANKL promoter activity via STAT5a, contributing to increased RANKL expression in MECs. RANKL may have a negative regulatory effect on STAT5a activity.

Comparison of the Effects of Recombinant and Native Prolactin on the Proliferation and Apoptosis of Goose Granulosa Cells.

In poultry, prolactin (PRL) plays a key role in the regulation of incubation behavior, hormone secretion, and reproductive activities. However, previous in vitro studies have focused on the actions of PRL in ovarian follicles of poultry, relying on the use of exogenous or recombinant PRL, and the true role of PRL in regulating ovarian granulosa cell (GC) functions in poultry awaits a further investigation using endogenous native PRL. Therefore, in this study, we first isolated and purified recombinant goose PRL protein (rPRL) and native goose PRL protein (nPRL) using Ni-affinity chromatography and rabbit anti-rPRL antibodies-filled immunoaffinity chromatography, respectively. Then, we analyzed and compared the effects of rPRL and nPRL at different concentrations (0, 3, 30, or 300 ng/mL) on the proliferation and apoptosis of both GCs isolated from goose ovarian pre-hierarchical follicles (phGCs) and from hierarchical follicles (hGCs). Our results show that rPRL at lower concentrations increased the viability and proliferation of both phGCs and hGCs, while it exerted anti-apoptotic effects in phGCs by upregulating the expression of Bcl-2. On the other hand, nPRL increased the apoptosis of phGCs in a concentration-dependent manner by upregulating the expressions of caspase-3 and Fas and downregulating the expressions of Bcl-2 and Becn-1. In conclusion, this study not only obtained a highly pure nPRL for the first time, but also suggested a dual role of PRL in regulating the proliferation and apoptosis of goose GCs, depending on its concentration and the stage of follicle development. The data presented here can be helpful in purifying native proteins of poultry and enabling a better understanding of the roles of PRL during the ovarian follicle development in poultry.

High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by L-PRLR and S-PRLR.

High prolactin (PRL) concentration has been shown to induce the apoptosis of ovine ovarian granulosa cells (GCs), but the underlying mechanisms are unclear. This study aimed to investigate the mechanism of apoptosis induced by high PRL concentration in GCs. Trial 1: The optimal concentration of glutathion was determined according to the detected cell proliferation. The results showed that the optimal glutathione concentration was 5 µmol/mL. Trial 2: 500 ng/mL PRL was chosen as the high PRL concentration. The GCs were treated with 0 ng/mL PRL (C group), 500 ng/mL PRL (P group) or 500 ng/mL PRL, and 5 µmol/mL glutathione (P-GSH group). The results indicated that the mitochondrial respiratory chain complex (MRCC) I-V, ATP production, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and thioredoxin peroxidase (TPx) in the C group were higher than those in the P group (p < 0.05), while they were lower than those in the P-GSH group (p < 0.05). Compared to the C group, the P group exhibited elevated levels of reactive oxygen species (ROS) and apoptosis (p < 0.05) and increased expression of ATG7 and ATG5 (p < 0.05). However, MRCC I-V, ATP, SOD, A-TOC, TPx, ROS, and apoptosis were decreased after the addition of glutathione (p < 0.05). The knockdown of either L-PRLR or S-PRLR in P group GCs resulted in a significant reduction (p < 0.05) in MRCC I-V, ATP, T-AOC, SOD and TPx, while the overexpression of either receptor showed an opposite trend (p < 0.05). Our findings suggest that high PRL concentrations induce apoptotic cell death in ovine ovarian GCs by downregulating L-PRLR and S-PRLR, activating oxidative stress and autophagic pathways.

Prolactin-Induced Protein facilitates corneal wound healing.

The purpose of the study was to investigate the role of Prolactin-Induced Protein (PIP) in corneal wound healing, in vivo and in vitro. In C57BL/6J mice, corneal epithelia was removed using an ocular burr. Phosphate buffered saline (PBS) or PIP (0.5 and 1.0 µg/mL) was applied topically or subconjunctivally injected. PIP accelerated wound closure as early as 24 h. PIP treatment promoted corneal wound healing and epithelial integrity and thickness. Integrin α6, integrin ß4, Thrombospondin-1, and TGF-ß1 expressions were all downregulated by PIP after wound closure. In vitro, scratch assays were performed using primary human epithelial cells (HCECs) and human corneal fibroblasts (HCFs), stimulated with PIP at various dosages. PIP treatment promoted both HCECs and HCFs migration. PIP upregulated expression of integrin α6, integrin ß4, and Thrombospondin-1 in HCECs. Expression of TGF-ß1 in HCECs and expression of smooth muscle actin (SMA) and Type III Collagen (Col III) in HCFs were significantly downregulated at 150 ng/mL PIP. PIP exhibits noteworthy anti-fibrotic potentiality. While the mechanism of how PIP is impactful on the corneal wound healing cascade is unknown, our findings are novel and further studies are warranted in order to unravel any therapeutic potential.

Sex-dependent pain trajectories induced by prolactin require an inflammatory response for pain resolution.

Pain development and resolution patterns in many diseases are sex-dependent. This study aimed to develop pain models with sex-dependent resolution trajectories, and identify factors linked to resolution of pain in females and males. Using different intra-plantar (i.pl.) treatment protocols with prolactin (PRL), we established models with distinct, sex-dependent patterns for development and resolution of pain. An acute PRL-evoked pain trajectory, in which hypersensitivity is fully resolved within 1 day, showed substantial transcriptional changes after pain-resolution in female and male hindpaws and in the dorsal root ganglia (DRG). This finding supports the notion that pain resolution is an active process. Prolonged treatment with PRL high dose (1 µg) evoked mechanical hypersensitivity that resolved within 5-7 days in mice of both sexes and exhibited a pro-inflammatory transcriptional response in the hindpaw, but not DRG, at the time point preceding resolution. Flow cytometry analysis linked pro-inflammatory responses in female hindpaws to macrophages/monocytes, especially CD11b+/CD64+/MHCII+ cell accumulation. Prolonged low dose PRL (0.1 µg) treatment caused non-resolving mechanical hypersensitivity only in females. This effect was independent of sensory neuronal PRLR and was associated with a lack of immune response in the hindpaw, although many genes underlying tissue damage were affected. We conclude that different i.pl. PRL treatment protocols generates distinct, sex-specific pain hypersensitivity resolution patterns. PRL-induced pain resolution is preceded by a pro-inflammatory macrophage/monocyte-associated response in the hindpaws of mice of both sexes. On the other hand, the absence of a peripheral inflammatory response creates a permissive condition for PRL-induced pain persistency in females.

Prolactin promotes parental responses and alters reproductive axis gene expression, but not courtship behaviors, in both sexes of a biparental bird.

Prolactin, a hormone involved in vertebrate parental care, is hypothesized to inhibit reproductive hypothalamic-pituitary-gonadal (HPG) axis activity during parenting, thus maintaining investment in the current brood as opposed to new reproductive efforts. While prolactin underlies many parental behaviors in birds, its effects on other reproductive behaviors, such as courtship, remain unstudied. How prolactin affects neuropeptide and hormone receptor expression across the avian HPG axis also remains unknown. To address these questions, we administered ovine prolactin (oPRL) or a vehicle control to both sexes in experienced pairs of the biparental rock dove (Columba livia), after nest removal at the end of incubation. We found that oPRL promoted parental responses to novel chicks and stimulated crop growth compared to controls, consistent with other studies. However, we found that neither courtship behaviors, copulation rates nor pair maintenance differed with oPRL treatment. Across the HPG, we found oPRL had little effect on gene expression in hypothalamic nuclei, but increased expression of FSHB and hypothalamic hormone receptor genes in the pituitary. In the gonads, oPRL increased testes size and gonadotropin receptor expression, but did not affect ovarian state or small white follicle gene expression. However, the oviducts of oPRL-treated females were smaller and had lower estrogen receptor expression compared with controls. Our results highlight that some species, especially those that show multiple brooding, may continue to express mating behavior despite elevated prolactin. Thus, mechanisms may exist for prolactin to promote investment in parental care without concurrent inhibition of reproductive function or HPG axis activity.

The crucial role of prolactin-lactogenic hormone in Covid-19.

Prolactin (PRL) is a peptide hormone secreted from anterior pituitary involved in milk production in the females and regulation of sex drive in both sexes. PRL has pro-inflammatory and anti-inflammatory functions. High PRL serum level or hyperprolactinemia is associated with different viral infections. In coronavirus disease 2019 (Covid-19), which caused by positive-sense single-strand RNA virus known as severe acute respiratory distress syndrome coronavirus type 2 (SARS-CoV-2), PRL serum level is increased. PRL in Covid-19 may exacerbate the underlying inflammatory status by induction release of pro-inflammatory cytokines. However, PRL through its anti-inflammatory effects may reduce the hyperinflammatory status in Covid-19. The underlying mechanism of increasing PRL in Covid-19 is poorly understood. Therefore, in this review we try to find the potential anti-inflammatory or pro-inflammatory role of PRL in Covid-19. As well, this review was aimed to discuss the underlying causes and mechanisms for Covid-19-induced hyperprolactinemia.

Prolactin Reduces Hippocampal Parvalbumin and GABAA Receptor Expression in Female Mice.

INTRODUCTION: Parvalbumin (PV)-positive cells are strategic elements of neuronal networks capable of influencing memory and learning processes. However, it is not known whether pituitary hormones may be related to PV expression in the hippocampus - a part of the limbic system with important functions in learning and memory. OBJECTIVE: Since previous studies indicate that prolactin (PRL) plays a significant role in hippocampal-dependent learning and synaptic plasticity, we hypothesized that a rise in PRL levels can modify PV expression in the hippocampus. METHODS: We employed biochemical, immunohistochemistry, and densitometry techniques - as well as a behavioural assay - in a hyperprolactinemia model using subcutaneous osmotic pumps in female mice. RESULTS: PRL treatment via osmotic pump induced an increase in PRL receptor (PRLR) expression in most regions of the hippocampus analysed by Western blotting and immunohistochemistry methods. Fluorescent densitometry analysis revealed that PV expression decreases in the same layers in the hippocampus following PRL treatment, while double labelling immunostaining indicated close localization of PV and PRLR in PV-positive interneurons. In addition, we found that PRL induced a reduction in the ß2/3 subunit of GABAA receptor (GABAAR) expression that was linearly correlated with the reduction in PV expression. This reduction in the ß2/3 subunit of GABAAR expression was maintained in trained animals in which PRL treatment improved the learning of a spatial memory task. CONCLUSIONS: These data show, for the first time, that an increase in PRL level is associated with changes in key constituent elements of inhibitory circuits in the hippocampus and may be of relevance for the alterations in cognitive function reported in hyperprolactinemia.

Prior parental experience attenuates hormonal stress responses and alters hippocampal glucocorticoid receptors in biparental rock doves.

In the face of challenges, animals must balance investments in reproductive effort versus their own survival. Physiologically, this trade-off may be mediated by glucocorticoid release by the hypothalamic-pituitary-adrenal axis and prolactin release from the pituitary to maintain parental care. The degree to which animals react to and recover from stressors likely affects maintenance of parental behavior and, ultimately, fitness. However, less is known about how gaining parental experience may alter hormonal stress responses and their underlying neuroendocrine mechanisms. To address this gap, we measured the corticosterone (CORT) and prolactin (PRL) stress response in individuals of both sexes of the biparental rock dove (Columba livia) that had never raised chicks versus birds that had fledged at least one chick. We measured both CORT and PRL at baseline and after an acute stressor (30 min restraint). We also measured negative feedback ability by administering dexamethasone, a synthetic glucocorticoid that suppresses CORT release, and measured CORT and PRL after 60 min. All hormones were measured when birds were not actively nesting to assess whether effects of parental experience extend beyond the breeding bout. Experienced birds had lower stress-induced and negative-feedback CORT, and higher stress-induced PRL than inexperienced birds. In a separate experiment, we measured glucocorticoid receptor subtype expression in the hippocampus, a key site of negative feedback regulation. Experienced birds showed higher glucocorticoid receptor expression than inexperienced controls, which may mediate their ability to attenuate CORT release. Together, these results shed light on potential mechanisms by which gaining experience may improve parental performance and fitness.

Associations among the TREM-1 Pathway, Tau Hyperphosphorylation, Prolactin Expression, and Metformin in Diabetes Mice.

INTRODUCTION: Diabetes mellitus (DM) is a risk factor for Alzheimer's disease (AD). Increasing evidence indicates that the triggering receptor expressed on myeloid cells (TREM)-1 amplifies chronic inflammation, as well as the roles of prolactin (PRL) and metformin (MET) in tau hyperphosphorylation. However, the associations among TREM-1, tau hyperphosphorylation, PRL expression, and MET in DM remain unclear. METHODS: Streptozotocin was used to induce experimental DM in C57BL/6N mice. MET was orally administered at a dose of 400 mg/kg body weight for 6 weeks prior to hippocampal collection in DM mice. Various parameters pertaining to the TREM-1 pathway, tau hyperphosphorylation, PRL, and related factors were analyzed. RESULTS: Quantitative polymerase chain reaction and Western blot analysis demonstrated that the expression levels of TREM-1, DAP12, casp1, interleukin-1ß, Cox2, inducible nitric oxide synthase, pituitary transcriptional factor-1 (Pit-1), and PRL were significantly increased in the hippocampus of DM mice; the expression levels of these pro-inflammatory mediators, PRL receptor (PRLR) short or long (PRLR-S and PRLR-L), and PRL regulatory element-binding (Preb) protein in DM mice treated with MET (DM + MET) were significantly decreased compared with those in control (CON) mice. The levels of p-Tau and glycogen synthase kinase-3 in the DM group were significantly higher than those in the CON group and significantly lower than those in the DM + MET group. CONCLUSION: We confirmed the therapeutic potential of MET for both DM and neurodegeneration. Our findings shed new light on the effects of DM on the pathophysiology of AD via the TREM-1 pathway and PRL expression. Thus, an improved understanding of the TREM-1 pathway in hyperglycemic conditions, as well as PRL, Preb, Pit-1, PRLR-L, and PRLR-S gene expression in the liver, brain, and other sites, may help unravel the pathogenesis of insulin resistance and neurodegeneration.

Prolactin Protects the Structural Integrity of Human Fetal Membranes by Downregulating Inflammation-induced Secretion of Matrix Metalloproteinases.

Prolactin (PRL) is a pleiotropic hormone with a key role in pregnancy. In fetal membranes, PRL can regulate the secretion of pro-inflammatory factors, which induces the activation of matrix metalloproteinases (MMPs). The increase and activation of MMPs deregulate the turnover of the extracellular matrix in the fetal membranes, altering its structure and function, causing premature rupture of the membranes and preterm labor. In this work, we evaluate the effect of PRL upon the secretion of MMP-1, MMP-2, MMP-9, MMP-13, and the tissue inhibitors of metalloproteinases (TIMPs) in human fetal membranes after lipopolysaccharide (LPS) challenge. Nine fetal membranes from healthy non-laboring cesarean deliveries at term were cultured in a 2-independent chamber system and pre-treated with 250, 500, 1000 or 4000 ng/ml of PRL for 24 h, then choriodecidual region was stimulated with 500 ng/ml of LPS plus fresh PRL for 24 h. The MMPs and TIMPs secretion were quantified by ELISA, additionally MMP-2 and MMP-9 gelatinolytic activity was measured by zymography. LPS induced the MMP-9 and MMP-1 secretion, but no MMP-2 or MMP-13 in comparison with basal levels. PRL co-treatment decreased the MMP-2, MMP-9 and MMP-1 secretion induced by LPS. The active forms were present in the tissue extract, showing a response consistent with the secretion profile. TIMP-1 and TIMP-2 secretion was decreased after LPS treatment and the PRL co-treatment reverts this effect. The present results support that PRL may favor the balance between these factors involved in the structural maintenance of fetal membranes in an inflammatory event.

Expression of Opsin Genes in the Retina of Female and Male Three-Spined Sticklebacks Gasterosteus aculeatus L.: Effect of Freshwater Adaptation and Prolactin Administration.

Color vision sensitivity is crucial for fish adaptation during migration and reproduction. Prolactin and prolactin-like hormone are important regulators in both these processes. We hypothesized that prolactin influences the color vision sensitivity during freshwater migrations in fish. We studied the effects of prolactin and freshwater adaptation during the spawning period on the expression of opsin genes (SWS1, SWS2, RH2, LWS) in the retina of female and male three-spined sticklebacks Gasterosteus aculeatus L. Expression of the prolactin gene increased in the brain of females, but not males, while expression of the prolactin-like hormone decreased in the brain of both male and female sticklebacks during freshwater adaptation. Expression of the SWS2 gene decreased in the retina of females and males during freshwater adaptation and after prolactin administration. Expression of the SWS1 gene decreased in the retina of male sticklebacks after prolactin administration, but not during freshwater adaptation. Expression of the RH2 and LWS genes did not depend on prolactin administration in male and female sticklebacks. We conclude that expression of some opsin genes in the retina of sticklebacks is regulated by prolactin and depends on sex and freshwater adaptation. This expands our knowledge of the adaptive effects of prolactin on fish during freshwater migrations.

Phospho-Tudor-SN coordinates with STAT5 to regulate prolactin-stimulated milk protein synthesis and proliferation of bovine mammary epithelial cells.

Tudor staphylococcal nuclease (Tudor-SN) participates in milk synthesis and cell proliferation in response to prolactin (PRL) and plays a regulatory role on mTOR phosphorylation. However, the complicated molecular mechanism of Tudor-SN regulating milk protein synthesis and cell proliferation still remains to be illustrated. In present study, we observed that the proteins level of phosphorylated Tudor-SN and phosphorylated STAT5 were simultaneously enhanced upon PRL treatment in bovine mammary epithelial cells (BMECs). Tudor-SN overexpression and knockdown experiment showed that Tudor-SN positively regulated the synthesis of milk protein, cell proliferation and the phosphorylation of STAT5, which was dependent on Tudor-SN phosphorylation. STAT5 knockdown experiment showed that Tudor-SN stimulated mTOR pathway through regulating STAT5 activation, which was required for PRL to activate the mTOR pathway. Thus, these results demonstrate the primary mechanism of Tudor-SN coordinating with STAT5 to regulate milk protein synthesis and cell proliferation under stimulation of PRL in BMECs, which may provide some new perspectives for increasing milk production.

Maternal prolactin levels during late pregnancy and nurturing behavior of offspring in mice.

Elucidating the mechanisms underlying nurturing and neglect behaviors is meaningful but challenging. Recently, we found that CIN85-deficient mice had reduced pituitary hormone prolactin secretion during late pregnancy, and their pups later showed an inhibited nurturing behavior. To examine whether this phenomenon could be reproduced in normal mice and not just CIN85-deficient mice, we investigated the nurturing behavior of offspring born to mothers whose blood prolactin levels had been reduced by bromocriptine administration during late pregnancy. First, to determine when bromocriptine treatment should be started, we investigated the detailed changes in blood prolactin levels in late pregnancy in mice, resulting in the identification of the prepartum prolactin surge. Furthermore, prolactin receptors in the fetal hypothalamus were expressed to the same extent as in the adult hypothalamus. Treatment with bromocriptine decreased the plasma concentrations of prolactin to the basal range throughout late pregnancy. However, against expectations, the proportion of the resultant pups exhibiting nurturing behaviors as adults was as high as that in the mice without bromocriptine treatment. In conclusion, the elimination of prolactin secretion during late pregnancy alone does not induce neglect-like behavior in offspring, suggesting that CIN85-deficient mice appear to involve another factor due to CIN85 deficiency besides prolactin deficiency.

Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation.

In most tissues, the prevailing view is that stem cell (SC) niches are generated by signals from within the nearby tissue environment. Here, we define genetic changes altered in hair follicle (HF) SCs in mice treated with a potent SC activator, cyclosporine A (CSA), which inhibits the phosphatase calcineurin (CN) and the activity of the transcription factor nuclear factor of activated T cells c1 (Nfatc1). We show that CN/Nfatc1 regulates expression of prolactin receptor (Prlr) and that canonical activation of Prlr and its downstream signaling via Jak/Stat5 drives quiescence of HF SCs during pregnancy and lactation, when serum prolactin (Prl) levels are highly elevated. Using Prl injections and genetic/pharmacological loss-of-function experiments in mice, we show that Prl signaling stalls follicular SC activation through its activity in the skin epithelium. Our findings define a unique CN-Nfatc1-Prlr-Stat5 molecular circuitry that promotes persistent SC quiescence in the skin.

Effect of Copper on the Function of Isolated Porcine Kidneys Stored Using Simple Hypothermia.

Renal ischemia in the peri-transplant period causes a number of changes that adversely affect the initiation of normal vital functions in grafts after transplantation. To minimise the extent of ischemic damage, organs are stored in preservation fluid. The components of the fluid are supposed to ensure stabilisation of the cell cytoskeleton, protect against oxygen free radicals, reduce cell swelling, and ensure endothelial cell integrity. The aim of this study was to analyse the protective effect of Cu2+, as a component of Biolasol preservative fluid, in the prevention of nephron damage occurring during the graft storage period. Analyses of the effectiveness of copper in the presence of prolactin added to Biolasol fluid were also carried out. Forty isolated pig slaughter kidneys were used in the study, avoiding the use of laboratory animals. The kidneys were stored using simple hypothermia. After 2 h and 48 h of graft storage, selected biochemical indicators of renal function were determined in the collected perfusates. The addition of Cu2+ at a dose of 1 µg/L to the composition of Biolasol fluid was found to affect the generation of ischemic damage in the isolated pig kidney. The intensity of the occurrence of these processes is exacerbated by the presence of prolactin at a dose of 0.1 µg/L.