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Theriogenology Jul 2023Physiological mechanisms of seasonal changes in testicular function in birds are not fully elucidated. The balance between androgens and estrogens and testis sensitivity...
Physiological mechanisms of seasonal changes in testicular function in birds are not fully elucidated. The balance between androgens and estrogens and testis sensitivity for gonadotropin and gonadal steroids are still unclear. The aim of the study was to examine: (1) the changes in circulating and intra-testicular steroid hormone levels and their relationship; (2) the mRNA expression of testicular gonadotropin, prolactin (PRL), progesterone (P4), androgen, and estrogen receptors, and (3) key steroidogenesis processes-related genes with immunofluorescent localization of aromatase in gander testes during the annual period. Testes from ganders (n = 25) in the first reproduction season were obtained at five breeding stages, i.e., prebreeding (PrB), peak of reproduction (PR), postbreeding (PoB), nonbreeding (NB), and onset of reproduction (OR). Males were kept under breeding conditions. It was found that plasma P4 levels decreased at the PoB and NB stages, whereas intra-testicular P4 was the highest in the NB stage. Intra-testicular estradiol (E2) levels were higher at the PoB and NB stages than the other stages, whereas testosterone (T) levels showed a nearly opposite pattern. The plasma estradiol-to-testosterone ratios were higher at the PrB, PoB and NB stages compared to other stages. The transcript abundances for luteinizing hormone receptor (LHR), PRL receptor (PRLR), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ) also change in testicular tissue during the annual period. Moreover, StAR mRNA expression was upregulated at the PoB and NB stages, and CYP11A1 transcript level was the highest at the PoB stage. Stage-dependent changes in the CYP19A1 mRNA and aromatase protein levels with higher abundances of transcript at PoB and NB stages and protein at the NB stage were observed. Localization and immunofluorescent signal intensity for aromatase also differed in relation to the examined stages. It may be suggested that differential E2 levels, as well as aromatase expression and localization across annual stages are responsible for the seasonal activation/inactivation stages of testis spermatogenesis in domestic ganders. These data strongly suggest a role of aromatase in the control of gander steroidogenesis as changes in this enzyme level are associated with alternation in gonadal steroid hormones. In addition, joint action with others hormones, like PRL and LH, seems to be important in the final effect of seasonal reproduction potential.
Topics: Animals; Male; Androgens; Aromatase; Estradiol; Gene Expression; Gonadal Steroid Hormones; Prolactin; Receptors, Estrogen; RNA, Messenger; Testis; Testosterone; Gonadotropins; Steroids; Geese
PubMed: 37105092
DOI: 10.1016/j.theriogenology.2023.04.019 -
Archivos Espanoles de Urologia May 2021Prolactin (PRL) binds its receptor (PRLR) and stimulates cell proliferation, differentiation and survival in prostate cancer (PCa) cell lines via STAT5a, MAPK and AKT.
INTRODUCTION
Prolactin (PRL) binds its receptor (PRLR) and stimulates cell proliferation, differentiation and survival in prostate cancer (PCa) cell lines via STAT5a, MAPK and AKT.
OBJECTIVE
To evaluate the expression of PRL and PRLR in normal and tumor prostate tissues with different Gleason patterns.
METHODS
Samples of normal, benign prostatic hyperplasia and PCa with different Gleason patterns were selected from radical prostatectomy. The intensity, location and percentage of stained cells for PRL and PRLR were evaluated by Immunohistochemistry. Co-localization was observed by confocal microscopy.
RESULTS
PRL was expressed diffusely and with a mild intensity in the cytoplasm of normal and tumor prostate luminal cells. Its expression only augmented in the Gleason 3 pattern (p< 0.0001). The immunostaining intensity and the percentage of positive cells for PRLR did not vary between normal and tumor tissues. However, the location of the PRLR was modified by the tumorigenic process.In non-tumor tissues, PRLR expression was mostly in plasma membrane in the apical zone of epithelial cells. In tumor tissues, it was expressed in intracellular vesicles.The co-localization of PRL and PRLR was demonstrated in normal and tumor tissues suggesting that PRL could be acting in an autocrine and paracrine manner.
CONCLUSION
PRL and its receptor were present in the cytoplasm of the epithelial cells of the normal and tumor prostate gland. In tumor tissues, the change in the location and appearance of cryptic PRLRs that store PRL may keep active the different signaling pathways related to cell proliferation and survival.
Topics: Humans; Male; Prolactin; Prostatic Neoplasms; Receptors, Prolactin; Signal Transduction
PubMed: 33942735
DOI: No ID Found -
Journal of Investigative Medicine : the... Oct 2022The prolactin hormone (PRL) is often secreted by lactotrophic cells of the anterior pituitary and has been shown to play a role in various biological processes,... (Review)
Review
The prolactin hormone (PRL) is often secreted by lactotrophic cells of the anterior pituitary and has been shown to play a role in various biological processes, including breast feeding and reproduction. The predominant form of this hormone is the 23 kDa form and acts through its receptor (PRLR) on the cell membrane. This receptor is a member of the superfamily of hematopoietic/cytokine receptors. PRL also has a 16 kDa subunit with anti-angiogenic, proapoptotic, and anti-inflammatory effects which is produced by the proteolytic breakdown of this hormone under oxidative stress. Although the common side effects of hyperprolactinemia are exerted on the reproductive system, new studies have shown that hyperprolactinemia has a wide variety of effects, including playing a role in the development of autoimmune diseases and increasing the risk of cardiovascular disease, peripartum cardiomyopathy, and diabetes among others. The range of PRL functions is increasing with the discovery of multiple sites of PRL secretion as well as PRLR expression in various tissues. This review summarizes current knowledge of the biology of PRL and its receptor, as well as the role of PRL in human pathophysiology.
Topics: Anti-Inflammatory Agents; Humans; Hyperprolactinemia; Prolactin; Receptors, Cytokine; Receptors, Prolactin; Signal Transduction
PubMed: 35768141
DOI: 10.1136/jim-2022-002351 -
Journal of Neuroendocrinology Mar 2019Our understanding of the neural actions of prolactin (PRL) and its biochemical basis has expanded greatly over the past three decades. During this time, major progress... (Review)
Review
Our understanding of the neural actions of prolactin (PRL) and its biochemical basis has expanded greatly over the past three decades. During this time, major progress has been made, including clarification of how PRL accesses the brain, identification of the PRL receptor and the sites where it is expressed within the brain, determination of the neurochemical mechanism of action of PRL and its effect on genomic expression in neurones, identification of the neural sites where PRL acts to stimulate maternal behaviour and related affective states, and exploration of how life experiences impact neural PRL receptor activity and actions. The next 30 years promise to reveal a myriad of basic and clinical findings regarding new roles for PRL and a greater indepth understanding of how and where PRL affects physiological and behavioural processes.
Topics: Animals; Brain; Gene Expression; History, 20th Century; History, 21st Century; Humans; Maternal Behavior; Neuroendocrinology; Neurosecretory Systems; Prolactin; Receptors, Prolactin
PubMed: 30549349
DOI: 10.1111/jne.12669 -
Renal Failure 2023Astragalus polysaccharide (APS) is a major bioactive component of the Chinese herb astragalus, with well-established protective effects on the kidney. However, the...
BACKGROUND
Astragalus polysaccharide (APS) is a major bioactive component of the Chinese herb astragalus, with well-established protective effects on the kidney. However, the effect of APS on diabetic nephropathy (DN) is unclear.
METHODS
Long non-coding RNA (lncRNA) expression profiles in kidney samples from control, db/db, and APS-treated db/db mice were evaluated using RNA high-throughput sequencing techniques. Additionally, rat renal tubular epithelial (NRK-52E) cells were cultured in high glucose (HG) media. We inhibited the expression of Gm41268 and prolactin receptor (PRLR) by transfecting NRK-52E cells with Gm41268-targeting antisense oligonucleotides and PRLR siRNA.
RESULTS
We found that APS treatment reduced 24-h urinary protein levels and fasting blood glucose and improved glucose intolerance and pathological renal damage in db/db mice. Furthermore, APS treatment enhanced autophagy and alleviated fibrosis in the db/db mice. We identified a novel lncRNA, Gm41268, which was differentially expressed in the three groups, and the cis-regulatory target gene PRLR. APS treatment induced autophagy by reducing p62 and p-mammalian target of rapamycin (mTOR) protein levels and increasing the LC3 II/I ratio. Furthermore, APS alleviated fibrosis by downregulating fibronectin (FN), transforming growth factor-β (TGF-β), and collagen IV levels. In addition, APS reversed the HG-induced overexpression of Gm41268 and PRLR. Reduction of Gm41268 decreased PRLR expression, restored autophagy, and ameliorated renal fibrosis . Inhibition of PRLR could enhance the protective effect of APS.
CONCLUSIONS
In summary, we demonstrated that the therapeutic effect of APS on DN is mediated via the Gm41268/PRLR pathway. This information contributes to the exploration of bioactive constituents in Chinese herbs as potential treatments for DN.
Topics: Mice; Rats; Animals; Diabetic Nephropathies; RNA, Long Noncoding; Receptors, Prolactin; Autophagy; Polysaccharides; Fibrosis; Mammals; Diabetes Mellitus
PubMed: 37994436
DOI: 10.1080/0886022X.2023.2284211 -
Neuroendocrinology 2022Parvalbumin (PV)-positive cells are strategic elements of neuronal networks capable of influencing memory and learning processes. However, it is not known whether...
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 β2/3 subunit of GABAA receptor (GABAAR) expression that was linearly correlated with the reduction in PV expression. This reduction in the β2/3 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.
Topics: Animals; Female; Hippocampus; Hyperprolactinemia; Mice; Parvalbumins; Prolactin; Receptors, GABA-A; Receptors, Prolactin
PubMed: 34666336
DOI: 10.1159/000520279 -
Journal of Neuroendocrinology Nov 2020In addition to its critical role in lactation, the anterior pituitary hormone prolactin also influences a broad range of other physiological processes. In particular,...
In addition to its critical role in lactation, the anterior pituitary hormone prolactin also influences a broad range of other physiological processes. In particular, widespread expression of prolactin receptor (Prlr) in the brain has highlighted pleiotropic roles for prolactin in regulating neuronal function, including maternal behaviour, reproduction and energy balance. Research into the central actions of prolactin has predominately focused on effects on gene transcription via the canonical JAK2/STAT5; however, it is evident that prolactin can exert rapid actions to stimulate activity in specific populations of neurones. We aimed to investigate how widespread these rapid actions of prolactin are in regions of the brain with large populations of prolactin-sensitive neurones, and whether physiological state alters these responses. Using transgenic mice where the Cre-dependent calcium indicator, GCaMP6f, was conditionally expressed in cells expressing the long form of the Prlr, we monitored changes in levels of intracellular calcium ([Ca ] ) in ex vivo brain slice preparations as a surrogate marker of cellular activity. Here, we surveyed hypothalamic regions implicated in the diverse physiological functions of prolactin such as the arcuate (ARC) and paraventricular nuclei of the hypothalamus (PVN), as well as the medial preoptic area (MPOA). We observed that, in the ARC of males and in both virgin and lactating females, prolactin can exert rapid actions to stimulate neuronal activity in the majority of Prlr-expressing neurones. In the PVN and MPOA, we found a smaller subset of cells that rapidly respond to prolactin. In these brain regions, the effects we detected ranged from rapid or sustained increases in [Ca ] to inhibitory effects, indicating a heterogeneous nature of these Prlr-expressing populations. These results enhance our understanding of mechanisms by which prolactin acts on hypothalamic neurones and provide insights into how prolactin might influence neuronal circuits in the mouse brain.
Topics: Animals; Arcuate Nucleus of Hypothalamus; Calcium Signaling; Female; Humans; Hypothalamus; Immunohistochemistry; Lactation; Male; Mice; Mice, Transgenic; Neurons; Paraventricular Hypothalamic Nucleus; Preoptic Area; Prolactin; Receptors, Prolactin
PubMed: 33034148
DOI: 10.1111/jne.12908 -
Cancer Research Oct 2019Pancreatic ductal adenocarcinoma (PDAC) is associated with significant fibrosis. Recent findings have highlighted the profibrotic activity of tissue-resident macrophages...
Pancreatic ductal adenocarcinoma (PDAC) is associated with significant fibrosis. Recent findings have highlighted the profibrotic activity of tissue-resident macrophages in the pancreatic cancer microenvironment. Here, we show that neoplastic pancreatic epithelium, as well as a subset of tissue-resident macrophages, expresses the prolactin-receptor (PRLR). High mobility group box 1-induced prolactin expression in the pancreas maintained FAK1 and STAT3 phosphorylation within the epithelium and stroma. Gain-of-function and loss-of-function experiments demonstrated the essential role of prolactin in promoting collagen deposition and fibrosis. Finally, the signaling cascade downstream of prolactin/PRLR activated STAT3 rather than STAT5 in PDAC. These findings suggest that targeting prolactin together with IL6, a known major activator of STAT3, could represent a novel therapeutic strategy for treating pancreatic cancer. SIGNIFICANCE: Prolactin is a key factor in the cross-talk between the stroma and neoplastic epithelium, functioning to promote fibrosis and PDAC progression.
Topics: Animals; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Collagen; Disease Progression; Epithelium; Female; Fibrosis; Focal Adhesion Kinase 1; Genes, Reporter; HMGB1 Protein; Humans; Macrophages; Male; Metoclopramide; Mice; Mice, Knockout; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Pancreatic Neoplasms; Phosphorylation; Pregnancy; Prolactin; Protein Processing, Post-Translational; RNA Interference; RNA, Small Interfering; Receptors, Prolactin; Recombinant Proteins; STAT3 Transcription Factor; Stromal Cells
PubMed: 31395607
DOI: 10.1158/0008-5472.CAN-18-3064 -
European Journal of Histochemistry : EJH Oct 2023Prolactin (PRL) is a hormone crucial for normal reproduction, functioning as an autocrine, paracrine, and endocrine factor. This study aimed to examine the...
Prolactin (PRL) is a hormone crucial for normal reproduction, functioning as an autocrine, paracrine, and endocrine factor. This study aimed to examine the immunolocalization and expression patterns of PRL, prolactin receptor (PRLR), and signal transducer and activator of transcription 5 (STAT5) in the ovaries of wild ground squirrels during both breeding and non-breeding periods. Significant seasonal variations were observed in ovarian weights, with higher values during the breeding season and relatively lower values during the nonbreeding season. PRL, PRLR, STAT5, and p-STAT5 were immunolocalized in granulosa cells and luteal cells during the breeding season, whereas they were exclusively found in granulosa cells during the non-breeding season. The mRNA expression levels of Prl, Prlr, and Stat5 were increased in ovarian tissues during the breeding season compared to the non-breeding season. Moreover, the mean mRNA levels of Prl, Prlr, and Stat5 exhibited a positive correlation with ovarian weights. Both circulating PRL and ovarian PRL concentrations were significantly elevated during the breeding season. Additionally, transcriptomic analysis of ovarian tissues revealed differentially expressed genes possibly associated with ovarian function and mammary gland development, including ovarian follicle development, steroid synthesis, and regulation of reproductive process. These findings suggest that PRL might play an essential endocrine, autocrine, or paracrine role in the regulation of seasonal changes in the ovarian functions in wild ground squirrels.
Topics: Female; Animals; Prolactin; Receptors, Prolactin; Seasons; Ovary; STAT5 Transcription Factor; Sciuridae; RNA, Messenger
PubMed: 37781865
DOI: 10.4081/ejh.2023.3825 -
The Journal of Steroid Biochemistry and... Feb 2018Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in... (Review)
Review
Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy. Indeed, these pathways are fully integrated via activation of shared signaling pathways (i.e. JAKs, MAPKs) as well as by the convergence of PRs and STATs at target genes relevant to both mammary gland biology and breast cancer progression (i.e. proliferation, stem cell outgrowth, tissue cell type heterogeneity). Thus, rather than a single mediator such as ER, transcription factor cascades (ER>PR>STATs) are responsible for rapid proliferative and developmental programming in the normal mammary gland. It is not surprising that these same mediators typify uncontrolled proliferation in a majority of breast cancers, where ER and PR are most often co-expressed and may cooperate to drive malignant tumor progression. This review will primarily focus on the integration of PR and PRL signaling in breast cancer models and the importance of this cross-talk in cancer progression in the context of mammographic density. Components of these PR/PRL signaling pathways could offer alternative drug targets and logical complements to anti-ER or anti-estrogen-based endocrine therapies.
Topics: Animals; Breast Neoplasms; Disease Models, Animal; Female; Humans; Prolactin; Receptor Cross-Talk; Receptors, Progesterone; Receptors, Prolactin; STAT Transcription Factors; Signal Transduction
PubMed: 28442393
DOI: 10.1016/j.jsbmb.2017.04.011