DOCSLIB.ORG

Interactions Between Prolactin and Kisspeptin to Control Reproduction

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

review Interactions between prolactin and kisspeptin to control reproduction Jose Donato Jr.1, Renata Frazão2 ABSTRACT Prolactin is best known for its effects of stimulating mammary gland development and lactogenesis. 1 Departamento de Fisiologia e However, prolactin is a pleiotropic hormone that is able to affect several physiological functions, Biofísica, Instituto de Ciências including fertility. Prolactin receptors (PRLRs) are widely expressed in several tissues, including several Biomédicas, Universidade de São brain regions and reproductive tract organs. Upon activation, PRLRs may exert prolactin’s functions Paulo (USP), São Paulo, SP, Brasil 2 Departamento de Anatomia, through several signaling pathways, although the recruitment of the signal transducer and activator Instituto de Ciências Biomédicas, of transcription 5 causes most of the known effects of prolactin. Pathological hyperprolactinemia USP, São Paulo, SP, Brasil is mainly due to the presence of a prolactinoma or pharmacological effects induced by drugs that interact with the dopamine system. Notably, hyperprolactinemia is a frequent cause of reproductive dysfunction and may lead to infertility in males and females. Recently, several studies have indicated Correspondence to: Renata Frazão that prolactin may modulate the reproductive axis by acting on specific populations of hypothalamic Av. Prof. Lineu Prestes, 2415 neurons that express the Kiss1 gene. The Kiss1 gene encodes neuropeptides known as kisspeptins, 05508-000 – São Paulo, SP, Brasil which are powerful activators of gonadotropin-releasing hormone neurons. In the present review, [email protected] we will summarize the current knowledge about prolactin’s actions on reproduction. Among other Received on July/11/2016 aspects, we will discuss whether the interaction between prolactin and the Kiss1-expressing neurons Accepted on Sep/26/2016 can affect reproduction and how kisspeptins may become a novel therapeutic approach to treat DOI: 10.1590/2359-3997000000230 prolactin-induced infertility. Arch Endocrinol Metab. 2016;60(6):587-95 Keywords Prolactin receptor; pSTAT5; hypothalamus; Kiss1; infertility INTRODUCTION cell populations also express PRLRs, including different rolactin is a protein hormone produced and brain regions, as well as the bone, adipose tissue, gut, P secreted by the anterior pituitary gland. Sparse skin, immune system and reproductive tract (2,4-9). evidence, at least in rodents, suggests that prolactin may Clinical evidence indicates that hyperprolactinemia also be locally produced in some brain areas, but the is a frequent cause of reproductive dysfunction and physiological importance of this production is unknown may lead to infertility in males and females (10-13). (1). Prolactin secretion is controlled by hypothalamic Pathological hyperprolactinemia is mainly caused by the endocrine neurons, especially the tuberoinfundibular presence of a prolactinoma or is due to pharmacological dopamine (TIDA) neurons located in the arcuate effects induced by drugs that interact with the nucleus of the hypothalamus (ARH). These neurons dopamine system. Loss-of-function mutations in the secrete dopamine into the hypophyseal portal system, gene that encodes the PRLRs can also be a rare cause of which leads to the activation of dopamine D2 receptors hyperprolactinemia (11). The objective of the present in pituitary lactotrophs, causing suppression of prolactin review is to summarize and discuss recent advances in gene expression and prolactin secretion (1). Prolactin the discovery of possible mechanisms linking prolactin is transported by the circulatory system and acts on signaling and the control of reproduction, especially target cells via specific receptors located on the plasma regarding the role of kisspeptins as novel potential membrane (1,2). Serum prolactin crosses the blood- targets to treat prolactin-induced infertility. brain barrier by a PRLRs-independent mechanism (3). The function of PRLRs in TIDA neurons is to allow PROLACTIN SIGNALING these cells to sense circulating prolactin levels and Multiple isoforms of membrane-bound PRLRs have AE&M all rights reserved. consequently regulate pituitary prolactin secretion been identified, differing in the length and composition © through negative feedback mechanisms. Several other of their cytoplasmic tail. In rats, for example, the Copyright Arch Endocrinol Metab. 2016;60/6 587 Prolactin, kisspeptin and reproduction following three major PRLRs isoforms were identified: PROLACTIN-MEDIATED REPRODUCTIVE short (291 amino acids), intermediate (393 amino FUNCTIONS IN PERIPHERAL ORGANS acids), and long (591 amino acids). In mice, one Prolactin is best known for its role in mammopoiesis and long and three short isoforms of the PRLRs have lactogenesis. Mammary gland development includes the been described (2). After PRLRs activation, different formation of a branched ductal system that is decorated intracellular signaling pathways can be recruited to with terminal and lateral lobules in wild-type virgin adult induce prolactin biological effects. The receptor mice. Following pregnancy and in response to prolactin activation results in a rapid phosphorylation of Janus production, the alveolar development of the mammary kinase 2 (JAK2), which is constitutively associated gland is greatly amplified. Several studies have provided with the intracellular domain of PRLRs. Activation of consistent evidence that such progression is directly JAK2 leads to the phosphorylation of tyrosine residues. modulated by the recruitment of STAT5 proteins upon Phosphotyrosines serve as binding sites for transducer PRLRs activation. In PRL-/- or PRLR-/- female mice, molecules, such as the signal transducer and activator terminal end buds form during puberty and the ductal of transcription (STAT) protein family. Three members tree grows normally. However, in adult PRL-/- mice, the of this family are recognized as transducer molecules mammary gland ductal system grows into an extended of PRLRs, including STAT1, STAT3 and STAT5a/b. branching network that is devoid of both terminal and STAT5, earlier known as mammary gland factor, lateral lobulations (19). The differentiation of ductal is recognized as the most important transducer of elements also occurs in the global STAT5a, STAT5b the PRLRs. STAT proteins become phosphorylated and double knockout STAT5a/b female mice; however, by the PRLR/JAK2 complex and form hetero- or development of terminal buds occurs to a lesser extent homodimers through its phosphotyrosine residues as compared to wild-type mice (20,21). Deficiencies in with another phosphorylated STAT molecule. STAT mammary gland development were even observed in dimers then translocate to the nucleus, where genomic non-lactating heterozygous PRLRs knockout female effects on target genes can occur. The phosphotyrosine mice, indicating that such development is dependent residues of the activated PRLR may also serve as a upon prolactin signaling (22). Of note, mammary gland docking site for others adapter proteins which can development upon pregnancy could not be observed lead to the activation of different signaling pathways, in PRLR-/- female mice, as well as in global double such as the mitogen-activated protein kinase (MAPK) STAT5a/b knockout females due to their infertility. cascade or the phosphatidylinositol 3-kinase (PI3K) The total body of research has led to the determination cascade (1,2). In addition, it has been demonstrated that STAT5 is the principal transcription factor that PRLRs activation is also involved in rapid acute mediating mammopoiesis and lactogenesis. Global effects that lead to changes in membrane excitability. STAT5a knockout mice fail to lactate due to incomplete For example, prolactin acutely induces rapid effects on mammary gland development, even after maximal the membrane excitability of neurons (14-18). Such stimulation of prolactin secretion induced by suckling. effects occur because PRLRs activation can activate Conversely, mammary gland development occurs in a fast-acting signaling mechanisms, such as the PI3K relatively normal manner in STAT5b knockout mice pathway, tyrosine kinase-dependent K+ channels or (20,21). In addition, the specific deletion of theStat5 the production of intracellular messengers that open locus only from the mammary epithelium, using Cre- voltage-independent Ca2+ channels, which in turn loxp-mediated recombination, determined that this allows for ionic changes across the cell membrane protein is essential not only for pregnancy-mediated (1,15). One of the final mechanisms induced by PRLRs cell proliferation/differentiation but also for the activation is protein synthesis that can in turn desensitize survival of mammary epithelium and maintenance of the receptor itself. The JAK/STAT complex can be differentiation (23). inhibited by suppressors of cytokine signaling (SOCS) The effects of prolactin on fertility have been proteins, which inhibit JAK kinases and compete with well-characterized using knockout mouse models, STAT for docking sites on PRLRs. These proteins indicating that reproduction is clearly dependent upon AE&M all rights reserved. © include SOCS1, SOCS3 and cytokine-inducible SH2- the signaling of this hormone, at least in rodents. Copyright containing protein (CIS) (1). Both short and long isoforms of PRLRs have been 588 Arch Endocrinol Metab. 2016;60/6 Prolactin, kisspeptin and reproduction described to be expressed in the granulosa, interstitial THE HYPOTHALAMUS AS A TARGET OF and luteal
Recommended publications
  • Leptin Stimulates Pituitary Prolactin Release Through an Extracellular Signal-Regulated Kinase-Dependent Pathway

    Leptin Stimulates Pituitary Prolactin Release Through an Extracellular Signal-Regulated Kinase-Dependent Pathway

    275 Leptin stimulates pituitary prolactin release through an extracellular signal-regulated kinase-dependent pathway Christian K Tipsmark, Christina N Strom, Sean T Bailey and Russell J Borski Department of Zoology, North Carolina State University, Raleigh, North Carolina 27695-7617, USA (Correspondence should be addressed to C K Tipsmark who is now at Institute of Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark; Email: [email protected]) Abstract Leptin was initially identified as a regulator of appetite and leptin are mediated by the activation of extracellular signal- weight control centers in the hypothalamus, but appears to be regulated kinase (ERK1/2) but nothing is known about the involved in a number of physiological processes. This study cellular mechanisms by which leptin might regulate PRL was carried out to examine the possible role of leptin in secretion in vertebrates. We therefore tested whether regulating prolactin (PRL) release using the teleost pituitary ERK1/2 might be involved in the leptin PRL response and model system. This advantageous system allows isolation of a found that the ERK inhibitor, PD98059, hindered leptin- nearly pure population of lactotropes in their natural, in situ induced PRL release. We further analyzed leptin response by aggregated state. The rostral pars distalis were dissected from quantifying tyrosine and threonine phosphorylation of tilapia pituitaries and exposed to varying concentrations of ERK1/2 using western blots. One hour incubation with leptin (0, 1, 10, 100 nM) for 1 h. Release of PRL was leptin induced a concentration-dependent increase in stimulated by leptin in a potent and concentration-dependent phosphorylated, and thus active, ERK1/2.
  • Distress Regulates Different Pathways in the Brain of Common Carp: a Preliminary Study

    Distress Regulates Different Pathways in the Brain of Common Carp: a Preliminary Study

    animals Communication Distress Regulates Different Pathways in the Brain of Common Carp: A Preliminary Study Alexander Burren and Constanze Pietsch * School of Agricultural, Forest and Food Sciences (HAFL), Applied University Berne (BFH), 3052 Zollikofen, Switzerland; [email protected] * Correspondence: [email protected] Simple Summary: The aquaculture sector provides for nearly half of the world’s seafood consump- tion, thanks to its large expansion over the last 30 years. Despite this intense growth, clear guidelines for responsible practices and animal wellbeing are lacking. Gene expression studies are a fundamen- tal tool for understanding welfare, but stress-markers in aquaculture fish species are poorly studied. In addition, the biostatistical analysis of gene expression data is not trivial, and this study applies different statistical methods in order to evaluate potential differences in the gene expression levels between control fish and fish acutely stressed by exposure to air. Abstract: In this study, a stress trial was conducted with common carp, one of the most important species in aquaculture worldwide, to identify relevant gene regulation pathways in different areas of the brain. Acute distress due to exposure to air significantly activated the expression of the immediate early gene c-fos in the telencephalon. In addition, evidence for regulation of the two corticotropin-releasing factor (crf ) genes in relation to their binding protein (corticotropin-releasing hormone-binding protein, crh-bp) is presented in this preliminary study. Inferences on the effects Citation: Burren, A.; Pietsch, C. of due to exposure to air were obtained by using point estimation, which allows the prediction of Distress Regulates Different a single value.
  • Relaxin: a Missing Link in the Pathomechanisms of Systemic Lupus Erythematosus?

    Relaxin: a Missing Link in the Pathomechanisms of Systemic Lupus Erythematosus?

    http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2014; 24(4): 547–551 © 2014 Japan College of Rheumatology DOI: 10.3109/14397595.2013.844297 REVIEW ARTICLE Relaxin: A missing link in the pathomechanisms of Systemic Lupus Erythematosus? Madhusoothanan Bhagavathi Perumal1 and Saranya Dhanasekaran2 1 Queensland Brain Institute, The University of Queensland, Brisbane, Australia and 2 Chhatrapati Shahuji Maharaj Hospital, Lucknow, India Downloaded from https://academic.oup.com/mr/article/24/4/547/6303646 by guest on 01 October 2021 Abstract Keywords Systemic Lupus Erythematosus (SLE) is an autoimmune rheumatic disease which predominantly Autoimmunity , Endometrium , Macrophages , aff ects women of reproductive age. Despite signifi cant progress in recent years to elucidate Relaxin , Systemic Lupus Erythematosus many potential mechanisms involved in the generation of autoimmunity the factors behind the high incidence among women, the relapsing – remitting clinical course and pregnancy-related History complications in SLE remain unclear. In this review, we hypothesize a potential role for uterine Received 5 February 2013 endometrium through its production of relaxin, a peptide hormone, as a “ missing-link ” to explain Accepted 15 May 2013 this female predominance, variable clinical course and obstetric complications operating in SLE. Published online 16 October 2013 Background In contrast, M2 macrophages are important in tissue repair and wound healing. They express high levels of anti-infl ammatory Systemic Lupus Erythematosus (SLE) is an autoimmune disease cytokines (such as IL10) as well as growth factors such as vascular which can aff ect any part of the body leading to a myriad of clini- endothelial growth factor (VEGF) and basic Fibroblast growth fac- cal manifestations.
  • Supplementary Table 2

    Supplementary Table 2

    Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942
  • Galanin and Prolactin in 2 Cichlids 2021.Pdf

    Galanin and Prolactin in 2 Cichlids 2021.Pdf

    General and Comparative Endocrinology 309 (2021) 113785 Contents lists available at ScienceDirect General and Comparative Endocrinology journal homepage: www.elsevier.com/locate/ygcen Research paper Galanin and prolactin expression in relation to parental care in two sympatric cichlid species from Lake Tanganyika Filipa Cunha-Saraiva a,*, Rute S.T. Martins b, Deborah M. Power b, Sigal Balshine c,1, Franziska C. Schaedelin a,1 a Konrad Lorenz Institute of Ethology, Department of Interdisciplinary Life Sciences, University of Veterinary Medicine Vienna, Austria b Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal c Aquatic Behavioural Ecology Laboratory, Department of Psychology, Neuroscience, & Behaviour, McMaster University, Ontario, Canada ARTICLE INFO ABSTRACT Keywords: Our understanding of the hormonal mechanisms underlying parental care mainly stems from research on species Gene expression with uniparental care. Far less is known about the physiological changes underlying motherhood and fatherhood Breeding cycle in biparental caring species. Here, using two biparental caring cichlid species (Neolamprologus caudopunctatus and Neurogenomic mechanisms Neolamprologus pulcher), we explored the relative gene-expression levels of two genes implicated in the control of Cooperative breeding parental care, galanin (gal) and prolactin (prl). We investigated whole brain gene expression levels in both, male Biparental care Neolamprologus caudopunctatus and female caring parents, as well as in non-caring individuals of both species. Caring males had higher prl and Neolamprologus pulcher gal mRNA levels compared to caring females in both fsh species. Expression of gal was highest when young were mobile and the need for parental defense was greatest and gal was lowest during the more stationary egg tending phase in N.
  • Rfamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential

    Rfamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential

    Pharmaceuticals 2011, 4, 1248-1280; doi:10.3390/ph4091248 OPEN ACCESS Pharmaceuticals ISSN 1424-8247 www.mdpi.com/journal/pharmaceuticals Review RFamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential Maria Findeisen †, Daniel Rathmann † and Annette G. Beck-Sickinger * Institute of Biochemistry, Leipzig University, Brüderstraße 34, 04103 Leipzig, Germany; E-Mails: [email protected] (M.F.); [email protected] (D.R.) † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +49-341-9736900; Fax: +49-341-9736909. Received: 29 August 2011; in revised form: 9 September 2011 / Accepted: 15 September 2011 / Published: 21 September 2011 Abstract: Different neuropeptides, all containing a common carboxy-terminal RFamide sequence, have been characterized as ligands of the RFamide peptide receptor family. Currently, five subgroups have been characterized with respect to their N-terminal sequence and hence cover a wide pattern of biological functions, like important neuroendocrine, behavioral, sensory and automatic functions. The RFamide peptide receptor family represents a multiligand/multireceptor system, as many ligands are recognized by several GPCR subtypes within one family. Multireceptor systems are often susceptible to cross-reactions, as their numerous ligands are frequently closely related. In this review we focus on recent results in the field of structure-activity studies as well as mutational exploration of crucial positions within this GPCR system. The review summarizes the reported peptide analogs and recently developed small molecule ligands (agonists and antagonists) to highlight the current understanding of the pharmacophoric elements, required for affinity and activity at the receptor family.
  • Co-Regulation of Hormone Receptors, Neuropeptides, and Steroidogenic Enzymes 2 Across the Vertebrate Social Behavior Network 3 4 Brent M

    Co-Regulation of Hormone Receptors, Neuropeptides, and Steroidogenic Enzymes 2 Across the Vertebrate Social Behavior Network 3 4 Brent M

    bioRxiv preprint doi: https://doi.org/10.1101/435024; this version posted October 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Co-regulation of hormone receptors, neuropeptides, and steroidogenic enzymes 2 across the vertebrate social behavior network 3 4 Brent M. Horton1, T. Brandt Ryder2, Ignacio T. Moore3, Christopher N. 5 Balakrishnan4,* 6 1Millersville University, Department of Biology 7 2Smithsonian Conservation Biology Institute, Migratory Bird Center 8 3Virginia Tech, Department of Biological Sciences 9 4East Carolina University, Department of Biology 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 1 bioRxiv preprint doi: https://doi.org/10.1101/435024; this version posted October 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Running Title: Gene expression in the social behavior network 2 Keywords: dominance, systems biology, songbird, territoriality, genome 3 Corresponding Author: 4 Christopher Balakrishnan 5 East Carolina University 6 Department of Biology 7 Howell Science Complex 8 Greenville, NC, USA 27858 9 [email protected] 10 2 bioRxiv preprint doi: https://doi.org/10.1101/435024; this version posted October 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
  • Suppression of Breast Cancer by Small Molecules That Block the Prolactin Receptor

    Suppression of Breast Cancer by Small Molecules That Block the Prolactin Receptor

    cancers Article Suppression of Breast Cancer by Small Molecules That Block the Prolactin Receptor Dana C. Borcherding 1,† , Eric R. Hugo 1,† , Sejal R. Fox 1, Eric M. Jacobson 2, Brian G. Hunt 1, Edward J. Merino 3 and Nira Ben-Jonathan 1,* 1 Department of Cancer Biology, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA; [email protected] (D.C.B.); [email protected] (E.R.H.); [email protected] (S.R.F.); [email protected] (B.G.H.) 2 Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA; [email protected] 3 Department of Chemistry, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-513-558-4821; Fax: +1-513-558-4823 † Contributed equally to this investigation as first authors. Simple Summary: Unabated tumor growth, metastasis, and resistance to hormone therapy and/or to chemotherapy constitute serious impediments for combating breast cancer (BC). With the exception of targeted anti-HER2/neu therapy and combination therapies, there have been no radical changes in the standard of care for BC patients in the past two decades. In addition, there are only limited options for treating BC-derived brain metastases that cause high morbidity and mortality. This report describes the use of high throughput screening (HTS) for identifying novel small molecules that blocked the prolactin receptor (PRLR) and suppressed BC in a laboratory setting. These small Citation: Borcherding, D.C.; Hugo, molecules have a great potential to become effective therapeutics in patients with BC.
  • A Role for Placental Kisspeptin in Β Cell Adaptation to Pregnancy

    A Role for Placental Kisspeptin in Β Cell Adaptation to Pregnancy

    A role for placental kisspeptin in β cell adaptation to pregnancy James E. Bowe, … , Stephanie A. Amiel, Peter M. Jones JCI Insight. 2019;4(20):e124540. https://doi.org/10.1172/jci.insight.124540. Research Article Endocrinology Reproductive biology During pregnancy the maternal pancreatic islets of Langerhans undergo adaptive changes to compensate for gestational insulin resistance. Kisspeptin has been shown to stimulate insulin release, through its receptor, GPR54. The placenta releases high levels of kisspeptin into the maternal circulation, suggesting a role in modulating the islet adaptation to pregnancy. In the present study we show that pharmacological blockade of endogenous kisspeptin in pregnant mice resulted in impaired glucose homeostasis. This glucose intolerance was due to a reduced insulin response to glucose as opposed to any effect on insulin sensitivity. A β cell–specific GPR54-knockdown mouse line was found to exhibit glucose intolerance during pregnancy, with no phenotype observed outside of pregnancy. Furthermore, in pregnant women circulating kisspeptin levels significantly correlated with insulin responses to oral glucose challenge and were significantly lower in women with gestational diabetes (GDM) compared with those without GDM. Thus, kisspeptin represents a placental signal that plays a physiological role in the islet adaptation to pregnancy, maintaining maternal glucose homeostasis by acting through the β cell GPR54 receptor. Our data suggest reduced placental kisspeptin production, with consequent impaired kisspeptin-dependent β cell compensation, may be a factor in the development of GDM in humans. Find the latest version: https://jci.me/124540/pdf RESEARCH ARTICLE A role for placental kisspeptin in β cell adaptation to pregnancy James E.
  • THE ROLE of RELAXIN in PROSTATE CANCER by VANESSA

    THE ROLE of RELAXIN in PROSTATE CANCER by VANESSA

    THE ROLE OF RELAXIN IN PROSTATE CANCER by VANESSA CAMILLE THOMPSON B.Sc, The University of Victoria, 2001 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE STUDIES (Genetics) THE UNIVERSITY OF BRITISH COLUMBIA July 2007 © Vanessa Camille Thompson, 2007 Abstract Prostate cancer is the leading cause of cancer in men, and there is currently a lack of novel treatment options for this disease. Relaxin, part of the insulin superfamily, is a potent peptide hormone normally produced and secreted by the human prostate. cDNA and tissue microarray analyses, indicated that relaxin is highly overexpressed in prostate cancer progression to androgen independence (Al), and is negatively regulated by androgens. Characterization of the relaxin receptor, LGR7, in xenografts and human patient tissue microarrays (TMAs) indicated that LGR7 is expressed in the stroma and epithelia, suggesting that relaxin may act in an autocrine and/or paracrine fashion. Relaxin is known to increase angiogenesis through upregulation of vascular endothelial growth factor, and matrix metalloproteases. To elucidate novel pathways that may be upregulated by relaxin in prostate cancer, the effects of relaxin overexpression in the LNCaP prostate cancer xenograft model were analysed by gene expression microarrays. A novel discovery is that the protocadherinY (PCDHY)/Wnt pathway is upregulated by relaxin, resulting in P-catenin translocation from the cell membrane to the cytoplasm and upregulation of Wntll, which can stimulate proliferation, transformation, and migration. Relaxin is well characterized in the uterus and ovary to increase insulin-like growth factor-I (IGF-I); relaxin may also increase IGF-I in prostate cancer.
  • Lactation and Appetite-Regulating Hormones: Increased Maternal Plasma Peptide YY Concentrations 3–6 Months Postpartum

    Lactation and Appetite-Regulating Hormones: Increased Maternal Plasma Peptide YY Concentrations 3–6 Months Postpartum

    Downloaded from British Journal of Nutrition (2015), 114, 1203–1208 doi:10.1017/S0007114515002536 © The Authors 2015 https://www.cambridge.org/core Lactation and appetite-regulating hormones: increased maternal plasma peptide YY concentrations 3–6 months postpartum Greisa Vila1,*, Judith Hopfgartner1, Gabriele Grimm2, Sabina M. Baumgartner-Parzer1, . IP address: Alexandra Kautzky-Willer1, Martin Clodi1 and Anton Luger1 1Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, 170.106.34.90 Vienna 1090, Austria 2Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna 1090, Austria – – – (Submitted 12 October 2014 Final revision received 27 May 2015 Accepted 11 June 2015 First published online 24 August 2015) , on 28 Sep 2021 at 07:22:14 Abstract Breast-feeding is associated with maternal hormonal and metabolic changes ensuring adequate milk production. In this study, we investigate the impact of breast-feeding on the profile of changes in maternal appetite-regulating hormones 3–6 months postpartum. Study participants were age- and BMI-matched lactating mothers (n 10), non-lactating mothers (n 9) and women without any history of pregnancy or breast-feeding in the previous 12 months (control group, n 10). During study sessions, young mothers breast-fed or bottle-fed their babies, and maternal blood , subject to the Cambridge Core terms of use, available at samples were collected at five time points during 90 min: before, during and after feeding the babies. Outcome parameters were plasma concentrations of ghrelin, peptide YY (PYY), leptin, adiponectin, prolactin, cortisol, insulin, glucose and lipid values. At baseline, circulating PYY concentrations were significantly increased in lactating mothers (100·3(SE 6·7) pg/ml) v.
  • From Galactorrhea to Osteopenia: Rethinking Serotonin– Prolactin Interactions

    From Galactorrhea to Osteopenia: Rethinking Serotonin– Prolactin Interactions

    Neuropsychopharmacology (2004) 29, 833–846 & 2004 Nature Publishing Group All rights reserved 0893-133X/04 $25.00 www.neuropsychopharmacology.org From Galactorrhea to Osteopenia: Rethinking Serotonin– Prolactin Interactions ,1,2 1,3 Ana BF Emiliano* and Julie L Fudge 1 2 Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA; Department Medicine, University of Rochester Medical 3 Center, Rochester, NY, USA; and Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, NY, USA The widespread use of the selective serotonin reuptake inhibitors (SSRIs) has been accompanied by numerous reports describing a potential association with hyperprolactinemia. Antipsychotics are commonly known to elevate serum prolactin (PRL) through blockade of dopamine receptors in the pituitary. However, there is little awareness of the mechanisms by which SSRIs stimulate PRL release. Hyperprolactinemia may result in overt symptoms such as galactorrhea, which may be accompanied by impaired fertility. Long-term clinical sequelae include decreased bone density and the possibility of an increased risk of breast cancer. Through literature review, we explore the possible pathways involved in serotonin-induced PRL release. While the classic mechanism of antipsychotic-induced hyperprolactinemia directly involves dopamine cells in the tuberoinfundibular pathway, SSRIs may act on this system indirectly through GABAergic neurons. Alternate pathways involve serotonin stimulation of vasoactive intestinal peptide (VIP) and oxytocin (OT) release. We conclude with a comprehensive review of clinical sequelae associated with hyperprolactinemia, and the potential role of SSRIs in this phenomenon. Neuropsychopharmacology (2004) 29, 833–846, advance online publication, 3 March 2004; doi:10.1038/sj.npp.1300412 Keywords: hyperprolactinemia; fertility; bone density; breast cancer; vasoactive intestinal peptide; SSRI INTRODUCTION only beginning to be investigated (Klibanski et al, 1980; Wang et al, 2002).