Estrogen Receptors and Signaling Pathways in Lactotropes and Somatotropes

Estrogens are crucial determinants in the regulation of anterior pituitary function and maintenance of tissue homeostasis. Estrogen actions in this gland are exerted through both classical and non-classical mechanisms of action. This review summarizes the expression of classical α- and β-estrogen receptors and variant isoforms of estrogen receptors in anterior pituitary cell subpopulations. We also analyze estrogen receptor signaling pathways involved in estrogenic actions in the anterior pituitary gland, especially in lactotropes and somatotropes. Complex interactions between multiple signaling pathways are involved in estrogen regulation of hormone secretion, cell proliferation and cell death in this gland. Insight into these pituitary responses to estrogens would help to understand pituitary function and tumorigenesis.

[1]  A. Seilicovich,et al.  Estradiol Increases the Expression of TNF-α and TNF Receptor 1 in Lactotropes , 2011, Neuroendocrinology.

[2]  A. Seilicovich,et al.  Role of estrogens in anterior pituitary gland remodeling during the estrous cycle. , 2010, Frontiers of hormone research.

[3]  A. Seilicovich Cell Life and Death in the Anterior Pituitary Gland: Role of Oestrogens , 2010, Journal of neuroendocrinology.

[4]  S. Kansra,et al.  Selective Estrogen Receptor Down-Regulator and Selective Estrogen Receptor Modulators Differentially Regulate Lactotroph Proliferation , 2010, PloS one.

[5]  J. Arita,et al.  Absence of ligand-independent transcriptional activation of the estrogen receptor via the estrogen response element in pituitary lactotrophs in primary culture , 2010, The Journal of Steroid Biochemistry and Molecular Biology.

[6]  P. Micevych,et al.  Estradiol-Induced Estrogen Receptor-α Trafficking , 2009, The Journal of Neuroscience.

[7]  E. Levin Plasma membrane estrogen receptors , 2009, Trends in Endocrinology & Metabolism.

[8]  J. Bender,et al.  Membrane-initiated actions of estrogen on the endothelium , 2009, Molecular and Cellular Endocrinology.

[9]  C. Watson,et al.  Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases , 2009, BMC Cancer.

[10]  Yi Zhang,et al.  Minireview: role of protein methylation and demethylation in nuclear hormone signaling. , 2009, Molecular endocrinology.

[11]  A. Seilicovich,et al.  Estradiol Increases the Bax/Bcl-2 Ratio and Induces Apoptosis in the Anterior Pituitary Gland , 2009, Neuroendocrinology.

[12]  Kyung-Chul Choi,et al.  In vitro exposure to xenoestrogens induces growth hormone transcription and release via estrogen receptor-dependent pathways in rat pituitary GH3 cells , 2009, Steroids.

[13]  S. Kansra,et al.  Epidermal growth factor receptor cross-talks with ligand-occupied estrogen receptor-alpha to modulate both lactotroph proliferation and prolactin gene expression. , 2009, American journal of physiology. Endocrinology and metabolism.

[14]  T. Charlier,et al.  Who’s in charge? Nuclear receptor coactivator and corepressor function in brain and behavior , 2009, Frontiers in Neuroendocrinology.

[15]  G. Stalla,et al.  Molecular interaction of BMP-4, TGF-beta, and estrogens in lactotrophs: impact on the PRL promoter. , 2009, Molecular endocrinology.

[16]  A. Seilicovich,et al.  Estrogens exert a rapid apoptotic action in anterior pituitary cells. , 2009, American journal of physiology. Endocrinology and metabolism.

[17]  Kyung-Chul Choi,et al.  Estrogen receptors are involved in xenoestrogen induction of growth hormone in the rat pituitary gland. , 2009, The Journal of reproduction and development.

[18]  A. Levy,et al.  Prolonged oestrogen treatment does not correlate with a sustained increase in anterior pituitary mitotic index in ovariectomized Wistar rats , 2008, The Journal of endocrinology.

[19]  C. Otto,et al.  G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol. , 2008, Endocrinology.

[20]  C. Watson,et al.  Nongenomic actions of estradiol compared with estrone and estriol in pituitary tumor cell signaling and proliferation , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[21]  B. Komm,et al.  Nuclear and extranuclear pathway inputs in the regulation of global gene expression by estrogen receptors. , 2008, Molecular endocrinology.

[22]  J. Weiss,et al.  New insights into the classical and non-classical actions of estrogen: Evidence from estrogen receptor knock-out and knock-in mice , 2008, Molecular and Cellular Endocrinology.

[23]  P. Mermelstein,et al.  Membrane Estrogen Receptors Acting Through Metabotropic Glutamate Receptors: An Emerging Mechanism of Estrogen Action in Brain , 2008, Molecular Neurobiology.

[24]  J. Gustafsson,et al.  Biological functions and clinical implications of oestrogen receptors alfa and beta in epithelial tissues , 2008, Journal of internal medicine.

[25]  L. D. Sosa,et al.  Estradiol interacts with insulin through membrane receptors to induce an antimitogenic effect on lactotroph cells , 2008, Steroids.

[26]  D. Sarkar,et al.  Alteration in G proteins and prolactin levels in pituitary after ethanol and estrogen treatment. , 2008, Alcoholism, clinical and experimental research.

[27]  A. Seilicovich,et al.  Apoptosis of Lactotrophs Induced by D2 Receptor Activation Is Estrogen Dependent , 2008, Neuroendocrinology.

[28]  Claire V. Harper,et al.  Human prolactin gene promoter regulation by estrogen: convergence with tumor necrosis factor-alpha signaling. , 2008, Endocrinology.

[29]  R. Alonso,et al.  Oestrogen receptor α and β in female rat pituitary cells: An immunochemical study , 2008 .

[30]  N. Ben-Jonathan,et al.  What can we learn from rodents about prolactin in humans? , 2008, Endocrine reviews.

[31]  S. Shimodaira,et al.  Estrogen actions on lactotroph proliferation are independent of a paracrine interaction with other pituitary cell types: a study using lactotroph-enriched cells. , 2007, Endocrinology.

[32]  J. Dong,et al.  Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane. , 2007, Endocrinology.

[33]  Margaret Warner,et al.  Estrogen receptors: how do they signal and what are their targets. , 2007, Physiological reviews.

[34]  James D. Yager,et al.  Mitochondrial estrogen receptors – new insights into specific functions , 2007, Trends in Endocrinology & Metabolism.

[35]  M. Castro,et al.  Estrogens up-regulate the Fas/FasL apoptotic pathway in lactotropes. , 2005, Endocrinology.

[36]  J. P. Petiti,et al.  Antagonic effects of oestradiol in interaction with IGF-1 on proliferation of lactotroph cells in vitro , 2005, Histochemistry and Cell Biology.

[37]  S. Kansra,et al.  Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release , 2005, Molecular and Cellular Endocrinology.

[38]  G. Unabia,et al.  Bipotential effects of estrogen on growth hormone synthesis and storage in vitro. , 2005, Endocrinology.

[39]  C. Watson,et al.  Mechanisms of membrane estrogen receptor-alpha-mediated rapid stimulation of Ca2+ levels and prolactin release in a pituitary cell line. , 2005, American journal of physiology. Endocrinology and metabolism.

[40]  C. Watson,et al.  Xenoestrogens at Picomolar to Nanomolar Concentrations Trigger Membrane Estrogen Receptor-α–Mediated Ca2+ Fluxes and Prolactin Release in GH3/B6 Pituitary Tumor Cells , 2005, Environmental health perspectives.

[41]  J. Argente,et al.  The regulation of GH secretion by sex steroids. , 2004, European journal of endocrinology.

[42]  C. Watson,et al.  Xenoestrogen-Induced ERK-1 and ERK-2 Activation via Multiple Membrane-Initiated Signaling Pathways , 2004, Environmental health perspectives.

[43]  Y. Oiso,et al.  Effects of Hormones Targeting Nuclear Receptors on Transcriptional Regulation of the Growth Hormone Gene in the MtT/S Rat Somatotrope Cell Line , 2004, Neuroendocrinology.

[44]  J. Sánchez-Criado,et al.  Regulation of Estrogen Receptor (ER) Isoform Messenger RNA Expression by Different ER Ligands in Female Rat Pituitary1 , 2004, Biology of reproduction.

[45]  C. Watson,et al.  Quantitative measurement of estrogen-induced ERK 1 and 2 activation via multiple membrane-initiated signaling pathways , 2004, Steroids.

[46]  K. Yamakawa,et al.  Cross-talk between the estrogen receptor-, protein kinase A-, and mitogen-activated protein kinase-mediated signaling pathways in the regulation of lactotroph proliferation in primary culture , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[47]  S. Melmed Mechanisms for pituitary tumorigenesis: the plastic pituitary. , 2003, The Journal of clinical investigation.

[48]  E. Resnick,et al.  Truncated Estrogen Receptor Product-1 Stimulates Estrogen Receptor α Transcriptional Activity by Titration of Repressor Proteins* , 2003, Journal of Biological Chemistry.

[49]  K. Sugiura,et al.  Expression of estrogen receptor α and β genes in the mediobasal hypothalamus, pituitary and ovary during the canine estrous cycle , 2003, Neuroscience Letters.

[50]  C. Tiffoche,et al.  Regulation of the intronic promoter of rat estrogen receptor alpha gene, responsible for truncated estrogen receptor product-1 expression. , 2003, Endocrinology.

[51]  M. Low,et al.  Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[52]  C. Tiffoche,et al.  Expression of estrogen receptor subtypes in rat pituitary gland during pregnancy and lactation. , 2002, Endocrinology.

[53]  M. Candolfi,et al.  TNF-α Induces Apoptosis of Lactotropes from Female Rats , 2002 .

[54]  J. Morris,et al.  Rapid actions of 17β‐oestradiol on a subset of lactotrophs in the rat pituitary , 2002, The Journal of physiology.

[55]  M. Shupnik Oestrogen Receptors, Receptor Variants and Oestrogen Actions in the Hypothalamic‐Pituitary Axis , 2002, Journal of neuroendocrinology.

[56]  G. Unabia,et al.  Differential Expression of Estradiol Receptors Alpha and Beta by Gonadotropes During the Estrous Cycle , 2001, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[57]  J. Gorski,et al.  Estrogen modulation of prolactin gene expression requires an intact mitogen-activated protein kinase signal transduction pathway in cultured rat pituitary cells. , 2000, Molecular endocrinology.

[58]  G. Unabia,et al.  Differential expression of growth hormone messenger ribonucleic acid by somatotropes and gonadotropes in male and cycling female rats. , 2000 .

[59]  A. Periasamy,et al.  Truncated Estrogen Receptor Product-1 Suppresses Estrogen Receptor Transactivation by Dimerization with Estrogen Receptors α and β* , 2000, The Journal of Biological Chemistry.

[60]  G. Nagy,et al.  Prolactin: structure, function, and regulation of secretion. , 2000, Physiological reviews.

[61]  C. Watson,et al.  Estrogen Receptor-α Detected on the Plasma Membrane of Aldehyde-Fixed GH3/B6/F10 Rat Pituitary Tumor Cells by Enzyme-Linked Immunocytochemistry. , 1999, Endocrinology.

[62]  N. Ben-Jonathan,et al.  Differential Regulation and Action of Estrogen Receptors α and β in GH3 Cells. , 1999, Endocrinology.

[63]  T. Pappas,et al.  Rapid actions of estrogens in GH3/B6 pituitary tumor cells via a plasma membrane version of estrogen receptor-α , 1999, Steroids.

[64]  D. Sarkar,et al.  Interaction between estrogen receptor and Pit-1 protein is influenced by estrogen in pituitary cells , 1999, The Journal of Steroid Biochemistry and Molecular Biology.

[65]  N. Ben-Jonathan,et al.  Cellular Distribution and Gene Regulation of Estrogen Receptorsα and β in the Rat Pituitary Gland. , 1998, Endocrinology.

[66]  D. Sarkar,et al.  Differential regulation by estrogens of growth and prolactin synthesis in pituitary cells suggests that only a small pool of estrogen receptors is required for growth. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[67]  B. Gellersen,et al.  Pituitary-type transcription of the human prolactin gene in the absence of Pit-1. , 1995, Molecular endocrinology.

[68]  R. Maurer,et al.  Multiple Pit-1-binding sites facilitate estrogen responsiveness of the prolactin gene. , 1994, Molecular endocrinology.

[69]  S. Koike,et al.  Both Pit-1 and the estrogen receptor are required for estrogen responsiveness of the rat prolactin gene. , 1990, Molecular endocrinology.

[70]  J. Simard,et al.  Stimulation of growth hormone release and synthesis by estrogens in rat anterior pituitary cells in culture. , 1986, Endocrinology.

[71]  R. Pietras,et al.  Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells , 1977, Nature.

[72]  S. Kansra,et al.  Estrogen Receptor- (cid:1) Mediates the Epidermal Growth Factor-Stimulated Prolactin Expression and Release in Lactotrophs , 2009 .

[73]  M. Shupnik,et al.  Stimulation of the novel estrogen receptor-alpha intronic TERP-1 promoter by estrogens, androgen, pituitary adenylate cyclase-activating peptide, and forskolin, and autoregulation by TERP-1 protein. , 2006, Endocrinology.

[74]  D. Sarkar Genesis of prolactinomas: studies using estrogen-treated animals. , 2006, Frontiers of hormone research.

[75]  F. Labrie,et al.  Differentiation of Pituitary Cells , 2003 .

[76]  K. Grandien,et al.  Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors a and b , 1997 .

[77]  K. Grandien,et al.  Printed in U.S.A. Copyright © 1997 by The Endocrine Society Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors � and � , 2022 .