Uterine development and fertility are dependent on gene dosage of the nuclear receptor coregulator REA.

Abstract:

:Although the effectiveness of nuclear hormone-receptor complexes is known to depend on coregulator partner proteins, relatively little is known about the roles of coregulators in uterine development and early stages of pregnancy and implantation. Because conventional genetic deletion of the coregulator, repressor of estrogen receptor activity (REA), was embryonic lethal, we here study REA conditional knockout mice generated by cre-loxP recombination, in which REA function was abrogated only in progesterone receptor-expressing tissues, to define the roles of REA in postembryonic stages and in a tissue-specific manner. We find that REA has gene dose-dependent activity impacting uterine development and fertility. Conditional homozygous mutant (REA(d/d)) mice developed to adulthood and showed normal ovarian function, but females were infertile with severely compromised uterine development and function characterized by cell cycle arrest, apoptosis, and altered adenogenesis (endometrial gland morphogenesis), resulting in failure of implantation and decidualization. By contrast, mice heterozygous for REA (REA(f/d)) had a very different phenotype, with estradiol treatment resulting in hyperstimulated, large uteri showing increased proliferation of luminal epithelial cells, and enhanced fluid imbibition associated with altered regulation of aquaporins. These REA(f/d) female mice showed a subfertility phenotype with reduced numbers and sizes of litters. These findings highlight that uterine development and regulation of estrogen receptor activities show a bimodal dependence on the gene dosage of REA. Optimal uterine development and functional activities require the normal gene dosage of REA, with partial or complete deletion resulting in hyperresponsiveness or underresponsiveness to hormone and subfertility or infertility, respectively.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Park S,Yoon S,Zhao Y,Park SE,Liao L,Xu J,Lydon JP,DeMayo FJ,O'Malley BW,Bagchi MK,Katzenellenbogen BS

doi

10.1210/en.2012-1044

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

3982-94

issue

8

eissn

0013-7227

issn

1945-7170

pii

en.2012-1044

journal_volume

153

pub_type

杂志文章
  • Topology of 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4-isomerase in adrenal cortex mitochondria and microsomes.

    abstract::3 beta-Hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD) is a NAD(+)-dependent membrane-bound enzyme that catalyzes the oxidation of delta 5-3 beta-hydroxysteroids to delta 4-3-keto structures during adrenal, gonadal, and placental steroidogenesis. Enzyme activity is located in both microsomes...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.134.2.8299570

    authors: Sauer LA,Chapman JC,Dauchy RT

    更新日期:1994-02-01 00:00:00

  • Insulin-like growth factor binding protein-4 proteolytic degradation in ovine preovulatory follicles: studies of underlying mechanisms.

    abstract::The regulation of insulin-like growth factor binding protein (IGFBP)-4 proteolytic degradation by insulin-like growth factors (IGFs) has been largely studied in vitro, but not in vivo. The aim of this study was to investigate the involvement of IGFs, IGFBP-2, IGFBP-3, and IGFBP-3 proteolytic fragments in the regulatio...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.140.9.6979

    authors: Mazerbourg S,Zapf J,Bar RS,Brigstock DR,Lalou C,Binoux M,Monget P

    更新日期:1999-09-01 00:00:00

  • Effects of ovariectomy and season on plasma luteinizing hormone in mares.

    abstract::Six pony mares were ovariectomized (OVX) on day 16 of diestrus during June and July, 1972, to study short term changes in plasma luteinizing hormone (LH) concentrations. Plasma LH was higher (P less than .05) 3 days after OVX (1.76 ng/ml) than the day after OVX (1.01 ng/ml), and a gradual increase occurred over the fi...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-98-4-958

    authors: Garcia MC,Ginther OJ

    更新日期:1976-04-01 00:00:00

  • Sodium chloride suppression of renin release in the unanesthetized rat.

    abstract::Previous studies have shown that increased sodium chloride in drinking water failed to suppress serum renin activity (SRA) in the etheranesthetized rat. In the absence of anesthesia, sodium chloride decreased SRA by 76% and serum aldosterone by 72%. Deoxycorticosterone acetate, when given alone, produced similar resul...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-97-6-1394

    authors: Campbell WB,Pettinger WA

    更新日期:1975-12-01 00:00:00

  • Role of leptin in peroxisome proliferator-activated receptor gamma coactivator-1 expression.

    abstract::Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1), a cold-induced protein expressed in brown adipose tissue (BAT), plays a role in adaptive thermogenesis by up-regulating uncoupling proteins (UCP). Here, we explore its relationship to the thermogenic actions of leptin, which also up-regulates UCPs...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.141.12.7804

    authors: Kakuma T,Wang ZW,Pan W,Unger RH,Zhou YT

    更新日期:2000-12-01 00:00:00

  • Transforming growth factor-alpha is a potential mediator of estrogen action in the mouse uterus.

    abstract::To better understand the role of peptide growth factors in sex steroid hormone-mediated growth of the female reproductive tract, the effect of estrogen on the expression of transforming growth factor-alpha (TGF alpha) in mouse uterus was investigated. Our results show that estrogen induces the expression of TGF alpha ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.131.4.1396310

    authors: Nelson KG,Takahashi T,Lee DC,Luetteke NC,Bossert NL,Ross K,Eitzman BE,McLachlan JA

    更新日期:1992-10-01 00:00:00

  • Effects of polypeptide YY(3-36) upon luteinizing hormone-releasing hormone and gonadotropin secretion in prepubertal rats: in vivo and in vitro studies.

    abstract::Polypeptide YY(3-36) (PYY(3-36)) is a gastrointestinal secreted molecule, agonist of neuropeptide Y (NPY) receptor subtypes Y2 and Y5, recently involved in the control of food intake. Notably, several factors with key roles in energy homeostasis conduct pleiotropic effects upon the reproductive axis. However, whether ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2004-0858

    authors: Fernandez-Fernandez R,Aguilar E,Tena-Sempere M,Pinilla L

    更新日期:2005-03-01 00:00:00

  • Glucocorticoids induce rapid up-regulation of mitogen-activated protein kinase phosphatase-1 and dephosphorylation of extracellular signal-regulated kinase and impair proliferation in human and mouse osteoblast cell lines.

    abstract::A central feature of glucocorticoid (GC)-induced osteoporosis is decreased bone formation, secondary to decreased numbers of functional osteoblasts. We find that ERK activity is essential for serum-induced osteoblast proliferation in vitro because inhibition of MAPK/ERK kinase activity by U0126 completely abolished bo...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2002-220769

    authors: Engelbrecht Y,de Wet H,Horsch K,Langeveldt CR,Hough FS,Hulley PA

    更新日期:2003-02-01 00:00:00

  • Stimulation of hepatic signal transducer and activator of transcription 5b by GH is not altered by 3-methylcholanthrene.

    abstract::We are investigating the mechanisms by which aromatic hydrocarbons, such as 3-methylcholanthrene (MC), suppress hepatic cytochrome P450 2C11 (CYP2C11) gene expression. CYP2C11 is an enzyme expressed in the liver of male rats and is regulated by a pulsatile pattern of GH secretion. We have previously shown that MC atte...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2002-220212

    authors: Timsit YE,Riddick DS

    更新日期:2002-09-01 00:00:00

  • Antenatal dexamethasone treatment in midgestation reduces system A-mediated transport in the late-gestation murine placenta.

    abstract::Clinically, approximately 30% of women who receive synthetic glucocorticoids (sGC) for risk of preterm labor carry to term. In vitro studies have shown that sGC acutely regulate the placental system A amino acid transporter, but there are no comparable data in vivo. Hence, the objective of our study was to examine the...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2011-0104

    authors: Audette MC,Challis JR,Jones RL,Sibley CP,Matthews SG

    更新日期:2011-09-01 00:00:00

  • Insulin-like factor 3 promotes wound healing at the ocular surface.

    abstract::Tear fluid is known to contain many different hormones with relevance for ocular surface homeostasis. We studied the presence and functional role of insulin-like factor 3 (INSL3) and its cognate receptor RXFP2 (relaxin/insulin-like family peptide receptor 2) at the ocular surface and in tears. Expression of human INSL...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2012-2201

    authors: Hampel U,Klonisch T,Sel S,Schulze U,Garreis F,Seitmann H,Zouboulis CC,Paulsen FP

    更新日期:2013-06-01 00:00:00

  • Effect of electrical stimulation of mammary nerve upon pituitary and plasma prolactin concentrations in anesthetized lactating rats.

    abstract::A 50-70% depletion in the anterior pituitary concentration of PRL occurred within 5 min of electrical stimulation of a single abdominal mammary nerve of urethane-anesthetized lactating rats previously nonsuckled for 6-8 h. The stimulus parameters were: 1-msec pulses, 10-20/sec at 5-30 V applied 5 sec on and 10 sec off...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-106-2-458

    authors: Mena F,Pacheco P,Grosvenor CE

    更新日期:1980-02-01 00:00:00

  • Rosiglitazone Improves Insulin Resistance Mediated by 10,12 Conjugated Linoleic Acid in a Male Mouse Model of Metabolic Syndrome.

    abstract::Trans-10, cis-12 conjugated linoleic acid (10,12 CLA) is a dietary fatty acid that promotes weight loss and disproportionate fat loss. Obese mice fed a high-fat, high-sucrose (HFHS) diet containing 10,12 CLA are resistant to weight gain and contain markedly reduced subcutaneous fat and adiponectin, with a concurrent l...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2017-00213

    authors: Wang S,Goodspeed L,Turk KE,Houston B,den Hartigh LJ

    更新日期:2017-09-01 00:00:00

  • Interleukin-6 stimulates placental lactogen expression by human trophoblast cells.

    abstract::Interleukin-6 (IL-6) stimulates the release of hCG from syncytiotrophoblast cells, but the effects of IL-6 and other cytokines on the release of placental lactogen (hPL) are unknown. To determine the effect of IL-6 on hPL release, we exposed an enriched fraction of trophoblast cells (prepared by the isopycnic centrifu...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.135.2.8033820

    authors: Stephanou A,Handwerger S

    更新日期:1994-08-01 00:00:00

  • Genomic characterization of human and rat prolactinomas.

    abstract::Although prolactinomas can be effectively treated with dopamine agonists, about 20% of patients develop dopamine resistance or tumor recurrence after surgery, indicating a need for better understanding of underlying disease mechanisms. Although estrogen-induced rat prolactinomas have been widely used to investigate th...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2012-1056

    authors: Tong Y,Zheng Y,Zhou J,Oyesiku NM,Koeffler HP,Melmed S

    更新日期:2012-08-01 00:00:00

  • Hypoxia induces vascular endothelial growth factor gene transcription in human osteoblast-like cells through the hypoxia-inducible factor-2alpha.

    abstract::VEGF is produced by osteoblasts and has been postulated to function as an angiogenic stimulus during normal skeletal development and in fracture repair. In this study, we characterized the molecular mechanisms by which experimental hypoxia increases VEGF mRNA in human MG63 osteoblast-like cells. Exposure of MG63 cells...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.142.2.8112

    authors: Akeno N,Czyzyk-Krzeska MF,Gross TS,Clemens TL

    更新日期:2001-02-01 00:00:00

  • Adaptive Significance of ERα Splice Variants in Killifish (Fundulus heteroclitus) Resident in an Estrogenic Environment.

    abstract::The possibility that chronic, multigenerational exposure to environmental estrogens selects for adaptive hormone-response phenotypes is a critical unanswered question. Embryos/larvae of killifish from an estrogenic-polluted environment (New Bedford Harbor, MA [NBH]) compared with those from a reference site overexpres...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2016-1052

    authors: Cotter KA,Nacci D,Champlin D,Yeo AT,Gilmore TD,Callard GV

    更新日期:2016-06-01 00:00:00

  • ALK2/ALK3-BMPR2/ACVR2A Mediate BMP2-Induced Downregulation of Pentraxin 3 Expression in Human Granulosa-Lutein Cells.

    abstract::Bone morphogenetic protein 2 (BMP2) belongs to the transforming growth factor-β superfamily and plays a critical role in regulating ovarian follicle function. Currently, the role of BMP2 during cumulus expansion remains to be determined. The aim of this study was to investigate the effect of BMP2 on the regulation of ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2017-00436

    authors: Bai L,Chang HM,Cheng JC,Chu G,Leung PCK,Yang G

    更新日期:2017-10-01 00:00:00

  • Progesterone stimulates mammary gland ductal morphogenesis by synergizing with and enhancing insulin-like growth factor-I action.

    abstract::Progestins have been implicated in breast cancer development, yet a role for progesterone (Pg) in ductal morphogenesis (DM) has not been established. To determine whether Pg could cause DM, we compared relative effects of Pg, estradiol (E2) and IGF-I on anatomical and molecular biological parameters of IGF-I-related D...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2004-1360

    authors: Ruan W,Monaco ME,Kleinberg DL

    更新日期:2005-03-01 00:00:00

  • Lactotransferrin gene expression in the mouse uterus and mammary gland.

    abstract::The mouse mammary gland and uterus expressed the gene for the secretory protein lactotransferrin under various physiological conditions. Lactotransferrin, however, was induced by estrogen in a time- and dose-dependent fashion in the uterus of the immature mouse, but was not affected by estrogen in the mammary gland. D...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-124-2-992

    authors: Teng CT,Pentecost BT,Chen YH,Newbold RR,Eddy EM,McLachlan JA

    更新日期:1989-02-01 00:00:00

  • Addition of Estradiol to Cross-Sex Testosterone Therapy Reduces Atherosclerosis Plaque Formation in Female ApoE-/- Mice.

    abstract::The contributions of estradiol and testosterone to atherosclerotic lesion progression are not entirely understood. Cross-sex hormone therapy (XHT) for transgender individuals dramatically alters estrogen and testosterone levels and consequently could have widespread consequences for cardiovascular health. Yet, no prec...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2017-00884

    authors: Goetz TG,Mamillapalli R,Sahin C,Majidi-Zolbin M,Ge G,Mani A,Taylor HS

    更新日期:2018-02-01 00:00:00

  • Regulatory effect of lithium on thyroxine metabolism in murine neural and anterior pituitary tissue.

    abstract::The conversion of T4 to T3 in the brain and anterior pituitary gland contributes significantly to the T3 content of these tissues and appears to be an important modulator of thyroid hormone action. In the present study, the antimanic agent lithium was demonstrated in cultured neural and pituitary tissue to have a sign...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-120-4-1430

    authors: St Germain DL

    更新日期:1987-04-01 00:00:00

  • The relative contribution of thyroxine and triiodothyronine to the hormone secretion from the perfused canine thyroid during various degrees of stimulation.

    abstract::The effect of constant infusions of bovine TSH in different concentrations on the pattern of T4 and T3 secretion was examined in perfused canine thyroids isolated in situ. Each of the thyroid lobes was isolated and perfused in each animal. It was thus possible to examine the effect of two different concentrations of T...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-100-3-656

    authors: Laurberg P

    更新日期:1977-03-01 00:00:00

  • Evidence for an interaction between CB1 cannabinoid and melanocortin MCR-4 receptors in regulating food intake.

    abstract::Melanocortin receptor 4 (MCR4) and CB(1) cannabinoid receptors independently modulate food intake. Although an interaction between the cannabinoid and melanocortin systems has been found in recovery from hemorrhagic shock, the interaction between these systems in modulating food intake has not yet been examined. The p...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2004-0059

    authors: Verty AN,McFarlane JR,McGregor IS,Mallet PE

    更新日期:2004-07-01 00:00:00

  • A novel inhibitory protein in adipose tissue, the aldo-keto reductase AKR1B7: its role in adipogenesis.

    abstract::The aldo-keto reductase 1B7 (AKR1B7) encodes an aldose-reductase that has been reported as a detoxification enzyme until now. We have demonstrated that AKR1B7 is differently expressed in various mouse white adipose tissues depending on their location. Its expression is associated with a higher ratio of preadipocytes v...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2006-1707

    authors: Tirard J,Gout J,Lefrançois-Martinez AM,Martinez A,Begeot M,Naville D

    更新日期:2007-05-01 00:00:00

  • The mechanism of parathyroid hormone action on calcium reabsorption by the distal tubule.

    abstract::PTH increases calcium reabsorption exclusively in the distal nephron. Two mechanisms of Ca++ transport through the basolateral membrane (BLM) have been described: the ATP-dependent and the sodium gradient-dependent transport. In the present study, we investigated the effect of PTH and (Bu)2cAMP on these two mechanisms...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-128-1-251

    authors: Bouhtiauy I,Lajeunesse D,Brunette MG

    更新日期:1991-01-01 00:00:00

  • Cytokine-inducible SH2 protein up-regulation is associated with desensitization of GH signaling in GHRH-transgenic mice.

    abstract::The effects of continuous high GH levels on GH signal transduction through the GH receptor (GHR)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) pathway as well as the desensitization of this pathway by suppressors of cytokine signaling (SOCS) were studied in transgenic mice overexpres...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.143.2.8616

    authors: González L,Miquet JG,Sotelo AI,Bartke A,Turyn D

    更新日期:2002-02-01 00:00:00

  • Disparate changes in kisspeptin and neurokinin B expression in the arcuate nucleus after sex steroid manipulation reveal differential regulation of the two KNDy peptides in rats.

    abstract::Kisspeptin, neurokinin B (NKB) and dynorphin A are coexpressed in a population of neurons in the arcuate nucleus (ARC), termed KNDy neurons, which were recently recognized as important elements for the generation of GnRH pulses. However, the topographic distribution of these peptides and their regulated expression by ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2014-1200

    authors: Overgaard A,Ruiz-Pino F,Castellano JM,Tena-Sempere M,Mikkelsen JD

    更新日期:2014-10-01 00:00:00

  • Chemerin suppresses ovarian follicular development and its potential involvement in follicular arrest in rats treated chronically with dihydrotestosterone.

    abstract::In the present study, we have investigated the cellular mechanisms of androgen-induced antral follicular growth arrest and the possible involvement of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) in this process, using a chronically androgenized rat model. We hypothesize that hyperandrogenism induces a...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2013-1001

    authors: Kim JY,Xue K,Cao M,Wang Q,Liu JY,Leader A,Han JY,Tsang BK

    更新日期:2013-08-01 00:00:00

  • Activation of the phosphatidylinositol pathway in the primate corpus luteum by prostaglandin F2 alpha.

    abstract::The current study was designed to investigate the ability of prostaglandin F2 alpha (PGF2 alpha) to activate a second messenger system (phosphatidylinositol pathway) in corpora lutea (CL) of rhesus monkeys. Activation of this pathway was assessed by monitoring the hydrolysis of phosphatidylinositol to inositol phospha...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.131.2.1639020

    authors: Houmard BS,Guan Z,Stokes BT,Ottobre JS

    更新日期:1992-08-01 00:00:00