Abstract:
:Reproductive function is dependent on the interaction between GnRH and its cognate receptor found on gonadotrope cells of the anterior pituitary gland. GnRH activation of the GnRH receptor (GnRHR) is a potent stimulus for increased expression of multiple genes including the gene encoding the GnRHR itself. Thus, homologous regulation of the GnRHR is an important mechanism underlying gonadotrope sensitivity to GnRH. Previously, we have found that GnRH induction of GnRHR gene expression in alpha T3-1 cells is partially mediated by protein kinase C activation of a canonical activator protein-1 (AP-1) element. In contrast, protein kinase A and a cAMP response element-like element have been implicated in mediating the GnRH response of the GnRHR gene using a heterologous cell model (GGH(3)). Herein we find that selective removal of the canonical AP-1 site leads to a loss of GnRH regulation of the GnRHR promoter in transgenic mice. Thus, an intact AP-1 element is necessary for GnRH responsiveness of the GnRHR gene both in vitro and in vivo. Based on in vitro analyses, GnRH appeared to enhance the interaction of JunD, FosB, and c-Fos at the GnRHR AP-1 element. Although enhanced binding of cFos reflected an increase in gene expression, GnRH appeared to regulate both FosB and JunD at a posttranslational level. Neither overexpression of a constitutively active Raf-kinase nor pharmacological blockade of GnRH-induced ERK activation eliminated the GnRH response of the GnRHR promoter. GnRH responsiveness was, however, lost in alpha T3-1 cells that stably express a dominant-negative c-Jun N-terminal kinase (JNK) kinase, suggesting a critical role for JNK in mediating GnRH regulation of the GnRHR gene. Consistent with this possibility, we find that the ability of forskolin and membrane-permeable forms of cAMP to inhibit the GnRH response of the GnRHR promoter is associated with a loss of both JNK activation and GnRH-mediated recruitment of the primary AP-1-binding components.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Ellsworth BS,White BR,Burns AT,Cherrington BD,Otis AM,Clay CMdoi
10.1210/en.2002-220784subject
Has Abstractpub_date
2003-03-01 00:00:00pages
839-49issue
3eissn
0013-7227issn
1945-7170journal_volume
144pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::The conceptus and endometrium secrete large amounts of prostaglandin E₂ (PGE₂) into the porcine uterine lumen during the periimplantation period. We hypothesized that PGE₂ acts on conceptus/trophoblast cells through auto- and paracrine mechanisms. Real-time RT-PCR analysis revealed that PGE₂ receptor (PTGER)2 mRNA was...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-2271
更新日期:2013-10-01 00:00:00
abstract::Sertoli cell intracellular protein 1 (SCc1) and 2 (SCc2) are polypeptides found in rat Sertoli cell cultures incubated with either FSH or (Bu)2cAMP. They were first identified in [35S]methionine-labeled Sertoli cell lysates using two-dimensional gel electrophoresis. Here we extend these observations by showing that SC...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.131.5.1330490
更新日期:1992-11-01 00:00:00
abstract::Growth hormone-releasing factor-like immunoreactivity (GRF-LI) was detected in partially purified extracts of rat hypothalamus and duodenum with a highly specific RIA for rat GRF (rGRF). The concentration of rGRF-LI in the rat hypothalamus was 32.5 fmol/mg dry weight (455 fmol or 3.18 ng/region), while the rat duodenu...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-4-1710
更新日期:1985-10-01 00:00:00
abstract::To determine the relative role of the androgenic and/or estrogenic components of the action of dehydroepiandrosterone (DHEA) on the histomorphology and structure of the rat mammary gland, ovariectomized (OVX) female animals received DHEA administered alone or in combination with the pure antiandrogen flutamide or the ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.139.2.5762
更新日期:1998-02-01 00:00:00
abstract::The present study employed the dehydroepiandrosterone (DHA) loading test to determine if the placenta in baboons remains functional following fetectomy. A bolus iv injection of 100 mg DHA was given to 4 baboons prior to and at various intervals following fetectomy at midgestation. Blood samples were withdrawn over a 4...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-2-843
更新日期:1985-02-01 00:00:00
abstract::Maternal immune tolerance is required for extravillous trophoblasts (EVTs) to invade the decidua without rejection. Endoplasmic reticulum aminopeptidase-1 (ERAP1) generates human leukocyte antigen (HLA) class I-adapted antigenic peptides, but its function in trophoblasts lacking classical HLA class I molecules remains...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-1449
更新日期:2006-04-01 00:00:00
abstract::Pulmonary surfactant is a developmentally and hormonally regulated lipoprotein synthesized exclusively in alveolar type II cells. Surfactant protein-A (SP-A) gene transcription in human fetal lung in culture is stimulated by glucocorticoids and cAMP; cAMP also enhances the rate of type II cell differentiation. The CCA...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.12.5637
更新日期:1997-12-01 00:00:00
abstract::Male and female Wistar-Furth rats bearing the pituitary tumor MtT/W15 had serum GH and PRL levels several hundred-fold higher, and immunoreactive somatomedin levels 3-fold higher, than those of controls. The presence of tumor appeared to have no effect on specific binding of radioiodinated bovine GH to liver microsoma...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-111-3-1020
更新日期:1982-09-01 00:00:00
abstract::Pancreatic islets express the superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, but its role remains unknown. To address this, we studied the mechanisms of impaired insulin secretion induced by diphenyleneiodium (DPI), an NADPH oxidase inhibitor. We investigated the effects of DP...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-0186
更新日期:2008-11-01 00:00:00
abstract::Dopamine D2 receptor agonists are commonly used in the control of PRL-secreting adenomas, and the sensitivity of dopamine agonists during long term therapy is exquisite. However, the molecular mechanisms responsible for the maintenance of this cellular sensitivity to dopamine agonists remain poorly understood. In the ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.10.5433
更新日期:1997-10-01 00:00:00
abstract::Estrogen is generally considered to maintain bone mass through suppression of bone resorption. We have previously demonstrated that administration of pharmacological doses of estrogen increases bone formation in rats. Because such high doses of estrogen might induce bone formation through some mechanism other than the...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.5.1572310
更新日期:1992-05-01 00:00:00
abstract::We have investigated the effect of GH on microtubular physiology in Chinese hamster ovary (CHO) cells stably transfected with the complementary DNA for the rat GH receptor (CHO-GHR(1-638)). We show here that after 30 min of human GH (hGH) treatment of CHO-GHR(1-638) cells, there was a significant increase in the level...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.139.10.6237
更新日期:1998-10-01 00:00:00
abstract::The impact of clinical progestins used in contraception and hormone therapies on the metabolic capacity of the brain has long-term implications for neurological health in pre- and postmenopausal women. Previous analyses indicated that progesterone and 17β-estradiol (E2) sustain and enhance brain mitochondrial energy-t...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2010-1061
更新日期:2011-02-01 00:00:00
abstract::To study the role of the epithelial calcium channel transient receptor potential vanilloid type 6 (TRPV6) and the calcium-binding protein calbindin-D9k in intestinal calcium absorption, TRPV6 knockout (KO), calbindin-D9k KO, and TRPV6/calbindin-D(9k) double-KO (DKO) mice were generated. TRPV6 KO, calbindin-D9k KO, and...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-1655
更新日期:2008-06-01 00:00:00
abstract::GH promotes not only longitudinal growth in children but is active throughout life in protein, fat, and carbohydrate metabolism. The multiple actions of GH start when GH binds to the cell surface-expressed GH receptor. Effectiveness of the hormone depends both on its presence in the circulation and the availability of...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.143.4.8755
更新日期:2002-04-01 00:00:00
abstract::Reproductive fitness in females is susceptible to obesogenic diets. Energy balance and reproduction are tightly regulated, in part, by hypothalamic neurons in the arcuate nucleus (ARC), and high-fat diet (HFD) can steadily increase estradiol levels in rodents. Estradiol regulates the reproductive axis via negative fee...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endocr/bqaa146
更新日期:2020-10-01 00:00:00
abstract::We have used immunohistochemistry to define the cellular distribution of GH receptors in the gastrointestinal tract (GIT) and its derivatives. Immunohistochemistry was performed in the adult rat GIT with a panel of characterized monoclonal antibodies to the GH receptor. The most intense and heterogeneous immunoreactiv...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-126-1-299
更新日期:1990-01-01 00:00:00
abstract::To evaluate the possible existence of masked gonadotropin receptors in the corpus luteum, we characterized the effects of alcohols and neuraminidase on [125I]iodohuman LH binding to in vitro preparations of luteal tissue from the rhesus monkey and pseudopregnant rat. The presence of 1-8% (vol/vol) ethanol enhanced spe...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-2-747
更新日期:1985-08-01 00:00:00
abstract::The gene encoding the human TNF alpha receptor (TNFR) 2 contains polymorphisms in the 3' untranslated region (UTR). Previous studies have shown that some variant alleles in this region are associated with obesity and insulin resistance. However, the effect of these polymorphisms on the expression of TNFR2 has not been...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-1366
更新日期:2005-05-01 00:00:00
abstract::To investigate further brain-pituitary-gonadal interrelationships we have generated mice in which the gene encoding the FSH receptor has been disrupted. Female FSH receptor knockout (FSHRKO) mice were infertile. The ovaries were significantly reduced in size, with follicular development arrested at the preantral stage...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.5.7456
更新日期:2000-05-01 00:00:00
abstract::The mechanism of the inhibitory effect of long term treatment with estradiol on dopamine synthesis in tuberoinfundibular dopaminergic (TIDA) neurons was studied by using hypothalamic slices from ovariectomized rats. Treatment with 2 mg estradiol valerate (EV) at a 3-week interval increased the weight of the anterior p...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-121-2-692
更新日期:1987-08-01 00:00:00
abstract::The binding of [125I]iodo-low density lipoprotein ([125I]iodo-LDL) to isolated membranes was determined for the outer (glomerulosa/fasciculata) and inner (reticularis) zones of the guinea pig adrenal cortex. Binding of [125I]iodo-LDL to membranes from both zones was found to be highly specific and dependent on the pre...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-118-2-653
更新日期:1986-02-01 00:00:00
abstract::Glutamate (Glu) is the most prevalent excitatory neurotransmitter in the brain and has been implicated in the regulation of GnRH secretion in several mammalian species, including the monkey. To investigate the neuroanatomical basis for Glu-GnRH interactions, we performed an immunocytochemical study at both the light a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.134.2.7905410
更新日期:1994-02-01 00:00:00
abstract::We have examined the expression, postnatal ontogeny, and localization of mouse GH (mGH) and its relative expression during pregnancy, lactation, and weaning in the mouse. mGH mRNA and protein was expressed predominantly in the epithelial component of the mammary gland, and maximal expression was observed during the pu...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-1082
更新日期:2006-04-01 00:00:00
abstract::3-Iodothyronamine (T(1)AM) is an endogenous thyroid hormone derivative with unknown biosynthetic origins. Structural similarities have led to the hypothesis that T(1)AM is an extrathyroidal metabolite of T(4). This study uses an isotope-labeled T(4) [heavy-T(4) (H-T(4))] that can be distinguished from endogenous T(4) ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-1254
更新日期:2012-11-01 00:00:00
abstract::We have examined the regulation of an insulin-like growth factor-binding protein-3 (IGFBP-3) protease secreted by MCF-7 human breast cancer cells using a ligand-binding assay that relies on the decrease in affinity for des(1-3)IGF-I that occurs when IGFBP-3 becomes proteolyzed. IGFBP-3 protease activity was not altere...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.9.7684
更新日期:2000-09-01 00:00:00
abstract::Folliculostellate (FS) cells are known to communicate with each other and with endocrine cells via gap junctions in the anterior pituitary. We investigated whether TGFbeta3 and estradiol, known to regulate FS cell production and secretion of basic fibroblast growth factor (bFGF), increases gap junctional communication...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0122
更新日期:2005-09-01 00:00:00
abstract::The estrogen receptor-alpha (ERalpha) pituitary-specific variant, TERP-1, is regulated dramatically by physiological status. We examined hormonal regulation of the TERP-1 promoter in transient transfection assays in GH3 somatolactotrope cells. We found that 17beta-estradiol (E2), genistein, androgen, pituitary adenyla...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-1053
更新日期:2006-01-01 00:00:00
abstract::Apoptosis is the process of cellular self-destruction, and genes such as bcl-2 and bax are known to inhibit and promote apoptosis, respectively. In this study, we show that apoptosis can be induced in pancreatic beta-cell lines, and we investigate the apoptotic pathways through the bcl-2 and bax genes and intracellula...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.139.3.5798
更新日期:1998-03-01 00:00:00
abstract::The present studies investigated whether insulin inhibits the stimulatory effect of dexamethasone (DEX) on angiotensinogen (ANG) gene expression and induction of hypertrophy in rat immortalized renal proximal tubular cells (IRPTCs) in a high-glucose milieu. Rat IRPTCs were cultured in monolayer. ANG and ANG mRNA expre...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2002-220408
更新日期:2002-12-01 00:00:00