Abstract：
:A central question in glucocorticoid mechanism of action via the glucocorticoid receptor (GR) is what determines ligand-selective transcriptional responses. Using a panel of 12 GR ligands, we show that the extent of GR phosphorylation at S226 and S211, GR half-life and transcriptional response, occur in a ligand-selective manner. While GR phosphorylation at S226 was shown to inhibit maximal transcription efficacy, phosphorylation at S211 is required for maximal transactivation, but not for transrepression efficacy. Both ligand-selective GR phosphorylation and half-life correlated with efficacy for transactivation and transrepression. For both expressed and endogenous GR, in two different cell lines, agonists resulted in the greatest extent of phosphorylation and the greatest extent of GR downregulation, suggesting a link between these functions. However, using phosphorylation-deficient GR mutants we established that phosphorylation of the GR at S226 or S211 does not determine the rank order of ligand-selective GR transactivation. These results are consistent with a model whereby ligand-selective GR phosphorylation and half-life are a consequence of upstream events, such as ligand-specific GR conformations, which are maintained in the phosphorylation mutants.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Avenant C,Ronacher K,Stubsrud E,Louw A,Hapgood JPdoi
10.1016/j.mce.2010.06.007subject
Has Abstractpub_date
2010-10-07 00:00:00pages
72-88issue
1-2eissn
0303-7207issn
1872-8057pii
S0303-7207(10)00333-3journal_volume
327pub_type
杂志文章abstract：:The production of glucocorticoids and aldosterone in the adrenal cortex is regulated at multiple levels. Biosynthesis of these hormones is initiated when cholesterol, the substrate, enters the inner mitochondrial membrane for conversion to pregnenolone. Unlike most metabolic pathways, the biosynthesis of adrenocortica...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章,评审
doi：10.1016/j.mce.2012.11.014
更新日期：2013-05-22 00:00:00
abstract：:Glucocorticoid hormones suppress circulating concentrations of thyrotrophin (TSH), but their effect on synthesis of TSH in the pituitary gland is unclear. We have examined the influence of the glucocorticoid dexamethasone on serum TSH, pituitary TSH content and TSH beta- and alpha-subunit mRNA concentrations in pituit...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/0303-7207(89)90064-6
更新日期：1989-06-01 00:00:00
abstract：:Insulin receptor substrate-1 (IRS-1) is a protein expressed in 3T3-L1 adipocytes that is involved in most, if not all of the biological responses to insulin. Chronic exposure of these cells to insulin down-regulates IRS-1 by stimulating its degradation (Rice, K.M., Turnbow, M.A. and Garner, C.W. (1993) Biochem. Biophy...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/0303-7207(96)03875-0
更新日期：1996-08-30 00:00:00
abstract：:P450 oxidoreductase (POR) is the obligate electron donor for microsomal cytochrome P450s and mutations in POR cause several metabolic disorders. We have modeled the structure of human P450 oxidoreductase by in silico amino acid replacements in the rat POR crystal structure. The rat POR has 94% homology with human POR ...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2009.09.001
更新日期：2009-12-10 00:00:00
abstract：:The CYP11A1 gene encodes cytochrome P450scc, the enzyme catalyzing the first step of steroid biosynthesis in the adrenal and gonad. We generated transgenic mice containing 2.3 kb of the 5'-flanking region of CYP11A1 driving LacZ reporter gene expression, in order to study hormonal control of CYP11A1 gene expression in...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/s0303-7207(01)00388-4
更新日期：2001-04-25 00:00:00
abstract：:Increasing evidence in recent years has demonstrated the regulatory effects of arachidonic acid and its metabolites on steroid hormone production in various steroidogenic tissues. In trophic hormone-stimulated steroidogenesis, arachidonic acid is rapidly released from phospholipids. This release is dependent upon horm...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章,评审
doi：10.1016/s0303-7207(99)00130-6
更新日期：1999-12-20 00:00:00
abstract：:Peroxisome proliferator-activated receptors (PPAR)α have been shown to exert immunomodulatory effects in autoimmune disorders; no study evaluated the effect of PPARα activation in Graves' ophthalmopathy (GO). We show the presence of PPARα, δ and γ in GO fibroblasts and preadipocytes. PPARα activators have a potent inh...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2011.11.001
更新日期：2012-02-26 00:00:00
abstract：:The enzyme aromatase converts androgens to estrogens, which have recently been postulated to be essential for testicular development and fertility. Understanding the mechanisms that regulate aromatase activity in the testis may therefore have implications for treatment of male infertility. Aromatase is encoded by the ...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2010.03.001
更新日期：2010-07-29 00:00:00
abstract：:Hypospadias is one of the most common congenital malformations. It is considered to be a mild form of the 46,XY disorders of sex development (DSD), but its precise etiology remains to be elucidated. Compromised androgen synthesis or effects can cause this frequent malformation, although the mutational analyses of the ...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章,评审
doi：10.1016/j.mce.2011.01.006
更新日期：2011-03-30 00:00:00
abstract：:The transcription factors involved in the activation of cardiac gene expression by angiotensin II (Ang II) in vivo are not well understood. Here we studied the contribution of transcriptional elements to the activation of the cardiac B-type natriuretic peptide (BNP) gene promoter by Ang II in conscious rats and in ang...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2007.05.003
更新日期：2007-07-15 00:00:00
abstract：:Using primary cultures of porcine Sertoli cells as a model, the effects of ovine prolactin (oPRL) on Sertoli cell function were investigated through FSH binding. PRL treatment (0.3-5 ng/ml) induced a dose-dependent increase (ED50 = 5.10(-11) M) of 125I-FSH binding to Sertoli cells to a maximal stimulation (about 2.5-f...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/0303-7207(96)03891-9
更新日期：1996-09-18 00:00:00
abstract：:Serine/threonine protein phosphatase 2A (PP2A) regulates diverse physiological processes such as cell cycle, growth, apoptosis, and signal transduction. Previously, we demonstrated that silencing of the α-isoform of PP2A catalytic subunit (PP2A Cα) in osteoblasts accelerated osteoblast differentiation, whereas its ove...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2017.11.005
更新日期：2018-07-15 00:00:00
abstract：:TRESK (TWIK-related spinal cord K(+) channel, KCNK18) belongs to the two-pore domain (K2P) background (leak) potassium channel family. Unlike other K2P channels, TRESK is activated by the calcium signal in heterologous expression systems. The activation is mediated by the calcium/calmodulin-dependent protein phosphata...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章,评审
doi：10.1016/j.mce.2011.11.009
更新日期：2012-04-28 00:00:00
abstract：:A cDNA for a prostaglandin E(2) (PGE(2)) receptor subtype 4, EP4b (Ptger4b), was cloned from the medaka ovary. The effect of PGE(2) was examined using COS-7 cells expressing the recombinant Ptger4b protein. An increase in intracellular cAMP levels was observed when the cells were incubated with PGE(2), but the increas...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2012.05.013
更新日期：2012-10-15 00:00:00
abstract：:The functional significance of two unlinked human vitamin D receptor (hVDR) gene polymorphisms was evaluated in twenty human fibroblast cell lines. Genotypes at both a Fok I restriction site (F/f) in exon II and a singlet (A) repeat in exon IX (L/S) were determined, and relative transcription activities of endogenous ...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/s0303-7207(01)00406-3
更新日期：2001-05-25 00:00:00
abstract：:South African Angora goats are susceptible to cold stress, due to their inability to produce sufficient levels of cortisol. During adrenal steroidogenesis the production of cortisol relies on the activity of two key enzymes, namely cytochrome P450 17alpha-hydroxylase and 3beta-hydroxysteroid dehydrogenase. Cytochrome ...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2009.07.026
更新日期：2010-02-05 00:00:00
abstract：:The mouse mammary tumor virus (MMTV) initiates infection when the envelope protein, gp52, binds to a cell surface protein and triggers internalization. The hormonal regulation of this protein was studied both in vitro and in vivo. In mammary gland explant culture, levels of the MMTV binding protein were maintained onl...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/0303-7207(91)90024-m
更新日期：1991-12-01 00:00:00
abstract：:Insulin-like growth factor-I (IGF-I) is involved in the growth and development of liver and brain during fetal life by acting through specific plasma membrane receptors. In an attempt to determine how the changes in IGF-I receptor number are regulated during development, we have compared [125I]IGF-I binding to membran...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/0303-7207(94)90222-4
更新日期：1994-05-01 00:00:00
abstract：:Enzymatically dispersed rat pituitary cells were grown in primary culture, and LHRH-stimulated LH secretion was measured. Testosterone (T) decreased and 17 beta-estradiol (E) increased pituitary responsiveness to LHRH. The effect of E on LH secretion was partly due to an increase in LH content. There was a latent peri...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/0303-7207(82)90013-2
更新日期：1982-04-01 00:00:00
abstract：:Studies were conducted in vitro and in vivo to determine whether or not inhibin affects the transcription rate of the gene for the beta subunit of follicle stimulating hormone (FSH beta). Pituitary cells in primary culture were incubated with 0-3000 milli-units/ml inhibin; a dose-related decrement in mRNA was obtained...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/0303-7207(93)90274-n
更新日期：1993-02-01 00:00:00
abstract：:Humans maintain core temperature through a complex neuroendocrine circuitry, coupling environmental thermal and nutritional cues to heat-producing and dissipating mechanisms. Up to 40% of resting energy expenditure contributes to thermal homeostasis maintenance. Recent re-discovery of thermogenic brown adipose tissue ...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章,评审
doi：10.1016/j.mce.2015.05.025
更新日期：2015-12-15 00:00:00
abstract：:The juvenoid, methyl farnesoate (MF), is synthesized in the mandibular organs (MOs) of crustaceans, under the control of mandibular organ-inhibiting hormone (MO-IH). Using an in vitro assay to measure synthesis of MF by MOs, the effect of a variety of agents that affect signal transduction pathways was investigated. O...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/s0303-7207(99)00090-8
更新日期：1999-08-20 00:00:00
abstract：:Both constitutive and ligand-mediated membrane trafficking regulate Epidermal Growth Factor Receptor (EGFR) signaling. The constitutive endocytosis and recycling of the unliganded EGFR is a critical determinant of cell surface EGFR expression and the cell's sensitivity to ligands. We report that two proteins with esta...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2013.07.029
更新日期：2013-12-05 00:00:00
abstract：:The role of cannabinoid receptor I (CBR-1) in the induction of decidualization was examined using decidual fibroblasts and human endometrial stromal cells as model systems. Decidual fibroblasts decidualized in vitro for 3 and 6 days in the presence of the CBR-1 agonist R(+)-WIN 55,212-2 mesylate (WIN, 0.1-10 microM) e...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2004.09.007
更新日期：2005-01-14 00:00:00
abstract：:Wnt signaling is an evolutionarily conserved pathway that regulates cell proliferation, differentiation and apoptosis. To investigate the possible role of Wnt signaling in the regulation of ovarian follicular development, secondary follicles were isolated and cultured in vitro in the presence or absence of its activat...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2013.11.007
更新日期：2014-02-15 00:00:00
abstract：:Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipogenesis. It is also a central player in energy metabolism, inflammation and immunity. As an important nuclear transcription factor, PPARγ can regulate the expression and function of genes or biological processes directly or indirectly ...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2017.07.037
更新日期：2018-08-15 00:00:00
abstract：:The purpose of this paper is to review potential novel functional pathways by which estradiol and estrogenic compounds elicit biological responses in mammals. We will limit our approach to those novel functions suggested by phenotypes associated with estrogen receptor-alpha (ER alpha) gene mutations and polymorphisms....
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章,评审
doi：10.1016/s0303-7207(98)00170-1
更新日期：1998-10-25 00:00:00
abstract：:Members of the dual specificity tyrosine phosphorylated and regulated kinase family (Dyrk) were shown to have a highly testis-abundant or testis-restricted expression pattern. Furthermore, for some members of the family an involvement in gene expression regulation by phosphorylating transcription factors has been show...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2006.12.041
更新日期：2007-03-15 00:00:00
abstract：:The molecular basis of the organogenesis, homeostasis, and tumorigenesis of the adrenal cortex has been the subject of intense study for many decades. Specifically, characterization of tumor predisposition syndromes with adrenocortical manifestations and molecular profiling of sporadic adrenocortical tumors have led t...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章,评审
doi：10.1016/j.mce.2015.11.031
更新日期：2016-02-05 00:00:00
abstract：:Berberine has been shown to have insulin-sensitizing effect, but the molecular mechanism underlying remains elusive. In this work, we investigated the effect of berberine on insulin-induced signal transduction and glucose uptake in both insulin-sensitive and insulin-resistant rat skeletal muscle cells. Berberine incre...
journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章
doi：10.1016/j.mce.2009.12.027
更新日期：2010-04-12 00:00:00
