Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) is an extracellular binding protein that regulates the bioavailability of sex steroids. ABP/SHBG is closely related to the globular (G) domain of vitamin K-dependent protein S family of proteins and more distantly related to the G domains of several extracellular matrix proteins. ABP/SHBG appears to have evolved from the fusion of two ancestral G domains. Expanding evidence suggests that ABP/SHBG has other functions that are mediated through membrane binding, including signal transduction; however, the types of binding proteins (receptors) have not been identified. Sequence comparisons of ABP/SHBG with G domains of its homologs protein S, Gas6, laminin, and agrin have identified regions of ABP/SHBG that may bind receptors related to homolog receptors. These membrane receptors include beta-integrins, alpha-dystroglycan, and receptor tyrosine kinases. The G domains of laminin and related proteins have clearly evolved from a common ancestor to interact with specific receptors and binding proteins. It remains to be determined if ABP/SHBG followed this evolutionary pathway.
Steroids
PMID:Sequence and functional relationships between androgen-binding protein/sex hormone-binding globulin and its homologs protein S, Gas6, laminin, and agrin. 929 33

Previous work from our laboratory demonstrated that 1,25(OH)2D3 rapidly stimulated hydrolysis of membrane polyphosphoinositides (PI) in rat colonocytes and in Caco-2 cells, generating the second messengers DAG and IP3. [Ca2+]i subsequently increased due to IP3-mediated release of intracellular Ca2+ stores, and to Ca2+ influx through a receptor-mediated Ca channel. Studies examining purified antipodal plasma membranes and experiments using Caco-2 cell monolayers found that 1,25(OH)2D3 influenced PI turnover only in the basolateral (BLM) and not brush border (BBM) membranes. Vitamin D analogues with poor affinity for the vitamin D receptor were found to effectively stimulate PI turnover, suggesting the presence of a unique vitamin D receptor in the BLM. Studies from our laboratory have demonstrated saturable, reversible binding of 1,25(OH)2 D3 to colonocyte BLM. Recently, we found that 1,25(OH)2D3 activated the tyrosine kinase c-src in colonocyte BLM by a heterotrimeric guanine nucleotide binding protein (G-protein)-dependent mechanism, with subsequent phosphorylation, translocation to the BLM, and activation of PI-specific phospholipase C gamma. Due to the rise in [Ca2+]i and DAG, two isoforms of protein kinase C (PKCalpha and PKCbeta2), but not other isoforms were activated by 1,25(OH)2D3 in rat colonocytes. Recent studies demonstrated that the seco-steroid translocated the beta2 isoform to the BLM, but not the BBM. In contrast, the alpha isoform did not translocate to either antipodal plasma membrane, but modulated IP3-mediated Ca2+ release from the endoplasmic reticulum. Preliminary studies have shown that 1,25(OH)2D3 also activated phosphatidylcholine phospholipase D (PLD) in Caco-2 cells, generating phosphatidic acid and contributing to the sustained rise in DAG. PLD stimulation occurred by both PKC-dependent and -independent mechanisms. Inhibitors of G-proteins, c-src, and PKC blunted the seco-steroid-mediated activation of PLD. Cells stably transfected with sense PKCalpha showed increased 1,25(OH)2D3-stimulated PLD activation, whereas transfectants with antisense PKCalpha had an attenuated response. In addition, 1,25(OH)2D3 also regulated PLD by activating the monomeric G-protein rho A by a mechanism independent of the G-protein/ c-src/PKC pathway.
Steroids
PMID:Rapid effects of 1,25(OH)2 vitamin D3 on signal transduction systems in colonic cells. 1032 82

Rapid biologic responses to injected steroids were described as early as 60 years ago. More recently, evidence has been presented that 17beta-estradiol given i.v. will double the uterine cAMP activity within 15 s (Proc Natl Acad Sci USA 1967;58:1711-8), and also that estrogens will bind to the outer surfaces of endometrial cells (Nature 1977;265:69-72), suggesting that these steroids can both engage and direct intracellular events. Unfortunately, studies of such rapid membrane effects of steroids have languished due to the accumulation of compelling data for the more slowly manifest actions of these compounds at the level of nuclear DNA. We report a number of observations in women, in experimental animals, and in isolated organ or cell systems using 17beta-estradiol, progesterone or glucocorticoids which provide ample evidence for rapid intracellular metabolic responses to these steroids, mediated by their actions at the cellular plasma membrane. Such rapid responses have been shown in various classic targets or not, such as the B cell of the endocrine pancreas and the fat cell. They involve plasma membrane binding, changes in membrane electrical activity, Ca2+ handling, G and Ras proteins, cAMP, cGMP, IP(3), DAG, phosphodiesterases, protein kinases, tyrosine kinases, ER kinases, and mitogen activated protein kinases (MAPks) and nitric oxide synthase. These recent findings are discussed in detail and should lead to a fuller understanding of the cellular effects of the steroid hormones.
Steroids 2002 Feb
PMID:Rapid non-genomic and genomic responses to progestogens, estrogens, and glucocorticoids in the endocrine pancreatic B cell, the adipocyte and other cell types. 1175 72

Extranuclear or nongenomic effects of thyroid hormones do not require interaction with the nuclear receptor, but are probably mediated by specific membrane receptors. This review will focus on the extranuclear effects of thyroid hormones on plasma membrane transport systems in non mammalian cells: chick embryo hepatocytes at two different stages of development, 14 and 19 days. At variance with mammals, the chick embryo develops in a closed compartment, beyond the influence of maternal endocrine factors. Thyroid hormones inhibit the Na+/K+-ATPase but stimulate the Na+/H+ exchanger and amino acid transport System A with different dose-responses: a bell-shaped curve in the case of the exchanger and a classic saturation curve in the case of System A. These effects are mimicked by the analog 3,5-diiodothyronine. Signal transduction is mediated by interplay among kinases, mainly protein kinase C and the MAPK pathway, initially primed by second messengers such as Ca2+, IP3, and DAG as in mammalian cells. Thyroid hormones and 3,5-diiodothyronine stimulate thymidine incorporation and DNA synthesis, associated with the increased levels and activity of cyclins and cyclin-dependent kinases involved in the G1/S transition, and also these effects have their starting point at the plasma membrane. Increasing evidence now demonstrates that thyroid hormones act as growth factors for chick embryo hepatocytes and their extranuclear effects are important for prenatal development and differentiation.
Steroids
PMID:Short-term effects of thyroid hormone in prenatal development and cell differentiation. 1586 27

Previously we demonstrated that estrone non-genomically regulates rat aortic NOS and COX activity and that this effect depends on ovarian activity. The purpose of the present study was to characterize this effect and investigate the participation of phospholipase C and phophatidylinositol-3-kinase system in the intracellular transduction pathway involved in the response. Using aortic strips isolated from female fertile rats we showed that estrone stimulate nitric oxide synthase and cyclooxygenase in a short time interval (5-20 min), and that NO production was dependent in part on PGI2 production since 1 microM indomethacin significantly reduced this free radical production. Injection of 17-beta-estradiol to ovariectomized rats restored tissue capacity to rapidly increase NO production in response to "in vitro" treatment with 1 nM estrone. We also demonstrated that in aortic strips isolated from intact animals estrone elicited a rapid phospholipase C activation, inducing a biphasic increase in diacylglycerol generation (peaking at 45 s and 5 min). The presence of protein kinase C inhibitor chelerythrine did not prevent the increase of NO released in response to hormone treatment. We proved that PI3K-Akt system does not mediate NOS and COX activation. However, PLC activation was dependent on PI3K since presence of LY 294002 in the incubation medium abolished estrone-induced DAG increment. We concluded that, estrone rapid action on vascular tissue involves a cross talk between NOS and COX system, and the activation of PLC/DAG/PKC transduction pathways.
Steroids 2006 Oct
PMID:Signal transduction pathways involved in non-genomic action of estrone on vascular tissue. 1686 Aug 31

Dienogest was introduced as an oral progestin. Yet its strong oral potency on endometrial activity is not clearly explained. To circumvent this situation, steroid hormone receptor profiling using transactivation assay and endometrial activity test in rabbits were carried out with determination of plasma drug concentration. Agonistic/antagonistic activity on human progesterone receptor (PR), androgen receptor (AR), glucocorticoid receptor (GR), mineralocorticoid receptor (MR), estrogen receptor alpha (ERalpha), or estrogen receptor beta (ERbeta) were determined. Dienogest activate PR (EC50=3.4 or 10.5 nmol/l) with antagonistic activity on AR (EC50=420.6 or 775.0 nmol/l) but not agonistic nor antagonistic action on GR, MR (3000 nmol/l). Dienogest activate neither ERalpha nor ERbeta (3000 nmol/l). Progesterone activated PR with antagonistic activity on AR and on MR. Dydrogesterone showed a similar profile to progesterone. Norethisterone activated PR, AR, and ERalpha. Medroxyprogesterone acetate activated PR, AR, and GR. Danazol activated PR and AR. Collectively, dienogest has a good specificity to PR compared with the other drugs. By oral treatment, dienogest showed the strongest endometrial activity (ED50=0.0042 mg/kg) in McPhail test among other progestins (ED50 values for MPA, DYG, NES were 0.074, 1.9, >0.05 mg/kg, respectively). Dienogest showed higher plasma concentrations than those of the other progestins with higher doses. The estimated plasma concentration of dienogest at ED50 (3.66 nmol/l) was close to its EC50 value to activate PR. Thus, the stronger oral activity of dienogest could be explained simply by its in vitro potency on PR and its oral pharmacokinetic profile.
Steroids 2008 Feb
PMID:Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. 1806 38