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)

The sequence of events within the ovary during the process of ovulation discussed in this review is schematically represented in Fig. 1. It is obvious that LH, perhaps with some contribution from FSH, is the normal physiological trigger for the ovulatory sequence of events, and it appears from the available information that the effects of LH are mainly mediated via adenylate cyclase and increased cAMP levels. The cAMP in turn, via cAMP-dependent protein kinase, influences at least three distinct steps in the ovulatory process which seem to be of crucial importance, namely 1) the stimulation of steroidogenesis; 2) the stimulation of cyclooxygenase/lipooxygenase leading to increased prostaglandin/leukotriene synthesis; and 3) the stimulation of plasminogen activator which catalyzes the conversion of plasminogen to plasmin. A fourth crucial step in the ovulatory mechanism is the LH-induced increase in latent collagenase, but it remains to be determined if this step is mediated via cAMP. Concomitant with the increase in latent collagenase, there also appears to be an LH-dependent increase in collagenase inhibitors. The latent collagenase is then activated, and it appears that leukotrienes and prostaglandins, as well as plasmin, may be involved in this process. The active collagenase causes a digestion of the collagen in the follicle wall, and plasmin, as well as possibly other proteolytic enzymes such as proteoglycanases, may cause a further dissociation of the follicular wall. These processes of digestion of collagen and dissociation of the collagen fibers result in an opening in the follicular wall with the formation of the stigma and rupture. While the weakening of the follicular wall takes place throughout the entire wall, rupture remains for the most part a localized process at the apex of the follicle. This localization of the rupture may be explained on the basis of mechanical factors operating when the follicle wall thins and weakens. While it is clear that prostaglandins and leukotrienes can influence smooth muscle by causing contractions and that these compounds can cause vascular changes such as increased permeability, vasodilation, and vasoconstriction, it is not clear what the exact role of these latter processes are in ovulation. It appears that progesterone and not estrogen play an important role in the mechanism of LH-induced follicular rupture, but the locus of action of progesterone and its mechanism of action remains to be determined.(ABSTRACT TRUNCATED AT 400 WORDS)
Steroids 1989 Nov
PMID:Mechanism of mammalian ovulation. 255 97

The transcription of steroid hydroxylase genes is controlled by ACTH and cAMP in the adrenal cortex. In most instances the regulation appears to rely on transcription factors traditionally not associated with cAMP-dependent gene expression. For the non-traditional factors it remains necessary to elucidate the coupling of increases in intracellular cAMP and cAMP-dependent protein kinase (PKA) activity to the function of these proteins. The bovine CYP17 gene, which encodes the steroid 17 alpha-hydroxylase, contains two discrete DNA elements within its promoter and upstream region (CRS1 and CRS2) that individually can confer cAMP responsiveness. The CRS1 element is a target for PKA signalling and for negative regulation via the protein kinase C signal transduction pathway. The homeodomain protein Pbx1 enhances CRS1-dependent transcription, but additional CRS1-binding proteins remain to be identified. Furthermore it is not known how PKA regulates the activity of Pbx1 or its possible binding partners. Closer to the promoter, the nuclear orphan receptors SF-1 and COUP-TF have overlapping binding sites in CRS2 and they bind in a mutually exclusive manner with very similar affinities; 8 and 10 nM, respectively. SF-1 stimulates whereas COUP-TF inhibits transcription from the bovine CYP17 promoter. Together, the data suggest that cAMP-dependent control of the amounts of the activator SF-1 vs. the repressor COUP-TF could influence CRS2-dependent transcription. In addition, PKA may influence the phosphorylation of SF-1, thus increasing its activity. In vitro, PKA will elicit phosphorylation of SF-1. However, although SF-1 can be immunoprecipitated from adrenocortical cells as a phosphroprotein, we have not been able to show cAMP-dependent increase in net phosphorylation in intact cells. More careful examination of individual phosphorylation sites in SF-1 may still reveal hormone- and cAMP-induced phosphorylation of SF-1.
Steroids 1997 Jan
PMID:Transcriptional regulation of the bovine CYP17 gene by cAMP. 902 13

P450c17 is a single microsomal enzyme that catalyzes two distinct steroid biosynthetic activities: 17 alpha-hydroxylase and 17,20 lyase. Human beings have only one gene that encodes only one form of P450c17. Three clinical observations indicated that these were independently regulated activities. First, several cases of isolated 17,20 lyase deficiency were reported, in which 17 alpha-hydroxylase activity was spared. Second, most adrenal steroidogenesis in children stops after 17 alpha-hydroxylation, thus permitting the synthesis of cortisol, whereas most gonadal steroidogenesis proceeds to C19 sex steroids as a result of both activities. Third, the 17,20 lyase activity of the human adrenal is developmentally activated during adrenarche. To catalyze these two activities, P450c17 must receive reducing equivalents from electron donors (redox partners). Previous observations showed that the molar ratio of P450 oxidoreductase to P450c17 was 3-fold higher in the testis than in the adrenal, and that increasing the molar ratio of the redox partner to P450c17 would increase the ratio of 17,20 lyase activity to 17 alpha-hydroxylase. We have recently shown that P450c17 must be phosphorylated on serine and threonine residues by a cAMP-dependent protein kinase to acquire 17,20 lyase activity. We have also recently found two cases of isolated 17,20 lyase deficiency that have mutations of residues in the proposed redox partner binding site. Together, these studies suggest a unified view of the regulation of 17,20 lyase activity. The ratio of 17,20 lyase to 17 alpha-hydroxylase activity of P450c17 is regulated by the availability of reducing equivalents flowing to the enzyme. This can be increased by increasing the molar concentration of electron-donating redox partners, such as P450 oxidoreductase or possibly cytochrome b5, as appears to be the case in the gonads. Alternatively, the affinity of P450c17 for redox partners may be selectively increased by Ser/Thr phosphorylation, or selectively decreased by certain mutations in the redox partner binding site, in either case altering an electrostatic interaction between P450c17 and the redox partner. This model is consistent with all present observations about the biochemistry, genetics, enzymology, and clinical phenomenology of P450c17.
Steroids 1997 Jan
PMID:The regulation of 17,20 lyase activity. 902 28

Glucocorticoids are anti-inflammatory molecules classically described as acting through a genomic pathway. Similar to many steroid hormones, glucocorticoids also induce rapid non-genomic responses. The present paper provides a general overview of the rapid non-genomic effects of glucocorticoids in airway and will be mainly focused on a retrospective of the authors work on rapid effects of glucocorticoids in airway epithelial cell transport. Using fluorescence microscopy, short circuit current measurements in human bronchial epithelial (16HBE14o(-)) cells, we reported rapid non-genomic effects of dexamethasone on cell signalling and ion transport. Dexamethasone (1 nM) rapidly stimulated Na(+)/H(+) exchanger activity and pH(i) regulation in 16HBE14o(-) cells. Dexamethasone also produced a rapid decrease of intracellular [Ca(2+)](i) to a new steady state concentration and inhibited the large and transient [Ca(2+)](i) increase induced by apical adenosine tri-phosphate (ATP). Dexamethasone also reduced by 1/3 the Ca(2+)-dependent Cl(-) secretion induced by apical ATP. The rapid effects of dexamethasone on intracellular pH and Ca(2+) were not affected by inhibitors of transcription, cycloheximide or by the classical glucocorticoid and mineralocorticoid receptors antagonists, RU486 and spironolactone, respectively. The rapid responses to glucocorticoid were reduced by the inhibitors of adenylated cyclase, cAMP-dependent protein kinase (PKA) and mitogen-activated protein kinase (ERK1/2). Our results demonstrate, that dexamethasone at low concentrations, rapidly regulates intracellular pH, Ca(2+) and PKA activity and inhibits Cl(-) secretion in human bronchial epithelial cells via a non-genomic mechanism which neither involve the classical glucocorticoid nor mineralocorticoid receptor.
Steroids 2006 Apr
PMID:Rapid anti-secretory effects of glucocorticoids in human airway epithelium. 1629 6