Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The product of the CYP11A gene, cholesterol side chain cleavage cytochrome P450, catalyzes the initial step of steroidogenesis. A major mechanism whereby steroid hydroxylase gene transcription is regulated in the adrenal cortex requires the pituitary peptide hormone, ACTH, which acts via cAMP. We have previously identified a transcriptional enhancer in the 5'-flanking sequence [-183 to -83 base pairs (bp)] of the bovine CYP11A gene, which activates transcription of a beta-globin promoter/reporter gene in transiently transfected mouse Y1 adrenocortical tumor cells in response to the activator of adenylate cyclase, forskolin. Further deletion analysis has located the minimal cAMP-responsive sequence (CRS) to -118 to -100 bp. Analysis of DNA-protein interactions using nuclear extracts from Y1 cells revealed two protein binding sites, which were shown by competition analysis to be closely related to the two protein binding sites identified previously in the CRS of the human CYP21 gene. Namely, within the cAMP responsive fragment -118 to -100 bp, a sequence with a high degree of similarity to the consensus binding sequence for the ubiquitous transcription factor Sp1 is present, and binding of protein to this site was abolished by competition with excess GC box oligonucleotide. The second partially overlapping site is located 3' of the putative Sp1-binding site and binds to a protein identical or closely related to a putative adrenal-specific protein. Whereas the adrenal-specific protein binding site of the CYP21 CRS was previously shown to be sufficient to confer cAMP-responsive activation of transcription, the homologous site within the CYP11A CRS appears to have an attenuating effect on transcription.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:3',5'-cyclic adenosine monophosphate-dependent transcription of the CYP11A (cholesterol side chain cleavage cytochrome P450) gene involves a DNA response element containing a putative binding site for transcription factor Sp1. 133 53

The adenylate cyclase activator forskolin and its pharmacologically inactive derivative 1,9-dideoxyforskolin were found to inhibit in a dose-dependent fashion the ecdysone 20-monooxygenase activity associated with wandering stage larvae of Drosophila melanogaster and fat body and midgut from last instar larvae of the tobacco hornworm, Manduca sexta. The concentrations of these labdane diterpenes required to elicit a 50% inhibition of the cytochrome P-450 dependent steroid hydroxylase activity in the insect tissues ranged from approximately 5 x 10(-6) to 5 x 10(-4) M.
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PMID:Effects of the adenylate cyclase activator forskolin and its inactive derivative 1,9-dideoxyforskolin on insect cytochrome P-450 dependent steroid hydroxylase activity. 173 75

Total RNA from normal and anencephalic human fetal adrenals was examined by blot analysis for transcripts encoding P-450scc, P-450(11) beta, P-450(17) alpha, P-450C21 and adrenodoxin using bovine cDNA clones specific for these different enzymes. The specific contents of RNA encoding these components of the adrenocortical steroidogenic pathway were found to be similar in both types of adrenal tissue. Likewise, immunoblot analysis showed comparable concentrations of P-450scc, P450(17) alpha and adrenodoxin protein to be present in adrenal tissues from normal and anencephalic human fetuses. Immunoblot analysis of homogenates of fetal sheep adrenals of increasing gestational age (85-145 days) showed constant levels of P-450scc and P-450(11) beta, but increasing P-450(17) alpha content, especially near term. Both sheep fetuses prior to 136 days gestational age and human anencephalic fetuses are known to have extremely low circulating levels of immunoreactive ACTH as well as very low adrenal adenylate cyclase activity. Thus, it is concluded that factors other than pituitary ACTH which operate independent of adenylate cyclase activation are required for the initial expression (imprinting) of steroid hydroxylase genes.
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PMID:Ontogeny of adrenal steroid hydroxylases: evidence for cAMP-independent gene expression. 243 59

Adrenocorticotropic hormone and angiotensin II stimulate cortisol secretion from bovine adrenal zona fasciculata cells by the activation of adenylate cyclase and phospholipase C-coupled receptors. Curcumin (1- 20 muM), a compound found in the spice turmeric, inhibited cortisol secretion stimulated by ACTH, AngII, and 8CPT-cAMP. Curcumin also suppressed ACTH-stimulated increases in mRNAs coding for steroid acute regulatory protein and CYP11a1 steroid hydroxylase. In whole cell patch clamp recordings from AZF cells, curcumin at slightly higher concentrations also inhibited Ca(v)3.2 current. These results identify curcumin as an effective inhibitor of ACTH- and AngII-stimulated cortisol secretion. The inhibition of Ca(v)3.2 current by curcumin may contribute to its suppression of secretion.
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PMID:Curcumin inhibits ACTH- and angiotensin II-stimulated cortisol secretion and Ca(v)3.2 current. 1965 44