Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.3 (HSD)
 3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the steroidogenic pathway, 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta HSD) catalyzes the formation of hormonally active delta 4-3-ketosteroids from delta 5-3 beta-hydroxysteroids. In the present study the regulation of 3 beta HSD by ACTH action on bovine adrenocortical (BAC) cells in primary culture was evaluated. Western blot analysis was accomplished using an antibody against human placental 3 beta HSD. The relative molecular mass of 3 beta HSD in these cells was 45K, which was similar to that in human placenta. A significant effect of ACTH was not detected until day 6 of culture due to the high basal levels of the enzyme in BAC cells. Treatment of cells with ACTH on day 8 of culture resulted in a marked increase in the amount of 3 beta HSD protein, and this effect was correlated directly with enzymatic activity. The effects of ACTH were time and dose dependent, with an increase detectable only after 48 h of treatment; the maximal response was obtained with 10(-9) M ACTH. As demonstrated by Northern analysis, ACTH action was manifested by increasing the steady state level of 3 beta HSD mRNA. A human 3 beta HSD cDNA probe, which was used in this study, hybridized to a 1.7-kilobase species of BAC RNA. The effects of ACTH on 3 beta HSD activity and increases in 3 beta HSD protein and mRNA in BAC cells were mimicked by treatment with (Bu)2cAMP. The findings of this study suggest that ACTH controls 3 beta HSD gene expression in BAC cells by a cAMP-dependent mechanism similar to that involved in the expression of steroid hydroxylase genes. However, because the different stabilities of 3 beta HSD and hydroxylase proteins and/or mRNAs may play a critical role in determining the zone-specific steroids secreted from the adrenal cortex, other cAMP-dependent or independent regulatory mechanisms may also be important in regulating the expression of adrenal 3 beta HSD.
 ...
PMID:Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase expression by adrenocorticotropin in bovine adrenocortical cells. 184 95

In this report we examined the effects of growth factors and phorbol esters on steroid hydroxylase activity in cultured human thecal and granulosa-lutein cells. Treatment of thecal cells with epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor-beta (TGF beta), and tetradecanoyl phorbol acetate (TPA) resulted in the inhibition of forskolin- and dibutyryl cAMP-stimulated 17 alpha-hydroxylase activity and 17 alpha-hydroxyprogesterone and dehydroepiandrosterone production. In contrast, cAMP-stimulated 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) activity was enhanced by FGF and TGF beta, and treatment with EGF enhanced cAMP-stimulated progesterone production. cAMP stimulated 3 beta HSD activity was unaffected by TPA (10 nmol/L) treatment, yet TPA inhibited cAMP-stimulated progesterone production. Basal 3 beta HSD activity and progesterone production were inhibited by TPA. In contrast to the inhibitory actions of EGF, FGF, and TGF beta on 17 alpha-hydroxylase expression, insulin and insulin-like growth factor-I enhanced forskolin-stimulated 17 alpha-hydroxylase activity. In granulosa-lutein cells, forskolin-stimulated aromatase activity was suppressed by EGF, FGF, and TPA. TGF beta had no effect on forskolin-stimulated aromatase activity. EGF, FGF, and TGF beta did not affect forskolin-stimulated progesterone production, whereas treatment with TPA inhibited cAMP-stimulated progesterone secretion. These data suggest that growth factors may differentially regulate cAMP-dependent processes in human thecal and granulosa cells of the developing follicle.
 ...
PMID:The effects of growth factors and phorbol esters on steroid biosynthesis in isolated human theca interna and granulosa-lutein cells in long term culture. 802 14