Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.12.7.2 (hydrogenase)
 3,522 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenal cortisol secretion is greater in female than male guinea-pigs and declines with maturation in animals of both sexes. In an attempt to determine the intra-adrenal mechanisms responsible for age and sex influences on corticosteroid output, adrenocortical enzyme activities were compared in sexually immature (3 weeks) and mature (17 weeks) animals. Adrenal mitochondrial protein concentration decreased with maturation in male and female guinea-pigs. 11beta-Hydroxylase activity in adrenal mitochondria was also lower in mature than immature guinea-pigs but greater in males than females. Neither mitochondrial cytochrome P-450 concentration nor cholesterol side-chain cleavage activity varied with age or sex. Adrenal microsomal protein concentration and 21-hydroxylase activity were similar in male and female guinea-pigs of the same age but far greater in mature than immature animals. Microsomal cytochrome P-450 concentration was unaffected by age or sex. Adrenal delta4-steroid (cortisol) hydrogenase activity increased with maturation in both male and female guinea-pigs and was higher in males than females. These observations indicate that cortisol secretion, as modified by age and sex, correlates closely with adrenal steroid reductive but not oxidative metabolism, suggesting that changes in delta4-hydrogenase activity are responsible, at least in part, for the decline in adrenal secretion during maturation in guinea-pigs.
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PMID:Changes in adrenocortical function in male and female guinea-pigs during maturation. 18 Feb 25

Spironolactone administration (50 mg/kg/day for 3 days) to make guinea pigs decreased cortisol production by adrenal slices in vitro. Adrenal microsomal and mitochondrial cytochrome P-450 levels were also decreased after treatment with spironolactone. The decline in adrenal cytochrome P-450 content was accompanied by decreases in microsomal 21-hydroxylase and mitochondrial cholesterol side-chain cleavage and 11beta-hydroxylase activities. Activities of other adrenal enzymes, such as delta4-hydrogenase and NADPH-cytochrome c reductase, were unaffected by spironolactone treatment. Cortisone administration to guinea pigs failed to mimic the effects of spironolactone on adrenal function, which indicates specificity of spironolactone action and excludes inhibition of adrenocorticotropin secretion as a mode of action. Addition of spironolactone to isolated adrenal mitochondria or microsomes produced type I spectral changes with spectral dissociation constants similar to those for endogenous steroid substrates. Spironolactone, in vitro, inhibited 11beta- but not 21-hydroxylase activity. The results indicate that spironolactone administration diminishes the activity of adrenal mitochondrial as well as microsomal cytochrome P-450-containing enzymes, resulting in a fall in corticosteroid output.
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PMID:Mechanism of action of spironolactone on adrenocortical function in guinea pigs. 97 70