Adrenal function was assessed in control rats and in rats treated for 2 and 4 weeks with 17 alpha-methylandrostenediol (MAD; 17 alpha-methyl-5-androstene-3 beta-diol), a synthetic androgen known to produce hypertensive cardiovascular disease. In both groups and at both time periods, a circadian rhythm of blood corticosteroid concentrations was observed. The high point for serum corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18-hydroxy-DOC), and 11-deoxycorticosterone (DOC) concentrations occurred at the beginning of the dark period (1800 hours), and the low point occurred at the onset of the light period (0600 hours). Serum concentrations of DOC were always found to be higher in MAD-treated rats as compared with controls. The serum concentrations of B and 18-hydroxy-DOC were lower than control values at 1800 hours but higher than control concentrations at 0600 hours. The in vitro 11 beta- and 18-hydroxylation of DOC was markedly reduced with MAD treatment. In contrast, cholesterol side-chain cleavage activity was higher in animals treated with MAD. These in vitro findings correlated with spectral studies that showed a decreased binding of DOC to cytochrome P450(11) beta and increased binding of cholesterol to cytochrome P450scc. These studies suggest that MAD treatment selectively decreases 11 beta- and 18-hydroxylation in adrenal mitochondria, and this results in an increased serum concentration of DOC, a hypertensinogenic steroid. This effect of MAD on peripheral serum DOC concentration is most readily observed in quiescent animals at the high point of the circadian rhythm.

18-Hydroxycorticosterone↗

PubMedDate not supplied

Sex differences in the steroidogenic and respiratory electron transport chains in the rat adrenal cortex.

Both steroid 11 beta-hydroxylation and cholesterol side chain cleavage occur in the mitochondria of adrenocortical cells and they require reducing power in the form of NADPH. There are direct sources of NADPH in rat adrenal mitochondria but another potential source of NADPH is the energy-linked transhydrogenase reaction. This suggests that there is a relationship between the steroidogenic and respiratory chains. We have elaborated upon this relationship by exploring the expression of cytochrome c oxidase (CO) and cytochrome P-45011 beta. We have studied the regulation of one mitochondrial-encoded (COII) and one nuclear-encoded (COIV) subunit. Normal, untreated male rats had higher basal levels of activity of CO in adrenal (255%) and liver (144%) mitochondria, compared to normal, untreated female rats. They also had increased COII (300% and 138%) and COIV (300% and 135%). Cytochrome P-45011 beta levels, however, were lower (48%) in adrenal mitochondria of male rats than those of female rats. Androgen treatment of male rats caused an increase in the activity of CO in the mitochondria of the adrenal gland with the levels being 171% of the corresponding controls. This increase in activity paralleled an increase in the levels of COII and COIV in the adrenal as measured by Western analysis. In contrast, adrenal cytochrome P-45011 beta levels were lower (68%). Androgen treatment caused no significant change in the levels of mRNA's for COII and COIV whereas cytochrome P-45011 beta mRNA was significantly lower than normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

PubMedDate not supplied

Professionalism.

Explore the source record for details and available documents.

Education, Nursing, Continuing↗