Effects of testosterone on the zona fasciculata of the male rat adrenal cortex. A correlated stereological and biochemical study.

The effects of long-term testosterone administration on the adrenal cortex of male rats were investigated by coupled morphometric and biochemical methods. Morphometry showed that testosterone treatment provoked a time-dependent atrophy of the zona fasciculata cells, which was mainly due to the decrease in the volume of the mitochondrial compartment and smooth endoplasmic reticulum (SER). Biochemical assays demonstrated that the decrease in the surface area per cell of SER membranes and mitochondrial cristae was tightly paralleled by the decrease in the activity per cell of two key enzymes of steroid synthesis contained in them (delta 5-3 beta-hydroxysteroid dehydrogenase and 11 beta-hydroxylase). The testosterone-induced inhibition of the growth maintenance and steroidogenic capacity of adrenocortical cells provoked a significant fall in the plasma concentration of corticosterone and a consequential increase in the level of circulating ACTH. Chronic administration of testosterone caused a notable suppression of the activity of the adrenal 5 alpha-reductase and this in turn provoked a rise in the intracellular concentration of corticosterone. Moreover, testosterone inhibited the incorporation of 3H-uridine into the nuclear and mitochondrial fractions of male rat adrenocortical cells. These findings exclude the possibility that the testosterone-provoked atrophy of the male rat adrenal glands is mediated by the suppression of the hypothalamo-hypophyseal axis, and suggest that the mechanism underlying this action of testosterone involves inhibition of nuclear and mitochondrial RNA synthesis. Whether this effect of testosterone is directly or indirectly mediated by the rise in the intracellular content of corticosterone due to the inhibition of 5 alpha-reductase activity, remains to be elucidated.