EFFECT OF CHRONIC ACTH TREATMENT ON GUINEA-PIG ADRENAL STEROIDOGENESIS - STEROID PLASMA-LEVELS, STEROID ADRENAL LEVELS, ACTIVITY OF STEROIDOGENIC ENZYMES AND THEIR STEADY-STATE MESSENGER-RNA LEVELS

We report here the effects of a 7-day treatment of guinea-pigs with ACTH on adrenal mRNA levels for steroid-transforming enzymes. Adrenal 3-beta-hydroxysteroid dehydrogenase 4-ene-5-ene-isomerase (3-beta-HSD), 17-hydroxylase, 17,20-lyase, 21-hydroxylase and 11-hydroxylase activities were also examined as well as plasma and adrenal steroid levels. Our data reveal that chronic ACTH-treatment stimulated all post-pregnenolone enzyme activities in glomerulosa-fasciculata cells. Plasma steroid levels increased 8 h after the last injection of ACTH and returned to the control levels 24 h later whereas, in the adrenal, the content in steroids in the group sacrified 8 h after the last injection of ACTH were similar to the values suggested that the steroid turn-over in the adrenal may be affected by the chronic ACTH treatment. On the other hand, despite the significant stimulation in steroid-transforming enzyme activities, our data reveal that chronic ACTH adminsitraion casued a decreased in mRNA levels fro P450c21 and P450c17 while P450scc, 3 BETA-HSD adn p450c11 remained unchanged. Taken together, these results suggest that in vivo chronic ACTH-treatment of guinea-pigs increases adrenal steroidoenic capacity by increasing steroid secretion and steroid enzyme activity. Moreover, the chronic treatment with ACTH may have a post-transcriptional effect on steroidogenic enzymes gene expression by affecting the half-life of their mRNAs.