ACTH, ANGIOTENSIN-II AND TGF-BETA PARTICIPATE IN THE REGULATION OF STEROIDOGENESIS IN BOVINE ADRENAL GLOMERULOSA CELLS

Bovine zona glomerulosa cells, on the first day of culture, produce al dosterone as their major steroid with no detectable cortisol secretion . Continuous incubation with ACTH had no effect on aldosterone product ion nor on aldosterone synthase activity. This treatment resulted in a dose and time dependent rise in 17 alpha-hydroxylase activity, in par allel with an increase in cytochrome P-450(17 alpha) (CYP17) protein a nd mRNA. We have previously shown that TGF beta 1 is a potent inhibito r of differentiated functions of bovine fasciculata-reticularis cells and that CYP17 and AIT receptors are the major targets explaining this effect. The present study examined whether 17 alpha-hydroxylase activ ity in glomerulosa cells could be regulated by angiotensin II (AII) an d transforming growth factor-beta 1 (TGF beta 1).AII inhibits the indu ction of CYP17 by ACTH in a dose dependent manner. TGF beta 1 also blo cks almost completely the stimulatory effect of ACTH. In order to supp ress the endogenous action of TGF beta 1, incubations were performed w ith an anti-TGF beta antibody. This specific antibody induces the expr ession of CYP17 resulting in increased activity and mRNA levels. These results show that AII is able to modulate the expression of CYP17 in adrenal glomerulosa cells following ACTH stimulation. Furthermore, TGF beta 1 exerts an autocrine effect on the differentiation of glomerulo sa cells through a regulatory loop repressing CYP17 activity.