MULTIPLE SIGNAL-TRANSDUCTION SYSTEMS REGULATE ANGIOTENSIN-II TYPE-1 (AT(1)) RECEPTOR MESSENGER-RNA EXPRESSION IN BOVINE ADRENOCORTICAL-CELLS

Regulation of AT(1) receptor mRNA expression is an important determina nt of angiotensin II-induced steroidogenesis. We have PCR-amplified th e bovine adrenal AT(1) receptor coding region using primers designed f rom the published bovine AT(1) receptor sequence. This has been used a s a probe on Northern blots to detect changes in the levels of AT(1) r eceptor mRNA in primary cultures of bovine zona fasciculata cells in r esponse to activation of several different signal transduction mechani sms in additon to two major adrenal steroid products, cortisol and ald osterone. AT(1) receptor mRNA decreased in response to 6hr AII (10 nM) treatment, but returned to basal levels following 48h AII treatment. This effect was mimicked by the phorbol ester PMA (1 mu M) and the cal cium ionophore A23187 (1 mu M), both singly and in combination. Activa tion of the cAMP pathway by ACTH (1 nM) and 8-bromo-cAMP (0.1 CIM) als o decreased AT(1) receptor mRNA levels. In contrast, both IGF-1 (10 ng /ml) and potassium ions (12 mM) increased the levels of AT(1) receptor mRNA. Finally, cortisol (10 mu M) but not aldosterone (100nM) decreas ed AT(1) receptor mRNA. We conclude that the regulation of AT(1) recep tor mRNA in bovine zona fasciculata cells could involve several differ ent signal transduction systems in addition to adrenocortical steroids themselves.