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.