Key result
AT1 receptor mRNA expression in bovine zona fasciculata cells is regulated by multiple signal transduction systems, decreasing with AII, PMA, A23187, ACTH, and cortisol, and increasing with IGF-1 and potassium.
Multiple signal transduction systems and adrenocortical steroids regulate AT1 receptor mRNA expression in bovine adrenocortical cells.
AT1 mRNA regulation in bovine zona fasciculata is multifaceted; leaves open whether analogous pathways modulate human adrenocortical AT1 expression or function.
Regulation of AT1 receptor mRNA expression is an important determinant of angiotensin II-induced steroidogenesis. We have PCR-amplified the bovine adrenal AT1 receptor coding region using primers designed from the published bovine AT1 receptor sequence. This has been used as a probe on Northern blots to detect changes in the levels of AT1 receptor mRNA in primary cultures of bovine zona fasciculata cells in response to activation of several different signal transduction mechanisms in addition to two major adrenal steroid products, cortisol and aldosterone. AT1 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 microM) and the calcium ionophore A23187 (1 microM), both singly and in combination. Activation of the cAMP pathway by ACTH (1 nM) and 8-bromo-cAMP (0.1 microM) also decreased AT1 receptor mRNA levels. In contrast, both IGF-1 (10 ng/ml) and potassium ions (12 mM) increased the levels of AT1 receptor mRNA. Finally, cortisol (10 microM) but not aldosterone (100 nM) decreased AT1 receptor mRNA. We conclude that the regulation of AT1 receptor mRNA in bovine zona fasciculata cells could involve several different signal transduction systems in addition to adrenocortical steroids themselves.
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Dell et al. (1996) studied this question. Signal transduction activators (AII, PMA, A23187, ACTH, 8-bromo-cAMP, IGF-1, potassium, cortisol) vs. Basal levels was evaluated on AT1 receptor mRNA levels. AT1 receptor mRNA expression in bovine zona fasciculata cells is regulated by multiple signal transduction systems, decreasing with AII, PMA, A23187, ACTH, and cortisol, and increasing with IGF-1 and potassium.
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