Autocrine role of adrenomedullin in the human adrenal cortex

Previous studies from our laboratory have reported that adrenomedullin is s ynthesised in rat zona glomemlosa cells. In the present studies, it was fou nd that the human adrenocortical cell Line H295R expresses the gene encodin g adrenomedullin, and that immunoreactive adrenomedullin is released into t he culture medium. Furthermore, it was found that secretion of adrenomedull in is regulated by angiotensin II and forskolin. Studies on the actions of adrenomedullin and calcitonin gene-related peptid e (CGRP) revealed a stimulatory effect ne of adrenomedullin, but not of CGR P, on aldosterone and cortisol secretion. These data suggest that adrenomed ullin is not acting by a CGRP receptor-mediated mechanism in the H295R cell line. Adrenomedullin was also found to increase cAMP production, suggestin g that in the adrenal, as in other cell types, cAMP is a second messenger f or adrenomedullin action. However, the effects of adrenomedullin were not f ully mimicked by forskolin, possibly suggesting a role for an additional se cond messenger. The presence of mRNA encoding both the putative adrenomedullin receptors, L 1 and calcitonin receptor like receptor/receptor-associated modulatory prot ein 2 (CRLR/RAMP-2), was demonstrated in H295R cells, but RAMP-1 was not de tected, suggesting that these cells do not express the CGRPI receptor CRLR/ RAMP-1. Taken together, these data have demonstrated that adrenomedullin is synthes ised and secreted by H295R cells. The observed rate of adrenomedullin synth esis suggests that this peptide exerts a paracrine/autocrine effect in this adrenocortical cell Line, probably acting through a specific adrenomedulli n receptor, to stimulate steroidogenesis and increase aldosterone synthase expression.