Endocrine Abstracts

THE REGULATION OF ADRENOMEDULLIN AND PROADRENOMEDULLIN N-TERMINAL 20 PEPTIDE IN THE ADRENAL GLAND: THE DIFFERENCE BETWEEN ADRENOCORTICAL CELLS AND CHROMAFFIN CELLS.

Vakharia K, Hinson JP.

Department of Endocrinology, Lab 1.2 Dominion House, Queen Mary University of London, London E, UK.

It has been established that the adrenomedullin gene is expressed in the adrenal cortex and adrenal medulla, and that both adrenomedullin and proadrenomedullin N-terminal 20 peptide (PAMP) are synthesised by these cells. However, there are few studies on the regulation of adrenomedullin and PAMP in the adrenal gland. This study was carried out to elucidate the factors affecting both adrenomedullin and PAMP production in the rat pheochromocytoma cell line, PC12, and the human adrenocortical cell line H295R. Normal PC12 cells, PC12 cells differentiated by pretreatment with dexamethasone and the human adrenocortical, H295R cells were stimulated with various agents for 24 hours. We found that there were differences between the responses of different cell types. Stimulation by bacterial lipopolysaccharide (LPS) significantly increased both adrenomedullin and PAMP production in differentiated and undifferentiated PC12 cells but had no effect on their production in H295R cells. Thyroid hormone significantly increased adrenomedullin and PAMP production in H295R cells but decreased production in both PC12 phenotypes. Stimulation with phorbol ester decreased adrenomedullin production in both PC12 cell phenotypes but had no effect on either hormone production in H295R cells. There was also evidence for differential regulation of adrenomedullin and PAMP. Dibutyryl cAMP increased adrenomedullin but not PAMP production in H295R cells and decreased PAMP production without affecting adrenomedullin production in differentiated and undifferentiated PC12 cells. Forskolin treatment significantly and selectively decreased adrenomedullin production in differentiated PC12 cells but had no effect on any other cell type.

Our conclusion is that adrenomedullin and PAMP production is differentially regulated in the adrenal gland and that there are also differences in their regulation within the adrenal cortex and adrenal medulla.