ADRENOMEDULLIN, PAMP AND ADRENOCORTICAL FUNCTION
Abstract
Adrenomedullin (AM) and pro-adrenomedullin N-terminal 20-peptide (PAMP)
are peptides recently identified from a rat pheochromocytoma. Both of these
peptides are cleavage products of pre-pro-AM. Specific receptors for AM have
been characterised in several species, including rat and human. The aim of this
study was to investigate the role of PAMP and AM in the adrenal cortex.
Using an intact rat capsule preparation PAMP was shown to cause a dosedependent
increase in aldosterone secretion, which was accompanied by a dosedependent
increase in cAMP release. The effects of PAMP were inhibited by
HA1004, an inhibitor of protein kinase A. These results suggest that PAMP
stimulates aldosterone secretion from the zona glomerulosa via cAMP. Ligandbinding
studies were then used to demonstrate the presence of specific PAMP
receptors. Two classes of receptor were shown in the rat zona glomerulosa (Kdi
1.9 nmol/l, Bmai, 53 fmol/mg protein; Kd2 10 nmol/l, Bmac,2 225 fmol/mg
protein). At the latter receptor PAMP was displaced by AM. None of the other
competitors tested displaced PAMP.
Using the H295R cell line, both PAMP and AM were shown to increase
aldosterones ecretion in a dose-dependenmt anner. In both casesa corresponding
dose-dependent increase in cAMP was observed. Both PAMP and AM also
effected a dose dependent increase in cortisol secretion. mRNA analysis showed
that the gene encoding pre-pro-AM was expressed in these cells.
Immunocytochemistry confirmed that these cells were producing both PAMP
and AM. Immunocytochemistry and mRNA analysis also revealed that both of
the candidate receptors for AM, L1 and CRLR, are expressed in this cell line.
Taken together these findings demonstrate that both AM and PAMP are
produced by adrenocortical cells and likely to have a role in regulating adrenal
steroidogenesis. Furthermore, these studies suggest the presence of a specific
PAMP receptor in the rat adrenal gland.
Authors
Thomson, Laura MCollections
- Theses [4144]