Pro-gamma-melanocyte-stimulating hormone cleavage in adrenal gland undergoing compensatory growth.

Abstract:

:Regulation of the rapid compensatory growth seen in the remaining adrenal gland of rats following unilateral adrenalectomy is poorly understood. The role of adrenocorticotropic hormone (ACTH) is obscure as immunoneutralization of circulating ACTH does not affect the observed compensatory growth or hyperplasia. This finding, together with the fact that mechanical manipulation of one adrenal without extirpation is followed by growth only in the contralateral gland, has led to the concept of neural regulation of compensatory adrenal growth via a loop from one adrenal through the hypothalamus and back to the contralateral gland which is independent of ACTH secretion. We recently showed that peptides from the N terminal of ACTH precursor proopiocortin (POC), not containing the gamma-melanocyte-stimulating hormone (gamma-MSH) sequence, can stimulate adrenal mitogenesis and proposed that normal long-term adrenal growth and proliferation involves post-secretional proteolytic cleavage of pro-gamma-MSH [or N-POC(1-74)] to generate the mitogenic factor N-POC(1-48/49) and a C-terminal fragment N-POC(50-74), or rat gamma 3-MSH. We have now investigated this hypothesis further in rats by selectively quenching different regions of circulating POC peptides with specific antisera and observing the effect on the increases in weight, RNA and DNA normally seen in the remaining gland following unilateral adrenalectomy. Our results, reported here, suggest that neurally mediated proteolytic cleavage of the circulating inactive mitogenic precursor pro-gamma-MSH at the adrenal gland is the major mechanism of control of compensatory growth.

journal_name

Nature

journal_title

Nature

authors

Lowry PJ,Silas L,McLean C,Linton EA,Estivariz FE

doi

10.1038/306070a0

subject

Has Abstract

pub_date

1983-11-03 00:00:00

pages

70-3

issue

5938

eissn

0028-0836

issn

1476-4687

journal_volume

306

pub_type

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