AJP - Endocrinology and Metabolism, Vol 266, Issue 3 E495-E500, Copyright © 1994 by American Physiological Society
Interactions between TGF-beta and adrenocorticotropin in growth regulation of human adrenal fetal zone cells
A. K. Stankovic, W. E. Grizzle, C. R. Stockard and C. R. Parker Jr
Department of Obstetrics and Gynecology, University of Alabama at Birmingham 35233-7333.
The factors that regulate growth and function of the human adrenal gland
during intrauterine development and thereafter are ill defined. Whereas
others have reported that adrenocorticotropic hormone (ACTH) augments the
inhibitory effect of transforming growth factor-beta (TGF-beta) on growth
of fetal zone (FZ) cells of the human fetal adrenal, we recently found that
ACTH interferes with TGF-beta's inhibition of growth of fetal adrenal
neocortex cells. In this study we sought to assess independently the
effects of TGF-beta in the absence and presence of ACTH on growth of FZ
cells. TGF-beta, in a time- and dose-dependent manner, inhibited growth
(i.e., [3H]thymidine incorporation) of FZ cells. ACTH (Cortrosyn), at 90 pM
to 90 nM, was found to interfere with the TGF-beta inhibition of FZ growth.
ACTH 1-24 and human ACTH 1-39, both from Sigma Chemical, also were found to
blunt the response of FZ cells to TGF-beta. Growth inhibition due to
TGF-beta action and the reversal by ACTH of TGF-beta effects on FZ cell
growth were confirmed by the results of immunohistochemical analyses of
5'-bromo-2'-deoxyuridine incorporation into nuclei of FZ cells and by
indirect evaluations of cell numbers. Both forskolin (10 microM) and
dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM), but not phorbol
12-myristate 13-acetate (1 or 100 mM), were able to mimic ACTH actions in
blunting the inhibitory effects of TGF-beta on DNA synthesis. We conclude
that ACTH, possibly via activation of adenylate cyclase, interferes with,
rather than augments, the growth-inhibitory effect of TGF-beta on FZ cell
growth.
