Regulation of Adrenocortical Cell Proliferation in Culture

Abstract

The regulation of the proliferation of adrenocortical cells in culture is reviewed. The hormones and growth factors affecting adrenocortical proliferation in culture and their physiological relevance are discussed. The following general conclusions are made: (i) ACTH is growth-stimulatory in vivo, but directly replication-inhibitory both in culture and in vivo, and is therefore an indirect mitogen. (ii) Insulin, IGFs, some pituitary and brain growth factors, and other unknown factors in serum, stimulate growth in culture, but their role in control of adrenocortical size in vivo is unknown. (iii) Pure, known pituitary hormones, other than ACTH, have no effect on adrenocortical proliferation in culture. (iv) Angiotensin is mitogenic in culture and perhaps also in vivo under some circumstances.

Vias de sinalização e efeito biológico da corticotropina (ACTH), do peptídeo NH2-terminal da pró-opiomelanocortina (N-POMC) e do fator de crescimento de fibroblastos (FGF2) em culturas primárias de células da suprarrenal de rato.

“…The similarity between this effect and that of FGF2 prompted us to examine the effects of ACTH and FGF2 on rat adrenal cells in primary culture. In agreement with the proposal that ACTH is not a direct mitogen (Hornsby, 1985), we found that ACTH does not act as a mitogenic agent in rat glomerulosa and fasciculata/reticularis cells. In contrast to the Y1 cell line, ACTH does not resemble FGF2 in normal adrenal cells.…”

Proliferative signaling initiated in ACTH receptors

“…In the intact organism ACTH seems to be a mitogen, but in cultures of isolated adrenocortical cells ACTH behaves like a growth inhibitory hormone (1).…”

Unmasking a Growth-promoting Effect of the Adrenocorticotropic Hormone in Y1 Mouse Adrenocortical Tumor Cells

“…These PKA mutants are resistant to the growth-inhibitory actions of ACTH and cAMP analogs (7,8), indicating that cAMP and PKA are obligatory components of this effect of ACTH on cell proliferation. The inhibition of proliferation seen in isolated adrenocortical cells contrasts sharply with the growth-promoting effects of ACTH on the adrenal gland in vivo and has led to the widely held view that ACTH serves as an indirect mitogen for the adrenal cortex in intact animals (2). Paradoxically, however, ACTH induces expression of genes often associated with enhanced cell proliferation such as ornithine decarboxylase (9) and fos and jun protooncogenes (10 -12) in isolated adrenocortical cells, raising the possibility of an underlying growth-promoting action of the hormone.…”