Angiotensin stimulation of bovine adrenocortical cell growth.

Abstract

Factors controlling proliferation of adrenocortical cells have been studied in Although several purified polypeptides have been reported to stimulate the proliferation of animal cells-in culture, a high degree of cell specificity has not been observed. Fibroblast growth factor (FGF) is mitogenic for fibroblast, adrenocortical, myoblast, smooth muscle, chondrocyte, vascular endothelial, granulosa, and luteal cells, whereas epidermal growth factor (EGF) is mitogenic for fibroblast, corneal epithelial, certain mammary epithelial, and granulosa cells (1). Several pituitary polypeptides long considered trophic for specific target cells in ivo either inhibit DNA synthesis when added directly to target cells in culture or have no effect on growth (2-6). Understanding of the mechanisms controlling organ-specific growth is, therefore, incomplete; interaction of several growth factors and hormones may be involved (7).A recently developed strain of bovine adrenocortical cells in culture has been used to study factors controlling proliferation of the adrenal cortical cell (8). FGF but not EGF stimulates proliferation of these cells, whereas corticotropin (ACTH) and prostaglandin El (PGE1), which stimulate cyclic AMP formation, inhibit proliferation (8, 9). Corticotropin and PGE1 both stimulate steroidogenesis and induce the steroid biosynthetic pathway. The present studies indicate that angiotensin II and III at low concentrations stimulate DNA synthesis as well as steroidogenesis in adrenocortical cells. The growth-stimulatory effect of angiotensin appears specific because several cell types, including cells reported to possess angiotensin II receptors, do not increase DNA synthesis with addition of angiotensin II (Schwarz/Mann) was routinely added to cultures 12 hr after addition of growth stimuli. Twelve hours later, medium was removed and 1 ml of a 1% aqueous solution of Triton X-100 was added. The cells were incubated with this solution for 5 min and the entire contents of the plate

Mechanism of hyperthyroidism-induced renal hypertrophy in rats

“…Accordingly, the mechanism of thyroxine-induced renal hypertrophy involves the activation of circulating or intrarenal RAS, which is mediated by the upregulation of renal expression of renin mRNA. It is well known that ANG II has potent cell proliferation effects in vitro (Gill et al 1977) and in vivo (Casellas et al 1997). Therefore, it is understandable that activation of RAS caused renal hypertrophy.…”

“…As well, ANG II plays a prime role in the regulation of blood pressure because of its potent pressor effect (Mitchell & Navar 1995), and it is very important in cell proliferation owing to its mitogenic actions (Gill et al 1977, Casellas et al 1997.…”

Absence of angiotensin II type 1 receptor gene mutations in human adrenal tumors

“…Its regulatory actions are mediated by two pharmacologically distinguishable classes of G-protein-coupled cell-surface receptors (AT1 and AT2), of which the AT1 class has been now regarded as a mediator of the major pathophysiological actions of AngII (2). In the adrenals, locally formed AngII might play an important role as an autocrine or paracrine regulator of adrenal function, whereas an abnormal activity of the local renin-angiotensin system might be involved in the pathogenesis of abnormal adrenal growth, abnormal mineralocorticoid production, and hypertension (25). Therefore, similar to the constitutive activation of G-protein-coupled TSH and LH receptors by somatic mutations (7,8), a constitutive activation or a genetic variant of AT1 receptor could lead to increased AngII actions on target cells.…”

The renin–angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations

“…Bradley et al (1974) reported that T 4 -induced renal hypertrophy in vivo is associated with a rise in the mitotic index, and Stephan et al (1982) found an increase in DNA content. The mechanism is not fully understood, but participation of the RAS has been proposed, because AII is known to have potent cell proliferation effects in several tissues in vitro (Gill et al 1977) and in vivo (Casellas et al 1997). Kobori et al (1998) observed that T 4 produces renal hypertrophy in rats, with an increase in renal renin mRNA expression and in renal renin and AII levels.…”