Hormonal regulation of the adrenocortical cell

Abstract

Monolayer cultures of bovine and human adrenocortical cells have been used to study regulation of growth and function. Homogeneous bovine adrenocortical cells exhibit a finite life span of approximately 60 generations in culture. Full maintenance of differentiated function (steroid hormone synthesis) requires an inducer such as ACTH and antioxidizing conditions. Full induction of differentiated function occurs only when cellular hypertrophy is stimulated by growth factors such as fibroblast growth factor and serum. ACTH and other agents that increase cellular cAMP inhibit replication but do not block growth factor-induced cellular hypertrophy. ACTH and growth factors together result in a hypertrophied, hyperfunctional cell. Replication ensues only when desensitization to the growth inhibitory effects of ACTH occurs. Cultures of the definitive and fetal zones of the human fetal adrenal cortex synthesize the steroids characteristic of the two zones in vivo. ACTH stimulates production of dehydroepiandrosterone (DHA), the major steroid product of the fetal zone, and of cortisol, the characteristic steroid product of the definitive zone. Prolonged ACTH treatment of fetal zone cultures results in a preferential increase in cortisol production so that the pattern of steroid synthesis becomes that of the definitive zone. The preferential increase in cortisol production by fetal Zone cultures results from induction of 3 beta-hydroxysteroid dehydrogenase, delta 4,5 isomerase activity, which is limiting in fetal zone cells. ACTH thus causes a phenotypic change in fetal zone cells to that of definitive zone cells. In both bovine and human adrenocortical cells, the principal effect of ACTH is to induce full expression of differentiated function. This occurs only under conditions where growth substances and nutrients permit full amplification.

Primary Cultures and Cell Lines for <i>In Vitro</i> Modeling of the Human Adrenal Cortex

“…Multiple groups were able to isolate and culture the two zones. Cells from both zones were shown to be ACTHsensitive with the definitive zone producing more cortisol and the fetal zone cells producing more DHEA (Gill et al 1980;Simonian and Gill 1981). Interestingly, cultured fetal zone and definitive zone cell cultures were also instrumental in demonstrating a direct role for corticotropin-releasing hormone (CRH) in the regulation of both DHEA and cortisol (Sirianni et al 2005a, b).…”

Mixed parenchymal-stromal populations of rat adrenocortical cells support the proliferation and differentiation of steroidogenic cells

“…9). As CAMP-induced rounding has long been considered to be a characteristic of steroidogenic cells [7,12,241, this difference suggested that the fibroblastic cells might be stromal in origin. However, like the refractile cells, the underlying fibroblastic cells ex- Rounded cells began to emerge from the multilayer and only a percentage were P-45Oscc positive.…”

“…The existence of such cells has been inferred from the remarkable capacity of the adrenal cortex to regenerate [16,31,351, but since adrenocortical stem cells have never been isolated, the regulation of their growth and differentiation is not understood. In monolayer culture, pure populations of adrenocortical parenchymal cells rapidly lose their steroidogenic char-acteristics unless they are exposed to trophic hormones such as adrenocorticotropin (ACTH) [7,11,231. In addition, with time or passaging the steroidogenic potential is eventually irrecoverably lost even in the face of chronic trophic hormone treatment.…”

Stimulatory effect of prolactin on the mitotic activity of the adrenal cortex in snell mice with hereditary dwarfism

“…II/08 5 Present address: Dept. of Physiology, Southern Illinois University, Carbondale, IL, USA Offprint requests to: A. Lewifiski, MD (address see above) fibroblast growth factor (FGF), or angiotensin II has been well documented (for review see [10]), however, ACTH can exert both mitogenic effect when applied in vivo [14,19] and antimitotic action in cell [13,20] and organ culture (Sewerynek et al, unpublished observations) of the adrenals. In some other studies the role of prolactin (Prl) [3] and growth hormone (GH) [4,6], as the stimulators of adrenal growth, has been reported.…”