Adrenocortical zonation and ACTH

Abstract

The clear morphological distinction between the cells of the different adrenocortical zones has attracted speculation and experiment to interpret their functions and the ways in which they are regulated. Considerable data have been produced in recent years that has benefited a fuller understanding of the processes of steroidogenesis and of cell proliferation at the molecular level. This now enables the reexamination of earlier concepts. It is evident that there is considerable species variation, and this article, dealing mainly with the rat, reaches conclusions that do not necessarily apply to other mammals. In the rat adrenal, however, the evidence suggests that the greatest differences between the functions of the zones are between the glomerulosa and the fasciculata. Here the sometimes all-or-nothing demarcation in their complement of components associated with steroidogenesis or with cell proliferation suggests a stark division of labor. In this model the fasciculata is the main engine of steroid hormone output and the glomerulosa is the site of cell proliferation, recruitment, and differentiation. Regulating these functions are angiotensin II and other paracrine components that modulate and maintain the glomerulosa, and ACTH, that maintains the fasciculata, and recruits new fasciculata cells by transformation of proliferating glomerulosa cells. Grafted onto this mostly vegetative function of the glomerulosa is CYP11B2, limited to just a fraction of the outer glomerulosa in rats on a normal laboratory diet and generating aldosterone (and 18-hydroxycorticosterone) from precursors whose origin is not, from the evidence summarized here, very clear, but may include the fasciculata, directly or indirectly. The biosynthesis of aldosterone in the rat certainly requires reinterpretation.

Insulin and hyperandrogenism in women with polycystic ovary syndrome

“…However, rodents' adrenals do not produce androgens [15]. In women, adrenal gland contribution to androgen production is very important.…”

Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study

“…This differentiation is associated with the exclusive presence of aldosterone synthase (CYP11B2) in the glomerulosa whereas 11β-hydroxylase (CYP11B1) is exclusively present in the rat ZF/ZR (Ogishima et al 1992;Mitani et al 1994). Enzymes that catalyze those steroidogenic pathways are biochemically essential to partitioning mineralocorticoid-active steroids of the glomerulosa from the glucocorticoid-producing steroids of the inner zones (Vinson 2003). The hormone assays from blood obtained after the last ICV ghrelin dose showed a significant elevation in the principal ZG related mineralocorticoid, aldosterone, and an even more pronounced increased in cortisocosterone, the principal steroid with glucocorticoid activity usually associated with ZF/ZR.…”

“…Also, all of the steroidogenic enzymes can be induced in the glomerulosa under various conditions including elevations in ACTH (Vinson 2003). The ZG contains the transactivating factor SF-1 as does the fasciculata and this factor is required for the induction of a wide range of cellular components associated with steroidogenesis.…”

Differential mRNA expression of genes in the porcine adrenal gland associated with psychosocial stress

“…Thus, the simultaneous downregulation of growth-stimulating and -inhibiting factors in the highstress group may reflect the biphasic effect of ACTH on adrenocortical cell growth. The balance was perhaps shifted towards growth inhibition, as indicated by downregulation of angiotensinogen (AGT), the precursor of angiotensin II, an important factor in the positive regulation of adrenal growth (Huckle & Earp 1994, Vinson 2003. The systemic renin-angiotensin system is the principal activator of aldosterone production in the zona glomerulosa (Sewer et al 2007).…”

“…The systemic renin-angiotensin system is the principal activator of aldosterone production in the zona glomerulosa (Sewer et al 2007). However, in addition to its role in aldosterone secretion, the zona glomerulosa is considered to be the site of proliferation, recruitment and differentiation of adrenocortical cell under the control of the locally produced angiotensin II (Vinson 2003). In vascular smooth muscle, angiotensin II stimulates cell growth through activation of IGF1R transcription.…”