ACTH aldosterone secretion regulated

Without ACTH, aldosterone secretion falls to about half the normal rate, indicating that other factors, eg, angiotensin, are able to maintain and perhaps regulate its secretion (see Chapter 17). Independent variations between cortisol and aldosterone secretion can also be demonstrated by means of lesions in the nervous system such as decerebration, which decreases the secretion of cortisol while increasing the secretion of aldosterone. 

In addition to the angiotensin II effects, aldosterone secretion is regulated by increased plasma potassium levels.75,83 Presumably, elevated plasma potassium serves as a stimulus to increase aldosterone release, thus causing increased potassium excretion and a return to normal plasma levels. Finally, there is evidence that ACTH may also play a role in aldosterone release. Although ACTH is primarily involved in controlling glucocorticoid secretion, this hormone may also stimulate mineralocorticoid release to some extent.75... 

It was concluded from these and other studies in hypophysectomized animals that ACTH had no effect on aldosterone release. The volume-sensitive renal mechanism appears to be mainly responsible for postoperative aldosterone changes (S4), but it would now appear that ACTH also plays a part in regulating aldosterone secretion (S4). Removal of the pituitary leads to an immediate fall in aldosterone levels in adrenal venous blood (H9). A linear dose response relationship exists between the infusion rate of ACTH and aldosterone secretion rates (H9). Volume receptors in the right atrium and in the vascular tree respond to minor reductions in blood volume and play an important part in stimulating the aldosterone response (Bl, FI). Patients with suppression of cortisol production due to prolonged administration of steroids continue to secrete aldosterone and are able to increase their output after stress indicating the presence of another trophic factor as well as ACTH (T3). 

The major regulators of aldosterone secretion are the renin-angiotensin system and extracellular potassium ions (K+). The former is sensitive to changes in intravascular volume and arterial pressure, while the latter is an aldosterone-regulated substance that feeds back to reduce aldosterone synthesis (simple negative feedback). Aldosterone secretion is also influenced (but not regulated) by ACTH and, directly and indirectly, by atrial natriuretic factor (ANF). 

A. Aldosterone The major natural mineralocorticoid in humans is aldosterone, which has already been mentioned in connection with hypertension (see Chapter 11) and control of its secretion by angiotensin II (see Chapter 17). The secretion of aldosterone is regulated by ACTH and by the renin-angiotensin system and is very important in the regulation of blood volume and blood pressure (see Figure 6 ). Aldosterone has a short half-life and little glucocorticoid activity (Table 39-1). Its mechanism of action is the same as that of the glucocorticoids. 

The adrenocorticotrophic hormone ACTH (corticotropin) stimulates the adrenal cortex to secrete the glucocorticoids hydrocortisone (cortisol) and corticosterone, the mineralocorticoid aldosterone, and a number of weakly androgenic substances, as well as a small amount of testosterone. Aldosterone synthesis is also regulated by renin and angiotensin. 

Yet, experiments on changes in intracellular Ca2+ levels in adrenal glomerulosa cells exposed to ACTH or Ang II strongly suggest that hormone receptors may also stimulate Ca2+ channels, and that regulation may be directly by a G protein (Gs ). Glomerulosa cells respond to both hormones by secreting aldosterone. However,... 

Fig. 10. Hypothesis for the interaction of the A-kinase (A-K) system activated by ACTH with the C-kinase system (C-K) in the long-term regulation of the enzymes of steroidogenesis throughout the adrenal cortex. The primary determinant of zonation of A-kinase and C-kinase activities, via zonation of cell surface receptors or other mechanisms, is hypothesized to be a gradient (e.g., of steroids) created by the pattern of blood flow in the adrenal cortex. The resultant levels of induction of steroidogenic enzymes are indicated by to show particular elevation and by to show particular lack of induction or suppression of induction. Other enzymes involved in steroidogenesis are shown in parentheses. SCC=cholesterol side-chain cleavage enzyme 3/3=3/3-hydroxysteroid dehydrogenase 17a=17a-hy-droxylase 21 =21-hydroxylase 11/3= 11/3-hydroxylase CMO= corticosterone methyl oxidase activity of 11/3-hydroxylase. Secreted steroids are indicated as B=corticosterone Aldo=aldosterone F=cortisol DHEA(S)= dehydroepiandrosterone (sulfate).

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