Aldosterone Glomerulosa cells

Angiotensin II binds to specific adrenal cortex glomerulosa cell receptors. The hormone-receptor interaction does not activate adenylyl cyclase, and cAMP does not appear to mediate the action of this hormone. The actions of angiotensin II, which are to stimulate the conversion of cholesterol to pregnenolone and of corticosterone to 18-hydroxycorticosterone and aldosterone, may involve changes in the concentration of intracellular calcium and of phospholipid metabolites by mechanisms similar to those described in Chapter 43. 

Angiotensin II stimulates aldosterone synthesis and secretion from the glomerulosa cells of the adrenal cortex. The aldosterone secretion induced by angiotensin II in humans is not accompanied by an increase in glucocorticoid plasma levels. Chronic administration of angiotensin II will maintain elevated aldosterone secretion for several days to weeks unless hypokalemia ensues. 

Possibly relevant to the natriuretic activity of SK F 38393 is emerging evidence that dopamine may be a physiological regulator of aldosterone synthesis (28). Dopamine receptors in a particulate fraction of calf adrenal glomerulosa cells have been shown to bind 3H-2-amino-1,2,3,4-tetrahydro-6,7-dihydroxynaptha-lene (3H-ADTN) in a specific (displaceable by 10 pM dopamine) saturable manner (29) (Kj, 0.29 mM maximal binding capacity,... 

The 5-HT7 receptors also are expressed in the periphery, where their best characterized function is to mediate relaxation of vascular smooth muscle (397). In particular, 5-HT7 receptors are expressed throughout the gut (398) and stomach (399), as well as in vasculature (400,401). 5-HT7 receptors are also expressed in adrenal glomerulosa cells (402,403) and corneal epithelial cells (404). In the adrenal gland, 5-HT7 receptors stimulate the release of aldosterone from adrenal glomerulosa cells (402,403) by increasing cAMP levels. 

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,... 

An increase in the extracellular K+ concentration from 2 to 8 mM (the limits of the physiological range) leads to a 4-5-fold increase in the rate of aldosterone secretion by the adrenal glomerulosa cell [24,25]. This increase in [K+] leads to a depolarization of the plasma membrane of the cell. This depolarization causes the opening of two types of voltage-dependent Ca2+ channel in this membrane, and thus to a 4-fold increase in the rate of Ca2+ influx. The total cell calcium and the [Ca2+]j both... 

This shift in the substrate specificity of phospholipase C may persist for some time after the removal of agonist and may contribute to the phenomenon of cellular memory in the adrenal. When glomerulosa cells are sequentially exposed to All (20 minutes)-, no agonist (10 minutes), and again All, the character of the response elicited by the second addition of All differs dramatically from that elicited by the first the cell seems to remember its prior exposure to All [29], Although this second addition of All induces a smaller calcium transient, the rate of aldosterone secretion increases more rapidly and reaches a higher plateau value than is seen in response to the first exposure to the hormone. This result suggests either that the second addition of All elicits a smaller increase in 1,4,5-IP3 as a result of an altered... 

FIGURE 10.5 Results of a study on rat zona glomerulosa cells. The effect of angiotensin n was measured as the amount of aldosterone released into the medium by the cells. (Redrawn with permission from Braley et al, 1989.)... 

There are two distinct subtypes of angiotensin II receptors, designated as type 1 (ATj) and type 2 (AT2). The ATj-angiotensin-II-receptor subtype is located predominantly in vascular and myocardial tissue and also in brain, kidney, and adrenal glomerulosa cells, which secrete aldosterone. 

The role of nitric oxide in the regulation of aldosterone synthesis by adrenal glomerulosa cells. J Steroid Biochem Mol Biol 61 47-53... 

Sodium is excreted in the renal tubules, and this is partially regulated by aldosterone. Aldosterone is elaborated in the glomerulosa cells of the adrenal cortex (see Fig. 9-5). The biosynthesis of aldosterone is discussed in Chapter 8. One of the most dramatic obser-... 

The major mineralocorticoid, aldosterone, is secreted by cells of the zona glomerulosa. Primary hyperaldosteronism (Conn s syndrome) is associated with potassium depletion which is, in mm, responsible for the observed neuromuscular abnormalities seen in the disorder. These are similar to those seen in hypokalemic periodic paralysis (PP), with episodic and severe exacerbations of fixed muscle weakness. Muscle biopsy shows occasional muscle necrosis and vacuoles often these feamres are accompanied by mbular aggregates as in hypokalemic PP. All these changes can be attributed to the hypokalemia and not to excess aldosterone production per se. 

The adrenal gland appears to be one organ, but functionally it is two different organs. The inner core of the gland is the adrenal medulla. It is imder nervous control and secretes epinephrine (adrenaline) and norepinephrine (noradrenaline). The outer layer of the adrenal gland is the adrenal cortex. The cells of the adrenal cortex closest to the surface of the gland constitute the zona glomerulosa. These cells synthesize aldosterone and release it into the bloodstream. 

The steroid hormone aldosterone, synthesized in the zona glomerulosa of the adrenal cortex, also plays an important role in maintaining blood osmolar-ity. It binds its receptors in the cytoplasm of epithelial cells of the distal colon and the renal nephron, followed by translocation of the hormone-receptor complex to the nucleus and activation of transolption of ion transport genes to increase Na reabsorption and secretion. Water follows Na+ movement by osmosis. These transporters include the luminal amiloride-sensitive epilheUal Na+ channel, the luminal channel, the serosal Na, K+-ATPase, the Na+/H+exchanger, and the NaVCT cotransporter. 

In addition, Brizuela et al. (Brizuela et al., 2006) reported that SIP stimulate aldosterone secretion in bovine glomerulosa adrenal cells. This aldosterone modulation is mediated by SIP binding to its cognate SIPR and... 

A stratum of cells that did not contain both aldosterone synthase cytochrome P450 (cytochrome P-450aid) and cytochrome P-450np was found immu-nohistochemically between the zona glomerulosa... 

---