Zona glomerulosa

The adrenal cortex is functionally divided into three zones, the zona glomerulosa, fasciculata, and reticularis. Only the outermost zone, the zona glomerulosa, synthesizes aldosterone. The other zones are responsible for the generation of glucocorticoids and androgens. 

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. 

Steroidogenic agents—including ACTH and cAMP in the adrenal cortex angiotensin 11, K", serotonin, ACTH, and cAMP in the zona glomerulosa of the adrenal LH in the ovary and LH and cAMP in the Ley dig cells of the testes—have been associated with increased amounts of phosphatidic acid, phosphatidylinositol, and polyphosphoinositides (see Chapter 14) in the respective target tissues. Several other examples could be cited. 

The adrenal gland is located on the upper segment of the kidney (Fig. 42-1). It consists of an outer cortex and an inner medulla. The adrenal medulla secretes the catecholamines epinephrine (also called adrenaline) and norepineprhine (also called noradrenaline), which are involved in regulation of the sympathetic nervous system. The adrenal cortex consists of three histologically distinct zones zona glomerulosa, zona fasciculata, and an innermost layer called the zona reticularis. Each zone is responsible for production of different hormones (Fig. 42-2). 

Adrenal steroid synthesis. The adrenal cortex consists of three histologically distinct zones the zona glomerulosa, zona fasciculata, and an innermost layer called the zona reticularis. Each zone is responsible for production of different hormones. (17 =... 

The zona glomerulosa is responsible for the production of the mineralocorticoids aldosterone, deoxycorticosterone, and 18-hydroxy-deoxycorticosterone. Aldosterone promotes renal sodium retention and excretion of potassium. Its synthesis and release are regulated by renin in response to decreased vascular volume and renal perfusion. Adrenal aldosterone production is regulated by the renin-angiotensin-aldosterone system. 

Aldosterone A hormone produced in and secreted by the zona glomerulosa of the adrenal cortex. Aldosterone acts on the kidneys to reabsorb sodium and excrete potassium. It is also a part of the renin-angiotensin-aldosterone system, which regulates blood pressure and blood volume. 

The mammalian adrenal cortex is divided into three concentric zones the zona glomerulosa, zona fascicu-lata, and zona reticularis. The zona glomerulosa produces hormones, such as aldosterone, that are responsi-... 

In the treatment of secondary adrenocortical insufficiency, lower doses of cortisol are generally effective, and fluid and electrolyte disturbances do not have to be considered, since patients with deficient corticotrophin secretion generally do not have abnormal function of the zona glomerulosa. Since cortisol replacement therapy is required for life, adequate assessment of patients is critical to avoid the serious long-term consequences of excessive or insufficient treatment. In many cases, the doses of glucocorticoid used in replacement therapy are probably too high. Patients should ideally be administered three or more doses daily. To limit the risk of osteoporosis, replacement therapy should be carefully assessed on an individual basis and overtreatment avoided. 

Ang II acts directly on the zona glomerulosa of the adrenal cortex to stimulate aldosterone synthesis and release. At higher concentrations, Ang II also stimulates glucocorticoid synthesis. 

Aldosterone is synthesized mainly in the zona glomerulosa of the adrenal cortex. Its structure and synthesis are illustrated in Figure 39-1. 

Heparin-induced hypoaldosteronism is well documented, both in patients treated with standard heparin, even at low doses, and in patients treated with low molecular weight heparin (477,478). The most important mechanism of aldosterone inhibition appears to be a reduction in both the number and affinity of angiotensin II receptors in the zona glomerulosa (477). A direct effect of heparin on aldosterone synthesis, with inhibition of conversion of corticosterone to 18-hydroxycorticosterone, has also been suggested. This effect is believed to be responsible for the hyperkalemia that can occur in heparin-treated patients with impaired renal function and particularly in patients on chronic hemodialysis (479), or with diabetes mellitus, or who are taking other potentially hyperkalemic drugs. 

Silver is cleared from the system via the liver (Furchner et al. 1968 Scott and Hamilton 1950). Deposition of uncleared silver can occur along the renal glomerular basement membrane (Creasey and Moffat 1973 Danscher 1981 Ham and Tange 1972 Moffat and Creasey 1972) and mesangium (Day et al. 1976), and in the Kupffer cells and the sinusoid endothelium cells of the liver (Danscher 1981). Silver has also been detected intra- and extracellularly in the skin and mucosa of the tongue, in the chromaffin cells, cells of the zona glomerulosa, and zona fasciculata of the adrenal glands, and in the exocrine and endocrine sections of the pancreas (Danscher 1981). 

The adrenal gland, which is located at the cap of the kidney, is divided histologically into three zones the outer zone or zona glomerulosa, the middle zone or zona fasciculata, and the inner zone or zona reticularis. The adrenal cortex synthesizes cholesterol and pregnenolone through the interaction of a group of enzymatic reactions (Figure 61.1). 

Adrenal glucocorticoid and androgen production is controlled predominantly by the hypothalamic-pituitary axis, whereas the production of aldosterone by the zona glomerulosa is predominantly regulated by the renin-angiotensin system and potassium concentration. The hypothalamus, pituitary, and adrenal form a neuroendocrine axis whose primary function is to regulate the production of both cortisol and some of the adrenal steroids (Figure 61.4). 

Steroid hormones are produced in the adrenal cortex and the sex glands. All such hormones originate from cholesterol. Figure 16.4 shows the overall scheme for steroid hormone biosynthesis that is applicable to all tissues. The final products may be divided into the following groups mineralocorticoids (e.g., aldosterone), produced by the zona glomerulosa of the adrenal cortex glucocorticoids (e.g., cortisol), produced by the zona fasciculata of the adrenal cortex and the... 

In the adrenal cortex, the outermost zona glomerulosa secretes the mineralocorticoid aldosterone, and corticosterone. The middle zona fasciculata and the inner zona reticularis secrete predominately the glucocorticoids cortisol and corticosterone. In the human, the inner zona reticularis secretes large amounts of the adrenal androgens, DHEA and DHEAS, as well as cortisol [12]. Whereas steroidogenesis in the... 

Activators of plasma membrane Gj protein may inhibit adenylate cyclase. The zona glomerulosa has higher levels of receptors which activate G, such as those for angiotensin and somatostatin [44,45], which may inhibit ACTH-stimulated adenylate cyclase [34]. Alternatively, activation of protein kinase C and phosphoryla-... 

Fig. 9. The interaction of ACTH with the cyclic AMP and calcium intracellular messenger systems in the regulation of steroidogenesis in the adrenocortical zona glomerulosa cell comparison with angiotensin II and potassium. ACTH activates both adenylate cyclase and calcium influx, here shown as involving two receptor subtypes (R, and R2) although such receptor subtypes have not been identified. The A-kinase and calmodulin systems produce individual responses of characteristic amplitudes and time-courses, which combine to give the observed response of the intact cell. The sequence of events for ACTH is compared to those for the other two major stimuli of steroidogenesis in the zona glomerulosa cell, angiotensin II and potassium. From Ref. 41.

Calcium, via calmodulin, also activates cyclic AMP phosphodiesterases which inactivate cyclic AMP by metabolism to AMP. Inhibition of phosphodiesterase yields a small increase in ACTH-stimulated steroidogenesis [2], This is relatively slight in the adrenocortical zona fasciculata-reticularis cell, which has a low phosphodiesterase level the zona glomerulosa cell has a higher activity [60,61], which may result from higher level of activation of the calcium/calmodulin intracellular messenger system in the zona glomerulosa. 

The adrenal cortex (AC) produces the glucocorticoid cortisol (hydrocortisone) in the zona fasciculata and the mineralocorticoid aldosterone in the zona glomerulosa. Both steroid hormones are vitally important in adaptation responses to stress situations, such as disease, trauma, or surgery. Cortisol secretion is stimulated by hypophyseal ACTH aldosterone secretion by angiotensin II in particular (p. 128). In AC failure (primary adrenocortical insuf ciency, Addison disease), both cortisol and aldosterone must be replaced when ACTH production is deficient (secondary adrenocortical insuf ciency), cortisol alone needs to be replaced. Cortisol is effective when given orally (30 mg/day, 2/3 a.m 1 /3 p.m.). In stress situations, the dose is raised 5- to 10-fold. Aldosterone is poorly effective via the oral route instead, the mineralocorticoid fludrocortisone (0.1 mg/day) is given. 

Q1 Each adrenal gland is composed of an outer cortex and an inner medulla. The cortex consists of three layers where several steroid hormones, synthesized from cholesterol, are produced and secreted. The outer layer of the cortex, the zona glomerulosa, produces the mineralocorticoid aldosterone. The zona fasciculata lies under this layer and, together with the inner layer, the zona reticularis, secretes glucocorticoids, mainly cortisol, corticosterone and androgens. 

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