A.S. Belloni

Effects of substance P on the rat adrenal zona glomerulosa in vivo

Substance P (SP) acutely enhanced the plasma concentration of aldosterone in rats whose hypothalamo-hypophyseal-adrenal axis and renin-angiotensin system were pharmacologically interrupted. The maximal response was obtained with a dose of 100 micrograms/kg. A prolonged (7 days) subcutaneous infusion with SP (50 micrograms/kg/hr) caused a notable hypertrophy of zona glomerulosa cells associated with significant rises in both basal and angiotensin-stimulated plasma levels of aldosterone. Zona fasciculata and the blood concentration of corticosterone were not affected. These findings suggest that SP is specifically involved in the stimulation of the growth and secretory activity of the rat zona glomerulosa.

Neuropeptide K enhances glucocorticoid release by acting directly on the rat adrenal gland: the possible involvement of zona medullaris

Neuropeptide K (NPK), a member of the kassinin-like tachykinin family, is contained in the rat hypothalamus and is known to stimulate pituitary ACTH release. The intraperitoneal bolus administration of NPK dose-dependently enhanced corticosterone blood level not only in intact rats, but also in hypophysectomized/ACTH replaced animals. NPK did not affect corticosterone secretion of dispersed rat adrenocortical cells; however, it concentration-dependently raised basal corticosterone production by decapsulated adrenal quarters (including both cortical and medullary tissues). Minimal and maximal effective concentrations were 10(-9) and 10(-8) M, respectively. 10(-8) M NPK potentiated corticosterone response of adrenal quarters elicited by 10(-12) M ACTH, but not that evoked by higher concentrations of ACTH. The direct corticosterone secretagogue effect of 10(-8) M NPK is annulled by 10(-6) M alpha-helical-CRH or corticotropin-inhibiting peptide, competitive inhibitors of CRH and ACTH, respectively. In light of these findings, the hypothesis is advanced that NPK exerts a direct stimulatory action on adrenocortical secretion and that the mechanism underlying this effect of NPK may involve the activation of the intra-medullary CRH/ACTH system.

Age-related changes in the morphology and function of the zona glomerulosa of the rat adrenal cortex

The age-related changes in the morphology and function of rat adrenal zona glomerulosa (ZG) were investigated by coupled stereological and radioimmunological techniques. For this purpose 4-, 8-, 16- and 24-month-old rats were studied. Aging caused a notable lowering in the plasma aldosterone concentration and a marked decrease in both basal and ACTH- or angiotensin II (ANG-II)-stimulated secretion of collagenase-dispersed ZG cells. Plasma renin activity (PRA) underwent an age-dependent decrease, while the plasma level of ACTH displayed a significant rise. ZG and its parenchymal cells did not evidence any age-related morphologically demonstrable alteration in their growth, nor ZG cells showed any marked ultrastructural change, with the exception of a severe lipid-droplet repletion. This last finding is in keeping with the aging-induced decrease in the secretory activity of ZG cells, inasmuch as lipid droplets are the intra-cellular stores of cholesterol esters, the obligate precursors of steroid hormones in rat adrenals. ACTH and ANG-II are well known to be involved in the maintenance of the growth of rat ZG; thus, the combined impairment of ANG-II production (as evidenced by PRA lowering) and increase in ACTH secretion may maintain unchanged ZG growth during aging.

Effect of ACTH on the zona reticularis of the rat adrenal cortex: an ultrastructural stereologic study.

The effects of ACTH on the rat adrenalzona reticularis were investigated by stereologic methods. It was found that thezona reticularis cell responsiveness to ACTH is similar to that of thezona fasciculata elements. This excludes that thezona reticularis of the adult rat can only function as the site of destruction of worn-out elements migrating from the adrenal outer zones.

Evidence that long-term administration of a methionine-enkephalin analogue stimulates the growth and steroidogenic capacity of rat inner adrenocortical cells.

A prolonged infusion with D-ala2-met-enkephalinamide (DALA) caused a significant increase in both basal and ACTH-stimulated corticosterone secretion by dispersed inner adrenocortical cells of rats whose hypothalamo-hypophyseal axis was pharmacologically interrupted. This effect of DALA was associated with a notable hypertrophy of isolated cells. These findings suggest that enkephalins are involved in the stimulation of the growth and steroidogenic capacity of the cells of the inner layers of rat adrenal cortex.

Fine structure of the rabbit adrenal cortex and the effects of short-term ACTH administration

SummaryThe fine structure of the rabbit adrenal cortex was investigated. The parenchymal cells display the ultrastructural features of steroid-producing cells, and also contain numerous electron-dense bodies frequently located near intercellular canaliculi, which open into the subendothelial space. Short-term ACTH-administration induced a noticeable decrease in the volume of the lipid compartment in the cells of all three cortical zones and a significant increase in the volume of dense bodies in the cells of zona fasciculata and zona reticularis. The hypothesis that these dense bodies are secretory granules is discussed in the light of biochemical evidence showing that ACTH increases the concentration of both corticosterone and cortisol in the decapsulated-enucleated adrenal homogenate and does not affect the activity of two lysosome-marker enzymes (i.e., acid phosphatase and β-glucuronidase).

Effect of mevinolin on rat hepatocytes : a morphometric study

A short-term (12 h) infusion with mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, significantly lowered plasma cholesterol concentration in rats. After 7 days of continuous treatment hypocholesterolaemia disappeared, and this was coupled with a notable increase in the average volume of hepatocytes. Liver-cell hypertrophy was associated with a striking proliferation of the membranes of both rough and smooth endoplasmic reticulum, as well as with a tremendous increase in the number of peroxisomes. These structural changes are interpreted as the morphologic counterpart of the compensatory response of rat liver to the prolonged inhibitory effect of mevinolin on cholesterol synthesis.

Investigations on the possible involvement of the dopaminergic system in the modulation of the growth and steroidogenic capacity of the rat adrenal zona glomerulosa: A coupled morphometric and biochemical study

SummaryThe effects of metoclopramide (MTC) and bromocriptine (BRC) (two drugs which act as antagonist and agonist of DOPA-receptors, respectively) on the zona glomerulosa of dexamethasone/ACTH-treated rats were investigated by coupled biochemical and morphometric techniques. Shortterm (1-h) MTC administration significantly increased the plasma concentration of aldosterone, while long-term (7-day) MTC administration, as well as short- and long-term treatment with BRC did not cause any apparent change. Long-term MTC administration was found to significantly potentiate both the rise in the plasma level of aldosterone and the hypertrophy of the zona glomerulosa and its parenchymal cells induced by a prolonged treatment with angiotensin II (AII), but not those evoked by a chronic sodium deprivation alone or combined with AII infusion. Long-term BRC administration notably counteracted the effects of sodium restriction (coupled or not with AII infusion), but not those induced by the administration of AII alone. Long-term MTC administration partially reversed both the lowering of the plasma concentration of aldosterone and the atrophy of the zona glomerulosa and its parenchymal cells caused by a prolonged sodium-loading (combined or not with captopril infusion), but not those produced by the administration of captopril alone. On the other hand, long-term BRC treatment induced a further significant reduction in the blood level of aldosterone and the volume of zona glomerulosa and its cells only in captopriltreated animals. These findings are consistent with the view that the dopaminergic system exerts a maximal tonic inhibitory effect not only on the secretory activity, but also on the growth and steroidogenic capacity of the rat zona glomerulosa. Furthermore, they suggest that the activity of the dopaminergic system is in turn controlled by the sodium balance, being almost completely suppressed by a prolonged sodium deprivation.

Investigations on the turnover of adrenocortical mitochondria. VII. Effects of ACTH on the half-life of mitochondria from the zona reticularis of the rat adrenal cortex

The half-life of mitochondria from the zona reticularis of the rat adrenal was calculated by determining the radioactivity decay curves of the mitochondrial compartment of 3H-thymidine-injected animals, using autoradiographic methods. ACTH was found to enhance significantly the half-life of the organelles.

A comparative study of the effect of atrial natriuretic peptide (ANP) on the secretory activity of rat adrenal cortex and angiotensin-II-responsive adrenocortical autotransplants

Rat adrenocortical autotransplants regenerated from capsular-tissue fragments implanted in the musculus gracilis displayed an in-vitro basal gluco- and mineralocorticoid secretion qualitatively similar to that of adrenal quarters from control rats. Moreover, like adrenal quarters, they responded to angiotensin-II (Ang-II, 10(-8) M) by raising their yield of 18-hydroxylated steroids (18-hydroxy-11-deoxycorticosterone, 18-hydroxycorticosterone and aldosterone). ANP (10(-8) M), one of the main negative modulators of the zona-glomerulosa (ZG) mineralocorticoid secretion, totally blocked the ANG-II stimulating effect on adrenal quarters, but not that on adrenocortical autotransplants. Autoradiography showed that, in contrast with ZG cells of control rats, ZG-like cells of transplants did not significantly bind 125I-ANP. The hypothesis is discussed that ZG-like cells of regenerated adrenocortical nodules lack specific receptors for ANP.