Claudia Robba

Short- and long-term effects of ACTH on the adrenal zona glomerulosa of the rat

SummaryShort-term ACTH treatment provoked a decrease in volume of the lipid-droplet compartment in rat zona glomerulosa cells, and a rise in plasma and intracellular concentrations of corticosterone and aldosterone. It enhanced activities of 3β-hydroxysteroid dehydrogenase (3βHSD), 11β-hydroxylase (11βOH) and 18-hydroxylase (18OH). Long-term ACTH administration produced a hypertrophy of the zona glomerulosa and its parenchymal cells, a result of the increase in volume of the smooth endoplasmic reticulum and the mitochondrial compartment. The surface area per cell of mitochondrial inner membranes increased; the tubular cristae were transformed into a homogeneous population of vesicles. The plasma and intracellular concentrations of corticosterone further increased, whereas those of aldosterone fell below basal levels (the “aldosterone-escape” phenomenon). The activities of 3βHSD and 11βOH were enhanced, that of 180H decreased. Therefore, ACTH stimulates zona glomerulosa growth and transforms parenchymal elements into zona fasciculata celltypes. Cyanoketone nullified acute ACTH effects on plasma and intracellular concentrations of corticosterone and aldosterone, but did not affect the activities of 11βOH and 18OH. Chronic ACTH treatment produced similar results, although 18OH activity was not suppressed. The mechanism underlying the “aldosterone-escape” phenomenon may thus involve a rise in the intracellular concentration of corticosterone, caused by the enhanced synthesis and activation of 3βHSD and 11βOH.

Inhibitory effect of somatostatin on the growth and steroidogenic capacity of rat adrenal zona glomerulosa

Chronic administration of somatostatin induced atrophy of zona glomerulosa cells of rat adrenals and lowering of plasma aldosterone concentration. Zona fasciculata cells did not display any significant change and corticosterone plasma concentration was not significantly affected. These findings are interpreted to indicate that somatostatin exerts a direct inhibitory effect on the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

Effect of somatostatin on the zona glomerulosa of rats treated with angiotensin ii or captopril: Stereology and plasma hormone concentrations

Chronic somatostatin (SRIF) administration induced atrophy of zona glomerulosa cells of the rat adrenal cortex and a noticeable fall in the plasma concentration of aldosterone. The effects of SRIF were comparable with those of captopril, a specific inhibitor of the angiotensin-converting enzyme. SRIF completely abrogated the adrenoglomerulotrophic effects of angiotensin II (AII); the inhibitory actions of SRIF and captopril were not additive. The slight but significant enhancement of zona fasciculata cell growth and plasma corticosterone levels caused by chronic AII administration were ot reversed by SRIF. We interpret these data to indicate that SRIF specifically modulates the stimulatory effects of AII on the growth and steroidogenic capacity of rat zona glomerulosa.

Investigations into the Mechanism of Hormone Release by Rat Adrenocortical Cells

SummaryVinblastine treatment blocks corticosterone release from rat adrenal zona fasciculata without impairing hormone synthesis, and induces the formation of acid phosphatase-positive granular clumps at the juxta-sinusoidal pole of the cells. Autoradiography shows that ACTH administration to vinblastine-treated animals mobilizes the 3H-cholesterol stored in the lipid droplets and leads to a noticeable labelling of the granular clumps. The possible significance of these granules is discussed.

An ultrastructural, morphometric and autoradiographic study of the effects of 7,12-dimethylbenzanthracene on the rat adrenal cortex

SummaryThe effects of chronic treatment (up to 9 consecutive days) with 7,12-dimethylbenzanthracene (DMBA) on the adrenal glands of adult male Wistar rats were investigated. Morphometry showed that DMBA provokes atrophy of the zona reticularis which was due to the decrease in both cell volume and number. The zona fasciculata showed only a decrease in the cell volume, whereas the zona glomerulosa did not display any significant changes. Autoradiography demonstrated that DMBA induces a significant increase in the number of mitoses and “S” phase cells in the zona glomerulosa and outer zona fasciculata, which may be interpreted as a repair mechanism of the DMBA-provoked slight necrosis in the inner adrenocortical layers. The mechanism(s) underlying the cytotoxic effect of DMBA is discussed in the light of our ultrastructural observations showing that the chemical causes a decrease in the volume of the mitochondrial and nuclear compartments and in the surface of smooth endoplasmic reticulum as well as an increase in the volume of the lipid compartment.

Effects of a prolonged treatment with aminoglutethimide on the zona fasciculata of rat adrenal cortex: a morphometric investigation

SummaryThe effects of a 7-day administration of aminoglutethimide (AG) on the adrenal zona fasciculata were examined in “normal” and dexamethasone/ACTH-treated rats. There was a 70–74% decrease in the concentration of corticosterone in blood, but no conspicuous qualitative changes suggesting cell degeneration occurred. Morphometry showed that AG induced a significant hypertrophy of the zona fasciculata and its parenchymal cells only in “normal” animals, which was due to an increase in the volume of the mitochondrial compartment and to proliferation of the smooth endoplasmic reticulum. This response to AG was considered to be non-specific and mediated by the enhanced secretion of ACTH following the decrease in the blood level of corticosterone. AG administration significantly increased the volume of the lipid-droplet compartment and the number of intramitochondrial lipid-like inclusions in both groups of animals. These changes were interpreted as the morphological counterpart of the AG-induced block of cholesterol utilization in steroid synthesis.

Effects of chronic administration of a methionine-enkephalin analogue on the zona glomerulosa of the rat adrenal cortex

SummaryThe effects of D-ala2-met-enkephalinamide (DALA) on the zona glomerulosa of dexamethasone-ACTH-treated rats were investigated by coupled radioimmunologic and morphometric techniques. Short-term DALA administration provoked a significant increase in the aldosterone plasma level along with a notable lipid droplet depletion in zona glomerulosa cells. Long-term DALA treatment induced a striking hypertrophy of zona glomerulosa cells and a further rise in the blood concentration of aldosterone. These findings seem to indicate that DALA is involved not only in the acute enhancement of aldosterone output but also in the stimulation of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

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.

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).

Evidence that long-term methionine-enkephalin administration stimulates rat adrenal zona fasciculata.

Short-term methionine-enkephalin (DALA) treatment did not induce evident changes in the adrenal zona fasciculata and in the basal corticosterone output of dexamethasone-treated rats administered with maintenance doses of ACTH. Conversely, prolonged (5 days) DALA treatment caused a notable hypertrophy of zona fasciculata cells, along with a significant increase in the plasma concentration of corticosterone. It is suggested that enkephalins exert a trophic action on the rat zona fasciculata.