GastoneG. Nussdorfer

Long-term trophic effect of ACTH on rat adrenocortical cells

SummaryThe changes occurring in rat adrenocortical cells (zona fasciculata) during an 8 day period of treatment with ACTH, were investigated by morphometric and autoradiographic methods.The most important ultrastructural change consists in a conspicuous increase in the smooth endoplasmic reticulum, that accounts for about 50% of the total increase of cellular volume. Also the mitochondrial fraction shows a significant increase, which is found to be due both to the increment in the number of mitochondria per cell and to the increase in the mean volume of organelles themselves.The quantitative autoradiographic data, indicating an increment in the incorporation of 3H-orotate and 3H-leucine into adrenocortical cells of the treated animals, allow us to conclude that the ACTH-induced ultrastructural changes are the morphological expression of a stimulation of the cellular protein synthesis.Since mitochondria are largely autonomous in the synthesis of their enzymes and structural proteins, it is possible to hypothesize that ACTH also intervenes in the regulation of the mitochondrial protein synthesis.

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.

Further studies on the effects of corticosterone on adrenocortical cells of hypophysectomized ACTH-treated rats

Con metodi morfometrici è stato studiato leffetto di dosi parafisiologiche di corticosterone sulle cellule corticosurrenaliche (zona fascicolata) di ratti ipofisectomizzati trattati con dosi di mantenimento di ACTH. I dati ottenuti indicano che tali dosi di ormone inibiscono direttamente la funzionalità delle cellule corticosurrenaliche. Questi risultati suggeriscono che la componente periferica dei meccanismi a feed-back che intervengono nella regolazione della funzione corticosurrenalica, giochi un ruolo fisiologico significativo.

Ultrastructure of accessory adrenocoriical nodules in Wistar rats

ULTRASTRUCTURE OF ACCESSORY ADRENOCORTICAL NODULES IN WlSTAR RATS. Anna S. BELLONI ( 1 ) , Francesco MUSAJO (2) , Giuseppina MAZZOCCHI (1) and Gastone G. NUSSDORFER ( 1 ) . (1) Department o f Anatomy and (2) 2nd S u r g i c a l C l i n i c , U n i v e r s i t y o f Padua, I t a l y . More than 70% o f b i l a t e r a l l y a d r e n a l e c t o m i z e d Wis t a r r a t s s u r v i v e and w i t h i n t h r e e months deve lop one o r two consp icuous a d r e n o c o r t i c a l nodules (2-3 mm in d i a m e t e r ) , which, thouEh d i s p l a y i n g an obvious histoloEical zonation, are not associated with chromaffin tissue. Middle and inner cells of the nodules are similar to zona fasciculata (ZF) and zona reticularis elements of the adult rat adrenal Eland, res pectively. Middle cells show numerous round mitochondria with vesicular cristae, while inner cells con tain ovoid mitochondria with tubule-convolute cristae. Both cell types possess abundant smooth endopla smic reticulum and few lipid droplets, as well as a very elaborated microvillous system. Conversely, outer (subcapsular) cells of the accessory nodules do not resemble lena Elomerulosa (ZG) elements, since they display ovoid mitochondria with vesicular cristae instead of elonEated orEanelles with tubu lo-laminar cristae. Moreover, morphometry shows that their volume is about two-fold that of the true ZG cells (1400 um3 versus 700 um3). These morpholoEical data accord well with the fact that basal plasm8 concentration of aldosterone, at variance with that of corticosterone, remains very low three months after bilateral adrenalectomy. The lack of differentiated ZG cells in the accessory adrenocortical nod ules could be explained by the very elevated blood level of ACTH (about 5-times hiEher than in shamoperated rats), in fact, chronic ACTH hypersecretion is known to transform ZG cells into ZF elements (i). Some lines of evidence suEEest the existence of a paracrine control of adrenal zona corticalis by zona medullaris (i). We think that accessory adrenocortical nodules, lackinE zona medullaris, could be a Eood experimental model to Eain insiEht into this problem.

Effects of mevinolin, an inhibition of cholesterol synthesis, on the morphological and functional responses of rat adrenal zona fasciculata to a prolonged treatment with 4‐aminopyrazolo‐pyrimidine

Rat adrenocortical cells are almost completely dependent upon the continuous supply of cholesterol derived from serum lipoproteins. However, a prolonged (5-day) administration of 4-aminopyrazolo-pyrimidine (4-APP), a potent hypocholesterolaemic drug, though provoking a notable decrease in the intra-adrenal concentration of esterified and free cholesterol, did not significantly affect basal plasma level of corticosterone. Morphometry showed a conspicuous hypertrophy of zona fasciculata cells, coupled with a striking proliferation of smooth endoplasmic reticulum (SER) and peroxisomes and with a profound lipid-droplet depletion. The secretory response of zona fasciculata cells to ACTH was still present, but reduced by half with respect to control rats. The simultaneous administration of mevinolin, an inhibitor of cholesterol synthesis, to 4-APP-treated rats caused an additional drop in the intracellular content of free cholesterol and notably lowered basal plasma corticosterone concentration. Mevinolin magnified the 4-APP-induced zona fasciculata cell hypertrophy, as well as SER and peroxisome proliferation. The secretory response to ACTH was completely suppressed. These data are compatible with the view that the morphological changes, which rat zona fasciculata cells undergo during prolonged hypocholesterolaemia, are the expression of the activation of the endogenous cholesterol synthesis. This compensatory response, enabling zona fasciculata cells to maintain a normal basal rate of hormonal output and to respond (though less efficiently) to their main physiological stimulus, seems to be completely independent of any activation of the hypothalamo-hyphophyseal axis, since dexamethasone/ACTH treated rats were used. The hypothesis is advanced that the mechanism underlying this response may involve the decrease of the intracellular free-cholesterol pool.