Effect of ACTH on the proliferative and secretory activities of the adrenal glomerulosa

Abstract

The mitotic, trophic and secretory responses of the adrenal cortex to various preparations and doses of ACTH were investigated in the rat. 1-24-ACTH depot (Synacthen) elicited the highest mitotic and trophic stimulation. The mitotic stimulation occurred exclusively in the glomerulosa, the trophic stimulation occurred mainly in the fasciculata-reticularis and the functional stimulation was found in both, as indicated by the plasma aldosterone and corticosterone levels. The functional changes occurred first, the trophic changes later. Large doses of ACTH inhibited cell proliferation in the fasciculata. The trophic action consisted in an enlargement of the adrenal, to a great extent in the fasciculata-reticularis, and to a lesser extent in the glomerulosa. This enlargement was due partly to parenchymal cell hypertrophy, but also and mostly to stromal hypertrophy, especially hyperaemia. The largest dose of ACTH caused a considerable widening of the sinusoids of the fasciculata-reticularis and medulla, and possibly caused a loss of parenchymal cells in the reticularis. These effects are reminiscent of the well documented haemorrhagic conditions of the adrenals in humans.In a previous work dealing with the hyperplastic stimulation of the adrenal glomerulosa by various hormones, we had found little effect of ACTH on the glomerulosa (Payet 8c Isler 1976). When we later examined the zona fasciculata, which is the acknowledged target tissue of ACTH, paradoxical¬ ly we found no effect on this layer. Therefore, we decided to investigate this lack of effect in more detail, using various plain and long acting ACTH preparations and doses. Our findings are reported in this paper. They again are paradoxical since we found a considerable hyperplastic stimulation of the zona glomerulosa and a lack of such stimulation of the fasciculata. We also investigated the relation¬ ship between mitotic and secretory activity of the cortical layers. Materials and MethodsThe general procedure was the same as that described in a previous article (Payet & Isler 1976). Two months old female hooded rats were kept in individual cages, fed purina laboratory chow and water ad libitum, and han¬ dled daily during the week prior to the experiment to minimize the stress due to manipulation under treat¬ ment.Plain 1-39-ACTH was obtained from Schwartz-Mann Biochemical division of Picker Nuclear, Montreal, as a porcine preparation of 70 IU/mg potency; a similar preparation from Nordic Pharmaceuticals Ltd. was also used (Duracton); it is available in aqueous solution con¬ taining carboxymethyl-cellulose, dextrose and phenol.1-39-ACTH Depot was the Acthar Gel (H.P.) prepara¬ tion of the Armour Pharmaceutial Company and consists in a highly purified ACTH in an aqueous solution of 16% gelatin, 0.15% phenol and 0.1% cysteine.

Neuromedin U enhances proliferation of ACTH-stimulated adrenocortical cells in the rat

“…It is well documented that in vivo ACTH administration or its hypersecretion causes primarily adrenocortical cellular hypertrophy, which is subsequently followed by hyperplasia (16,31,(49)(50)(51)(52)(53)(54)(55)(56)(57). On the contrary, the direct in vitro effect of ACTH involves inhibition of adrenocortical cell proliferation and stimulation of the cell specialized functions, that is corticosterone secretion (28,34,(58)(59)(60).…”

“…The stimulating effect of NMU8 on ZG cells in ACTH-treated rats was similar to that evoked by ACTH alone. ZG of adrenal cortex is a proliferative region provided with stem cells, and newly formed cells from that region differentiate and migrate centripetally through the ZF into the zona reticularis (ZR), where they undergo apoptosis (31,(51)(52)(53)56,(68)(69)(70)(71)(72)(73)(74).…”

The effect of colchicine on the in vivo and in vitro secretion of aldosterone by rat adrenocortical cells

“…The effect of this agent on aldosterone production by adrenal zona glomerulosa is not known. We have reported that in vivo administration of ACTH increased mitotic activity in rat adrenal zona glomerulosa [9,10]. Rats treated with ACTH produced an increase in plasma corticosterone and aldosterone levels when compared to controls injected with saline [lo].…”

“…Rats treated with ACTH produced an increase in plasma corticosterone and aldosterone levels when compared to controls injected with saline [lo]. However, when colchicine was administered to controls and to groups of rats treated with ACTH on purpose to block mitosis, no differences could be observed in plasma aldosterone and corticosterone levels between the groups studied [9]. To clarify discrepancies between results obtained when colchicine was included or omitted in our experiments, we have examined here the effect of the in vivo administration of colchicine, or ACTH, or colchicine with ACTH on rat plasma aldosterone and corticosterone levels.…”

“…Cell suspensions were prepared as in [ 11,141. Aldosterone was determined by specific radioimmunoassay [9] and corticosterone as in [ 131. …”