Warren W. Davis

Bilateral adrenal hyperplasia as a cause of primary aldosteronism with hypertension, hypokalemia and suppressed renin activity

Abstract A fifty-six year old man presented with benign hypertension, hypokalemia and overproduction of aldosterone which persisted on a high sodium intake. Urinary excretion of cortisol and 17-ketosteroids was persistently normal. Plasma renin was below normal, even with sodium deprivation and the upright posture. Following bilateral total adrenalectomy, histologic examination revealed bilateral hyperplasia. No adenoma was found. The occurrence of aldosteronism resulting from bilateral adrenal hyperplasia suggests that all adrenal tissue is responding to a tropic stimulus, other than ACTH or angiotensin.

Evidence for the stimulation by adrenocorticotropic hormone of the conversion of cholesterol esters to cholesterol in the adrenal, in, vivo

Abstract Previous studies demonstrated that the inhibition of adrenal protein synthesis in vivo by cycloheximide blocked the ACTH ∗ stimulation of corticosterone secretion (Garren, Ney, and Davis, 1965) . It has been shown that cycloheximide acts by inhibiting the first step in the conversion of cholesterol to δ5-pregnenolone in the adrenal (Davis, Ney, and Garren, 1966 ; Davis and Garren 1966). The present study demonstrates that ACTH activates the conversion of adrenal cholesterol esters to free cholesterol even when adrenal protein synthesis and steroidogenesis are inhibited by cycloheximide.

Puromycin analogs: action of adrenocorticotropic hormone and the role of glycogen.

The effect of the injection into rats of analogs of puromycin, 6-dimethylaminopurine, and the aminonucleoside of puromycin on the stimullation of steroidogenesis by adrenocorticotropic hormone was coin pared with that of puromycin and cycloheximide. This stimulation was blocked only by the antibiotics, which also inhibited adrenal protein synthesis. Glycogenolysis is not associated with the primary mechanism of the adrenocorticotropic hormone stimnulation of steroid hormone biosynthesis in rats.

Heterogeneity of Template RNA in Adrenal Glands

Template RNA in adrenal glands appears to be heterogeneous in stability. The RNA that regulates synthesis of a large fraction of adrenal protein has a turnover time of 4 hours or less. The remainder of adrenal-protein synthesis, including synthesis of protein that mediates the rapid steroidogenic response to ACTH, depends on RNA with considerably greater stability.

A Study of the Mechanisms by Which Adrenocorticotropic Hormone Maintains Adrenal Steroidogenic Responsiveness

Following hypophysectomy in the rat, there was a progressive decline in the rate of adrenal protein synthesis in vivo during the ensuing 24-48 hr, and an accompanying decrease in the acute corticosterone secretory response to an intravenous injection of ACTH. There was a similar decrease in the in vitro conversion of Delta(5)-pregnenolone, progesterone, and deoxycorticosterone to corticosterone. These in vivo and in vitro effects of hypophysectomy could be reversed by the administration of depot ACTH for an additional 7 hr period. However, if cycloheximide, an inhibitor of protein synthesis, was administered concomitantly with the depot ACTH, then the restorative actions of ACTH on the steroid biosynthetic pathway were prevented. These experiments suggest that ACTH maintains not only the general structure of the adrenal cortex, but also the level of the steroid biosynthetic mechanism, through its effects on adrenal protein synthesis.