Stimulation of steroid secretion by adrenocorticotropin injections and by arginine vasopressin infusions: no evidence for a direct stimulation of the human adrenal by arginine vasopressin

Abstract

Arginine vasopressin stimulates the secretion of adrenocorticotropin. A direct stimulatory effect of AVP on cortisol as well as aldosteron secretion has been postulated by several investigators. To study the possible role of a direct stimulatory action of AVP on the adrenal cortex, normal volunteers were treated with incremental injections of ACTH or with incremental infusions of AVP which raised plasma AVP levels to a maximum of 256\m=+-\16 pmol/l. In both situations, a significant (p<0.001) linear correlation between plasma ACTH and plasma cortisol was observed. The regression coefficients were not different (p>0.5). Plasma aldosterone was stimulated by both treatments, but the weakly positive correlation between plasma ACTH and plasma aldosterone was not significant for either stimulus. Thus, in man, a direct stimulatory effect of AVP on cortisol secretion cannot be demonstrated. A direct effect of AVP on aldosterone cannot be definitely excluded, but is certainly of minor importance.Arginine vasopressin is known to stimulate adre¬ nocorticotropin in man (1,2). Besides elevating plasma ACTH, AVP also induces a rise in plasma cortisol. The question whether this steroidogenic effect is solely due to stimulated ACTH levels or whether a direct effect of AVP on the adrenal cortex is of physiological importance, has not been resolved.In canine isolated perfused adrenal glands, AVP alone or in combination with ACTH stimulated the secretion of cortisol (3,4). AVP infusions in dogs pretreated with dexamethasone only resulted in stimulation of glucocorticoids when ACTH was infused simultaneously. These results suggest that in the dog, AVP directly stimulates adrenal glucocorticoid production, provided that background levels of ACTH are present (5). Perfused rat isolated adrenals were stimulated to secrete corticosterone and aldosterone (6) by a bolus of as little as 10 fmol AVP. Superfused rat adrenal cells are stimulated by AVP to secrete aldosterone (7,8). AVP receptors (Vrtype) on rat glomerulosa cells have been de¬ scribed (7). In these cells, AVP stimulates calcium influx and phosphoinositide turnover (9).We attempted to answer the question whether AVP, besides stimulating ACTH secretion, also has a direct steroidogenic effect on the human adrenal. If AVP had a direct stimulatory effect on steroid secretion or would enhance the stimulatory effect of ACTH at a dose that stimulates ACTH secre¬ tion, the relationship between plasma ACTH and plasma steroid levels should be changed: the rela¬ tionship between elevated ACTH levels by ACTH injection and steroid secretion should differ from the relationship of ACTH stimulated by AVP infu¬ sion and steroid secretion. Subjects and MethodsAfter having given informed consent according to the Declaration of Helsinki, 15 normal men (between 21 and 32 years of age, body weights between 65 and 84 kg) participated in the study. All were non-smokers and on an unrestricted diet. On the study days at 12.00 h, they were given a light, standardized fat-free meal.

In vivo and in vitro effects of AVP and V1a receptor antagonist on Cushing's syndrome due to ACTH‐independent bilateral macronodular adrenocortical hyperplasia

“…In the present case, a small dose of AVP iv (0.1 or 0.3 U), which has little effect on plasma ACTH level ( Arai & Takebe, 1991) and cortisol secretion ( Bähr et al ., 1991 ) in normal subjects, produced a significant cortisol response without any elevation in plasma ACTH levels ( Table 1). The dispersed AIMAH cells responded more to 10 −9 M AVP than normal adrenal cells ( Fig.…”

Steroidogenic enzymes: Structure, function, and role in regulation of steroid hormone biosynthesis

“…The blood levels of adrenocortical steroids rise rapidly in response to stress conditions that stimulate ACTH secretion [201]. After ACTH injection to human subjects, both plasma cortisol and aldosterone levels increase several fold within 1 h [139,202]. However, the plasma level of ACTH, after injection, highly correlates with cortisol, but not aldosterone levels, indicating that while cortisol secretion is mainly determined by ACTH, aldosterone secretion is affected by multiple factors secondary to ACTH stimulation [202].…”

“…After ACTH injection to human subjects, both plasma cortisol and aldosterone levels increase several fold within 1 h [139,202]. However, the plasma level of ACTH, after injection, highly correlates with cortisol, but not aldosterone levels, indicating that while cortisol secretion is mainly determined by ACTH, aldosterone secretion is affected by multiple factors secondary to ACTH stimulation [202]. The hypothalmus-pituitary-adrenal system can also be stimulated by cytokines, e.g.…”

Plasma corticotrophin releasing hormone, vasopressin, ACTH and Cortisol responses to acute myocardial infarction

“…Plasma ACTH levels were however rising gradually, and if the sensitivity of the adrenal gland to ACTH were initially increased, the delayed fall in plasma cortisol could be explained. In the human, it is unlikely that AVP would increase the responsiveness of the adrenal glands (Bahr et al, 1991). The shortterm administration of CRH has no effect on cortisol secretion when ACTH release is blocked by dexamethasone (Donald et af., 1983); nevertheless, a paracrine effect of adrenal CRH on cortisol secretion has been described (Andreis et al, 1992).…”