The Role of the Anterior Pituitary in the Control of Aldosterone Secretion in Experimental Secondary Hyperaldosteronism*

Abstract

Previous reports (1-9) have delegated a secondary role to anterior pituitary hormones in the control of aldosterone secretion.' Although hypophysectomy resulted in decreased aldosterone secretion (3) or reduced urinary aldosterone output (2), hyperaldosteronuria, marked sodium (Na) retention and ascites occurred in the absence of the adenohypophysis in dogs with thoracic inferior vena cava constriction (2). Also, in patients with hypopituitarism, Luetscher and Axelrad (6) and Hernando and associates (7) found that urinary aldosterone output was within normal limits in some patients on an unselected diet or a normal salt intake, and Liddle, Duncan 'and Bartter (8) reported hyperaldosteronuria in one patient with hypopituitarism on a low Na diet.However, no conclusive evidence of hypersecretion 1 of aldosterone in the absence of anterior pituitary hormones has been reported. The critical pertinent data on the rate of aldosterone secretion during stimulation which produces hypersecretion in normal animals have not been reported for hypophysectomized dogs or patients. It is important that studies in man be conducted on hypophysectomized patients since patients with so-called panhypopituitarism may not have loss of all anterior pituitary function. Furthermore, our knowledge is incomplete on the importance of specific anterior pituitary hormones. Several studies (3,7,(8)(9)(10) have demonstrated an increase in aldosterone secretion or urinary aldo-* This investigation was aided in part by Grant A-1944 from the National Institutes of Health, Bethesda, Md.1 The phrases "aldosterone secretion" or "hypersecretion of aldosterone" have been used to refer to actual measurements of the rate of secretion by the adrenal gland into the effluent plasma and are to be distinguished from urinary aldosterone excretion. sterone excretion following administration of various corticotropin preparations, but the data are inadequate to establish the role of ACTH in secondary hyperaldosteronism.2The question of the role of the anterior pituitary in the control of aldosterone secretion was reopened by the finding of a 76 to 97 per cent fall in adrenal vein aldosterone output following hypophysectomy of dogs with experimental secondary hyperaldosteronism ( 11). In the present report, data are presented on the efficacy of ACTH 3 in preventing this fall in aldosterone secretion which follows hypophysectomy. Large doses of cortisone have been administered to inhibit ACTH secretion in dogs with hyperaldosteronism secondary to caval constriction; the resultant effects on aldosterone and corticosterone production were observed. Subsequently, the effects of hypophysectomy and ACTH were studied in these animals. Also, the effects of synthetic a-melanophore-stimulating hormone (MSH) and of highly purified preparations of natural a-and ,B-MSH have been studied. Attempts have been made to stimulate hypersecretion of aldosterone in simple hypophysectomized dogs by 1) a low Na diet and 2) acute constriction of the thoracic inferior vena cava.2 In this pap...

Influence of the Pituitary and the Renin-Angiotensin System on the Secretion of Aldosterone, Cortisol, and Corticosterone

“…Our results indicate that aldosterone values may be essentially unchanged the day after hypophysectomy. Davis and his colleagues did indeed find low rates of aldosterone secretion in dogs with hypophysectomy of long standing which had been deprived of sodium after hypophysectomy (7). In another experiment however, in which dogs were hypophysectomized after sodium depletion had been produced (by dietary sodium deprivation and injections of Mercuhydrin), the rate of aldosterone secretion was high (32).…”

“…This is based on morphological studies in the rat (1), on indirect assessments of adrenal secretion during metabolic studies in man (2), and on direct estimations of adrenal hormone secretion in the rat (3,4) and dog (5)(6)(7). The morphological studies of Deane and Masson (8), which indicate that renin may stimulate the adrenal cortex in the rat, the results of Genest and his colleagues (9), which suggest that arterial hypertension may be associated with an increased excretion of aldosterone in man, and the demonstration by Genest ( 10,11 ) and Laragh (12) and their colleagues that angiotensin II stimulates excretion (10,11) and secretion (12,13) of aldosterone suggest that the kidney may have some influence on the rate of secretion of adrenal hormones.…”

Activation of aldosterone secretion in primary aldosteronism

“…Initial studies indicated that ACTH was not important in the control of aldosterone secretion (37,38). Subsequent studies have demonstrated that whereas aldosterone is still secreted in the absence of ACTH, secretion and responsiveness to alterations in the activity of the renin-angiotensin system is diminished (39)(40)(41).…”

The Effect of Bilateral Nephrectomy and Midcollicular Decerebration with Pinealectomy and Hypophysectomy on the Corticosteroid Secretion of Sodium-deficient Sheep *

“…Possible reasons for the continuance of aldosterone hypersecretion in these experiments are: 1) ACTH. In sufficiently high doses ACTH stimulates aldosterone secretion directly (2,(6)(7)(8).…”

“…Crosscirculation studies of Denton, Goding, and Wright (1) and Yankopoulos, Davis, Kliman, and Peterson (5) indicate that the stimulus to the adrenal is humoral. Three local humoral circumstances, ACTH infusion (2,(6)(7)(8), angiotensin II infusion (2,6,(9)(10)(11)(12), and low sodium and high potassium concentration of plasma (1,2,6,13), are known to cause an increase in aldosterone secretion, and the levels required for the reaction are not beyond those that are known or might be presumed to occur naturally. However, conscious unstressed dogs with thoracic caval constriction showed a 20-to 40-fold increase in aldosterone secretion rates associated with low corticosterone and Porter-Silber chromogen secretion (14).…”