The Effect of Hypophysectomy on the Conversion of Corticosterone to Aldosterone in the Sodium-Depleted Rat

Sodium depletion stimulates aldosterone secretion and the last steps in biosynthesis, the conversion of corticosterone to aldosterone. In the sodium-depleted rat, hypophysectomy markedly lowers aldosterone production within two days but does not lower the conversion of corticosterone to aldosterone. Presumably, hypophysectomy reduces the rate of earlier steps in biosynthesis. {Endocrinology 90: 827, 1972) T7ARLY histological studies demonstrated that ^ the zona glomerulosa maintains a normal or nearly normal appearance following hypophysectomy, which suggested that this zone of the adrenal gland is free of pituitary control. Moreover, sodium depletion widened the zona glomerulosa in the hypophysectomized animal as it did in the normal animal (1,2). Subsequent studies have shown, however, that the functional integrity of the zona glomerulosa was strikingly dependent upon intact pituitary function (3). It now appears that ACTH, growth hormone, and possibly other factors are important in maintaining normal aldosterone responses to sodium depletion (2,4,5). Previous studies from this laboratory have shown that in the sodium-depleted animal, aldosterone secretion in vivo, or aldosterone production in vitro fell markedly within two days following hypophysectomy (4). The conversion of corticosterone to aldosterone is a slow and possibly rate-limiting step in aldosterone biosynthesis which is stimulated by sodium deficiency (6). The purpose of this study was to determine whether the final step in aldosterone biosynthesis was normal or impaired in the sodium-depleted, hypophysectomized animal. Methods Male Sprague-Dawley rats, weighing 160-210 g were placed on a diet containing only a trace quantity of sodium and 132 mEq/kg potassium. After 6-7 days on this low sodium diet the rats were hypophysectomized transaurally, using the Hoffman-Reiter Hypophysectomy apparatus. Controls included those animals in which the hypophysectomy procedure failed to yield pituitary tissue, and some in which the ear drum was perforated only. The rats were then returned to their cages, and continued on the sodium-free diet for an added two days. Tetracycline (25 mg/100 ml) was added to the distilled drinking water one day before hypophysectomy and continued until sacrifice to improve overall survival. In other experiments it has been determined that this dose of tetracycline has no effect upon the rate of aldosterone production by either control or low sodium rats. On the day of sacrifice, those animals who had evidence of hypophysectomy at surgery, and an empty sella at autopsy were classed as hypophysectomized. Those sham operated rats, plus those failures at surgery which had an intact pituitary at autopsy were classed as intact controls. All equivocal animals were excluded. Corticosterone production was also reduced in the hypophysectomized animals. The rats were sacrificed by decapitation and the Received July 21, 1971. 1 Camm Research Institute, Wayne, New Jersey. 2 H. Newman & Company, Skokie, Illinois. 3 Boyd, J. E., and R. B. Page, unpublished observation. 828 NOTES AND COMMENTS Endo • 1972 Vol 90 • No 3 EFFECT OF HYPOPHYSECTOMY UPON ALDOSTERONE SECRETION, ALDOSTERONE PRODUCTION AND THE CONVERSION OF CORTICOSTERONE TO ALDOSTERONE