Adrenal Function During Bed Rest

Plasma 17-OH-CS levels as well as adrenal secretory rates of aldosterone and eortisol were measured in healthy subjeers before and during periods of bed rest. The circadian rhythm of plasma 17-OH-CS was well maintained during bed rest. There was no change in adrenal eortisol secretion rates during bed rest. Aldosterone secretory rate did not change with bed rest; however, following a period out of bed, there was a diminution of aldosterone secretory rate during a subsequent bed rest period. Inactivity from bed rest therefore does not appear to change adrenal cortisol production. Conclusions cannot be drawn as yet concerning aldosterone production. I T HAS BEEN shown by previous workers 8 that despite the maintenance of the normal diurnal rhythm of urinary 17-hydroxycorticosteroid excretion, changes in the normal day-night vertical-horizontal posture patterns abolish a normal diurnal peak and nocturnal nadir of aldosterone excretion. These studies assumed, quite justifiably, that these variations in the urinary levels of these steroids, reflected comparable changes in adrenal gland hormone production. Other workers 5 subsequently demonstrated that the urinary aldosterone output fell with only a few hours of the "weightless" state of standing in water. The present study was undertaken to measure by more direct methods the secretion rate by the adrenal gland and the plasma level of some of the adrenocortical hormones in the hypogravic state. MATERIAL A N D M E T H O D S Eleven airmen, age 17 to 23, were studied prior to, and after ten days of lying supine, but unrestrained in bed. Diet was constant except for an ad lib salt intake. After the subjects had finished fourteen days of bed rest, they were divided into Groups A through F. Groups B through F participated in an organized program of exercise during the subsequent four weeks. Following this period all groups returned to bed for two more weeks. During this time, Group C had cuffs inflated to a pressure of 60 ram. Hg for one minute out of every five from 0800 to 2200 hours. Group D had the head of the bed tilted 10 ~ from the horizontal to simulate lunar gravity. Group E had both cuffs and tilt and Group F performed standardized non-anti-gravity exercises during this second bed rest period. Only Groups A, C and F were studied. From the USAF School of Aerospace Medicine Aerospace Medical Division (AFSC) Brooks Air Force Base, Texas. The address of Dr. Katz is University of Chicago, 950 East 59th Street, Chicago, Illinois 60637. Although the metabolic ward used for the bed rest period had its ambient temperature controlled between 75 and 81 ~ F., the subjects were exposed to the outside temperatures of the day during control determinations, which were often in the uncomfortable, above 90 ~ F. range. In addition, activity was not controlled during the "control" days. Plasma 17-hydroxycorticosteroids (17-OH-CS) were measured by a modification ,2 of the technique of Silber and Porter. TM Cortisol secretion rates were measured by a method previously outlined 6 except that 3/zc. cortisol-1, 2-H 3, 50 /zc.//zg., obtained from the Endocrinology Study Section, National Institutes of Health, was the radioactive tracer utilized and the isolated tritiated urinary metabolites were acetylated with C 1~ labeled acetic anhydride. Aldosterone secretory rates were determined by an unpublished method of Barlow' based on the isolation of the "tetrahydro metabolite" of aldosterone from urine, n Three microcuries d-aldosterone-1, 2-H 3, (100 /zc.//zg., from the Endocrinology Study Section, National Institutes of Health, and later obtained commercially, and purified chromatographically on paper in the Bush B5 and E2B systems)2., were injected in 30 ml. isotonic saline. An aliquot of urine from the subsequent 24 hours was hydrolyzed with beef liver B-glucuronidase at pH 4.7 and 37 ~ C. for 48 hours. Ethyl acetate extracts, washed three times with 1/20 volume in NaOH and then with water were chromatographed in the B5 and E2B systems. The urinary metabolite was detected by radioactivity. Scanning with a Model 880 Vanguard Autoscanner as well as by the Rf of concommitantly chromatographed "tetrahydroaldosterone" (first obtained through the courtesy of Dr. Seymour Lieberman, and later isolated from human urine following the oral administration of 40 mg. d-aldosterone-21-acetate supplied by Dr. C. H. Sullivan, CIBA, Inc., Summit, N. J.). The metabolite was acetylated with C 1. labeled acetic anhydride and the resulting triacetate purified using alternating chromatography in the Bush A and B3 systems to attain radiochemical purity. This was considered attained when the tritium/carbon 14 ratio, measured as described elsewhere, r varied by less than 10 per cent between consecutive chromatograms. Quantitation could be obtained by acetylating crystalline cortisol with the same batch of acetic anhydride and measuring the specific activity of chromatographically purified cortisol-21acetate with the aid of the Porter-Silber reaction. TM