Evaluation of the effect of androgen administration on the maintenance of the individual

Abstract

Clinically, it is not rare that androgens, especially testosterone and its derivatives, are administered to aged men. However, there is no evident indication that testosterone has a beneficial effect on a prolongation of the human life span. Little work has been done to study biological effects of adrenal androgens from a point of view of the maintenance of individual. For the purpose of investigating of biological effects of adrenal androgen and its metabolism, studies were made on effects of administration of dehydroepiandrosterone acetate (DHA-Ac) and DHA-3H (DHA-T), alone or combined, in postmenopausal women, and adrenalectomized or hypophysectomized female rats. Injections of DHA-Ac, 50 mg in oil solutions, were given subcutaneously into postmenopausal women, and a single dose of 20 pc of DHA-T was injected. Approximately 50 per cent of the radioactivity was excreted in the urine during 5 to 6 days in all subject. Ten to 20 per cent of administered DHA was excreted in the urine as 17-KS. It was observed that in several subjects cumulative amounts of increased 17-KS were only 5 per cent of injected DHA, and it is suggested that consumption and catabolism of administered DHA extremely accelerate and that administration of DHA or adrenal androgens may induce beneficial effects in these cases. Radioactivity and Zimmermann chromogen in 17-KS were remarkably increased in III, IV and V fractions after administration of DHA. It was proposed that sum of III, IV and V fractions of 17-KS is styled adrenal fraction' in female. No increase of urinary estrogen level was induced by administration of DHA in postmenopausal women.Female Wistar strain rats (litter-sister) were divided in to six groups. Bilaterally total adrenalectomy was performed in 5groups and one per cent saline were supplied. Of these adrenalectomized groups, three groups were given daily injections of desoxycorticosterone acetate (DOC) and treated with either DHA, or cortisol (COL), or the combination of DHA and COL. The remaining three groups served as controls, i.e. adrenalectomized control groups treated with or without DOC, and a non-adrenalectomized normal control group. After 2 weeks animals were sacrificed and autopsy was performed. After the removal of the intestinal organs, the skin and fat were removed from the muscles. The skeleton with muscles and the skin with fat were weighed, respectively, and then dried at 100°C for 48 hrs, and weighed again. Administration of DHA to adrenalectomized female rats did induce an increase in body weight and in weight of both wet and dried carcasses. The increases in DHA-treated group were higher than those of non-adrenalectomized controls under this experimental conditions. Hypertrophy of the liver was greatest in DHA-and DHA-COL-treated groups. The weight and protein content of the kidney were higher in DHA-treated group. No significant differences were observed in the heart or brain. The myotrophic activity of DHA was observed to be about 37% of that of testosterone propionate (TP) and DHA has about 1.7% of the activity of TP on the male rat accessory sex organ. DHA induced hypertrophy of the liver in hypophysectomized female rats.Evaluation of administration of DHA and adrenal androgen was discussed from a point of view of the maintenance of individual.