Effects of Adrenal Androgens on Immature Female Mice

Abstract

Adrenal androgens were studied in immature female mice at nonvirilizing doses thought to be within the limits of endogenous secretion. Subcutaneous injections of 20, 50 and 100 μg of dehydroisoandrosterone (DHA), isoandrosterone (IA), δ⁵-androstene-3β, 17β-diol (5ADL), δ⁴-androstene- 3,17-dione (4AD), llβ-OH-δ⁴-androstene- 3,17-dione (110H4AD) and androstane- 3,17-dione (AD) were given daily for 3 weeks. DHA, IA, 5ADL and AD at 100 or 50 μg doses produced delay in maturation of the reproductive tract. Increased follicular atresia, numerous “deficient” interstitial cells and absence of preovulatory follicles and corpora lutea in the ovary indicated inhibition of gonadotrophins, possibly LH. In addition, direct effects of these steroids on the gonads were suggested by: (a) at 50 or 20 μg doses, increase in follicular atresia without other detectable changes of gonadotrophin deficiency; (b) in some mice, prominent interstitial tissue along with increased atresia, no large follicles or corpora lutea; (c) calcification in follicles following treatment with AD. At 20 or 50 μg doses, 4AD and 110H4AD caused an increase in the size of uteri and ovaries, with enhanced development of follicles, corpora lutea and elevated pituitary gland gonadotrophins. Mice given 110H4AD, 100 μg/day, were less sensitive to superovulation with PMS and HCG than were the controls, indicating a direct effect of steroid on the ovary. DHA, IA and 5ADL produced involution of the adrenal X-zone. Lipid degeneration of X-zone cells with both 11OH4AD and gonadotrophin stimulation suggested that Xzone changes could be produced by both these hormones. In addition, with most steroid treatments there were small cells in the zona fasciculata, zona glomerulosa and medulla. The cortical cells contained less lipid than the controls. Cytoplasm of the medullary cells stained darkly and lacked prominent basophilic granules. These cytologic features in the cortex and medulla were similar to those of the sexually immature mouse. Other observations were: (a) occasional increases of total body weight; (b) increased anterior abdominal and retroperitoneal fat; (c) an occasional rise in spleen weight with larger and more numerous lymph follicles; (d) no change in thymus weight or histology. These experiments suggest that the effects of adrenal androgens on the female reproductive tract and adrenal glands are produced by an influence on pituitary gonadotrophin activity and by direct action on these organs. These experiments suggest that the effects of adrenal androgens on the female reproductive tract and adrenal glands are produced by an influence on pituitary gonadotrophin activity and by direct action on these organs.