Effect of Chronic ACTH Treatment on Maturation of Intact Female Mice

Abstract

In experiment I, 29-day-old brown female mice, caged in groups of 5 or 6, received 0, 1, 2, 4 or 8 U of ACTH-gel sc daily for 10 days. In experiment II, 26 singly caged 22- to 33(avg 25)-day-old brown female mice received 4 U of ACTH-gel/day sc for 21 days. Twenty-six sibling mice matched for age and sex served as controls. Mice were sacrificed 24 hr after the last injection. In I, preputial weight increased, adrenal weight increased linearly with increasing ACTH dose, and weights of thymus, spleen, ovaries and uterus decreased. Uterine weight was infantile at 8 U/day. Involution of adrenal X-zone and increased preputial weight were attributed to increased adrenal androgen secretion. At 2 or more units of ACTH corpora lutea were absent from all ovaries, there were no mature follicles, and follicular atresia was increased. Follicular atresia apparently accounted for the absence of corpora lutea and mature follicles. Vaginal and uterine histology reflected ovarian status. At 4 and 8 U, most vaginae were intensely mucified (due to androgens?). In II, treatment for 21 days with 4 U of ACTH/day significantly increased adrenal weight, decreased weight gain, but did not affect preputial weight. These effects were less than in grouped mice after 10 days of treatment. The differences may have been due to lower responsiveness of singly caged mice to ACTH. Ovarian weight was decreased, follicular atresia increased, and mature follicles, ovulation and luteinization were absent, as after 10 days of treatment, but uterine weights were greater. All vaginae were cornified and some also were mucified. Most uteri were typically estrous, although 28% were small with dense stroma. Thus, some variation in estrogen secretion was indicated, although a more or less constant estrus seemed to be the rule. It was concluded that ACTH at high physiological levels can prevent sexual maturation for prolonged periods. The hormonal mechanisms involved are unknown, but suppression of gonadotropin secretion, directly by ACTH or indirectly by increased adrenal androgens, is suggested as a possible mechanism. Other possibilities, such as direct effects on the gonads, are not ruled out. (Endocrinology74: 669, 1964)