Actions of ACTH in Intact and Corticoid-Maintained Adrenalectomized Female Mice with Emphasis on the Reproductive Tract1

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Abstract
Immature female albino mice were used in 2 experiments to determine the effects of ACTH [4 U/day × 10 subcutaneously (sc) in gelatin vehicle] on maturation of intact and of adrenalectomized mice maintained on cortisol acetate (F) (100 μg/day sc) or corticosterone (B) (400 μg/day sc). Appropriate intact and adrenalectomized controls were used. Mice were adrenalectomized at 23 days of age. Corticoid injections were begun immediately and injections of ACTH at 25 days of age. ACTH injections continued for 10 days. The mice were sacrificed 24 hr after the last injections. In intact mice, ACTH increased follicular atresia, increased numbers of 3° follicles (follicles with antra), decreased maximum follicular size, and inhibited ovulation and luteinization in the ovaries. Uteri remained in an infantile condition. Despite immature appearance of uteri, vaginae sometimes were cornified. Either ACTH inhibited uterine responses to estrogens or vaginal cornification developed independently of apparent ovarian and uterine status. This difference between uterine and vaginal response with respect to apparent stages of the estrous cycle was independent of adrenal corticoids as it did not occur in F- or B-treated adrenalectomized mice. F and B maintained normal ovarian function with luteinization in adrenalectomized mice and normal uterine and vaginal estrous responses, although B was less effective than F in the doses used. Both corticoids increased follicular atresia. The most marked effect of ACTH on the ovaries of B- or Fmaintained adrenalectomized mice, similar to that in intact mice, was a complete absence of corpora lutea. Uterine weights and histology often were similar to those of intact untreated mice and, in contrast to uteri of intact ACTHtreated mice, some uteri appeared typically estrous. Completeness of adrenalectomy was indicated by examination at autopsy and by failure of ACTH to further decrease somatic growth and weights of thymus and spleen. Kidneys of adrenalectomized ACTH-treated mice were enlarged. ACTH apparently has profound suppressive effects on ovarian function which are not adrenal-mediated. Lack of corpora lutea suggests that LH secretion was inhibited by ACTH, although the site of action for this effect is unknown. ACTH also exerted a renotropic effect which was enhanced in F-maintained mice. In adrenalectomized mice the combination of F and ACTH produced a marked splenic hypertrophy due to increased sinusoidal lymphoid elements, in contrast to the splenic atrophy due to involution of the malpighian corpuscles produced by ACTH in intact or by F alone in adrenalectomized mice. (Endocrinology75: 653, 1964)