The purpose of our study was to assess the impact of subchronic administration of ACTH-(l-24) on ovarian function in the primate using a repeated measures experimental design. Osmotic pumps that released ACTH-(l-24) at a dose of 67 Mg/day were implanted sc in four cynomolgus monkeys for one menstrual cycle. The pumps were filled with saline for the two control cycles, one of which preceded and one of which followed peptide infusion. Administration of ACTH-(1~24) ele¬vated cortisol levels in serum 1.6-fold and those in urine 2.2-fold, without affecting adrenal androgen concentrations. In the follicular phase (FP) of the menstrual cycle, infusion of ACTH-(1-24) did not alter serum levels of estradiol, FSH, or LH. However, immunoreactive estrone excretion in urine was de¬creased by 71% (P < 0.05), and serum concentrations of sex hormone-binding globulin (SHBG) were increased by 100% (P < 0.01). In the luteal phase (LP) of the menstrual cycle, infusion of ACTH-(l-24) suppressed levels of serum estradiol by 54% (P < 0.001), urinary immunoreactive estrone by 72% (P < 0.05), serum progesterone by 53% (P < 0.001), and urinary immuno¬reactive pregnanediol by 71% (P < 0.01). Serum FSH concen¬trations were increased during treatment by 100% (P < 0.001) in LP, but LH concentrations were not altered. Also, serum levels of SHBG returned to control values in the LP. The lengths of menstrual cycles and the lengths of FP or LP were not affected during or after treatment. These data provide evidence that subchronic infusion of ACTH-(l-24) in primates: 1) suppresses estradiol production by the ovarian follicle as well as estradiol and progesterone produc¬tion by the corpus luteum, 2) compromises ovarian function without concomitant suppression of serum gonadotropin levels, and 3) induces a transitory elevation of SHBG levels in the circulation, which may compensate for reduced estrogen output.
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