Effects of cyclosporine on ovarian function in sham-operated and pituitary-grafted young female rats.

Effects of cyclosporine (CyA) on ovarian function and the possible role of prolactin in mediating these effects were examined in young female rats. The animals were sham-operated or rendered hyperprolactinemic by transplanting pituitary glands under the renal capsule. Cyclosporine prevented the increase in plasma prolactin levels in grafted rats. However, in sham-operated animals plasma prolactin levels were increased after 8 days of CyA treatment. Plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were reduced 8 days after pituitary grafting and increased by CyA at both Day 2 and Day 8 of treatment. The content of LHRH in the hypothalamus was not affected on Day 2 but was reduced on Day 8 after grafting on CyA therapy. Plasma estradiol levels were increased by CyA in sham-operated rats on Day 2 and 8 of treatment, and in pituitary-grafted rats on Day 8 of therapy. In sham-operated rats, ovarian estradiol content was reduced after 2 and after 8 days of CyA administration. In pituitary-grafted rats, the ovarian estradiol content was suppressed after 8 days, and CyA treatment prevented this effect. Ovarian estradiol release in vitro under basal conditions was greater in ovaries derived from 38-day-old than in those from 32-day-old animals. The ovarian estradiol response to human chorionic gonadotropin (hCG) in vitro was increased 2 days after pituitary transplantation. Administration of CyA for 8 days increased basal and hCG-stimulated estradiol release in both sham-operated and pituitary-grafted animals. The present findings suggest that CyA can alter ovarian function by acting directly at the gonadal level. However, a hypothalamic-hypophyseal site of action cannot be ruled out.