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 rol e of prolactin in mediating these effects were examined in young femal e rats. The animals were sham operated or rendered hyperprolactinemic by transplanting pituitary glands under the renal capsule. Cyclosporin e prevented the increase in plasma prolactin levels in grafted rats. H owever, in sham-operated animals plasma prolactin levels were increase d 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 tre atment. The content of LHRH in the hypothalamus was not affected on Da y 2 but was reduced on Day 8 after grafting on CyA therapy. Plasma est radiol 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 ov arian 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 tho se from 32-day-old animals. The ovarian estradiol response to human ch orionic gonadotropin (hCG) in vitro was increased 2 days after pituita ry transplantation. Administration of CyA for 8 days increased basal a nd hCG-stimulated estradiol release in both sham-operated and pituitar y-grafted animals. The present findings suggest that CyA can alter ova rian function by acting directly at the gonadal level. However, a hypo thalamic-hypophyseal site of action cannot be ruled out.