THE GONADOTROPIN-RELEASING-HORMONE AGONIST LEUPROLIDE AFFECTS THE THYMUS AND OTHER NONREPRODUCTIVE SYSTEMS OF FEMALE RATS

To evaluate the effects of a gonadotropin-releasing hormone agonist on non-reproductive systems, we administered [D-Leu6,Des-gly10]-GnRH ethylamide (leuprolide; 5-mu-g/day) for 21 days to female Sprague-Dawley rats. In Experiment 1, continuous infusion (Alzet minipumps sc) was compared to injection. Increased thymus and body weights and decreased estradiol and uterine weights were noted for both administration methods. Spleen weight increased only in rats treated by continuous infusion. Ovary, kidney and liver weights did not change. Only leuprolide-injected rats had elevated LH with decreased corticosterone and ACTH levels, possibly related to the injection process. Glucose, insulin, progesterone, FSH and corticosterone/ACTH were not different. In Experiment 2, intact and ovariectomized rats were implanted with minipumps delivering leuprolide or 0.9% NaCl. Body and thymus weights increased, whereas uterine weight and estradiol declined in both leuprolide-treated and ovariectomized rats. No synergism between leuprolide and ovariectomy was noted. Thymosin-alpha-1, but not thymosin-beta-4, increased in leuprolide-treated ovariectomized rats. Peripheral white blood cell count was elevated in leuprolide-treated intact rats and ovariectomized rats. In bone marrow, non-nucleated cell count declined in leuprolide-treated intact rats, contributing to the decreased total cell count in this group. Nucleated cell count was unaffected. Therefore, thymus weight gain was accompanied only in some cases by functional changes. Our results demonstrate that leuprolide affects non-reproductive systems, in a similar manner to ovariectomy. We suggest that such alterations may be due to the hypoestrogenic environment produced by leuprolide.