EFFECTS OF CYCLOSPORINE AT THE HYPOTHALAMIC-PITUITARY AXIS IN PITUITARY-GRAFTED YOUNG FEMALE RATS

This work was designed to investigate the effects of cyclosporine on p rolactin secretion by an ectopically grafted heterologous pituitary gl and, and on the hypothalamic content of norepinephrine, dopamine and s erotonin. The administration of cyclosporine prevented the augmentatio n in plasma prolactin levels which occurred following an ectopic graft of a litter-mate pituitary gland. In contrast, in sham-operated rats, cyclosporine increased prolactin levels on day 8 of treatment. Both p ituitary grafting and cyclosporine treatment in sham-operated rats dec reased hypothalamic norepinephrine content. In grafted rats, cyclospor ine returned hypothalamic norepinephrine to normal. Hypothalamic serot onin content decreased 8 days after pituitary grafting but increased t o the values of control animals after cyclosporine administration. Cyc losporine treatment for 2 and 8 days increased serotonin content in sh am-operated animals. As expected, the hypothalamic dihydroxyphenylacet ic acid/dopamine index increased after pituitary grafting and administ ration of cyclosporine for 8 days resulted in a further increase. Cycl osporine administration for 2 days, however, decreased this index to t he values observed in control animals while drug treatment of control rats for 8 days decreased the dihydroxyphenylacetic acid/dopamine inde x. In vitro release of prolactin from the ectopic gland was markedly d ecreased in animals treated with cyclosporine for 2 days and this effe ct was less evident in 8-day treated rats. These data suggest that the impairment of the local immune reaction after pituitary grafting, by cyclosporine administration for 2 days, prevents the augmentation of p lasma prolactin levels and normalizes the hypothalamic catecholamine p arameters, thus suggesting that the effects of cyclosporine at the hyp othalamo-pituitary axis are exerted through changes in prolactin secre tion by the graft, although chronic administration of cyclosporine may also have a direct effect on the hypothalamus.