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 prolactin secretion by an ectopically grafted heterologous pituitary gland, and on the hypothalamic content of norepinephrine, dopamine and serotonin. The administration of cyclosporine prevented the augmentation 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 pituitary grafting and cyclosporine treatment in sham-operated rats decreased hypothalamic norepinephrine content. In grafted rats, cyclosporine returned hypothalamic norepinephrine to normal. Hypothalamic serotonin content decreased 8 days after pituitary grafting but increased to the values of control animals after cyclosporine administration. Cyclosporine treatment for 2 and 8 days increased serotonin content in sham-operated animals. As expected, the hypothalamic dihydroxyphenylacetic acid/dopamine index increased after pituitary grafting and administration of cyclosporine for 8 days resulted in a further increase. Cyclosporine administration for 2 days, however, decreased this index to the values observed in control animals while drug treatment of control rats for 8 days decreased the dihydroxyphenylacetic acid/dopamine index. In vitro release of prolactin from the ectopic gland was markedly decreased in animals treated with cyclosporine for 2 days and this effect 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 plasma prolactin levels and normalizes the hypothalamic catecholamine parameters, thus suggesting that the effects of cyclosporine at the hypothalamo-pituitary axis are exerted through changes in prolactin secretion by the graft, although chronic administration of cyclosporine may also have a direct effect on the hypothalamus.