Synergistic effects of estrogen and serotonin-receptor agonists on the development of pituitary tumors in aging rats.

The purpose of this study was to determine if pituitary 5-HT levels change as a function of age or endocrine state, and further if such changes are associated with pituitary pathology. Middle-aged constant estrous (CE) rats had larger (p less than 0.05) pituitary glands containing more (p less than 0.05) serotonin (5-HT) than those from young females or comparably aged, irregularly cycling rats. Ovariectomy lowered pituitary 5-HT content in middle aged CE rats. In contrast, pituitary weight and 5-HT content were increased in young rats of both sexes bearing subcutaneous, steroid-containing capsules that produced elevated levels of serum estradiol 17 beta. However, exogenous estrogen failed to raise pituitary 5-HT concentrations since pituitary weight increased more than 5-HT levels, even though the total amount of amine was significantly increased (p less than 0.05) compared with controls. These findings suggest that pituitary 5-HT increases during aging regardless of ovarian status and in addition, that total 5-HT content of the gland is increased further in hyperestrogenic states such as CE. Since pituitary adenomas occur more frequently in aged CE rats than in diestrous females or males, it was of interest to determine if 5-HT contributes to the tumorigenic effect of estrogen. Thus, the 5-HT receptor agonists zimelidine or quipazine were administered to ovariectomized rats bearing estrogen containing capsules. Rats treated with drugs had larger pituitaries containing more tumors than those receiving the steroid alone. However, these effects were dependent upon estrogen since pituitary pathology did not increase when ovariectomized rats were given 5-HT neuroleptics without the steroid.(ABSTRACT TRUNCATED AT 250 WORDS)