Pituitary gonadotroph adenomas in old Sprague-Dawley rats

Abstract

Light microscopic and immunocytologic investigation revealed focal or diffuse pituitary gonadotroph hyperplasia in 3/27 male and 3/39 female Sprague-Dawley rats over 2 years of age. Three male and 2 female rats exhibited proliferation of morphologically abnormal gonadotrophs which were described as nodules, and 4 male and 5 female rats possessed gonadotroph adenomas which contained both immunoreactive beta-LH and beta-FSH. On plastic sections at the ultrastructural level, a further female rat was found to possess focal gonadotroph hyperplasia, 2 male and 2 female rats, gonadotroph nodules and 2 male and 2 female rats gonadotroph adenomas. While extensive gonadotroph and thyrotroph hyperplasia was observed in the nontumorous portion of the 2 pituitaries harboring thyrotroph adenoma, widespread gonadrotroph hyperplasia was noted in only 2 of 13 pituitaries with gonadotroph adenoma. Gonadotroph adenomas appeared to develop from discrete foci of morphologically altered gonadotrophs. These foci probably then progressed to form nodules and subsequently adenomas. Gonadotrophs within the nodules were often similar in morphology to adenomatous gonadotrophs whereas the earlier, smaller lesions were pleomorphic or more commonly trabecular in appearance. Serum LH levels were measured in some animals. As a group, rats displaying changes in gonadotroph morphology had a higher mean serum LH level than those without these changes, however, the values ranging from 23-249 ng/ml were well within the normal serum LH levels reported in aging rats. Gonadotroph adenomas in human patients have only recently been identified with accuracy and are relatively uncommon. As in the case of rats, they do not appear to arise from a pre-existing end organ hypofunction or pre-existing gonadotroph hyperplasia. A suitable animal model, in the form of spontaneously occurring gonadotroph adenomas in aging rats, might be useful in establishing the etiology, biochemical properties and appropriate therapy for these tumors.