Gonadotropin-Prolactin Interrelationships in the Hre/+ Rat: A Longitudinal Study 1

Abstract

To further understand the endocrine pathophysiology of seminiferous tubule failure, a 1-yr cross-sectional study of hormonal secretion was undertaken in rats which are heterozygous for the Hre gene. These animals (Hre/+) develop progressive seminiferous tubular failure that has some features in common with a comparable disorder in humans. Blood samples were taken at 30, 60, 90, 120 and 360 days of age for luteinizing hormone (LH), FSH, prolactin (Prl) and testosterone determinations. At each time interval, the Prl response to metoclopramide, a dopaminergic antagonist, was evaluated. The gonadotropin responses to LHRH were determined at 360 days. By 30 days, FSH levels were significantly increased in Hre/+ rats and remained persistently elevated for the duration of the experiment. Castration at 1 yr resulted in an increase in FSH in normal rats, but not in Hre/+ rats. In Hre/+ rats, LH levels were elevated at 90 and 120 days over those of controls, while testosterone concentrations were much lower. Castration at 360 days produced a significant increase in LH in both groups. Despite the decline in LH levels in Hre/+ rats to near normal at 360 days, there was still an exaggerated response of this gonadotropin to LHRH. FSH levels did not change in either group after LHRH. There were no differences in basal Prl levels in the 2 groups. Both groups had a similar Prl response to metoclopramide. In both Hre/+ and normal rats, there was an age -related decline in gonadotropins and testosterone levels, while Prl increased. Gonadotropin profiles are similar in rats that carry the Hre gene and humans with seminiferous tubule failure. In contrast to humans, however, the Prl response to metoclopramide is normal in Hre/+ rats.