Abnormalities of the Pituitary-Gonadal-Axis of Hre Rats: A Study of Animals with an Inherited Disorder of

Male rats heterozygous for the Hre gene (Hre/+) develop seminiferous tubular failure after an initial period of fertility. The pituitary-gonadal axes of these rats were compared with those of normal male littermates (+1+) between 30 and 240 days of age. FSH levels rose in Hre/+ to 140-170 % of +1+ after 30 days of age. Surprisingly, LH levels were also elevated in Hre,+, rising to 3 times #{247}1+by 240 days of age. Even with increased plasma LH levels, testosterone concentrations remained below normal, suggesting that the Hre gene affected Leydig cell as well as seminiferous tubular function. Morphological studies indicated progressive focal degeneration of germinal elements in Hre,+ with advancing age. The loss of germ cells was associated with abnormal cytological features of the Sertoli cells, including extensive vacuolization. These observations are consistent with focal Sertoli cell dysfunction and subsequent loss of germ cells in the affected areas of the seminiferous tubular epithe-lium. Six enzymes (acid phosphatase, lactic acid dehydrogenase-X, sorbitol dehydrogenase, (1-glucoro-nidase, uridine diphosphatase and 5’-nucleotidase), which have been associated with specific cell types in the seminiferous tubular epithelium, were measured in testes from Hre,+ and +1+. The lack of expected correlation suggested that these enzymes do not accurately reflect alterations of seminiferous tubular morphology in H/+