Endocrine status of the testicular feminized male (TFM) rat

The plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), androstenedione (A), dihydrotestosterone (DHT), corticosterone and corticosterone binding globulin (CBG) were determined in 160- and 350-day testicular feminized male (tfm) and normal littermate (NL) rats. In the younger group the concentrations of T, A, DHT and 5α-androstan-3α,17β-diol (Adiol) were also determined in testis tissue.Tfm rats showed a greatly elevated plasma LH indicating lack of androgen feedback. Plasma FSH, however, was normal in both age groups, suggesting that inhibin production from tfm testes was relatively unaffected.Intratesticular concentrations of A were greatly elevated in the tfm animals at both ages whilst the testicular levels of T were highly reduced when compared to NL rats. This indicates a gonadal deficiency of the 17β-hydroxy steroid dehydrogenase (17β-HSD). Furthermore, the relatively low T: DHT ratio and high concentrations of Adiol in the tfm testes confirmed previous reports that the high 5α-reductase typical for the immature rat testis is maintained into adulthood in rats with the tfm condition. A considerable degree of peripheral conversion (A → T) probably helps to maintain normal or supranormal plasma levels of T. Gonadectomy rendered all plasma androgens undetectable, indicating that the adrenal contribution was negligible.Increasing age (350 days) was associated with a marked increase in circulating androgens in tfm rats. This is probably the reason for the observed significant reduction in circulating LH in this age group when compared to the 160-day animals. The aging tfm rat is predisposed to testicular tumors which, on the basis of histology, specific [¹²⁵I]hLH binding and in vitro responsiveness to hCG, appear to be of Leydig cell origin.Microflow fluorometry (MFF) of tfm testis cell suspensions revealed the presence of haploid cells, suggesting that meiosis proceeds to a limited extent.Plasma corticosterone levels in the tfm rat were normal although plasma CBG levels were highly significantly elevated at both ages when compared to the levels in NL rats. We suggest that the adrenal hyperplasia observed in tfm rats is secondary to reduced corticosterone production and diminished free corticosterone in the circulation.