Defective Testicular Testosterone Synthesis by the Pseudohermaphrodite Rat: An Abnormality of 17β-Hydroxy steroid Dehydrogenase

Abstract

Testes of the Stanley-Gumbreck pseudohermaphrotic (Ps) rat secrete only 12–25% as much testosterone as normal (Nl) rats. To explain the mechanism of this defect, minces of testes from Ps and Nl animals were incubated with 14C-steroids, and radioactive testosterone precursors wereisolated by reverse isotope dilution. Pregnenolone, 17-hydroxyprogesterone and androstenedione were converted to testosterone in Nl testes, but in testes from Ps rats androstenedione was the predominant steroid isolated, indicating defective 17β-hydroxysteroid dehydrogenase. This enzyme defect was not corrected by treatment of Ps rats with HCG or by addition of a TPNH generating system to the incubation flasks. Although the reduction of androstenedione to testosterone was markedly impaired, estrone reduction to estradiol was essentially normal, suggesting that the defective enzyme is specific for some rather than all 17-ketosteroids. The data suggest that the enzyme defect is inherited and is unrelated to other conditions associated with decreased testosterone synthesis such as cryptorchidism, estrogen treatment or immaturity of the gonad.(Endocrinology87: 864, 1970)