Developmental Defects of Testicular Morphology and Steroidogenesis in the Male Rat Pseudohermaphrodite and Response to Testosterone and Dihydrotestosterone

The pubertal development of testicular steroidogenic enzymes and sperm cell maturation has been studied in the rat pseudohermaphrodite and its King-X Holtzman male littermate. Enzymatic activity has been determined by the separation and quantitation of the products formed from labeled steroidal precursors by a partition system on thin-layer chromatography and by trimethylsilylether derivative formationand radio-gas-liquid chromatography. The separationshave been confirmed by formation of dinitrophenylhydrazones,by reverse isotope dilution and/or recrystallization. Three periods ofpubertal development of testicular steroidogenicenzymes have been delineated in the male. Thefirst is characterized by the onset of steroid 5areductaseactivity, beginning about 15 days of age,and rising to a maximum between 30 and 40 days.The second stage consists of the onset between20 and 30 days of activities of 17α-hydroxylase,C_17–20 lyase and 17β-hydroxysteroid dehydrogenase,the latter enzyme converting the 17β-alcoholof testosterone to the corresponding 17-ketone.During the third phase from 40 to 60 days, 17-ketoreductase, the enzyme converting the 17-ketone of androstenedione to the 17β-alcohol oftestosterone, appears and rises to adult levels,while inversely, activity of 5α-reductase and 17(5-hydroxysteroid dehydrogenase fall to adult levels.Sperm cell meiosis and maturation is completedduring the third stage. The development of thetestis of the pseudohermaphrodite differs fromthat of its littermate male by its failure to undergothe third stage, in that elevation of the 5α-reductaseand 17β-hydroxysteroid dehydrogenase is persistent,17-ketoreductase fails to appear, and onsetof the completion of sperm meiosis does not occur.Large doses of androgens administered postpubertallyeffect a significant correction of thepersistently elevated levels of 5α-reductase anddehydrogenase in the pseudohermaphrodite, suggestingthat the production of testosterone in thethird stage may be necessary for the decline ofthe levels of these enzymes to adult levels. Thefailure to bring about reappearance of the 17-ketoreductase or the completion of meiosis in thepseudohermaphrodite by large doses of androgenseither pre- or postpubertally suggests that thecontrol of these parameters by testosterone occursprior to puberty, i.e., in utero or shortly afterbirth. (Endocrinology94: 1, 1974)