SUPPRESSED EXPRESSION OF THE CYTOCHROME P450(17-ALPHA) PROTEIN IN THETESTICULAR FEMINIZED (TFM) MOUSE TESTES

The testes of testicular feminized (Tfm) mice synthesize and secrete a bnormally low amounts of testosterone, as a consequence of selectively decreased cytochrome P450(17 alpha) activity. To investigate the mech anism of this deficiency, three steroidogenic enzymes were immunolabel led in the testes of normal and Tfm adult (2.5-6 month old) mice. Chol esterol side-chain cleavage cytochrome P450 CP450(scc)) and Delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) were detected in the Le ydig cells of both normal and Tfm mice whereas, in contrast to normal mice, only a small proportion of Leydig cells were immunostained for c ytochrome P450-17 alpha-hydroxylase,C17-->20 lyase (CP450(17 alpha)) i n the testes of Tfm mice. The numbers of cells differed from male to m ale and interestingly were markedly higher in the right testis. Explan ts of testes from Tfm mice were kept in organ culture at 32 degrees C for 45 h, with or without dibutyryl cyclic AMP (100 or 500 mu mol/l). All Leydig cells remained positive for P450(scc) and 3 beta-HSD, and P 450(17 alpha) became detectable in the majority of Leydig cells in bot h left and right testes, showing that the lack of expression of P450(1 7 alpha) protein in Tfm mouse testes in vivo is not structural but is a regulatory phenomenon.