VARIATION IN THE EXPRESSION OF HUMAN 3-BETA-HYDROXYSTEROID DEHYDROGENASE

Polymorphic genetic variation shows that the genes for human 3 beta-hy droxysteroid dehydrogenases (3 beta-HSD) types I and II are closely li nked. The type II mutations A82T, S100N and L173R are associated with male pseudohermaphroditism and A82T is associated, with variable penet rance, with female premature puberty. When expressed in vitro A82T sho wed less than 5% of normal activity and L173R showed a 30-50% reductio n in activity. PCR experiments and direct genomic cloning show that th ere is a larger family of 3 beta-HSD sequences which require to be tes ted for expression. The phenomenon of epitopic heterogeneity of 3 beta -HSD is discussed and is now shown to apply to testicular Leydig cells as well as extra-uterine trophoblast. RT-PCR analyses indicate that t he phenomenon is most likely to be due to post-translational modificat ion affecting the carboxytermini 3 beta-HSD types I and II. This pheno menon may reflect a further level at which enzyme activity is regulate d.