Variation in the expression of human 3β-hydroxysteroid dehydrogenase

Abstract

Polymorphic genetic variation shows that the genes for human 3β-hydroxysteroid dehydrogenases (3β-HSD) types I and II are closely linked. The type II mutations A82T, S100N and L173R are associated with male pseudohermaphroditism and A82T is associated, with variable penetrance, with female premature puberty. When expressed in vitro A82T showed less than 5% of normal activity and L173R showed a 30-50% reduction in activity. PCR experiments and direct genomic cloning show that there is a larger family of 3β-HSD sequences which require to be tested for expression. The phenomenon of epitopic heterogeneity of 3β-HSD is discussed and is now shown to apply to testicular Leydig cells as well as extra-uterine trophoblast. RT-PCR analyses indicate that the phenomenon is most likely to be due to post-translational modification affecting the carboxytermini 3β-HSD types I and II. This phenomenon may reflect a further level at which enzyme activity is regulated.