Dihydrotestosterone regulates plasma sex-hormone-binding globulin in prepubertal males

Plasma levels of sex-hormone-binding globulin (SHBG) in man are known to be regulated up and down by oestradiol and testosterone, respectively. To determine whether testosterone reduces SHBG level directly or via its conversion into dihydrotestosterone before puberty, the changes of plasma SHBG, testosterone, oestradiol and dihydrotestosterone following human chorionic gonadotrophin stimulation are studied in ten 5 alpha-reductase-deficient and in six normal prepubertal boys. Three main observations provide evidence that dihydrotestosterone plays a major role in SHBG regulation. (1) Basal plasma SHBG in 5 alpha-reductase-deficient is higher than in normal boys (P less than 0.1). (2) Circulating SHBG fails to decrease (P greater than 0.1) after human chorionic gonadotrophin stimulation despite striking elevation of plasma testosterone in 5 alpha-reductase deficiency where negligible dihydrotestosterone response occurs. This is in contrast to normal boys where SHBG is significantly reduced (P less than 0.01) after stimulation. (3). In normal boys the magnitude of plasma dihydrotestosterone response to human chorionic gonadotrophin correlates with that of SHBG (r = 0.72) more than testosterone does versus SHBG (r = 0.36). It is concluded that dihydrotestosterone decreases SHBG concentration in plasma of prepubertal boys. At least part of the observed decrease in SHBG following testosterone administration in earlier reports must have occurred after its conversion to dihydrotestosterone.