Both gonadotropin and testosterone fail to reverse estrogen-induced cryptorchidism in fetal mice: further evidence for nonandrogenic control of testicular descent in the fetus

Abstract

Estradiol benzoate (E2B) causes cryptorchidism in fetal mice, with suppression of androgen secretion. Simultaneous gonadotropin (hCG) injection was reported to restore Leydig cell function and testosterone mediates testicular descent. To investigate whether hCG or testosterone fully reverses the cryptorchidism as well as testosterone secretion, fetal mice were exposed to E2B with or without hCG/testosterone. Normal transabdominal testicular descent was significantly inhibited by E2B or diethylstilbestrol injection on day 14 of gestation (n = 41; P < 0.005). Both hCG 50–100 IU (n = 59) and testosterone 5 mg (n = 45) given simultaneously with E2B failed to restore normal testicular descent (P < 0.005), with the testicular position the same as after E2B treatment alone. Mean testicular testosterone content at birth after E2B administration was 66±55 pg/testis (n = 15), while following E2B plus hCG it was 115±58 pg/testis (n = 10). Normal control mice had a testicular testosterone content of 882±422 pg/testis (n = 12). These results make the view that hCG or testosterone can reverse estrogen-induced cryptorchidism in the fetus questionable. It is proposed that estrogen not only suppresses the hypothalamic-pituitary axis and androgen secretion, but also has a direct inhibitory effect on testicular descent unrelated to androgen action. The action of mullerian inhibiting substance is known to be inhibited by estrogen during mullerian duct regression, and this may be the mechanism by which estrogen inhibits testicular descent.