Neonatal exposure to DES in BALB/c male mice: Effects on pituitary-gonadal function

Abstract

Neonatal male BALB/c mice were injected with diethylstilbestrol (DES), estradiol benzoate (E 2B), testosterone propionate (TP), progesterone or DES, in combination with E 2B, TP or progesterone and examined in adulthood. Body weight was reduced in males exposed to DES, TP or DES + TP, while testicular weight was reduced in animals injected with DES, E 2B, TP, DES + TP or DES + progesterone. Exposure to DES and/or E 2B also produced reproductive tract abnormalities and concomitant progesterone exposure did not further affect this parameter. Concomitant DES did not further alter the reduced plasma luteinizing hormone (LH) levels attributable to neonatal TP or E 2B treatment. Plasma follicle-stimulating hormone (FSH) levels in intact males were increased by DES, DES + progesterone or progesterone alone. Assessment of the feedback effects of exogenous gonadal steroids on pituitary gonadotropin release in castrated adults indicated that injection of 125 μg TP further increased the already elevated post-castration levels of LH and FSH in mice neonatally exposed to progesterone. The increase in testosterone (T) concentration after intratesticular human chorionic gonadotropin (hCG) administration was significantly attenuated in mice neonatally exposed to DES plus E 2B or to progesterone. Basal testicular T levels were significantly elevated in males exposed to DES, alone, or in combination with progesterone. Exposure to DES and TP increased hypothalamic serotonin (5-HT) levels in intact mice, while levels of 5-HT were lower after castration compared to controls. DES + E 2B-treated mice had higher norepinephrine (NE) levels, and E 2B-treated mice also had higher 5-HT levels. These findings indicate that alterations produced as a consequence of neonatal DES exposure include disruptions in pituitary-gonadal feedback and in brain biogenic amine levels, in addition to gross morphological abnormalities in the reproductive tract. Some of the effects of neonatal DES exposure were attenuated by simultaneous treatment with TP, E 2B or progesterone. In addition, treatment with these steroids was also capable of altering pituitary-gonadal feedback. However, gross genital abnormalities were apparent only in males receiving estrogenic preparations. Concomitant exposure to progesterone appeared to be capable of blocking DES-induced morphological effects.