Hormonal factors in carcinogenesis of the prostate and testis in humans and in animal models.
The etiology of human testicular tumors is poorly defined. With the possible exception of prenatal estrogen exposure, no specific chemical exposures have been associated with testicular cancer risk in men. Prenatal as well as postnatal estrogen treatments induce testicular tumors in some mouse strains, but not in other mouse strains or in rats. Prenatal estrogen exposure also causes cryptorchid testes in mice and possibly rats. Cryptorchidism is a consistent risk factor for testicular cancer in men, and estrogen- or surgically-induced cryptorchidism is associated with Leydig cell tumorigenesis in mice. In rats, however, surgically induced cryptorchidism inhibits Leydig cell tumor formation. Overall, it appears that the mouse is the most appropriate species as animal model for testicular tumorigenesis in humans. Any of the following hormonal exposures can cause testicular tumor formation in rodents: 1) chronic exposure to estrogenic compounds of adult mice and hamsters; 2) prenatal exposure to estrogenic compounds of mice and possibly humans; and 3) any treatment or condition that induces cryptorchidism in mice and humans. The mechanisms whereby these treatments or conditions may cause testicular tumorigenesis are poorly understood. Undefined local testicular factors appear to be dominant in tumorigenesis in cryptorchid human and rodent testes. Pituitary factors, most likely LH and perhaps prolactin, play a critical but poorly defined role in estrogen-induced and spontaneous testicular tumorigenesis in rodents. In the mouse, estrogen receptor-mediated mechanisms seem to be involved in induction of testicular tumors by prenatal estrogen exposure, and a direct, perhaps estrogen receptor-mediated, inhibiting effect of estrogens on the action of müllerian inhibiting substance is probably central in the induction of cryptorchidism in this species.
Bosland
M C
MC
Institute of Environmental Medicine, New York University Medical Center, Tuxedo 10987, USA.
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D005260:Female; D006728:Hormones / Q000502:physiology* / Q000633:toxicity; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000209:etiology*; D013736:Testicular Neoplasms / Q000209:etiology*
D002273:Carcinogens; D006728:Hormones