Human chorionic gonadotropin (hCG) is as efficient as pregnancy in protecting the rat mammary gland against carcinogenesis. The effect of both pregnancy and hCG is a lasting one, without secondary effect on body weight, and endocrine related organs. The protective effect of hCG as in pregnancy is due to gland differentiation associated with depression on cell proliferation and synthesis of inhibin by the mammary epithelial cells. The protective effect of hCG is further demonstrated after carcinogen administration indicating a decrease of tumor progression. Whereas hCG action is mediated mainly through the ovary, a direct effect has been demonstrated. This data has been further confirmed by showing that hCG treatment inhibits the proliferation of human breast epithelial cells. This inhibition is associated with synthesis of new gene products, some of which have been identified by immunoprecipitation and Northern blot analysis to be alpha and beta inhibin subunits. Collectively, all these data indicate that inhibin may play an important role in cell growth and differentiation of the mammary epithelia during the physiological process of pregnancy or by the action of hCG. Further studies delineating the pathway through which hCG and inhibin modulate the fate of neoplastic cells would allow us to utilize physiologic mechanisms controlling cell proliferation in breast cancer prevention and therapy.

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