ROLE OF ESTROGEN AND PROLACTIN IN STIMULATION OF CARCINOGEN-INDUCED MAMMARY-TUMOR DEVELOPMENT BY A HIGH-FAT DIET

Abstract

The role of estrogen and prolactin in high-fat (HF) dietary stimulation of carcinogen-induced mammary tumors was examined in female Sprague-Dawley rats. Injections of dimethylbenz(a)anthracene [DMBA] were followed by sham or bilateral ovariectomy. The rats were placed on either a 20.0% HF diet or a 4.5% control fat (CF) diet and were then subjected to various treatments to maintain uniform levels of circulating estrogen and prolactin: haloperidol to increase prolactin secretion, bromocryptine to decrease prolactin secretion, and/or estradiol benzoate (EB). The intact rats fed the HF diet showed significant stimulation of all parameters of mammary tumor development when compared to similarly treated rats fed the CF diet. In ovariectomized rats fed either diet, there was nearly complete inhibition of mammary tumor development. When the HF diet was given to ovariectomized rats treated with haloperidol or EB, or EB and bromocryptine, some parameters of mammary tumor development were enhanced. However, in all cases mammary tumorigenesis was reduced when compared to sham-operated control rats. Ovariectomized rats fed the HF diet and given EB and haloperidol exhibited significantly more tumors per rat, increased average tumor size, and reduced tumor latency period when compared to similarly treated rats fed the CF diet. However, these parameters of mammary tumorigenesis were still reduced when compared to those of sham-control rats fed the HF diet. Apparently mechanisms indepedendent of altered secretion of estrogens and/or prolactin are involved in promotion of mammary tumorigenesis by high levels of dietary fat.