Role of estrogen and prolactin in stimulation of carcinogen-induced mammary tumor development by a high-fat diet.

The role of estrogen and prolactin in high-fat (HF) dietary stimulation of carcinogen-induced mammary tumors was examined in female Sprague-Dawley rats. At 55 days of age, the rats were given injections i.v. of 5 mg of dimethylbenz(a)anthracene and, 5 days later, rats were sham- or bilaterally ovariectomized. Ten days after dimethylbenz(a)anthracene administration, 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 drug and endocrine treatments to maintain uniform levels of circulating estrogen and prolactin. Sham-operated intact rats and bilaterally ovariectomized rats were given daily injections of 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 the HF or CF diet, there was nearly complete inhibition of mammary tumor development. When the HF diet was given to ovariectomized rats treated daily with either haloperidol or EB, or EB and bromocryptine, some parameters of mammary tumor development were enhanced by the HF diet. However, in all cases, mammary tumorigenesis was reduced when compared to sham-operated control rats. Ovariectomized rats fed the HF diet and given both EB and haloperidol exhibited significantly greater tumor number 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. These results indicate that a HF diet requires adequate circulating levels of estrogen and prolactin to maximally promote increased mammary tumorigenesis in dimethylbenz(a)anthracene-treated rats. Moreover, the enhancing effects of a HF diet on mammary tumorigenesis can be achieved in the presence of similar circulating levels of estrogen and/or prolactin, whether decreased or increased. These results suggest, therefore, that mechanisms independent of altered secretion of estrogens and/or prolactin are involved in promotion of mammary tumorigenesis by high levels of dietary fat.