Effect of hormonal status on the expression of the cyclooxygenase 1 and 2 genes and prostaglandin synthesis in rat mammary glands

Abstract

Hormonal effects on mammary carcinogenesis have been linked to prostaglandin (PG) synthesis. The purpose of the present study was to examine the expression of the cyclooxygenase (COX) 1 and 2 genes and levels of PG synthesis in the mammary glands of rats that have different levels of susceptibility to mammary gland carcinogenesis associated with pregnancy, lactation, post-lactation involution, and ovariectomy. The expression of COX-1 mRNA, measured by Northern blot analysis, was similar in virgin, lactating, pregnant, and post-lactational animals of the same age. Ovariectomized animals exhibited significantly lower levels of COX-1 mRNA (∼40%) compared to the sham-operated controls or the ovariectomized animals treated with estradiol and progesterone. COX-2 mRNA, measured by RT-PCR, was detectable only in the mammary glands of lactating animals and ovariectomized animals administered estradiol and progesterone. Induction on COX-2 expression occurred in both stromal and epithelial cells in lactating rat mammary glands. COX enzymatic activities, determined by measuring the conversion rate of [1- 14C]-arachadonic acid to prostanoids, showed that lactating animals had a significantly higher activity compared to virgin (∼40%), pregnant (∼30%), or post-lactational animals (∼40%). Ovariectomized animals had significantly lower COX enzymatic activity compared to the sham operated animals. Significant induction of COX activity, however, was observed in ovariectomized animals administered estradiol and progesterone. These changes in COX enzymatic activity were paralleled by similar changes in the mammary gland PGE 2 content, measured by enzyme immunoassay. Our results suggest that the effect of hormones on the genesis of mammary cancer in the rat may be mediated, at least in part, by their effects on COX-2 expression and PG synthesis.