Af. Badawi et Mc. Archer, EFFECT OF HORMONAL STATUS ON THE EXPRESSION OF THE CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2 GENES AND PROSTAGLANDIN SYNTHESIS IN RAT MAMMARY-GLANDS, Prostaglandins, 56(2-3), 1998, pp. 167-181
Hormonal effects on mammary carcinogenesis have been linked to prostag
landin (PG) synthesis. The purpose of the present study was to examine
the expression of the cyclooxygenase (COX) 1 and 2 genes and levels o
f PG synthesis in the mammary glands of rats that have different level
s of susceptibility to mammary gland carcinogenesis associated with pr
egnancy, lactation, post-lactation involution, and ovariectomy. The ex
pression of COX-1 mRNA, measured by Northern blot analysis, was simila
r in virgin, lactating pregnant, and post-lactational animals of the s
ame age. Ovariectomized animals exhibited significantly lower levels o
f COX-I mRNA (similar to 40%) compared to the sham-operated controls o
r the ovariectomized animals treated with estradiol and progesterone.
COX-2 mRNA, measured by RT-PCR, was detectable only in the mammary gla
nds of lactating animals and ovariectomized animals administered estra
diol and progesterone. Induction on COX-2 expression occurred in both
stromal and epithelial cells in lactating rat mammary glands. COX enzy
matic activities, determined by measuring the conversion rate of [1-C-
14]-arachadonic acid to prostanoids, showed that lactating animals had
a significantly higher activity compared to virgin (similar to 40%),
pregnant (similar to 30%), or post-lactational animals (similar to 40%
). Ovariectomized animals had significantly lower COX enzymatic activi
ty compared to the sham operated animals. Significant induction of COX
activity, however, was observed in ovariectomized animals administere
d estradiol and progesterone. These changes in COX enzymatic activity
were paralleled by similar changes in the mammary gland PGE, 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 synthes
is.