Variations of progesterone receptor and c-fos gene expression in the rat uterus after treatment with norethisterone and its A-ring reduced metabolites

It has been suggested that some contraceptive derivatives of 19-nor-testost erone possess estrogenic activity that may facilitate the development of br east cancer. The aim of this work was to investigate the estrogenic propert ies of norethisterone (NET) and its A-ring-reduced derivatives by determini ng progesterone receptor (PR) and c-fos mRNA content of two estrogen-regula ted genes in the uterus of ovariectomized rats. mRNA content was evaluated by Northern blot 1-6 h after 17 beta-estradiol administration. The highest PR and c-fos mRNA content was observed 3 h and 2 h after 17 beta-estradiol administration, respectively. NET did not modify either PR or c-fos mRNA co ntent. In contrast, 5 alpha- and 3 beta, 5 alpha-NET significantly increase d mRNA content of both genes. The increase in c-fos mRNA content induced by these reduced compounds was lower than that found with estradiol treatment . The overall results indicate that NET administration can indirectly induc e estrogenic effects through the action of its 5 alpha-dihydro and 3 beta,5 alpha-tetrahydro derivatives. CONTRACEPTION 1999;59: 339-343 (C) 1999 Else vier Science Inc. All rights reserved.