ESTRADIOL INDUCES C-TYPE NATRIURETIC PEPTIDE GENE-EXPRESSION IN MOUSEUTERUS

Previous experiments have demonstrated that C-type natriuretic peptide (CNP) expression in the uterus varies during the estrous cycle with m aximal expression at proestrus. The present study was designed to dete rmine whether exogenous steroid hormones regulate uterine CNP expressi on in ovariectomized mice. Estradiol increased significantly (3-fold) uterine immunoreactive CNP (irCNP) rapidly and dose dependently in ova riectomized mice as measured by radioimmunoassay. Other steroids produ ced either no significant change (testosterone, 1 mg; 2-methoxyestradi ol, 1 mu g) or weak induction (estriol, 1 mu g) from vehicle controls. Progesterone (1 mg) significantly attenuated the estrogen-stimulated irCNP response by 50% when injected 30 min before estrogen (1 mu g) in estrogen-primed ovariectomized mice. Estrogen-stimulated increases in uterine CNP transcripts detected by ribonuclease protection analyses were blocked by actinomycin D (160 mu g) or ICI-164,384 (20 mu g), a s pecific nuclear estrogen receptor antagonist. These results indicate t hat a nuclear estrogen receptor is required for estrogen to stimulate uterine CNP transcription and that progesterone negatively regulates e strogen-stimulated CNP expression.