Progesterone Receptors in the Fetal Uterus and Ovary of the Guinea Pig: Evolution during Fetal Development and Induction and Stimulation In Estradiol-Primed Animals*

Abstract

Specific binding sites for [³H]progesterone ([³H]P) and for the synthetic progestagen [³H]R-5020 (17α,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione) are found in the cytosol and nuclear fractions of the fetal uterus of the guinea pig. P, R-5020, and 5α-dihydroprogesterone compete for binding with [³H]P and [³H]R-5020. Estradiol (E₂), estrone, testosterone, and cortisol do not compete. In the cytosol fraction, the dissociation constant (K_d) at 4 C is 3.3 ± 1.7 (sd) × 10⁻⁹m for [³H]P, and the concentration of sites (n) is 180 ± 28 fmol/mg protein. Two components are found in sucrose density gradients at 6–7S and 4S. Few if any [³H]P-specific sites can be detected in uterine cytosol until 37–42 days of gestation. By 50–52 days, the concentration of sites is 35.4 ± 6.34 fmol/mg protein. These sites increase at the end of gestation to 85.6 ± 15.7 fmol/mg protein. Similar specific binding sites are found in the fetal ovaries, and at the end of gestation reach concentrations of 25.6 ± 8.6 fmol/mg protein. In another series of studies, pregnant guinea pigs were treated with E₂ (1 mg/kg·day, sc to the mother for 3 days), and the [³H]P-specific binding sites in the fetal uteri and ovaries were assayed on the fourth day. E₂ priming increase [³H]P sites in the fetal uteri from nearly undetectable levels to 30.8 ± 6.8 fmol/mg protein at 37–42 days of gestation and from 85.6 ± 15.7 to 549 ± 87.9 fmol/mg protein at 55–65 days. In the fetal ovaries at 55–65 days of gestation, E₂ priming increased [³H]P binding from 25.6 ± 8.6 to 87 ± 25.5 fmol/mg protein. Little or no stimulatory effect of E₂ was found on P receptors in other fetal tissues (lung, kidney, brain, and heart) or placenta. It is concluded that the ability of E₂ to induce or stimulate P receptors can be expressed in the fetus. (Endocrinology 106: 1160, 1980)