Ligand specificity of progesterone-binding proteins in guinea pig and sheep

Abstract

Progesterone-binding proteins were isolated and partly purified from the uterine cytosol of pregnant guinea pigs, non-pregnant guinea pigs and sheep. In the latter two cases binding protein formation was induced by estrogen treatment. The progesterone-binding protein from pregnant guinea pig plasma was also investigated. All the cytosolic proteins displayed association constants for progesterone of 1–3 × 10 9 1/mol and that of the plasma protein was 3 × 10 8 1/mol. These values are characteristic of high-affinity binders. The ligand specificity of the proteins was investigated using a competitive protein-binding technique. The binding of a large group of natural and synthetic C 18, C 19, C 20 and C 21 steroids and their derivatives was investigated. Only 19-norprogesterone was bound by all the proteins isolated with an affinity comparable to that of progesterone. The binding proteins from pregnant guinea pig plasma and uterine cytosol showed similar binding patterns, whereas the protein induced with estradiol in the non-pregnant guinea pig uterus had different ligand specificity. This shows that binding characteristics are not identical in the same species under different experimental conditions. When the ligand specificity of the progesterone-binding proteins in two species, guinea pig and sheep, are compared, certain differences are also observed. Thus, certain changes in the D ring and the side chain decrease the binding more significantly in guinea pig than in sheep. These differences may be of great importance in choosing animal models in the development of steroidal drugs related to fertility.