Interaction of steroids with dexamethasone-binding receptor and corticosteroid-binding globulin in the mammary gland of the mouse in relation to lactation

Dexamethasone (9α-fluoro-llβ17, 21-trihydroxy-16α-methyl-pregna-l, 4-diene-3, 20-dione) binding by cytosolic components of mammary glands from pregnant and lactating mice was characterized and quantified. The unfilled receptor for dexamethasone lost binding activity rapidly by a process that was largely, but not completely, reversed by the addition of sulfhydryl reagents. The quantity of dexamethasone receptors increased 4-fold during the last 8 days of pregnancy. The apparent binding affinity (K_a) calculated from Scatchard plots was maximal at parturition (1.5 × 10⁸ M^-1), but declined gradually as lactation progressed. A mixture of cytosols from pregnancy and lactation gave a linear Scatchard plot, with a K_a that was the mean of the K_a values obtained in the separate cytosols. The decreased K_a in lactating mice was not due to a different class of receptors, but may be attributed to the increased levels of endogenous free steroids in the cytosol. Some differences, however, were noted between the sedimentation properties of the dexamethasone-receptor complexes in cytosols of pregnant and lactating mice. In addition to the dexamethasone-binding activity, a binding substance identical to corticosteroid-binding globulin (CBG) was identified in the cytosol fraction of mammary glands. CBG in glands of lactating mice was saturated with endogenous steroids, but that in pregnant mice was only 8% saturated. The presence of high concentrations of unsaturated CBG in the vicinity of the parenchymal cells would decrease the availability of corticosteroids to the receptors in pregnancy and may be an important mechanism for the control of the initiation of milk secretion.