Ontogeny of Rat Hepatic Glucocorticoid Receptors

Some glucocorticoid-inducible hepatic enzymes fail to respond to hormone administration prenatally but do respond soon after birth. One possible mechanism for this lack of responsivity is incomplete development of the glucocorticoid receptor system in the fetus. To evaluate this hypothesis, 3H-dexamethasone binding was studied in vitro in liver cytosol from fetuses (days 19–20) and young rats (days 1–29). Glucocorticoid receptors are present as early as days 19–20 of gestation and resemble adult receptors in affinity for 3H-dexamethasone and specificity for other steroid hormones. By Scatchard analysis the concentration of receptors is lower in the fetus (0.11 pmoles/mg cytosol protein) than at any postpartum date studied (0.26–0.55). However, since only unoccupied receptors are detected by the assay, this apparent difference in receptor concentration is felt to be the result of elevated levels of endogenous corticosterone in the fetus (37.8 μg/100 ml) compared to young rats (1.3–6.4 μg/100 ml). The fetal receptors are functional by the criterion of nuclear transfer of 3H-dexamethasone. Although glucagon administration o t the fetus has been shown to result in precocious development of some glucocorticoid-inducible hepatic enzymes, no significant change in receptor affinity or concentration is found after such treatment. The findings suggest that the fetal glucocor-ticoid receptors are intact and that the failure of prenatal glucocorticoid to result in enzyme induction is probably due to a block distal to the nuclear uptake step. (Endocrinology95: 1219, 1974)