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ABSTRACT
Adenylate cyclase activity was studied in crude adrenal membranes from fetal and newborn rats. Basal adenylate cyclase activity was higher in fetal than in newborn rats. ACTH(1–24) (1 μmol/l), guanosine (β,γ-imido diphosphate) (Gpp(NH)p) (10 μmol/l) and forskolin (100 μmol/l) stimulated the activity of the enzyme at all stages studied. The sensitivity of the enzyme to ACTH was maximal on days 17 and 19 of gestation. When Gpp(NH)p was added to ACTH(1–24), the response was significantly higher than that induced by Gpp(NH)p alone. Forskolin and Gpp (NH)p alone increased the adenylate cyclase activity and the sensitivity of the enzyme to these compounds was higher in newborn rats than in fetuses. Treatment of 21-day-old rat fetuses with ACTH increased the response of adenylate cyclase to Gpp(NH)p alone or to forskolin whereas treatment with dexamethasone did not modify the response of the enzyme to either Gpp(NH)p alone or forskolin. Our results show that the change in the responsiveness of adenylate cyclase takes place immediately after birth during the first week and ACTH is able to induce a maturation of the fetal adrenal adenylate cyclase system.
Journal of Endocrinology (1990) 126, 211–216
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ABSTRACT
Binding of ACTH to receptors was studied on crude adrenal membranes from fetal and newborn rats. 125I-Labelled ACTH(1–24) was used as the radioligand, the steroidogenic potency of which was 100-fold lower than that of unlabelled ACTH(1–24). Binding was specific, rapidly equilibrated and temperature dependent. Scatchard analysis of the binding data revealed a single class of binding sites with a dissociation constant of about 100 nmol/l at all stages of development studied. The concentration of ACTH receptors expressed per mg membrane proteins decreased in fetuses between days 17 and 21 of gestation and remained stable in newborn rats from weeks 1 to 4. The number of ACTH receptors expressed per adrenal increased regularly in fetal and newborn rats. The perinatal evolution of these concentrations of ACTH receptors is related to the increase in the size of the adrenals and the changes in cytoplasmic structures of the adrenocortical cells. When the number of ACTH-binding sites was expressed per μg DNA, maximum values occurred in fetuses on day 19 of gestation, and minimum values in newborn rats, 1 week after birth. There was an excellent correlation between the plasma levels of immunoreactive ACTH and corticosterone and the number of ACTH receptors per μg DNA during the perinatal period. Other results suggest that ACTH is able to up-regulate the number of its own receptors.
Journal of Endocrinology (1989) 123, 421–428
