Glucocorticoids and hypothyroidism modulate development of fetal lung insulin receptors

We investigated the development of insulin receptors in membranes of fetal rabbit lung during normal ontogeny and the effect of glucocorticoids and hypothyroidism. specific binding of ¹²⁵I-insulin to fetal lung membranes increased progressively to a peak at 29 days gestation, declining by 30 days. Scatchard plots were curvilinear and revealed a progressive increase in receptor numbers (x 10¹⁰/mg protein) from 129 ± 7 (mean ± SE) at 22-24 days to 575 ± 16 at 29 days, declining to 467 ± 12 at 30 days, term being ~ 31 days. Affinities did not change throughout gestation and were similar to those of adult lung; receptor numbers in adults were significantly lower than in fetuses at 26-30 days. Epinephrine and PGE₁ could evoke a doubling of cAMP production in adult and fetal lung membranes until 29 days. Concomitantly with the fall in fetal insulin receptor number at 30 days, cAMP production in response to epinephrine or PGE₁ increased fivefold. Induction of fetal hypothyroidism decreased insulin receptor numbers in the lung of the 28-day fetus by 70% from control (P < 0.001) without a change in receptor affinity. In contrast, betamethasone administration increased fetal lung insulin receptor numbers by 250% (P < 0.001) but did not alter their affinity; maternal lung insulin receptors were not altered. Thus, normal ontogeny of the fetal lung insulin receptor is characterized by a progressive increase in number followed by decline immediately before parturition associated with a sharp increase of cAMP responsiveness of the membranes. Hypothyroidism and glucocorticoid exposure can modulate the normal development of the fetal lung insulin receptor.