1644 THE DEVELOPMENT OF INSULIN RECEPTORS IN THE FETAL RABBIT LUNG

Abstract

Recent studies demonstrated higher insulin (I) binding to various fetal tissues when compared to the adult. We investigated the status of I receptors in developing fetal lung in rabbit. Plasma membranes were prepared from the lungs of fetuses at various gestations: 22-24D (n=5), 26-27D (n=5), 28-29D (n=8) and 30D (n=5); lungs from non-pregnant adult animals >2 years of age (n=3) and a younger group <4 months (n=6) were used as controls. I dose-response binding curves were done with I¹²⁵ insulin and native I at various doses (10⁻¹⁰ to 10⁻⁷M), and analysed by Scatchard plots. There was no change in total affinity of the I receptor sites at different gestational ages. However, the number of I receptors × 10¹⁶ per mg protein increased with gestational age from 2.1 ± 0.8 at 22-24D to a peak of 12 ± 4.8 at 29D, decreasing to 1.67 ± 0.66 prior to birth. The number of I receptors were markedly lower in the adult lung; 0.58 ± 0.23 in the younger group and 0.2 ± 0.08 in the older group; affinity was also significantly lower. This pattern differed from PGE₁ (1 × 10⁻⁴M) stimulated c-AMP generation which increased steadily from 26D to 30D gestation (30% to 300%) in these lung membranes. Conclusions: 1) The I receptor number and affinity are higher in fetal lung than in adult; 2) The decrease in I receptor number just prior to parturition does not parallel the progressive increase in adenylate cyclase sensitivity to PGE₁ and 3) Since c-AMP promotes lung maturation and I retards it, the fall in I receptors and increase in c-AMP responsiveness are appropriate maturational events.

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