Pubescence-related changes in hepatocyte insulin dynamics in female rats

Abstract

Insulin binding and receptor-mediated insulin processing were investigated in isolated hepatocytes from sexually maturing female rats and from age-matched animals that had undergone prepubertal ovariectomy or whose sexual dimorphism had been disrupted by neonatal androgen treatment. Equilibrium insulin binding was determined after 18 h of incubation with 125I-TyrA14-monoiodoinsulin at 4 degrees C. Receptor-mediated insulin processing was studied after overnight binding with 100 pM insulin at 4 degrees C and subsequent incubation at 37 degrees C. Insulin binding at tracer concentrations increased 50% from sexual immaturity at 3-4 wk through pubescence at 6-8 wk and was further increased into young adulthood at 10-12 wk. Scatchard analysis indicated that the altered binding was due primarily to an increase in receptor number. Increased binding with sexual maturation resulted in correspondingly higher levels of insulin in each of the four compartments of processing studied (cell surface bound, internalized, degraded, and released). A corresponding increase in receptor-mediated insulin degradation after 10 min at 37 degrees C was observed, as changes in insulin degradation were proportional to the increase in insulin receptor binding. The age-related increase in insulin binding and subsequent increase in degradation were abolished by prepubertal ovariectomy. Furthermore, disrupting sexual dimorphism by perinatal androgen treatment resulted in a reduction of the age-related increase in insulin binding, but the percentage of insulin degraded was significantly greater than that accounted for by the increase in receptor number. As a result, insulin degradation per unit of receptor-bound hormone was increased.(ABSTRACT TRUNCATED AT 250 WORDS)