AJP - Endocrinology and Metabolism, Vol 244, Issue 6 624-E631, Copyright © 1983 by American Physiological Society
Ontogeny of hepatic insulin and glucagon receptors and adenylate cyclase in rabbit
S. Ganguli, M. K. Sinha, B. Sterman, P. Harris and M. A. Sperling
In rabbit liver plasma membranes (LPM), specific binding of 125I-insulin
rapidly increased in late gestation and peaked at birth, declining
thereafter. In contrast, 125I-glucagon binding was lowest in late
gestation, somewhat higher at birth, and increased by 48 h although only to
20-25% of adult. These changes in binding were due to changing numbers of
receptors involving predominantly high affinity sites for insulin and low
affinity sites for glucagon, with only minor changes in affinity. Despite
measurable glucagon receptors by birth, fetal LPM produced no increment
above basal in cAMP production with maximal doses of glucagon (10(-6) M),
prostaglandin E1 (10(-4) M), or epinephrine (10(-4) M). Near birth only NaF
(10 mM) produced a modest but significant increment in cAMP. By 2 h
postbirth, all stimuli evoked significant increments in cAMP production
that increased progressively but was still only 15-20% of adult at 48 h.
Furthermore, although specific binding of cholera toxin was greater in
fetal LPM (11 +/- 1 vs. 6 +/- 1%), cholera toxin-stimulated cAMP production
increased by only 12-26% above basal in the fetus compared with 220% in
adult. Markers of membrane purity including 5'-nucleotidase,
phosphodiesterase, and insulin or glucagon degradation were not different
in fetus and adult. We conclude that receptors and components of the
adenylate cyclase complex mature independently; initial coupling occurs
between the G/F regulatory protein and the catalytic unit (NaF but not
hormonal activation) followed within hours of birth by coupling to the
hormone receptor.
