Steady state levels of hepatic alpha 1- and beta 2-adrenergic receptors and gene transcripts during development of the male rat.

Abstract

Metabolic events stimulated by epinephrine and norepinephrine in hepatocytes isolated from fetal and early postnatal male rats are largely mediated through the beta 2-adrenergic receptor-/cyclic AMP dependent-system, whereas the same stimuli are transduced through the alpha 1-adrenergic receptor-/phosphatidylinositol dependent-system in hepatocytes isolated from young adult male rats. This developmental transition was investigated by correlating hepatic alpha 1- and beta 2-adrenergic receptor gene transcript levels with receptor levels as determined with selective radioligands in livers from late fetal to postnatal day 120 male Sprague-Dawley rats. beta 2-Adrenergic receptor concentration, initially high in membrane preparations isolated from fetal livers (203 +/- 21 fmol/mg protein), dropped precipitously in postnatal day 6 livers (14 +/- 2 fmol/mg protein) and remained low throughout development out to postnatal day 90. beta 2-Adrenergic receptor mRNA levels were highest in fetal livers, were decreased somewhat in postnatal day 6 livers and were undetectable in livers beyond postnatal day 15. In contrast, hepatic alpha 1-adrenergic receptor concentration was relatively low in fetal livers (86 +/- 25 fmol/mg protein) and remained low until postnatal day 18. Thereafter, a steady increase in alpha 1-adrenergic receptors was observed until adult levels. (270 +/- 24 fmol/mg protein) were achieved at postnatal day 27. alpha 1-Adrenergic receptor mRNA levels increased approximately 3-fold, reaching a peak at postnatal day 24. Surprisingly, at postnatal day 30 hepatic alpha 1-adrenergic receptor mRNA levels dropped to fetal levels; but, gradually increased with continued development. Thus, hepatic alpha 1- and beta 2-adrenergic receptors appear to be under complex regulatory control which may include transcriptional, as well as post-transcriptional, mechanisms.