Abstract
Postnatal ontogeny of rat liver .alpha.1-adrenergic receptor was examined using .alpha.1-specific radioligand [3H]prazosin in control and propylthiouracil[PTU]-treated congenital hypothyroid rats at various ages. Partially purified rat liver membranes prepared by the Neville method had 8-fold purification of 5''-nucleotidase from the crude homogenates from postnatal day 5 to adulthood. [3H]Prazosin binding was typical of an .alpha.1-adrenergic receptor, and (-)epinephrine affinity for the [3H]prazosin-binding sites was not altered in the presence of 10-5 M guanylyl-imidodiphosphate. The receptor density was lower in 5- and 15-day-old rats than in 28-day-old or older rats in both control and hypothyroid groups (P < 0.01). At 28-34 days of age, hypothyroid pups had significantly lower .alpha.1-receptor density than controls (399 .+-. 10 vs. 869 .+-. 40 fmol mg protein-1; P < 0.01). Replacement therapy with daily T4 [thyroxine] injection from post-natal days 16-27 restored 54% of the deficit in PTU-treated hypothyroid pups at 28 days. The dissociation constant of [3H]prazosin did not change with advancing age or with different treatment and was consistent at 0.1 nM. The normal ontogeny of plasma membrane .alpha.1-adrenergic receptors is dependent upon thyroid hormone and matures postnatally in rat liver.