Normal ontogeny of alpha 1-adrenergic receptor in rat liver is thyroid hormone dependent.
Postnatal ontogeny of rat liver alpha 1-adrenergic receptor was examined using alpha 1-specific radioligand [3H]prazosin in control and propylthiouracil-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 less than 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 less than 0.01). Replacement therapy with daily T4 injection from postnatal 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. These findings indicate that the normal ontogeny of plasma membrane alpha 1-adrenergic receptors is dependent upon thyroid hormone and matures postnatally in rat liver.
D000375:Aging; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D007037:Hypothyroidism / Q000503:physiopathology*; D007700:Kinetics; D008099:Liver / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D011224:Prazosin / Q000378:metabolism*; D011441:Propylthiouracil / Q000494:pharmacology*; D011799:Quinazolines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013961:Thyroid Gland / Q000502:physiology*
D011799:Quinazolines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011441:Propylthiouracil; D011224:Prazosin