Upregulation of pancreatic polypeptide-sensitive neuropeptide Y (NPY) receptors in estrogen-induced hypertrophy of the anterior pituitary gland in the Fischer-344 rat.
Implants of diethylstilbestrol inducing anterior pituitary prolactinomas in female Fischer-344 rats produced a considerable elevation of high-affinity binding of either rat or human pancreatic polypeptide (hPP). No comparable upregulation of high-affinity binding sites was noted for the ligand [125I](Leu31,Pro34)hPYY (LP-PYY) (masked by 2 nM hPP to force selectivity for the Y1 sites), or of the Y2-selective ligand [125I]hPYY(3-36). The Y5-like sites displayed the rank order of potency of hPP = rPP, hNPY, LP-PYY > pPYY(1-36) > hNPY(2-36) > hPYY(3-36) >> aPP, similar to the previously described rabbit kidney or hypothalamic Y5-like receptors. The PP binding in the anterior pituitary was not sensitive to the Y1-selective non-peptidic antagonist BIBP-3226. The PP binding was highly sensitive to alkali metal cations, and to a N5-substituted amiloride antagonist of sodium transport, but not to a C2-guanido substituted amiloride antagonist of sodium channels. The binding was also sensitive to phospholipase C antagonist U-73122, and to alkylating alpha-adrenergic agonist chloroethylclonidine. Lactotrophs isolated in Percoll gradients after enzymic dispersion of the anterior pituitary gland retained the high-affinity PP binding. Following removal of estrogen implants, the hPP binding sites decreased to very low levels within 3 days, in parallel to the decrease of plasma prolactin.
Parker
M S
MS
Department of Pharmacology, University of Tennessee School of Medicine, Memphis 38163, USA.
Wang
J J
JJ
Fournier
A
A
Parker
S L
SL
D000818:Animals; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D006984:Hypertrophy; D010179:Pancreas / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000473:pathology / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D017476:Receptors, Neuropeptide Y / Q000502:physiology*; D015854:Up-Regulation
D004967:Estrogens; D017476:Receptors, Neuropeptide Y