The differential effects of galanin-(1-30) and -(3-30) on anterior pituitary hormone secretion in vivo in humans.
Intravenous injection of galanin increases plasma growth hormone (GH) and prolactin (PRL) concentrations. In the rat, the effects of galanin on GH appear to be mediated via the hypothalamic galanin receptor GAL-R(1), at which galanin-(3-29) is inactive. In contrast, the effect of galanin on PRL is mediated via the pituitary-specific galanin receptor GAL-R(W), at which galanin-(3-29) is fully active. We investigated the effects of an intravenous infusion of human galanin (hGAL)-(1-30) and -(3-30) on anterior pituitary hormone levels in healthy females. Subjects were infused with saline, hGAL-(1-30) (80 pmol. kg(-1). min(-1)), and hGAL-(3-30) (600 pmol. kg(-1). min(-1)) and with boluses of gonadotropin-releasing hormone, thyrotropin-releasing hormone, and growth hormone-releasing hormone (GHRH). Both hGAL-(1-30) and -(3-30) potentiated the rise in GHRH-stimulated GH levels [area under the curve (AUC), saline, 2,810 +/- 500 vs. hGAL-(1-30), 4,660 +/- 737, P < 0.01; vs. hGAL-(3-30), 6, 870 +/- 1,550 ng. min. ml(-1), P < 0.01]. In contrast to hGAL-(1-30), hGAL-(3-30) had no effect on basal GH levels (AUC, saline, -110 +/- 88 vs. hGAL 1-30, 960 +/- 280, P < 0.002; vs. hGAL-(3-30), 110 +/- 54 ng. min. ml(-1), P = not significant). These data suggest that the effects of galanin on basal and stimulated GH release are mediated via different receptor subtypes and that the human equivalent of GAL-R(W) may exist.
Todd
J F
JF
Endocrine Unit, Imperial College of Science, Technology and Medicine Hammersmith Hospital, London W12 ONN, United Kingdom.
Edwards
C M
CM
Ghatei
M A
MA
Bloom
S R
SR
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D019004:Galanin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone; D006339:Heart Rate / Q000187:drug effects; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D011388:Prolactin / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone
D010446:Peptide Fragments; D010908:Pituitary Hormones, Anterior; C410582:galanin (3-30); D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D019004:Galanin; D011388:Prolactin; D007986:Luteinizing Hormone; D013972:Thyrotropin