Galanin stimulates the neuroendocrine reproductive axis in the rat, but whether galanin acts similarly in primate species is unknown. To test the hypothesis that galanin acts within the hypothalamo-hypophyseal axis to stimulate luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) secretion in the primate, galanin was administered either systemically or directly into the arcuate nucleus-median eminence of ovariectomized macaques (pigtailed or rhesus, respectively) that were maintained on estradiol. The mean plasma levels of LH were significantly elevated in pigtailed macaques after peripheral injection of galanin (2 mg) as compared with vehicle treatment. In rhesus monkeys, galanin (80 µM) administered by push-pull perfusion into the arcuate nucleus-median eminence did not significantly alter either GnRH or LH release. To determine whether in the monkey, as in the rat, subpopulations of medial forebrain GnRH neurons coexpress galanin mRNA, we used single- and double-label in situ hybridization and computerized imaging techniques. GnRH mRNA-containing cells were identified in both the medial and lateral forebrain of the female pigtailed macaque. No galanin mRNA expression was detectable in GnRH neurons located in either the medial preoptic area or mediobasal hypothalamus; however, within the substantia innominata a subset of GnRH mRNA-expressing neurons did coexpress galanin mRNA. Taken together, these results suggest that galanin induces LH release in primates, but galanin may not act directly on hypothalamic GnRH neurons. Presently, we have confirmed in another primate species the existence of GnRH gene expression in the lateral forebrain and discovered that a small subset of these neurons coexpress galanin. These particular cells may have a unique and as of yet undefined physiological function that is distinct from those GnRH neurons serving a hypophysiotropic function.

Keywords:
Gonadotropin-releasing hormone, Gonadotropins, Galanin, Mediobasal, Hypothalamus, Monkey, In situ hybridization
1.
Merchenthaler I, López FJ, Negro-Vilar A: Anatomy and physiology of central galanin-containing pathways. Prog Neurobiol 1993;40:711–769.
2.
Finn PD, Clifton DK, Steiner RA: The regulation of galanin gene expression in gonadotropin-releasing hormone neurons. Mol Cell Endocrinol 1998;140:137–142.
3.
Merchenthaler I, López FJ, Negro-Vilar A: Colocalization of galanin and luteinizing hormone-releasing hormone in a subset of preoptic hypothalamic neurons: Anatomical and functional correlates. Proc Natl Acad Sci USA 1990;87:6326–6330.
4.
López FJ, Negro-Vilar A: Galanin stimulates luteinizing hormone-releasing hormone secretion from arcuate nucleus-median eminence fragments in vitro: Involvement of an α-adrenergic mechanism. Endocrinology 1990;127:2431–2436.
5.
Sahu A, Xu B, Kalra SP: Role of galanin in stimulation of pituitary luteinizing hormone secretion as revealed by a specific receptor antagonist, galantide. Endocrinology 1994;134:529–536.
6.
Sahu A, Crowley WR, Tatemoto K, Balasubramaniam A, Kalra SP: Effects of neuropeptide Y, NPY analog (norleucine4-NPY), galanin and neuropeptide K on LH release in ovariectomized (ovx) and ovx estrogen, progesterone-treated rats. Peptides 1987;8:921–926.
7.
López FJ, Meade EH, Negro-Vilar A: Endogenous galanin modulates the gonadotropin and prolactin proestrous surges in the rat. Endocrinology 1993;132:795–800.
8.
Coen C, Montagnese C, Opacka-Juffry J: Coexistence of gonadotropin-releasing hormone and galanin: Immunohistochemical and functional studies. J Neuroendocrinol 1990;2:107–111.
9.
Marks DL, Wiemann JN, Burton KA, Lent KL, Clifton DK, Steiner RA: Simultaneous visualization of two cellular mRNA species in individual neurons by use of a new double in situ hybridization method. Mol Cell Neurosci 1992;3:395–405.
10.
Marks DL, Smith MS, Vrontakis M, Clifton DK, Steiner RA: Regulation of galanin gene expression in gonadotropin-releasing hormone neurons during the estrous cycle of the rat. Endocrinology 1993;132:1836–1844.
11.
Marks DL, Lent KL, Rossmanith WG, Clifton DK, Steiner RA: Activation-dependent regulation of galanin gene expression in gonadotropin-releasing hormone neurons in the female rat. Endocrinology 1994;134:1991–1998.
12.
Rossmanith WG, Marks DL, Steiner RA, Clifton DK: Inhibition of steroid-induced galanin mRNA expression in GnRH neurons by a specific NMDA-receptor blockade. J Neuroendocrinol 1996;8:179–184.
13.
Finn PD, Steiner RA, Clifton DK: Temporal patterns of gonadotropin-releasing hormone (GnRH), c-fos, and galanin gene expression in GnRH neurons relative to the luteinizing hormone surge in the rat. J Neurosci 1998;18:713–719.
14.
Hulting AL, Meister B, Carlsson L, Hilding A, Isaksson O: On the role of the peptide galanin in regulation of growth hormone secretion. Acta Endocrinol (Copenh) 1991;125:518–525.
15.
Carey DG, Iismaa P, Ho KY, Rajkovic IA, Kelly J, Kraegen E, Ferguson J, Inglis AS, Shrine J, Chisholm DJ: Potent effects of human galanin in man: Growth hormone secretion and vagal blockade. J Clin Endocrinol Metab 1993;77:90–93.
16.
Arvat E, Gianott L, Ramunni J, Grottoli S, Brossa PC, Bertagna A, Camanni F, Ghigo E: Effect of galanin on basal and stimulated secretion of prolactin, gonadotropins, thyrotropin, adrenocorticotropin and cortisol in humans. Eur J Endocrinol 1995;133:300–304.
17.
Giustina A, Gastaldi C, Bugari G, Chiesa L, Loda G, Tironi C, Negro-Vilar A: Role of galanin in the regulation of somatotrope and gonadotrope function in young ovulatory women. Metabolism 1995;44:1028–1032.
18.
Silverman A-J, Livne I, Witkin JW: The gonadotropin-releasing hormone (GnRH), neuronal systems: Immunocytochemistry and in situ hybridization; in Knobil E, Neill JD (eds): The Physiology of Reproduction. New York, Raven Press, 1994, pp 1683–1709.
19.
Plant TM, Krey LC, Moossy J, McCormack JT, Hess DL, Knobil E: The arcuate nucleus and the control of gonadotropin and prolactin secretion in the female rhesus monkey (Macaca mulatta). Endocrinology 1978;102:52–62.
20.
Krey LC, Butler WR, Knobil E: Surgical disconnection of the medial basal hypothalamus and pituitary function in the rhesus monkey. I. Gonadotropin secretion. Endocrinology 1975;96:1073–1087.
21.
Rance NE, Young WS III, McMullen NT: Topography of neurons expressing luteinizing hormone-releasing hormone gene transcripts in the human hypothalamus and basal forebrain. J Comp Neurol 1994;339:573–586.
22.
Quanbeck C, Sherwood NM, Millar RP, Terasawa E: Two populations of luteinizing hormone-releasing hormone neurons in the forebrain of the rhesus macaque during embryonic development. J Comp Neurol 1997;380:293–309.
23.
Lescheid DW, Terasawa E, Abler LA, Urbanski HF, Warby CM, Millar RP, Sherwood NM: A second form of gonadotropin-releasing hormone (GnRH) with characteristics of chicken GnRH-II is present in the primate brain. Endocrinology 1997;138:5618–5629.
24.
Urbanski HF, White RB, Fernald RD, Kohama SG, Garyfallou VT, Densmore VS: Regional expression of mRNA encoding a second form of gonadotropin-releasing hormone in the macaque brain. Endocrinology 1999;140:1945–1958.
25.
Karsch FJ, Dierschke DJ, Weick RF, Yamaji T, Hotchkiss J, Knobil E: Positive and negative feedback control by estrogen of luteinizing hormone secretion in the rhesus monkey. Endocrinology 1973;92:799–804.
26.
Pau K-YF, Hess DL, Kaynard AH, Ji W-Z, Glissman PM, Spies HG: Suppression of mediobasal hypothalamic gonadotropin-releasing hormone and plasma luteinizing hormone pulsatile patterns by phentolamine in ovariectomized rhesus macaques. Endocrinology 1989;124:891–898.
27.
Pau K-YF, Berria M, Hess DL, Spies HG: Preovulatory gonadotropin-releasing hormone surge in ovarian-intact rhesus macaques. Endocrinology 1993;133:1650–1656.
28.
Adelman JP, Mason AJ, Hayflick JS, Seeburg PH: Isolation of the gene and hypothalamic cDNA for the common precursor of gonadotropin-releasing hormone and prolactin release-inhibiting factor in human and rat. Proc Natl Acad Sci USA 1986;83:179–183.
29.
Braissant O, Wahli W: A simplified in situ hybridization protocol using non-radioactively labeled probes to detect abundant and rare mRNAs on tissue sections. Biochemica 1998;1:10–16.
30.
Pau K-YF, Spies HG: Effects of cupric acetate on hypothalamic gonadotropin-releasing hormone release in intact and ovariectomized rabbits. Neuroendocrinology 1986;43:197–204.
31.
Ellinwood WE, Resko JA: Sex differences in biologically active and immunoreactive gonadotropins in the fetal circulation of rhesus monkeys. Endocrinology 1980;107:902–907.
32.
Baratta M, Saleri R, Mascadri C, Coy DH, Negro-Vilar A, Tamanini C, Giustina A: Modulation by galanin of growth hormone and gonadotropin secretion from perifused pituitary and median eminence of prepubertal male calves. Neuroendocrinology 1997;66:271–277.
33.
Marshall PE, Goldsmith PC: Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon. Brain Res 1980;193:353–372.
34.
Goldsmith PC, Thind KK, Song T, Kim EJ, Boggan JE: Location of the neuroendocrine gonadotropin-releasing hormone neurons in the monkey hypothalamus by retrograde tracing and immunostaining. J Neuroendocrinol 1990;2:157–168.
35.
Woller MJ, Terasawa E: Infusion of neuropeptide Y into the stalk-median eminence stimulates in vivo release of luteinizing hormone-release hormone in gonadectomized rhesus monkeys. Endocrinology 1991;128:1144–1150.
36.
Pau K-YF, Berria M, Hess DL, Spies HG: Hypothalamic site-dependent effects of neuropeptide Y on gonadotropin-releasing hormone secretion in rhesus macaques. J Neuroendocrinol 1995;7:63–67.
37.
Silverman AJ, Antunes JL, Abrams GM, Nilaver G, Thau R, Robinson JA, Ferin M, Krey LC: The luteinizing hormone releasing hormone pathways in rhesus (Macaca mulatta) and pigtailed (Macaca nemestrina) monkeys: New observations on thick, unembedded sections. J Comp Neurol 1982;211:309–317.
38.
Standish LJ, Adams LA, Vician L, Clifton DK, Steiner RA: Neuroanatomical localization of cells containing gonadotropin-releasing hormone messenger ribonucleic acid in the primate brain by in situ hybridization histochemistry. Mol Endocrinol 1987;1:371–376.
39.
Terasawa E, Sherwood NM, Millar RP, Jennes L, Glucksman MJ: The presence of a luteinizing hormone releasing hormone (LHRH) fragment in the fetal monkey forebrain. 79th Annual Meeting of the Endocrine Society, Minneapolis, Minnesota, USA, 1997, pp 380.
40.
Evans HF, Huntley GW, Morrison JH, Shine J: Localisation of mRNA encoding the protein precursor of galanin in the monkey hypothalamus and basal forebrain. J Comp Neurol 1993;328:203–212.
41.
Kordower JH, Mufson EJ: Galanin-like immunoreactivity within the primate basal forebrain: Differential staining patterns between human and monkeys. J Comp Neurol 1990;294:281–292.
42.
Walker LC, Rance NE, Price DL, Young WS III: Galanin mRNA in the nucleus basalis of Meynert complex of baboons and humans. J Comp Neurol 1991;303:113–120.
© 2000 S. Karger AG, Basel
2000
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.