Background: A number of peptides regulate luteinizing hormone (LH) release. In some cases, these peptides exert an effect at the pituitary, to directly regulate LH release and/or to modulate the effects of gonadotropin-releasing hormone (GnRH). A link between nutrition and reproductive function is well established. In this study we investigated the effects of two peptides associated with appetite control, galanin and leptin, on the regulation of LH release from the pituitary. Methods: Using perifused anterior pituitary tissue from freely fed rats, we investigated the effect of galanin on basal LH release and GnRH-stimulated LH release from pituitaries in a high-estrogen (proestrus) and a low-estrogen (metestrus) environment. In addition, we examined the effect of galanin on LH release following GnRH self-priming. The effect of inhibiting protein synthesis, with cycloheximide, was also studied under these conditions. Finally, the effects of leptin alone and on a galanin-modulated LH response were investigated. Results: There was no detectable effect of leptin, either alone or in conjunction with galanin. We observed that galanin enhanced GnRH stimulation of LH secretion, an effect that was dependent on protein synthesis and on an estrogenized environment. In addition, importantly, galanin also enhanced the LH response in GnRH self-primed pulses. Conclusion: Our results provide further details on the effect of galanin on the LH surge, particularly the effect on the response to pulsatile GnRH and the effect of protein production, and thereby indicate a means by which appetite- and nutrition-related peptides may act on the ovulatory cycle at the pituitary.

1.
Cameron JL, Helmreich DL, Schreihofer DA: Modulation of reproductive hormone secretion by nutritional intake: stress signals versus metabolic signals. Hum Reprod 1993;8(suppl 2):162–167.
2.
Wade GN, Schneider JE: Metabolic fuels and reproduction in female mammals. Neurosci Behav Rev 1992;16:235–272.
3.
Pettigrew R, Hamilton-Fairley D: Obesity and female reproductive function. Br Med Bull 1997;53:341–358.
4.
Stafford DE: Altered hypothalamic-pituitary-ovarian axis function in young female athletes: implications and recommendations for management. Treat Endocrinol 2005;4:147–154.
5.
Warren MP, Perlroth NE: The effects of intense exercise on the female reproductive system. J Endocrinol 2001;170:3–11.
6.
Halford JC: Pharmacology of appetite suppression: implication for the treatment of obesity. Curr Drug Targets 2001;2:353–370.
7.
Yuan CS, Dey L, Xie JT, Aung HH: Gastric effects of galanin and its interaction with leptin on brainstem neuronal activity. J Pharmacol Exp Ther 2002;301:488–493.
8.
Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F: Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995;269:540–543.
9.
Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM: Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543–546.
10.
Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P: Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995;269:546–549.
11.
Bray GA, York DA: The MONA LISA hypothesis in the time of leptin. Recent Prog Horm Res 1998;53:95–118.
12.
Pico C, Oliver P, Sanchez J, Palou A: Gastric leptin: a putative role in the short-term regulation of food intake. Br J Nutr 2003;90:735–741.
13.
Evans JJ: Modulation of gonadotropin levels by peptides acting at the anterior pituitary gland. Endocr Rev 1999;20:46–67.
14.
Evans JJ, Robinson G, Catt KJ: The luteinizing hormone response to oxytocin is steroid-dependent. Neuroendocrinology 1992;55:538–543.
15.
Lopez FJ, Merchenthaler I, Ching M, Wisniewski MG, Negro-Vilar A: Galanin: A hypothalamic-hypophysiotropic hormone modulating reproductive functions. Proc Natl Acad Sci USA 1991;88:4508–4512.
16.
Brann DW, Chorich LP, Mahesh VB: Effect of progesterone on galanin mRNA levels in the hypothalamus and the pituitary: correlation with the gonadotropin surge. Neuroendocrinology 1993;58:531–538.
17.
Kaplan LM, Gabriel SM, Koenig JI, Sunday ME, Spindel ER, Martin JB, Chin WW: Galanin is an estrogen-inducible, secretory product of the rat anterior pituitary. Proc Natl Acad Sci USA 1988;85:7408–7412.
18.
Hemmer A, Hyde JF: Regulation of galanin secretion from pituitary cells in vitro by estradiol and GnRH. Peptides 1992;13:1201–1206.
19.
Waters SM, Krause JE: Distribution of galanin-1, -2 and -3 receptor messenger RNAs in central and peripheral rat tissues. Neuroscience 2000;95:265–271.
20.
Moore JP, Cai A, Maley BE, Jennes L, Hyde JF: Galanin within the normal and hyperplastic anterior pituitary gland: localization, secretion, and functional analysis in normal and human growth hormone-releasing hormone transgenic mice. Endocrinology 1999;140:1789–1799.
21.
Crawley JN: Biological actions of galanin. Regul Pept 1995;59:1–16.
22.
Zieba DA, Amstalden M, Williams GL: Regulatory roles of leptin in reproduction and metabolism: a comparative review. Domest Anim Endocrinol 2005;29:166–185.
23.
Akhter N, Johnson BW, Crane C, Iruthayanathan M, Zhou YH, Kudo A, Childs GV: Anterior pituitary leptin expression changes in different reproductive states: in vitro stimulation by gonadotropin-releasing hormone. J Histochem Cytochem 2007;55:151–166.
24.
Popovic V, Damjanovic S, Dieguez C, Casanueva FF: Leptin and the pituitary. Pituitary 2001;4:7–14.
25.
Barash IA, Cheung CC, Weigle DS, Ren H, Kabigting EB, Kuijper JL, Clifton DK, Steiner RA: Leptin is a metabolic signal to the reproductive system. Endocrinology 1996;137:3144–3147.
26.
Yu WH, Kimura M, Walczewska A, Karanth S, McCann SM: Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci USA 1997;94:1023–1028; erratum in Proc Natl Acad Sci USA 1997;94:11108.
27.
Lloyd RV, Jin L, Tsumanuma I, Vidal S, Kovacs K, Horvath E, Scheithauer BW, Couce ME, Burguera B: Leptin and leptin receptor in anterior pituitary function. Pituitary 2001;4:33–47.
28.
Morash BA, Imran A, Wilkinson D, Ur E, Wilkinson M: Leptin receptors are developmentally regulated in rat pituitary and hypothalamus. Mol Cell Endocrinol 2003;210: 1–8.
29.
Teirmaa T, Luukkaa V, Rouru J, Koulu M, Huupponen R: Correlation between circulating leptin and luteinizing hormone during the menstrual cycle in normal-weight women. Eur J Endocrinol 1998;139:190–194.
30.
Cella F, Giordano G, Cordera R: Serum leptin concentrations during the menstrual cycle in normal-weight women: effects of an oral triphasic estrogen-progestin medication. Eur J Endocrinol 2000;142:174–178.
31.
Evans JJ, Pragg FL, Mason DR: Release of luteinizing hormone from the anterior pituitary in vitro can be concurrently regulated by at least three peptides: gonadotropin-releasing hormone, oxytocin and neuropeptide Y. Neuroendocrinology 2001;73:408–416.
32.
McIntosh RP, McIntosh JEA: Dynamic characteristics of luteinizing hormone release from perifused sheep anterior pituitary cells stimulated by combined pulsatile and continuous gonadotropin-releasing hormone. Endocrinology 1985;117:169–179.
33.
De Biasi SN, Apfelbaum LI, Apfelbaum ME: In vitro effect of leptin on LH release by anterior pituitary glands from female rats at the time of spontaneous and steroid-induced LH surge. Eur J Endocrinol 2001;145:659–665.
34.
Tezuka M, Irahara M, Ogura K, Kiyokawa M, Tamura T, Matsuzaki T, Yasui T, Aono T: Effects of leptin on gonadotropin secretion in juvenile female rat pituitary cells. Eur J Endocrinol 2002;146:261–266.
35.
Speight A, Fink G: Changes in responsiveness of dispersed pituitary cells to luteinizing hormone releasing hormone at different times of the oestrous cycle of the rat. J Endocrinol 1981;89:129–134.
36.
Speight A, Popkin R, Watts AG, Fink G: Oestradiol-17β increases pituitary responsiveness by a mechanism that involves the release and the priming effect of luteinizing hormone releasing factor. J Endocrinol 1981;88:301–308.
37.
Butcher RL, Collins WE, Fugo NW: Plasma concentration of LH, FSH, prolactin, progesterone and estradiol-17β throughout the 4-day estrous cycle of the rat. Endocrinology 1974;94:1704–1708.
38.
Turgeon JL, Waring DW: Rapid augmentation by progesterone of agonist-stimulated luteinizing hormone secretion by cultured pituitary cells. Endocrinology 1990;127:773–780.
39.
Leiva LA, Croxatto HB: Comparison of the effect of hypothalamic neuropeptides upon luteinizing hormone secretion by cultured rat anterior pituitary cells. Biol Res 1994;27:113–121.
40.
Splett CL, Scheffen JR, Desotelle JA, Plamann V, Bauer-Dantoin AC: Galanin enhancement of gonadotropin-releasing hormone-stimulated luteinizing hormone secretion in female rats is estrogen dependent. Endocrinology 2003;144:484–490.
41.
Smith JT, Clarke IJ: Kisspeptin expression in the brain: catalyst for the initiation of puberty. Rev Endocr Metab Disord 2007;8:1–9.
42.
Steel JH, Gon G, O’Halloran DJ, Jones PM, Yanaihara N, Ishikawa H, Bloom SR: Galanin and vasoactive intestinal polypeptide are colocalised with classical pituitary hormones and show plasticity of expression. Histochemistry 1989;93:183–189.
43.
Hammond PJ, Khandan-Nia N, Withers DJ, Jones PM, Ghatei MA, Bloom SR: Regulation of anterior pituitary galanin and vasoactive intestinal peptide by oestrogen and prolactin. J Endocrinol 1997;152:211–219.
44.
Turgeon JL, Waring DW: Acute progesterone and 17β-estradiol modulation of luteinizing hormone secretion by pituitaries of cycling rats superfused in vitro. Endocrinology 1981;108:413–419.
45.
Turgeon JL, Waring DW: cAMP augmentation of secretagogue-induced luteinizing hormone secretion. Am J Physiol 1986;250:E62–E68.
46.
Sánchez-Criado JE, Bellido C, Aguilar R, Garrido-Gracia JC: Antiprogestin RU486 blunts the stimulatory effect of galanin on LH secretion from rat pituitaries in vitro in an estrous cycle stage-dependent manner. Neurosci Lett 2001;305:73–75.
47.
Chappell PE, Schneider JS, Kim P, Xu M, Lydon JP, O’Malley BW, Levine JE: Absence of gonadotropin surges and gonadotropin-releasing hormone self-priming in ovariectomized, estrogen-treated, progesterone receptor knockout mice. Endocrinology 1999;140:3653–3658.
48.
Pickering AJMC, Fink G: Priming effect of luteinizing hormone releasing factor: in vitro and in vivo evidence consistent with its dependence upon protein and RNA synthesis. J Endocrinol 1976;69:373–379.
49.
Hurd SJ, Evans JJ, Mason DR: Oxytocin augmentation of gonadotropin-releasing hormone-stimulated luteinizing hormone release is modulated by cyclic AMP. Life Sci 1996;59:713–717.
50.
Barb CR, Barrett JB, Kraeling RR: Role of leptin in modulating the hypothalamic-pituitary axis and luteinizing hormone secretion in the prepuberal gilt. Domest Anim Endocrinol 2004;26:201–214.
51.
Ogura K, Irahara M, Kiyokawa M, Tezuka M, Matsuzaki T, Yasui T, Kamada M, Aono T: Effects of leptin on secretion of LH and FSH from primary cultured female rat pituitary cells. Eur J Endocrinol 2001;144:653–658.
52.
Gonzalez LC, Pinilla L, Tena-Sempere M, Dieguez C, Casanueva FF, Aguilar E: Effect of acute immunoneutralization of endogenous leptin on prolactin and LH secretion during the afternoon of pro-oestrus or in steroid-treated ovariectomized female rats. J Reprod Fertil 2000;118:39–45.
53.
Maciel MN, Zieba DA, Amstalden M, Keisler DH, Neves JP, Williams GL: Leptin prevents fasting-mediated reductions in pulsatile secretion of luteinizing hormone and enhances its gonadotropin-releasing hormone-mediated release in heifers. Biol Reprod 2004;70:229–235.
54.
Evans JJ, Hurd SJ, Mason DR: Oxytocin modulates the luteinizing hormone response of the rat anterior pituitary to gonadotrophin-releasing hormone in vitro. J Endocrinol 1995;145:113–119.
55.
Bray GA: The nutrient balance hypothesis: peptides, sympathetic activity, and food intake. Ann NY Acad Sci 1993;676:223–241.
56.
Billings LB, Spero JA, Vollmer RR, Amico JA: Oxytocin null mice ingest enhanced amounts of sweet solutions during light and dark cycles and during repeated shaker stress. Behav Brain Res 2006;171:134–141.
57.
Laughlin GA, Dominguez CE, Yen SS: Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 1998;83:25–32.
58.
Warren MP, Voussoughian F, Geer EB, Hyle EP, Adberg CL, Ramos RH: Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating. J Clin Endocrinol Metab 1999;84:873–877.
59.
Pirke KM, Schweiger U, Laessle R, Dickhaut B, Schweiger M, Waechtler M: Dieting influences the menstrual cycle: vegetarian versus nonvegetarian diet. Fertil Steril 1986;46:1083–1088.
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.