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Horm Metab Res 2014; 46(13): 927-832
DOI: 10.1055/s-0034-1387788
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Acute Fasting-Induced Repression of the Hypothalamic-Pituitary-Gonadal Axis is Reversed by RF-9 Administration in the Adult Male Macaque

A. Batool
1   Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
,
R. Naz
1   Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
,
M. Wazir
1   Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
,
A. Azam
1   Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
,
R. Ullah
1   Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
,
F. Wahab
2   Department of Physiology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan
,
M. Shahab
1   Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
› Author Affiliations
Further Information

Publication History

received 27 December 2013

accepted after second revision 05 August 2013

Publication Date:
02 September 2014 (online)

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Abstract

Recently, hypothalamic RFRP-3 (a mammalian ortholog of avian GnIH) signaling has been proposed as an important negative modulator of the reproductive axis. The current study examined whether repression of reproductive hormonal expression during short-term fasting conditions in higher-order primate is influenced by altered RFRP-3 signaling. Eight intact postpubertal male macaques (Macaca mulatta) were administered a single intravenous bolus of RF-9 (n=4), a potent and putative RFRP-3 receptor antagonist, or vehicle (n=4) following a 48-h fasting condition. Intermittent blood samples were collected every 30 min during the 4-h post-bolus period, and blood glucose, plasma cortisol, and testosterone concentrations were measured. Relative to fed conditions, fasting reduced glucose and testosterone levels (p<0.005) and increased cortisol levels (p<0.05). Relative to baseline, mean testosterone levels were elevated 150 min after RF-9 (p<0.05) but not vehicle administration. In addition, elevated mean plasma testosterone levels following RF-9 administration were equivalent to levels observed in normal fed monkeys. These results suggest an important role for RFRP-3 signaling in conveying metabolic state information to the reproductive axis in higher primates.

Key words

RFRP-3 - RF-9 - testosterone - GnIH - monkey - fasting
 

  • References

  • 1 Clarke IJ. Control of GnRH secretion: one step back. Front Neuroendocrinol 2011; 32: 367-375
    CrossrefPubMedGoogle Scholar
  • 2 Millar RP. GnRHs and GnRH receptors. Anim Reprod Sci 2005; 88: 5-28
    CrossrefPubMedGoogle Scholar
  • 3 Tsutsui K, Saigoh E, Ukena K, Teranishi H, Fujisawa Y, Kikuchi M, Ishii S, Sharp PJ. A novel avian hypothalamic peptide inhibiting gonadotropin release. Biochem Biophys Res Commun 2000; 275: 661-667
    CrossrefPubMedGoogle Scholar
  • 4 Rizwan MZ, Porteous R, Herbison AE, Anderson GM. Cells expressing RF-amide-related peptide-1/3, the mammalian gonadotropin-inhibitory hormone orthologs, are not hypophysiotropic neuroendocrine neurons in the rat. Endocrinology 2009; 150: 1413-1420
    CrossrefPubMedGoogle Scholar
  • 5 Kriegsfeld LJ, Mei DF, Bentley GE, Ubuka T, Mason AA, Inoue K, Ukena K, Tsutsui K, Silver R. Identification and characterization of a gonadotropin-inhibitory system in the brain of mammals. Proc Natl Acad Sci USA 2006; 103: 2410-2415
    CrossrefPubMedGoogle Scholar
  • 6 Clarke IJ, Sari IP, Qi Y, Smith JT, Parkington HC, Ubuka T, Iqbal J, Li Q, Tilbrook A, Morgan K, Pawson AJ, Tsutsui K, Millar RP, Bentley GE. Potent action of RF-amide-related peptide-3 on pituitary gonadotrops indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion. Endocrinology 2008; 149: 5811-5821
    CrossrefPubMedGoogle Scholar
  • 7 Hinuma S, Shintani Y, Fukusumi S, Iijima N, Matsumoto Y, Hosoya M, Fujii R, Watanabe T, Kikuchi K, Terao Y, Yano T, Yamamoto T, Kawamata Y, Habata Y, Asada M, Kitada C, Kurokawa T, Onda H, Nishimura O, Tanaka M, Ibata Y, Fujino M. New neuropeptides containing carboxy-terminal RF-amide and their receptor in mammals. Nat Cell Biol 2000; 2: 703-708
    CrossrefPubMedGoogle Scholar
  • 8 Ukena K, Ubuka T, Tsutsui K. Distribution of a novel avian gonadotropin-inhibitory hormone in the quail brain. Cell Tissue Res 2003; 312: 73-79
    PubMedGoogle Scholar
  • 9 Osugi T, Ukena K, Bentley GE, Obrien S, Moore IT, Wingfield JC, Tsutsui K. Gonadotropin inhibitory hormone in Gambel’s white-crowned sparrows: cDNA identification, transcript localization and functional effects in laboratory and field experiments. J Endocrinol 2004; 182: 33-42
    CrossrefPubMedGoogle Scholar
  • 10 Ukena K, Tsutsui K. Distribution of novel RF-amide-related peptide-like immunoreactivity in the mouse central nervous system. Neurosci Lett 2001; 300: 153-156
    CrossrefPubMedGoogle Scholar
  • 11 Ubuka T, Lai H, Kitani M, Suzuuchi A, Pham V, Cadigan PA, Wang A, Chowdhury VS, Tsutsui K, Bentley GE. Gonadotropin-inhibitory hormone identification, cDNA cloning, and distribution in rhesus macaque brain. J Comp Neurol 2009; 517: 841-855
    CrossrefPubMedGoogle Scholar
  • 12 Johnson MA, Tsutsui K, Fraley GS. Rat RF-amide-related peptide-3 stimulates GH secretion, inhibits LH secretion, and has variable effects on sex behavior in the adult male rat. Horm Behav 2007; 51: 171-180
    CrossrefPubMedGoogle Scholar
  • 13 Bentley GE, Perfito N, Ukena K, Tsutsui K, Wingfield JC. Gonadotropin-inhibitory peptide in song sparrows (Melospiza melodia) in different reproductive conditions, and in house sparrows (Passer domesticus) relative to chicken-gonadotropin releasing hormone. J Neuroendocrinol 2003; 15: 794-802
    CrossrefPubMedGoogle Scholar
  • 14 Smith JT, Coolen LM, Kriegsfeld LJ, Sari IP, Jaafarzadehshirazi MR, Maltby M, Bateman K, Goodman RL, Tilbrook AJ, Ubuka T, Bentley GE, Clarke IJ, Lehman MN. Variation in kisspeptin and RF-amide-related peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: a novel medium for seasonal breeding in the sheep. Endocrinology 2008; 149: 5770-5782
    CrossrefPubMedGoogle Scholar
  • 15 Qi Y, Oldfield BJ, Clarke IJ. Projections of RF-amide-related peptide-3 neurons in the ovine hypothalamus, with special reference to regions regulating energy balance and reproduction. J Neuroendocrinol 2009; 21: 690-697
    CrossrefPubMedGoogle Scholar
  • 16 Wu M, Dumalska I, Morozova E, van den Pol AN, Alreja M. Gonadotropin inhibitory hormone inhibits basal forebrain vGluT2-gonadotropin-releasing hormone neurons via a direct postsynaptic mechanism. J Physiol 2009; 587: 1401-1411
    CrossrefPubMedGoogle Scholar
  • 17 Bentley GE, Ubuka T, McGuire NL, Chowdhury VS, Morita Y, Yano T, Hasunuma I, Binns M, Wingfield JC, Tsutsui K. Gonadotropin inhibitory hormone and its receptor in the avian reproductive system. Gen Comp Endocrinol 2008; 156: 34-43
    CrossrefPubMedGoogle Scholar
  • 18 Ubuka T, Kim S, Huang YC, Reid J, Jiang J, Osugi T, Chowdhury VS, Tsutsui K, Bentley GE. Gonadotropin-inhibitory hormone neurons interact directly with gonadotropin-releasing hormone-I and -II neurons in European starling brain. Endocrinology 2008; 149: 268-278
    CrossrefPubMedGoogle Scholar
  • 19 Rizwan MZ, Poling MC, Corr M, Cornes PA, Augustine RA, Quennell JH, Kauffman AS, Anderson GM. RF-amide-related peptide-3 receptor gene expression in GnRH and kisspeptin neurons and GnRH-dependent mechanism of action. Endocrinology 2012; 153: 3770-3779
    CrossrefPubMedGoogle Scholar
  • 20 Zhao S, Zhu E, Yang C, Bentley GE, Tsutsui K, Kriegsfeld LJ. RF-amide-related peptide and messenger ribonucleic acid expression in mammalian testis: association with the spermatogenic cycle. Endocrinology 2010; 151: 617- 627
    CrossrefPubMedGoogle Scholar
  • 21 McGuire NL, Bentley GE. Neuropeptides in the gonads: from evolution to pharmacology. Front Pharmacol 2010; 114: 1-13
    PubMedGoogle Scholar
  • 22 Quennell JH, Rizwan MZ, Relf HL, Anderson GM. Developmental and steroidogenic effects on the gene expression of RF-amide related peptides and their receptor in the rat brain and pituitary gland. J Neuroendocrinol 2010; 22: 309-316
    CrossrefPubMedGoogle Scholar
  • 23 Kirby ED, Geraghty AC, Ubuka T, Bentley GE, Kaufer D. Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats. Proc Natl Acad Sci USA 2009; 106: 11324-11329
    CrossrefPubMedGoogle Scholar
  • 24 Ubuka T, Ukena K, Sharp PJ, Bentley GE, Tsutsui K. Gonadotropin-inhibitory hormone inhibits gonadal development and maintenance by decreasing gonadotropin synthesis and release in male quail. Endocrinology 2006; 147: 1187-1194
    CrossrefPubMedGoogle Scholar
  • 25 Bentley GE, Jensen JP, Kaur GJ, Wacker DW, Tsutsui K, Wingfield JC. Rapid inhibition of female sexual behavior by gonadotropin-inhibitory hormone (GnIH). Horm Behav 2006; 49: 550-555
    CrossrefPubMedGoogle Scholar
  • 26 Ciccone NA, Dunn IC, Boswell T, Tsutsui K, Ubuka T, Ukena K, Sharp PJ. Gonadotrophin inhibitory hormone depresses gonadotropin alpha and follicle-stimulating hormone beta subunit expression in the pituitary of the domestic chicken. J Neuroendocrinol 2004; 16: 999-1006
    CrossrefPubMedGoogle Scholar
  • 27 McGuire NL, Bentley GE. A functional neuropeptide system in vertebrate gonads: Gonadotropin-inhibitory hormone and its receptor in testes of field-caught house sparrow (Passer domesticus). Gen Comp Endocrinol 2010; 166: 565-572
    CrossrefPubMedGoogle Scholar
  • 28 Amano M, Moriyama S, Iigo M, Kitamura S, Amiya N, Yamamori K, Ukena K, Tsutsui K. Novel fish hypothalamic neuropeptides stimulate the release of gonadotropins and growth hormone from the pituitary of sockeye salmon. J Endocrinol 2006; 188: 417-423
    CrossrefPubMedGoogle Scholar
  • 29 Johnson MA, Fraley GS. Rat RFRP-3 alters hypothalamic GHRH expression and growth hormone secretion but does not affect KiSS-1 gene expression or the onset of puberty in male rats. J Neuroendocrinol 2008; 88: 305-315
    CrossrefPubMedGoogle Scholar
  • 30 Ubuka T, Inoue K, Fukuda Y, Mizuno T, Ukena K, Kriegsfeld LJ, Tsutsui K. Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone. Endocrinology 2012; 153: 373-385
    CrossrefPubMedGoogle Scholar
  • 31 Anderson GM, Relf HL, Rizwan MZ, Evans JJ. Central and peripheral effects of RF-amide-related peptide-3 on luteinizing hormone and prolactin secretion in rats. Endocrinology 2009; 150: 1834-1840
    CrossrefPubMedGoogle Scholar
  • 32 Ubuka T, Morgan K, Pawson AJ, Osugi T, Chowdhury VS, Minakata H, Tsutsui K, Millar RP, Bentley GE. Identification of human gonadotropin-inhibitory hormone homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis. PLoS One 2009; 4: e8400
    CrossrefPubMedGoogle Scholar
  • 33 Dubey AK, Cameron JL, Steiner RA, Plant TM. Inhibition of gonadotropin secretion in castrated male rhesus monkeys (Macaca mulatta) induced by dietary restriction: analogy with the pre-pubertal hiatus of gonadotropin release. Endocrinology 1986; 118: 518-525
    CrossrefPubMedGoogle Scholar
  • 34 Shahab M, Zaman W, Bashir K, Arslan M. Fasting induced suppression of hypothalamic-pituitary-gonadal axis in the adult rhesus monkey: evidence for involvement of excitatory amino acid neurotransmitters. Life Sci 1997; 61: 1293-1300
    CrossrefPubMedGoogle Scholar
  • 35 Wahab F, Aziz F, Irfan S, Zaman WU, Shahab M. Short-term fasting attenuates the response of the HPG axis to kisspeptin challenge in the adult male rhesus monkey (Macaca mulatta). Life Sci 2008; 83: 633-637
    CrossrefPubMedGoogle Scholar
  • 36 Wahab F, Ullah F, Chan YM, Seminara SB, Shahab M. Decrease in hypothalamus Kiss 1 and Kiss 1r expression: a potential mechanism for fasting-induced suppression of the HPG axis in the adult male rhesus monkey (Macaca mulatta). Horm Metab Res 2011; 43: 81-85
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Wahab F, Zaman WU, Shahab M. Differential response of the primate HPG-axis to N-methyl-D,L-aspartate, but not to kisspeptin challenge under euglycemic and hypoglycemic conditions. Horm Metab Res 2012; 44: 451-457
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Wahab F, Atika B, Shahab M. Kisspeptin as a link between metabolism and reproduction: Evidences from rodent and primate studies. Metabolism 2013; 62: 898-910
    CrossrefPubMedGoogle Scholar
  • 39 Cameron JL, Nosbisch C. Suppression of pulsatile luteinizing hormone and testosterone secretion during short term food restriction in the adult male rhesus monkey (Macaca mulatta). Endocrinology 1991; 128: 1532-1540
    CrossrefPubMedGoogle Scholar
  • 40 Chowdhury VS, Tomonaga S, Nishimura S, Tabata S, Cockrem JF, Tsutsui K, Furuse M. Hypothalamic gonadotropin inhibitory hormone precursor mRNA is increased during depressed food intake in heat-exposed chicks. Comp Biochem Physiol A Mol Integr Physiol 2012; 162: 227-233
    CrossrefPubMedGoogle Scholar
  • 41 Klingerman CM, Williams 3rd WP, Simberlund J, Brahme N, Prasad A, Schneider JE, Kriegsfeld LJ. Food Restriction-Induced Changes in Gonadotropin-Inhibiting Hormone Cells are Associated with Changes in Sexual Motivation and Food Hoarding, but not Sexual Performance and Food Intake. Front Endocrinol 2011; 101: 1-15
    PubMedGoogle Scholar
  • 42 Clarke IJ, Smith JT, Henry BA, Oldfield BJ, Stefanidis A, Millar RP, Sari IP, Chng K, Fabre-Nys C, Caraty A, Ang BT, Chan L, Fraley GS. Gonadotropin-inhibitory hormone is a hypothalamic peptide that provides a molecular switch between reproduction and feeding. Neuroendocrinology 2012; 95: 305-316
    CrossrefPubMedGoogle Scholar
  • 43 Simonin F, Schmitt M, Laulin JP, Laboureyras E, Jhamandas JH, Mac TD, Matifas A, Mollereau C, Laurent P, Parmentier M, Kieffer BL, Bourguignon JJ, Simonnet G. RF-9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyper algesia. Proc Natl Acad Sci USA 2006; 103: 466-471
    CrossrefPubMedGoogle Scholar
  • 44 Pineda R, Garcia-Galiano D, Sanchez-Garrido MA, Romero M, Ruiz-Pino F, Aguilar E, Dijcks FA, Blomenrohr M, Pinilla L, van Noort PI, Tena-Sempere M. Characterization of the potent gonadotropin activity of RF-9, a selective antagonist of RF-amide related peptides and neuropeptides FF receptors: physiological and pharmacological implications. Endocrinology 2010; 151: 1902-1913
    CrossrefPubMedGoogle Scholar
  • 45 Caraty A, Blomenrohr M, Vogel GM, Lomet D, Briant C, Beltramo M. RF-9 powerfully stimulates gonadotropin secretion in the ewe: evidence for a seasonal threshold of sensitivity. J Neuroendocrinol 2012; 24: 725-736
    CrossrefPubMedGoogle Scholar
  • 46 Wahab F, Bano R, Jabeen S, Irfan S, Shahab M. Effect of peripheral kisspeptin administration on adiponectin, leptin, and resistin secretion under fed and fasting condition in the adult male rhesus monkey (Macaca mulatta). Horm Metab Res 2010; 42: 570-574
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Wahab F, Atika B, Huma T, Shahab M. Primate HPT axis response to the peripheral kisspeptin challenge under different time periods of food restriction in monkeys. Horm Metab Res 2013; 46: 187-192
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Calisi RM, Rizzo NO, Bentley GE. Seasonal differences in hypothalamic EGR-1 and GnIH expression following capture-handling stress in house sparrows (Passer domesticus). Gen Comp Endocrinol 2008; 157: 283-287
    CrossrefPubMedGoogle Scholar
  • 49 Papargiris MM, Rivalland ET, Clarke IJ, Smith JT, Pereira A, Tilbrook AJ. Evidence that RF-amide related peptide-3 is not a mediator of the inhibitory effects of psychosocial stress on gonadotropin secretion in ovariectomised ewes. J Neuroendocrinol 2011; 23: 208-215
    CrossrefPubMedGoogle Scholar
  • 50 Handa RJ, Burgess LH, Kerr JE, O’Keefe JA. Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis. Horm Behav 1994; 28: 464-476
    CrossrefPubMedGoogle Scholar
  • 51 Tilbrook AJ, Clarke IJ. Neuroendocrine mechanisms of innate states of attenuated responsiveness of the hypothalamo-pituitary adrenal axis to stress. Front Neuroendocrinol 2006; 27: 285-307
    CrossrefPubMedGoogle Scholar
  • 52 Liu Q, Guan XM, Martin WJ, McDonald TP, Clements MK, Jiang Q, Zeng Z, Jacobson M, Williams Jr DL, Yu H, Bomford D, Figueroa D, Mallee J, Wang R, Evans J, Gould R, Austin CP. Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception. J Biol Chem 2001; 276: 36961-36969
    CrossrefPubMedGoogle Scholar
  • 53 Maletinska L, Ticha A, Nagelova V, Spolcova A, Blechova M, Elbert T, Zelezna B. Neuropeptide FF analog RF-9 is not an antagonist of NPFF receptor and decreases food intake in mice after its central and peripheral administration. Brain Res 2013; 8993: 1972-1975
    PubMedGoogle Scholar
  • 54 Smith JT, Young IR, Veldhuis JD, Clarke IJ. Gonadotropin inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system. Endocrinology 2012; 153: 3368-3375
    CrossrefPubMedGoogle Scholar
  • 55 Clarke IJ, Parkington HC. Gonadotropin inhibitory hormone (GnIH) as a regulator of gonadotrpes. Mol Cell Endocrinol 2013; 385: 36-44
    PubMedGoogle Scholar
  • 56 Sari IP, Rao A, Smith JT, Tilbrook AJ, Clarke IJ. Effect of RF-amide-related peptide-3 on luteinizing hormone and follicle-stimulating hormone synthesis and secretion in ovine pituitary gonadotrops. Endocrinology 2009; 150: 5549-5556
    CrossrefPubMedGoogle Scholar
  • 57 Kadokawa H, Shibata M, Tanaka Y, Kojima T, Matsumoto K, Oshima K, Yamamoto N. Bovine C-terminal octapeptide of RF-amide-related peptide-3 suppresses luteinizing hormone (LH) secretion from the pituitary as well as pulsatile LH secretion in bovines. Domest Anim Endocrinol 2009; 36: 219-224
    CrossrefPubMedGoogle Scholar
  • 58 Murakami M, Matsuzaki T, Iwasa T, Yasui T, Irahara M, Osugi T, Tsutsui K. Hypophysiotropic role of RF-amide-related peptide-3 in the inhibition of LH secretion in female rats. J Endocrinol 2008; 199: 105-112
    CrossrefPubMedGoogle Scholar
  • 59 Ducret E, Anderson GM, Herbison AE. RF-amide-related peptide-3, a mammalian gonadotropin-inhibitory hormone ortholog, regulates gonadotropin releasing hormone neuron firing in the mouse. Endocrinology 2009; 150: 2799-2804
    CrossrefPubMedGoogle Scholar
  • 60 Cooke JN, James VH, Landon J, Wynn V. Adrenocortical function in chronic malnutrition. Br Med J 1964; 1: 662-666
    CrossrefPubMedGoogle Scholar
  • 61 Kelly GS. Nutritional and botanical interventions to assist with the adaptation to stress. Altern Med Rev 1999; 4: 249-265
    PubMedGoogle Scholar
  • 62 Tsutsui K, Ubuka T, Bentley GE, Kriegsfeld LJ. Gonadotropin inhibitory hormone (GnIH): discovery, progress and prospect. Gen Comp Endocrinol 2012; 177: 305-314
    CrossrefPubMedGoogle Scholar
  • 63 Rivier C, Rivier J, Vale W. Stress-induced inhibition of reproductive functions: Role of endogenous corticotropin-releasing factor. Science 1986; 231: 607-609
    CrossrefPubMedGoogle Scholar
  • 64 Dubey AK, Plant TM. A suppression of gonadotropin secretion by cortisol in castrated male rhesus monkeys (Macaca mulatta) mediated by the interruption of hypothalamic gonadotropin releasing hormone release. Biol Reprod 1985; 33: 423-431
    CrossrefPubMedGoogle Scholar
  • 65 Sakakura M, Takebe K, Nakagawa S. Inhibition of luteinizing hormone secretion induced by synthetic LRH by long-term treatment with glucocorticoids in human subjects. J Clin Endocrinol Metab 1975; 40: 774-779
    CrossrefPubMedGoogle Scholar
  • 66 Soga T, Dalpatadu SL, Wong DW, Parhar IS. Neonatal dexamethasone exposure down-regulates GnRH expression through the GnIH pathway in female mice. Neuroscience 2012; 218: 56-64
    CrossrefPubMedGoogle Scholar
  • 67 Leonhardt S, Shahab M, Luft H, Wuttke W, Jarry H. Reduction of luteinzing hormone secretion induced by long-term feed restriction in male rats is associated with increased expression of GABA-synthesizing enzymes without alterations of GnRH gene expression. J Neuroendocrinol 1999; 11: 613-619
    PubMedGoogle Scholar
  • 68 Cameron JL, Helmreich DL, Schreihofer DA. Modulation of reproductive hormone secretion by nutritional intake: stress signals versus metabolic signals. Hum Reprod 1993; 2: 162-167
    PubMedGoogle Scholar