Kisspeptin Activation of Gonadotropin Releasing Hormone Neurons and Regulation of KiSS-1 mRNA in the Male Rat
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- 1 January 2004
- journal article
- research article
- Published by S. Karger AG in Neuroendocrinology
- Vol. 80 (4), 264-272
- https://doi.org/10.1159/000083140
Abstract
The KiSS-1 gene codes for a family of neuropeptides called kisspeptins which bind to the G-protein-coupled receptor GPR54. To assess the possible effects of kisspeptins on gonadotropin secretion, we injected kisspeptin-52 into the lateral cerebral ventricles of adult male rats and found that kisspeptin-52 increased the serum levels of luteinizing hormone (p < 0.05). To determine whether the kisspeptin-52-induced stimulation of luteinizing hormone secretion was mediated by gonadotropin-releasing hormone (GnRH), we pretreated adult male rats with a GnRH antagonist (acyline), then challenged the animals with intracerebroventricularly administered kisspeptin-52. The GnRH antagonist blocked the kisspeptin-52-induced increase in luteinizing hormone. To examine whether kisspeptins stimulate transcriptional activity in GnRH neurons, we administered kisspeptin-52 intracerebroventricularly and found by immunocytochemistry that 86% of the GnRH neurons coexpressed Fos 2 h after the kisspeptin-52 challenge, whereas fewer than 1% of the GnRH neurons expressed Fos following injection of the vehicle alone (p < 0.001). To assess whether kisspeptins can directly act on GnRH neurons, we used double-label in situ hybridization and found that 77% of the GnRH neurons coexpress GPR54 mRNA. Finally, to determine whether KiSS-1 gene expression is regulated by gonadal hormones, we measured KiSS-1 mRNA levels by single-label in situ hybridization in intact and castrated males and found significantly higher levels in the arcuate nucleus of castrates. These results demonstrate that GnRH neurons are direct targets for regulation by kisspeptins and that KiSS-1 mRNA is regulated by gonadal hormones, suggesting that KiSS-1 neurons play an important role in the feedback regulation of gonadotropin secretion.Keywords
This publication has 26 references indexed in Scilit:
- Peripheral administration of metastin induces marked gonadotropin release and ovulation in the ratBiochemical and Biophysical Research Communications, 2004
- TheGPR54Gene as a Regulator of PubertyNew England Journal of Medicine, 2003
- Cloning and Distribution of Galanin-Like Peptide mRNA in the Hypothalamus and Pituitary of the MacaqueEndocrinology, 2002
- The Metastasis Suppressor Gene KiSS-1 Encodes Kisspeptins, the Natural Ligands of the Orphan G Protein-coupled Receptor GPR54Journal of Biological Chemistry, 2001
- Stimulation Effect of Galanin-Like Peptide (GALP) on Luteinizing Hormone-Releasing Hormone-Mediated Luteinizing Hormone (LH) Secretion in Male RatsEndocrinology, 2001
- GnRH Antagonists: A New Generation of Long Acting Analogues Incorporatingp-Ureido-phenylalanines at Positions 5 and 6Journal of Medicinal Chemistry, 2000
- Distinct Functions of Gq and G11 Proteins in Coupling α1-Adrenoreceptors to Ca2+ Release and Ca2+ Entry in Rat Portal Vein MyocytesPublished by Elsevier BV ,1997
- Increased GnRH mRNA in the GnRH neurons expressing cFos during the proestrous LH surgeEndocrinology, 1995
- Identification of a Domain in the Angiotensin II Type 1 Receptor Determining Gq Coupling by the Use of Receptor ChimerasPublished by Elsevier BV ,1995
- Effects of neuropeptide Y, NPY analog (norleucine4-NPY), galanin and neuropeptide K on LH release in ovariectomized (ovx) and ovx estrogen, progesterone-treated ratsPeptides, 1987