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GnRH(1-5), a metabolite of gonadotropin-releasing hormone, enhances luteinizing hormone release via activation of kisspeptin neurons in female rats.
- Source :
-
Endocrine journal [Endocr J] 2020 Apr 28; Vol. 67 (4), pp. 409-418. Date of Electronic Publication: 2020 Jan 15. - Publication Year :
- 2020
-
Abstract
- Accumulating evidence suggests that kisspeptin neurons in the arcuate nucleus (ARC), which coexpress neurokinin B and dynorphin, are involved in gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) pulse generation, while the anteroventral periventricular nucleus (AVPV) kisspeptin neurons are responsible for GnRH/LH surge generation. The present study aims to examine whether GnRH(1-5), a GnRH metabolite, regulates LH release via kisspeptin neurons. GnRH(1-5) was intracerebroventricularly injected to ovariectomized and estrogen-treated Wistar-Imamichi female rats. Immediately after the central GnRH(1-5) administration at 2 nmol, plasma LH concentration increased, resulting in significantly higher levels of the area under the curve and baseline of plasma LH concentrations compared to vehicle-injected controls. On the other hand, in Kiss1 knockout rats, GnRH(1-5) administration failed to affect LH secretion, suggesting that the facilitatory effect of GnRH(1-5) on LH release is mediated by kisspeptin neurons. Double in situ hybridization (ISH) for Kiss1 and Gpr101, a GnRH(1-5) receptor gene, revealed that few Kiss1-expressing cells coexpress Gpr101 in both ARC and AVPV. On the other hand, double ISH for Gpr101 and Slc17a6, a glutamatergic marker gene, revealed that 29.2% of ARC Gpr101-expressing cells coexpress Slc17a6. Further, most of the AVPV and ARC Kiss1-expressing cells coexpress Grin1, a gene encoding a subunit of NMDA receptor. Taken together, these results suggest that the GnRH(1-5)-GPR101 signaling facilitates LH release via indirect activation of kisspeptin neurons and that glutamatergic neurons may mediate the signaling. This provides a new aspect of kisspeptin- and GnRH-neuronal communication with the presence of stimulation from GnRH to kisspeptin neurons in female rats.
- Subjects :
- Animals
Arcuate Nucleus of Hypothalamus cytology
Arcuate Nucleus of Hypothalamus metabolism
Estradiol pharmacology
Estrogens pharmacology
Female
Gene Knockout Techniques
Hypothalamus, Anterior cytology
Hypothalamus, Anterior metabolism
In Situ Hybridization
Injections, Intraventricular
Kisspeptins pharmacology
Luteinizing Hormone metabolism
Nerve Tissue Proteins genetics
Ovariectomy
Rats
Rats, Transgenic
Receptors, G-Protein-Coupled genetics
Receptors, N-Methyl-D-Aspartate genetics
Vesicular Glutamate Transport Protein 2 genetics
Arcuate Nucleus of Hypothalamus drug effects
Gonadotropin-Releasing Hormone pharmacology
Hypothalamus, Anterior drug effects
Kisspeptins genetics
Luteinizing Hormone drug effects
Neurons metabolism
Peptide Fragments pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1348-4540
- Volume :
- 67
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Endocrine journal
- Publication Type :
- Academic Journal
- Accession number :
- 31941848
- Full Text :
- https://doi.org/10.1507/endocrj.EJ19-0444