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Relaxin-3 stimulates the hypothalamic-pituitary-gonadal axis.

McGowan BM, Stanley SA, Donovan J, Thompson EL, Patterson M, Semjonous NM, Gardiner JV, Murphy KG, Ghatei MA, Bloom SR - Am. J. Physiol. Endocrinol. Metab. (2008)

Bottom Line: This effect was blocked by pretreatment with a peripheral GnRH antagonist.Central administration of human relaxin-2 showed no significant effect on plasma LH.H3 dose-dependently stimulated the release of GnRH from hypothalamic explants and GT(1)-7 cells, which express RXFP1 and RXFP3, but did not influence LH or follicle-stimulating hormone release from pituitary fragments in vitro.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Investigative Medicine, Division of Investigative Science, Imperial College London, Hammersmith Campus, Du Cane Road, London, UK.

ABSTRACT
The hypothalamus plays a key role in the regulation of both energy homeostasis and reproduction. Evidence suggests that relaxin-3, a recently discovered member of the insulin superfamily, is an orexigenic hypothalamic neuropeptide. Relaxin-3 is thought to act in the brain via the RXFP3 receptor, although the RXFP1 receptor may also play a role. Relaxin-3, RXFP3, and RXFP1 are present in the hypothalamic paraventricular nucleus, an area with a well-characterized role in the regulation of energy balance that also modulates reproductive function by providing inputs to hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Other members of the relaxin family are known to play a role in the regulation of reproduction. However, the effects of relaxin-3 on reproductive function are unknown. We studied the role of relaxin-3 in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. Intracerebroventricular (5 nmol) and intraparaventricular (540-1,620 pmol) administration of human relaxin-3 (H3) in adult male Wistar rats significantly increased plasma luteinizing hormone (LH) 30 min postinjection. This effect was blocked by pretreatment with a peripheral GnRH antagonist. Central administration of human relaxin-2 showed no significant effect on plasma LH. H3 dose-dependently stimulated the release of GnRH from hypothalamic explants and GT(1)-7 cells, which express RXFP1 and RXFP3, but did not influence LH or follicle-stimulating hormone release from pituitary fragments in vitro. We have demonstrated a novel role for relaxin-3 in the stimulation of the HPG axis, putatively via hypothalamic GnRH neurons. Relaxin-3 may act as a central signal linking nutritional status and reproductive function.

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Relaxin receptor expression in GT1-7 cells. Gel demonstrating PCR products following amplification with RXFP1-, RXFP3-, and RXFP4-specific primers of reverse transcribed GT1-7 cell RNA and murine genomic DNA as a control. L, ladder; RT+, reverse transcribed GT1-7 cell RNA; RT−, GT1-7 cell RNA without reverse transcriptase;, expected size of RXFP4 product;, expected size of RXFP1 and RXFP3 product; G, genomic DNA; W water.
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f7: Relaxin receptor expression in GT1-7 cells. Gel demonstrating PCR products following amplification with RXFP1-, RXFP3-, and RXFP4-specific primers of reverse transcribed GT1-7 cell RNA and murine genomic DNA as a control. L, ladder; RT+, reverse transcribed GT1-7 cell RNA; RT−, GT1-7 cell RNA without reverse transcriptase;, expected size of RXFP4 product;, expected size of RXFP1 and RXFP3 product; G, genomic DNA; W water.

Mentions: Reverse transcription of DNA extracted from GT1-7 cells followed by PCR demonstrated bands of the appropriate size for RXFP1 and RXFP3, but no band was identified following PCR for RXFP4. These results suggest that both RXFP1 and RXFP3 are expressed in GT1-7 cells and may be involved in mediating relaxin-3-stimulated GnRH release (Fig. 7).


Relaxin-3 stimulates the hypothalamic-pituitary-gonadal axis.

McGowan BM, Stanley SA, Donovan J, Thompson EL, Patterson M, Semjonous NM, Gardiner JV, Murphy KG, Ghatei MA, Bloom SR - Am. J. Physiol. Endocrinol. Metab. (2008)

Relaxin receptor expression in GT1-7 cells. Gel demonstrating PCR products following amplification with RXFP1-, RXFP3-, and RXFP4-specific primers of reverse transcribed GT1-7 cell RNA and murine genomic DNA as a control. L, ladder; RT+, reverse transcribed GT1-7 cell RNA; RT−, GT1-7 cell RNA without reverse transcriptase;, expected size of RXFP4 product;, expected size of RXFP1 and RXFP3 product; G, genomic DNA; W water.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2519759&req=5

f7: Relaxin receptor expression in GT1-7 cells. Gel demonstrating PCR products following amplification with RXFP1-, RXFP3-, and RXFP4-specific primers of reverse transcribed GT1-7 cell RNA and murine genomic DNA as a control. L, ladder; RT+, reverse transcribed GT1-7 cell RNA; RT−, GT1-7 cell RNA without reverse transcriptase;, expected size of RXFP4 product;, expected size of RXFP1 and RXFP3 product; G, genomic DNA; W water.
Mentions: Reverse transcription of DNA extracted from GT1-7 cells followed by PCR demonstrated bands of the appropriate size for RXFP1 and RXFP3, but no band was identified following PCR for RXFP4. These results suggest that both RXFP1 and RXFP3 are expressed in GT1-7 cells and may be involved in mediating relaxin-3-stimulated GnRH release (Fig. 7).

Bottom Line: This effect was blocked by pretreatment with a peripheral GnRH antagonist.Central administration of human relaxin-2 showed no significant effect on plasma LH.H3 dose-dependently stimulated the release of GnRH from hypothalamic explants and GT(1)-7 cells, which express RXFP1 and RXFP3, but did not influence LH or follicle-stimulating hormone release from pituitary fragments in vitro.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Investigative Medicine, Division of Investigative Science, Imperial College London, Hammersmith Campus, Du Cane Road, London, UK.

ABSTRACT
The hypothalamus plays a key role in the regulation of both energy homeostasis and reproduction. Evidence suggests that relaxin-3, a recently discovered member of the insulin superfamily, is an orexigenic hypothalamic neuropeptide. Relaxin-3 is thought to act in the brain via the RXFP3 receptor, although the RXFP1 receptor may also play a role. Relaxin-3, RXFP3, and RXFP1 are present in the hypothalamic paraventricular nucleus, an area with a well-characterized role in the regulation of energy balance that also modulates reproductive function by providing inputs to hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Other members of the relaxin family are known to play a role in the regulation of reproduction. However, the effects of relaxin-3 on reproductive function are unknown. We studied the role of relaxin-3 in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. Intracerebroventricular (5 nmol) and intraparaventricular (540-1,620 pmol) administration of human relaxin-3 (H3) in adult male Wistar rats significantly increased plasma luteinizing hormone (LH) 30 min postinjection. This effect was blocked by pretreatment with a peripheral GnRH antagonist. Central administration of human relaxin-2 showed no significant effect on plasma LH. H3 dose-dependently stimulated the release of GnRH from hypothalamic explants and GT(1)-7 cells, which express RXFP1 and RXFP3, but did not influence LH or follicle-stimulating hormone release from pituitary fragments in vitro. We have demonstrated a novel role for relaxin-3 in the stimulation of the HPG axis, putatively via hypothalamic GnRH neurons. Relaxin-3 may act as a central signal linking nutritional status and reproductive function.

Show MeSH
Related in: MedlinePlus