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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: However, the effects of relaxin-3 on reproductive function are unknown.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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Effect of H3 (10, 100, and 1,000 nM) on stimulation of GnRH release from GT1-7 cells at 0–1 h (data shown as %basal release with basal serum-free medium indicated as 100%). *P < 0.05 and ***P < 0.001 vs. serum-free medium by ANOVA with post hoc Tukey's test, n = 10/group.
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f6: Effect of H3 (10, 100, and 1,000 nM) on stimulation of GnRH release from GT1-7 cells at 0–1 h (data shown as %basal release with basal serum-free medium indicated as 100%). *P < 0.05 and ***P < 0.001 vs. serum-free medium by ANOVA with post hoc Tukey's test, n = 10/group.

Mentions: The effect of increasing doses of H3 (10–1,000 nM) on GnRH release from GT1-7 cells was examined at 1 h. Exposure of GT1-7 cells to H3 resulted in an increase in GnRH release at 1 h that became highly significant at a concentration of 1,000 nM H3 [100 ± 10.1 basal vs. 247.2 ± 8.3 (1,000 nM H3), data shown as %basal, P < 0.001 vs. serum-free medium] (Fig. 6). The positive control (100 nM GLP-1) significantly increased GnRH release at 1 h [100 ± 10.1 basal vs. 154.9 ± 14.2 (100 nM GLP-1), P < 0.05] (Fig. 6).


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)

Effect of H3 (10, 100, and 1,000 nM) on stimulation of GnRH release from GT1-7 cells at 0–1 h (data shown as %basal release with basal serum-free medium indicated as 100%). *P < 0.05 and ***P < 0.001 vs. serum-free medium by ANOVA with post hoc Tukey's test, n = 10/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Effect of H3 (10, 100, and 1,000 nM) on stimulation of GnRH release from GT1-7 cells at 0–1 h (data shown as %basal release with basal serum-free medium indicated as 100%). *P < 0.05 and ***P < 0.001 vs. serum-free medium by ANOVA with post hoc Tukey's test, n = 10/group.
Mentions: The effect of increasing doses of H3 (10–1,000 nM) on GnRH release from GT1-7 cells was examined at 1 h. Exposure of GT1-7 cells to H3 resulted in an increase in GnRH release at 1 h that became highly significant at a concentration of 1,000 nM H3 [100 ± 10.1 basal vs. 247.2 ± 8.3 (1,000 nM H3), data shown as %basal, P < 0.001 vs. serum-free medium] (Fig. 6). The positive control (100 nM GLP-1) significantly increased GnRH release at 1 h [100 ± 10.1 basal vs. 154.9 ± 14.2 (100 nM GLP-1), P < 0.05] (Fig. 6).

Bottom Line: However, the effects of relaxin-3 on reproductive function are unknown.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