Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men
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Published version
Author(s)
Type
Journal Article
Abstract
study question: How potently does the novel hypothalamic stimulator of reproduction, kisspeptin, increase gonadotrophin secretion
when compared with GnRH in healthy men?
summaryanswer: At the doses tested, intravenous administration of either of two major kisspeptin isoforms, kisspeptin-10 and -54, was
associated with similar levels of gonadotrophin secretion in healthy men; however, GnRH was more potent when compared with either kisspeptin
isoform.
what is known already: Kisspeptin-10 and -54 are naturally occurring hormones in the kisspeptin peptide family which potently stimulates
endogenous GnRH secretion from the hypothalamus, so have the potential to treat patients with reproductive disorders. Rodent studies
suggest that kisspeptin-54 is more potent when compared with kisspepitn-10; however, their effects have not previously been directly compared
in humans, or compared with direct pituitary stimulation of gonadotrophin secretion using GnRH.
study design, size and duration: A single-blinded placebo controlled physiological study was performed from January to December
2013. Local ethical approval was granted, and five participants were recruited to each dosing group.
participants/materials, setting, methods: Healthy men were administered vehicle, kisspeptin-10, kisspeptin-54 and
GnRH intravenously for 3 h on different study days. Each hormone was administered at 0.1, 0.3 and 1.0 nmol/kg/h doses (n ¼ 5 subjects per
group). Regular blood sampling was conducted throughout the study to measure LH and FSH. Study visits were conducted at least a week apart.
main results and the role of chance: Serum LH and FSH levels were 3-fold higher during GnRH infusion when compared
with kisspeptin-10 and 2-fold higher when compared with kisspeptin-54 [mean area under the curve serum LH during infusion (in hours times
international units per litre, h.IU/l): 10.81+1.73, 1.0 nmol/kg/h kisspeptin-10; 14.43+1.27, 1.0 nmol/kg/h kisspeptin-54; 34.06+5.18,
1.0 nmol/kg/h GnRH, P , 0.001 versus kisspeptin-10, P , 0.01 versus kisspeptin-54].
limitations, reasons for caution: This study had a small sample size.
wider implications of the findings: Kisspeptin offers a novel means of stimulating the reproductive axis. Our data suggest that
kisspeptin stimulates gonadotrophin secretion less potently when compared with GnRH; however, kisspeptin may stimulate gonadotrophins in a
more physiological manner when compared with current therapies. Kisspeptin is emerging as a future therapeutic agent, so it is important to establish
which kisspeptin hormones could be used to treat patients with infertility. Results of this study suggest that either isoform has similar effects
on reproductive hormone secretion in healthy men when administered intravenously.
when compared with GnRH in healthy men?
summaryanswer: At the doses tested, intravenous administration of either of two major kisspeptin isoforms, kisspeptin-10 and -54, was
associated with similar levels of gonadotrophin secretion in healthy men; however, GnRH was more potent when compared with either kisspeptin
isoform.
what is known already: Kisspeptin-10 and -54 are naturally occurring hormones in the kisspeptin peptide family which potently stimulates
endogenous GnRH secretion from the hypothalamus, so have the potential to treat patients with reproductive disorders. Rodent studies
suggest that kisspeptin-54 is more potent when compared with kisspepitn-10; however, their effects have not previously been directly compared
in humans, or compared with direct pituitary stimulation of gonadotrophin secretion using GnRH.
study design, size and duration: A single-blinded placebo controlled physiological study was performed from January to December
2013. Local ethical approval was granted, and five participants were recruited to each dosing group.
participants/materials, setting, methods: Healthy men were administered vehicle, kisspeptin-10, kisspeptin-54 and
GnRH intravenously for 3 h on different study days. Each hormone was administered at 0.1, 0.3 and 1.0 nmol/kg/h doses (n ¼ 5 subjects per
group). Regular blood sampling was conducted throughout the study to measure LH and FSH. Study visits were conducted at least a week apart.
main results and the role of chance: Serum LH and FSH levels were 3-fold higher during GnRH infusion when compared
with kisspeptin-10 and 2-fold higher when compared with kisspeptin-54 [mean area under the curve serum LH during infusion (in hours times
international units per litre, h.IU/l): 10.81+1.73, 1.0 nmol/kg/h kisspeptin-10; 14.43+1.27, 1.0 nmol/kg/h kisspeptin-54; 34.06+5.18,
1.0 nmol/kg/h GnRH, P , 0.001 versus kisspeptin-10, P , 0.01 versus kisspeptin-54].
limitations, reasons for caution: This study had a small sample size.
wider implications of the findings: Kisspeptin offers a novel means of stimulating the reproductive axis. Our data suggest that
kisspeptin stimulates gonadotrophin secretion less potently when compared with GnRH; however, kisspeptin may stimulate gonadotrophins in a
more physiological manner when compared with current therapies. Kisspeptin is emerging as a future therapeutic agent, so it is important to establish
which kisspeptin hormones could be used to treat patients with infertility. Results of this study suggest that either isoform has similar effects
on reproductive hormone secretion in healthy men when administered intravenously.
Date Issued
2015-06-18
Date Acceptance
2015-05-22
Citation
Human Reproduction, 2015, 30 (8), pp.1934-1941
ISSN
1460-2350
Publisher
Oxford University Press (OUP)
Start Page
1934
End Page
1941
Journal / Book Title
Human Reproduction
Volume
30
Issue
8
Copyright Statement
© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse,
distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse,
distribution, and reproduction in any medium, provided the original work is properly cited.
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Published