期刊
NEUROENDOCRINOLOGY
卷 102, 期 3, 页码 238-245出版社
KARGER
DOI: 10.1159/000439133
关键词
Kisspeptin; Novel therapies; Gonadotropin
资金
- Department of Health [CDF-2009-02-05] Funding Source: Medline
- Medical Research Council [G1000455] Funding Source: researchfish
- National Institute for Health Research [CDF-2009-02-05, ACF-2012-21-003] Funding Source: researchfish
- MRC [G1000455] Funding Source: UKRI
Over the last 10 years, kisspeptins-peptide products of varying lengths encoded by the KISS1 gene have been found to be key regulators of normal reproductive function throughout life in animals and humans. By activating the kisspeptin receptor [previously known as orphan G protein-coupled receptor 54 (GPR54)], they elicit an effect on the central gonadotropin-releasing hormone neurons. Administration of kisspeptin by either the subcutaneous or intravenous route potently stimulates endogenous gonadotropin hormone release in healthy men and women as well as in animals. Kisspeptin also stimulates endogenous release of gonadotropins in subfertile as well as healthy volunteers, and therefore it has potential as a novel therapeutic agent in reproductive disorders. Further human studies have shown that chronic, high-dose administration of kisspeptin causes desensitisation with rapid subsequent suppression of the hypothalamic-pituitary-gonadal axis, and therefore high-dose long-acting analogues may have a clinical role in treating sex hormone-dependent malignancies. By further elucidating the intricacies and mechanisms of the kisspeptin signalling system, and the tissues it acts on during different phases of the reproductive timeline (including during puberty, fertility, pregnancy and menopause), pharmacologic analogues could become clinically useful. (C) 2015 S. Karger AG, Basel
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