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GPR54 and KiSS-1: Role in the regulation of puberty and reproduction

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Abstract

The finding of inactivating mutations in GPR54 in IHH patients and the lack of reproductive maturation of the GPR54 null mouse have uncovered a previously unrecognized role for GPR54 and KiSS-1 in the physiologic regulation of puberty and reproduction. This newly identified function for GPR54 and its cognate ligand, kisspeptin, has led to additional studies that have localized GPR54 and KiSS-1 mRNA in the hypothalamus, colocalized GPR54 in GnRH neurons, demonstrated GnRH-dependent activation of LH and FSH release by kisspeptin, and shown increased hypothalamic KiSS-1 and GPR54 mRNA levels at the time of puberty. Taken together, these findings establish the role of the kisspeptin-GPR54 system in the stimulation of GnRH neurons during puberty. The mechanisms by which kisspeptin activates GnRH release, as well as the trigger for this pathway at the onset of puberty, are yet to be elucidated. In the future, modulators of GPR54 activity, including kisspeptin, may prove valuable in clinical applications in the fields of both cancer therapy and reproductive medicine.

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Acknowledgments

This work was supported by the NICHD/NIH through cooperative agreement U54 HD28138 as part of the Specialized Cooperative Centers Program in Reproduction Research (U.B.K.), and by the ASRM–NICHD Reproductive Scientist Development Program Fellowship 5K12 HD00849 (W.K.).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, MA, 02118, USA

    Wendy Kuohung

  2. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA

    Wendy Kuohung & Ursula B. Kaiser

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  1. Wendy Kuohung
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  2. Ursula B. Kaiser
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Correspondence to Ursula B. Kaiser.

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Kuohung, W., Kaiser, U.B. GPR54 and KiSS-1: Role in the regulation of puberty and reproduction. Rev Endocr Metab Disord 7, 257–263 (2006). https://doi.org/10.1007/s11154-006-9020-2

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  • DOI: https://doi.org/10.1007/s11154-006-9020-2

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