The gonadotropin-releasing hormone family of neuropeptides in the brain of human, bovine and rat: Identification of a third isoform

Dror Yahalom, Alon Chen, Nurit Ben-Aroya, Shai Rahimipour, Ella Kaganovsky, Eli Okon, Mati Fridkin, Yitzhak Koch

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The mammalian gonadotropin-releasing hormone (GnRH-I), which regulates reproduction, was the first isoform of GnRH that was identified in mammals. Recently, we and others have demonstrated the existence of a second isoform of GnRH in the brain of mammals. The presence of a third isoform of GnRH, GnRH-III, in the brain of mammals is reported herein. GnRH-III, extracted from the brain of bovine and human, was purified by high performance liquid chromatography, using two distinct elution programs. In both, GnRH-III was eluted at the same positions as synthetic salmon GnRH, as demonstrated by radioimmunoassay. The luteinizing hormone-releasing activity of purified GnRH-III, using dispersed rat pituitary cells, was found to be similar to that of synthetic salmon GnRH. The total amount of GnRH-III, determined by radioimmunoassay, in the hypothalamus and midbrain of humans and calves is similar to that of GnRH-I. Immunohistochemical studies demonstrated GnRH-III- containing neurons in the hypothalamus and midbrain of human and GnRH-III fibers in the median eminence of rats. The distribution of GnRH-III in the brain suggests that in addition to a putative function as a neurohormone at the hypothalamic-pituitary axis, GnRH-III may have other functions. Our present results suggest that multiple isoforms of GnRH are present in the brain of mammals, and further studies are required in order to elucidate their biological functions.

Original languageEnglish
Pages (from-to)289-294
Number of pages6
JournalFEBS Letters
Issue number3
StatePublished - 17 Dec 1999
Externally publishedYes

Bibliographical note

Funding Information:
The authors wish to thank Drs. K. Okuzawa (National Research Institute of Aquaculture, Watarai, Japan) and Dr. K. Aida (Fish Physiology Research Group, Department of Aquatic Bioscience, University of Tokyo, Bunkyo, Tokyo, Japan), for supplying the antibodies for GnRH-II and sGnRH, respectively. This study was supported by the Israel Science Foundation administered by the Israel Academy of Sciences and Humanities.


  • Gonadotropin-releasing hormone, third isoform in mammalian brain
  • Gonadotropin-releasing hormone/luteinizing hormone-releasing hormone isoform
  • Salmon gonadotropin-releasing hormone-like peptide in mammals


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