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Published-Ahead-of-Print December 8, 2005, DOI:10.2164/jandrol.05144

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Role of Metastin in the Release of Gonadotropin Releasing Hormone from the Hypothalamus of the Male Rat

Stanley J. Nazian *

* To whom correspondence should be addressed. E-mail: snazian{at}hsc.usf.edu .

Recent genetic analysis has suggested that the expression of the orphan receptor GPR54 is essential for the onset of puberty in both rodents and humans. Indirect evidence has suggested that this action is via gonadotropin releasing hormone induction of luteinizing hormone release. The experiments described here were intended to provide direct evidence that metastin, the naturally occurring ligand for GPR54 was capable of stimulating GnRH secretion by examining GnRH release from an immortalized hypothalamic cell line (GT1-7) and from male rat hypothalamic explants. GT1-7 cells were treated for 21/2 hours and overnight with the biologically active fragment of metastin, metastin(45-54) in amounts ranging from 0.1 nM through 1 µM. Hypothalamic fragments were obtained from infantile male rats and exposed to progressively increasing concentrations of metastin(45-54) (0.1nM through 1µM) for one hour periods. In both experiments GnRH release was measured by RIA. The release of metastin from hypothalami obtained from infantile and adult male rats was also determined. Explants were incubated for 6 hours and the release of metastin into the media determined by RIA. The results support the hypothesis that metastin stimulates GnRH secretion from the hypothalamus. The data indicate that an increase in the secretion of metastin, rather than the appearance of the receptor that is required for puberty onset. The results also suggest that metastin influences the GnRH secreting neurons indirectly via an interneuron rather than acting directly on the GnRH secreting neurons.





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