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Neuroendocrinology. 2008;88(4):305-15. doi: 10.1159/000145718. Epub 2008 Jul 15.

Rat RFRP-3 alters hypothalamic GHRH expression and growth hormone secretion but does not affect KiSS-1 gene expression or the onset of puberty in male rats.

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Department of Biology and Program in Neuroscience, Hope College, Holland, Mich 49423, USA.



RFRP-3 is a recently described neuropeptide that influences a variety of physiologic factors, including the inhibition of gonadotropin secretion and reproductive behaviors. We hypothesized that endogenous RFRP-3 could function to inhibit the onset of puberty in young male rats.


To test this hypothesis, we first placed cannulas into the third ventricle of 24-day-old male rat pups. The cannulas were attached to osmotic minipumps that infused antisense oligonucleotides (ODNs) against RFRP-3. Second, cannulas were placed in the ventricle of 35-day-old pups and infused with RFRP-3, NPFF (putatively, an alternative transcript of the RFRP gene), or vehicle.


No treatment altered the onset of puberty compared to controls. RFRP-3 ODN rats had significantly larger testes compared to control rats. Similarly, the RFRP-3 ODN-treated rats had a significant increase in plasma LH, but not FSH, compared to control rats. Rats infused with RFRP-3 exhibited significantly smaller testes compared to control rats. RFRP-3 rats also had a significant decrease in plasma LH levels. RFRP-3 infusion elicited a significant increase in growth hormone-releasing hormone mRNA and plasma growth hormone levels compared to control rats. Neither peptide had an effect on KiSS-1 mRNA expression.


These data suggest that endogenous rat RFRP-3 does not affect the timing of puberty in male rats but may be associated with peripubertal rise in growth hormone secretion.

[Indexed for MEDLINE]

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