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.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Johnson
Marlie A
MA
Department of Biology and Program in Neuroscience, Hope College, Holland, Mich 49423, USA.
Fraley
Gregory S
GS
D000818:Animals; D005640:Follicle Stimulating Hormone / Q000097:blood; D015870:Gene Expression; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007276:Injections, Intraventricular; D059648:Kisspeptins; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009479:Neuropeptides / Q000008:administration & dosage / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects*
C491406:Kiss1 protein, rat; D059648:Kisspeptins; D009292:Narcotic Antagonists; D009479:Neuropeptides; D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; D011506:Proteins; C416987:RFamide peptide; D012333:RNA, Messenger; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide