Pyroglutamylated RFamide peptide 43 stimulates the hypothalamic-pituitary-gonadal axis via gonadotropin-releasing hormone in rats.
Although it is established that other members of the RFamide family stimulate the hypothalamic-pituitary-gonadal axis, the influence of the novel pyroglutamylated RFamide peptide 43 (QRFP43) is not known. We show intracerebroventricular (icv) administration of QRFP43 (2 nmol) to male rats increased plasma LH and FSH levels at 40 min after injection. icv administration of 3 nmol QRFP43 did not affect food intake in ad-libitum-fed male rats. The icv administration of 2 nmol QRFP43 did not significantly influence behavior in male rats. Intraperitoneal administration of doses up to 1200 nmol/kg QRFP43 in male rats did not significantly influence circulating gonadotropin or sex steroid levels. In vitro, QRFP43 stimulated GnRH release from hypothalamic explants from male rats and from GT1-7 cells. Pretreatment with a GnRH receptor antagonist, cetrorelix, blocked the increase in plasma LH levels after icv administration of QRFP43 (2 nmol). These results suggest that icv QRFP43 activates the hypothalamic-pituitary-gonadal axis via GnRH.
Department of Investigative Medicine, Hammersmith Hospital, Imperial College London, 6th Floor Commonwealth Building, Du Cane Road, London W12 0NN, United Kingdom.
Sejal R
SR
Patel
Kevin G
KG
Murphy
Emily L
EL
Thompson
Michael
M
Patterson
Annette E
AE
Curtis
Mohammad A
MA
Ghatei
Stephen R
SR
Bloom
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002478:Cells, Cultured; D004435:Eating / Q000187:drug effects; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006066:Gonads / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood
D006727:Hormone Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C511787:QRFP peptide; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C062876:cetrorelix