The Role of Kisspeptin and Neurokinin B Signaling in the Pubertal Increase in GnRH Release in Male Rhesus Monkeys

Presentation Number: OR19-2
Date of Presentation: April 4th, 2017

James P Garcia*1, Kim L Keen1, Lucille K. Kohlenberg1, William B. Lundeen1, Stephanie Beth Seminara2 and Ei Terasawa3
1University of Wisconsin-Madison, Madison, WI, 2Massachusetts General Hospital, Boston, MA, 3Univ of Wisconsin, Madison, WI


An increase in GnRH release is essential for the onset of puberty and signaling of kisspeptin and neurokinin B (NKB) greatly contributes to the pubertal increase in GnRH release in female rhesus monkeys. In the present study, we investigated whether kisspeptin and NKB signaling plays a role in puberty in male rhesus monkeys (prepubertal: 17.8 ± 2.6 months of age, n=4; pubertal: 34.2 ± 3.8 months of age, n=4). Using a microdialysis method, dialysates were continuously collected from the stalk-median eminence (S-ME) of the hypothalamus in 20-min fractions, while artificial CSF with or without kisspeptin and NKB agonists and antagonists were infused into the S-ME. GnRH concentrations in dialysates were measured by RIA. Results are summarized as follows. 1) Basal release of GnRH increased along with the progress of puberty; 2) kisspeptin 10 (0.1 and 1 µM) stimulated GnRH release in a dose-responsive manner; 3) the NKB agonist, senktide (0.1 and 10 µM), also stimulated GnRH release, but without dose-response; 4) while in prepubertal males the kisspeptin 10-induced GnRH release was blocked in the presence of the NKB antagonist, SB222200 (1 µM), in pubertal males the kisspeptin 10-induced GnRH release was delayed, but not blocked by the same dose of SB222200; and 5) in both prepubertal and pubertal males the senktide-induced GnRH release was blocked in the presence of the kisspeptin antagonist, peptide 234 (0.1 µM). These results are interpreted to mean that in males 1) while the pubertal increase in kisspeptin signaling is very important for the pubertal increase in GnRH release, the contribution of NKB signaling to the pubertal increase in GnRH release appears to be minimal and 2) if there is any NKB signaling to GnRH release, it is mediated through kisspeptin neurons. Interestingly, the results found in males are significantly different from those in females, as both kisspeptin and NKB signaling are involved in the pubertal increase in GnRH release and there are reciprocal pathways between kisspeptin signaling and NKB signaling to GnRH release in females. Whether the pubertal increase in androgens is involved in the kisspeptin and NKB signaling in males remains to be investigated.


Nothing to Disclose: JPG, KLK, LKK, WBL, SBS, ET