2011
DOI: 10.1152/ajpendo.00517.2010
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Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat

Abstract: Neurokinin B (NKB) and its cognate receptor neurokinin 3 (NK3R) play a critical role in reproduction. NKB and NK3R are coexpressed with dynorphin (Dyn) and kisspeptin (Kiss1) genes in neurons of the arcuate nucleus (Arc). However, the mechanisms of action of NKB as a cotransmitter with kisspeptin and dynorphin remain poorly understood. We explored the role of NKB in the control of LH secretion in the female rat as follows. 1) We examined the effect of an NKB agonist (senktide, 600 pmol, administered into the l… Show more

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Cited by 232 publications
(268 citation statements)
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“…In turn, NKB may act on KNDy neurons to finely tune (predominantly, stimulate) kisspeptin release, therefore inducing GnRH secretion in an indirect manner. This possibility is, at least partially, supported by a solid body of experimental evidence, including the following observations: i) central senktide injection induces expression of C-fos in ARC KNDy neurons (34); ii) senktide elicits LH secretion in a GnRH-dependent manner (28); iii) the LH-releasing effects of senktide are not detected in the absence of proper Gpr54 signaling (35); iv) desensitization to the effects of continuous NKB stimulation takes place at a level upstream of GnRH neurons (28); v) substantial NK3R expression is detected in KNDy, but not GnRH neurons, in rodents and sheep (23); and vi) senktide induces the electrical activation of Kiss1 neurons, as revealed by electrophysiological recordings in Kiss1-CreGFP mice (40). To add further refinement to the system, the third partner of the KNDy trio, Dyn, has been long recognized as an inhibitor of gonadotropin secretion, likely via its ability to repress the release of kisspeptins on of GnRH neurons (12).…”
Section: Kisspeptins: Major Gatekeepers Of Pubertymentioning
confidence: 86%
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“…In turn, NKB may act on KNDy neurons to finely tune (predominantly, stimulate) kisspeptin release, therefore inducing GnRH secretion in an indirect manner. This possibility is, at least partially, supported by a solid body of experimental evidence, including the following observations: i) central senktide injection induces expression of C-fos in ARC KNDy neurons (34); ii) senktide elicits LH secretion in a GnRH-dependent manner (28); iii) the LH-releasing effects of senktide are not detected in the absence of proper Gpr54 signaling (35); iv) desensitization to the effects of continuous NKB stimulation takes place at a level upstream of GnRH neurons (28); v) substantial NK3R expression is detected in KNDy, but not GnRH neurons, in rodents and sheep (23); and vi) senktide induces the electrical activation of Kiss1 neurons, as revealed by electrophysiological recordings in Kiss1-CreGFP mice (40). To add further refinement to the system, the third partner of the KNDy trio, Dyn, has been long recognized as an inhibitor of gonadotropin secretion, likely via its ability to repress the release of kisspeptins on of GnRH neurons (12).…”
Section: Kisspeptins: Major Gatekeepers Of Pubertymentioning
confidence: 86%
“…In this context, proof of desensitization of NKB-induced LH responses has been presented in the monkey (28). This desensitization might account for the null or even inhibitory effect of senktide on LH secretion in GNX rodents and ewes (25,33,34,37), as they are expected to have pre-elevated, endogenous levels of NKB. Anyhow, the hypogonadotropic phenotype of humans with inactivating mutations of the NKB pathway, together with the reported effects of NKB agonists on LH release under physiological conditions in different species, solidly document the predominant stimulatory role of NKB in the central control of the HPG axis.…”
Section: Kisspeptins: Major Gatekeepers Of Pubertymentioning
confidence: 93%
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“…Kisspeptin is co-expressed with other neuropeptides including neurokinin B (NKB) and dynorphin (Dyn), leading to the name the "KNDy neuron" [27,28]. NKB also plays a stimulatory role in GnRH/ LH pulsatile secretion [29][30][31], whereas Dyn and its kappa-opioid receptor (KOR) suppress LH secretion [32,33] by modulating the activity of the KNDy neuron itself. These neuropeptides are regulated by estrogen and progestogen [34].…”
Section: Discussionmentioning
confidence: 99%
“…Effect of NELL2 synthesis blockade on the change in KiSS1 mRNA levels KiSS1 has emerged as the most important regulator of the GnRH neuronal apparatus under the influence of circulating E2 (Navarro et al, 2011), and changes in expression of KiSS1 and NELL2 follow similar patterns during the estrous cycle. Thus, to determine the effect of blocking NELL2 synthesis on the KiSS1 mRNA expression, the AS NELL2 ODN was injected icv into the brains of OVX female rats receiving E2.…”
Section: Resultsmentioning
confidence: 99%