Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 32 P684 | DOI: 10.1530/endoabs.32.P684

ECE2013 Poster Presentations Neuroendocrinology (42 abstracts)

Roles of kisspeptin partners, NKB and dynorphin, in the control of gonadotropin secretion: revisiting the KNDy paradigm

Francisco Ruiz-Pino 1, , David García-Galiano 1, , María Manfredi-Lozano 1, , Silvia Leon 1, , Miguel A Sanchez-Garrido 1, , Juan Roa 1, , Leonor Pinilla 1, , Victor Navarro 1, & Manuel Tena-Sempere 1,


1Physiology Section, University of Cordoba and IMIBIC, Cordoba, Spain; 2CIBER Fisiopatologia de la Obesidad y Nutricion, Cordoba, Spain; 3Brigham and Women’s Hospital, Boston, USA.


KNDy neurons, which co-express kisspeptins, neurokinin B (NKB) and dynorphin (Dyn), play a key role in the tonic control of gonadotropin secretion by modulating the GnRH release. The assumed KNDy model proposes that NKB and Dyn (as stimulatory and inhibitory signals, respectively) auto-regulate the secretion of kisspeptins onto GnRH neurons. However, some aspects of this paradigm remain poorly defined. In this context, the aims of this work were to characterize i) the putative effects of NKB signaling in the control of FSH secretion ii) the role of Dyn tone in shaping gonadotropin secretion and responses to NKB.

For the first goal, the effects of NKB agonist, senktide, on FSH release were explored across rat postnatal development; LH responses to senktide and FSH responses to kisspeptin-10 (Kp-10) were also assayed. Pre-pubertal rats displayed FSH (as well as LH) responses to central injection of senktide; FSH responses to Kp-10 were also detected at this age. In clear contrast, adult females were totally irresponsive to senktide in terms of FSH release, despite their proven LH responsiveness to NKB. In turn, adult males, which are highly responsive to Kp-10, did not display FSH (or LH) responses to senktide.

For the second goal, gonadotropin responses to NKB stimulation were explored in adult rats after blockade of Dyn receptors (KOR) with the antagonist, nor-BNI. Adult male rats became responsive to senktide in terms of stimulation of LH secretion after KOR blockade. Moreover, female rats displayed unambiguous FSH responses to senktide after treatment with nor-BNI.

In sum, we have documented i) the divergent patterns of gonadotropin (FSH vs LH) responses to NKB and Kp-10 stimulation ii) the role of Dyn signaling in inhibiting basal gonadotropin secretion and their responses to NKB. All in all, our data contribute to refine our present understanding on how different elements of the KNDy node participate in the dynamic and differential control of the secretion of both gonadotropins in both sexes and at different stages of postnatal maturation.

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