OR47-4 EXPANDING THE ROLES OF KISSPEPTIN PARTNERS, NKB AND DYNORPHIN, IN THE CONTROL OF GONADOTROPIN SECRETION: REVISITING THE KNDy PARADIGM

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR47-Hypothalamus-Pituitary Development & Biology
Basic/Translational
Tuesday, June 18, 2013: 9:15 AM-10:45 AM
Presentation Start Time: 10:00 AM
Room 130 (Moscone Center)
Francisco Ruiz-Pino1, David Garcia-Galiano1, Maria Manfredi1, Silvia Leon1, Miguel Angel Sanchez-Garrido1, Juan Roa1, Leonor Pinilla1, Victor Manuel Navarro*2 and Manuel Tena-Sempere1
1University of Cordoba, Cordoba, Spain, 2Brigham and Women's Hospital and Harvard Medical School, Boston, MA
Hypothalamic neurons in the arcuate nucleus (ARC) that co-express kisspeptins, neurokinin B (NKB) and dynorphin (Dyn), so-called KNDy neurons, are essential for the control of GnRH release. A model for the function of this system has been previously proposed in which the coordinated stimulatory and inhibitory actions of NKB and Dyn, respectively, auto-regulate the secretion of kisspeptins by KNDy neurons down to GnRH neurons. However, some aspects of this paradigm, such as (1) the specific roles of NKB in the control of FSH secretion, and (2) the relative importance of the endogenous Dyn tone in the KNDy control of GnRH release, await further characterization. In order to cover these issues, in this work, we first explored the effects of icv injection of the NKB agonist, senktide (600 pmol), on FSH release across rat postnatal development; LH responses to senktide and FSH responses to kisspeptin-10 (Kp-10, 1 nmol icv) were also assayed for comparative purposes. In addition, we studied the effects of the endogenous Dyn tone on gonadotropin responses to NKB by blocking Dyn receptors (KOR) with the specific antagonist, nor-BNI, prior to senktide administration.

Senktide induced a significant increase in LH and FSH release in pre-pubertal rats; FSH responses to Kp-10 were also detected at this age. In contrast, senktide failed to induce FSH release in adult female rats, either intact (at diestrus) or ovariectomized followed by sham or estradiol replacement, despite its ability to stimulate LH release. In turn, adult males, which were highly responsive to Kp-10, did not display FSH or LH responses to senktide. In addition, pre-treatment of adult rats with the KOR antagonist, nor-BNI, increased basal LH and FSH levels and permitted senktide-induced LH (but not FSH) release in males, as well as clear FSH responses in females.

In sum, in this work, we have documented (a) the divergent patterns of gonadotropin (FSH vs. LH) responses to NKB and Kp-10 stimulation; and (b) the role of Dyn signaling in inhibiting basal gonadotropin secretion and their responses to NKB. 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.

Nothing to Disclose: FR, DG, MM, SL, MAS, JR, LP, VMN, MT

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm