Author Interviews, Endocrinology, OBGYNE / 17.06.2014
Nervous System Peptides May Contribute To Ovarian Failure
MedicalResearch.com Interview with:
Sergio R. Ojeda, D.V.M.
Division Head and Senior Scientist Division of Neuroscience
Division of Neuroscience, OR National Primate Research Center/Oregon Health and Science University,
Beaverton OR 97006
MedicalResearch: What are the main findings of the study?
Dr. Ojeda: The study shows that a receptor for two growth factors (brain-derived neurotrophic factor [BDNF] and neurotrophin 4/5 [NT4/5]) that are known to be important for development of the nervous system is also essential for maintaining oocyte integrity and survival in the mammalian ovary. Intriguingly, the full-length form of this receptor (known as NTRK2-FL) is not expressed in oocytes until the time of the first ovulation. At this time, the pre-ovulatory gonadotropin discharge stimulates granulosa cells of ovarian follicles to produce not only more BDNF, but also more of a peptide known as kisspeptin, to induce the formation of NTRK2-FL in oocytes. To date, kisspeptin was known to be only critical for the hypothalamic control of reproduction. To induce NTRK2-FL, BDNF binds to truncated NTRK2 receptors (NTRK2-T1), which are abundant in oocytes throughout prepubertal development. Kisspeptin, on the other hand, does so by activating its receptor KISS1R, also expressed in oocytes. Once present after the first ovulation, NTRK2-FL is able to activate a survival pathway in oocytes following gonadotropin stimulation, presumably at every cycle. In the absence of NTRK2-FL, oocytes die, follicular structure disintegrates and a condition of premature ovarian failure ensues.
(more…)