Abstract
BackgroundKisspeptin and its G protein-coupled receptor (GPR) 54 are essential for activation of the hypothalamo-pituitary-gonadal axis. In the rat, the kisspeptin neurons critical for gonadotropin secretion are located in the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei. As the ARC is known to be the site of the gonadotropin-releasing hormone (GnRH) pulse generator we explored whether kisspeptin-GPR54 signalling in the ARC regulates GnRH pulses.Methodology/Principal FindingsWe examined the effects of kisspeptin-10 or a selective kisspeptin antagonist administration intra-ARC or intra-medial preoptic area (mPOA), (which includes the AVPV), on pulsatile luteinizing hormone (LH) secretion in the rat. Ovariectomized rats with subcutaneous 17β-estradiol capsules were chronically implanted with bilateral intra-ARC or intra-mPOA cannulae, or intra-cerebroventricular (icv) cannulae and intravenous catheters. Blood samples were collected every 5 min for 5–8 h for LH measurement. After 2 h of control blood sampling, kisspeptin-10 or kisspeptin antagonist was administered via pre-implanted cannulae. Intranuclear administration of kisspeptin-10 resulted in a dose-dependent increase in circulating levels of LH lasting approximately 1 h, before recovering to a normal pulsatile pattern of circulating LH. Both icv and intra-ARC administration of kisspeptin antagonist suppressed LH pulse frequency profoundly. However, intra-mPOA administration of kisspeptin antagonist did not affect pulsatile LH secretion.Conclusions/SignificanceThese data are the first to identify the arcuate nucleus as a key site for kisspeptin modulation of LH pulse frequency, supporting the notion that kisspeptin-GPR54 signalling in this region of the mediobasal hypothalamus is a critical neural component of the hypothalamic GnRH pulse generator.
Highlights
Inactivating mutations of the kisspeptin receptor (GPR54) in humans are associated with a failure to progress through puberty and adult infertility [1,2]
To further explore the relationship between kisspeptin-GPR54 signalling in the control of gonadotropinreleasing hormone (GnRH) pulse generator activity, we examined the effects of icv administration of kisspeptin antagonist on pulsatile luteinizing hormone (LH) secretion in the rat
To test the hypothesis that kisspeptin-GPR54 signalling in the ARC plays a critical role in controlling GnRH pulse generator activity, we examined the effects of kisspeptin or kisspeptin antagonist microinfused into this brain region on pulsatile LH secretion and compared the response to microinfusion into the medial preoptic area (mPOA)
Summary
Inactivating mutations of the kisspeptin receptor (GPR54) in humans are associated with a failure to progress through puberty and adult infertility (hypogonadotropic hypogonadism) [1,2]. Kisspeptin administration stimulates GnRH or LH secretion in various species including mice [3], rats [4,5], sheep [6], monkeys [7] and Humans [8]. Central administration of the kisspeptin antagonist, peptide 234, inhibited the post-castration rise in LH secretion in mice, blunted the LH response to exogenous kisspeptin in rats, suppressed LH pulse frequency and amplitude in ewes and suppressed GnRH pulses in monkeys [9]. Kisspeptin perikarya are located in two discrete hypothalamic regions in rodents; the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC) [3,10]. The kisspeptin neurons critical for gonadotropin secretion are located in the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei. As the ARC is known to be the site of the gonadotropinreleasing hormone (GnRH) pulse generator we explored whether kisspeptin-GPR54 signalling in the ARC regulates GnRH pulses
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
