Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat.
BACKGROUND
Kisspeptin 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.


RESULTS
We 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 17beta-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
These 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.
Li
Xiao-Feng
XF
Division of Reproduction and Endocrinology, King's College London, London, United Kingdom.
Kinsey-Jones
James S
JS
Cheng
Yewsong
Y
Knox
Alice M I
AM
Lin
Yuanshao
Y
Petrou
Nikoletta A
NA
Roseweir
Antonia
A
Lightman
Stafford L
SL
Milligan
Stuart R
SR
Millar
Robert P
RP
O'Byrne
Kevin T
KT
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007276:Injections, Intraventricular; D059648:Kisspeptins; D007986:Luteinizing Hormone / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
C106628:KISS1 protein, human; D059648:Kisspeptins; D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone