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Title: Neuropeptide signalling systems involved in the timing of puberty onset and regulation of the gonadotrophin-releasing hormone pulse generator in the rat
Author: Li, Shengyun
ISNI:       0000 0004 5921 3115
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2016
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The pulsatile release of luteinising hormone (LH) induced by intermittent release of the gonadotrophin-releasing hormone (GnRH) is essential for initiating puberty and maintaining normal reproductive functions. Many neuropeptides including neurokinin B (NKB), substance P, kisspeptin (Kiss1) and gonadotrophin-inhibiting hormone (GnIH) have been implicated in regulating the secretion of LH. However, few studies have demonstrated the effects of those neuropeptides on pulsatile LH release and the dynamic changes of LH secretion in different gonadal hormone conditions. Studies outlined in this thesis have shown that antagonism of NKB receptor inhibits the pulsatile release of LH and delays the timing of puberty onset in female rats. Furthermore, NKB receptor agonism suppresses pulsatile LH release in ovariectomised (OVX) adult rats, but stimulates LH secretion in OVX rats replaced with 17β-oestradiol (E2). Likewise, intra-arcuate nucleus (ARC) administration of substance P, a neuropeptide belonging to the same family of NKB, suppresses pulsatile LH release in OVX rats, but stimulates LH secretion in OVX rats replaced with E2. Kiss1, a potent stimulator of the hypothalamo-pituitary-gonadal (HPG) axis, has been studied extensively within the hypothalamus, but little is known about its extra-hypothalamic effects. Current studies have shown that administration of Kiss1 into the medial amygdala (MeA), a key limbic brain structure involved in reproduction, stimulates LH secretion in OVX rats. Furthermore, intra-MeA administration of Kiss1 receptor antagonist inhibits the pulsatile LH release in OVX rats and spontaneous LH surges in intact female rats. Unlike Kiss1, GnIH is a major inhibitor of the reproductive axis. Central administration of RFamide-related peptides-3 (RFRP-3), the mammalian orthologue of GnIH, suppresses the pulsatile LH release in OVX rats. This effect is partially mediated through the endogenous opioid peptides. RFRP-3 is also implicated in stress-induced suppression of pulsatile LH secretion. Furthermore, antagonism of RFRP-3 receptor in the ARC and the medial preoptic area (mPOA) stimulates LH secretion in OVX rats with E2 replacement, indicating that RFRP-3 may also regulate the E2-induced negative feedback control of LH release. Taken together, the present study has demonstrated that various neuropeptides signaling systems including NKB, substance P, Kiss1 and RFRP-3 regulate pulsatile LH secretion in female rats.
Supervisor: Poston, Lucilla ; O'Byrne, Kevin Thomas Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available