In-vivo analysis of hypothalamic kisspeptin neuron activity patterns
type: CreativeWork
description: Mammalian reproduction is regulated by the brain, pituitary gland, and gonads. In the brain, gonadotropin-releasing hormone (GnRH) is released to stimulate the pituitary gland. In females, two distinct modes of GnRH secretion are controlled by two populations of hypothalamic kisspeptin neurons located in the arcuate nucleus (ARNKISS), known as the pulse generator, and in the rostral periventricular area of the third ventricle (RP3VKISS) operating as the surge generator. The pituitary gland responds to GnRH by releasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) which regulate gametogenesis and steroidogenesis in the gonads. This thesis aims to understand the functional activity of these kisspeptin populations in female reproduction using in-vivo GCaMP fibre photometry in mice. Polycystic ovary syndrome (PCOS) affects approximately one in ten women of reproductive age, often presenting with subfertility and hyperandrogenism. Another hallmark of PCOS is increased LH pulsatility, suggesting potential dysfunction in the ARNKISS neuron pulse generator. I examined the activity of the pulse generator in two mouse models of PCOS. In the peripubertal androgen (PPA) model, there is a reduction in the frequency of ARNKISS neuron synchronisation events (SEs) that drive LH pulses. The prenatal androgen (PNA) model exhibited highly variable patterns of pulse generator activity with no significant differences detected in ARNKISS neuron SEs, pulsatile LH secretion, or serum testosterone, estradiol, and progesterone concentrations. However, a machine-learning approach revealed that acyclic PNA mice retained cyclical ARNKISS neuron activity, resembling the normal estrous cycles. The frequency of ARNKISS neuron SEs was significantly increased in algorithm-identified ‘diestrous stage’ PNA mice compared to controls. Further experiments showed reduced feedback suppression of progesterone on ARNKISS neurons in PNA mice and decreased gonadotroph sensitivity to GnRH. Th…
abstract: Mammalian reproduction is regulated by the brain, pituitary gland, and gonads. In the brain, gonadotropin-releasing hormone (GnRH) is released to stimulate the pituitary gland. In females, two distinct modes of GnRH secretion are controlled by two populations of hypothalamic kisspeptin neurons located in the arcuate nucleus (ARNKISS), known as the pulse generator, and in the rostral periventricular area of the third ventricle (RP3VKISS) operating as the surge generator. The pituitary gland responds to GnRH by releasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) which regulate gametogenesis and steroidogenesis in the gonads. This thesis aims to understand the functional activity of these kisspeptin populations in female reproduction using in-vivo GCaMP fibre photometry in mice. Polycystic ovary syndrome (PCOS) affects approximately one in ten women of reproductive age, often presenting with subfertility and hyperandrogenism. Another hallmark of PCOS is increased LH pulsatility, suggesting potential dysfunction in the ARNKISS neuron pulse generator. I examined the activity of the pulse generator in two mouse models of PCOS. In the peripubertal androgen (PPA) model, there is a reduction in the frequency of ARNKISS neuron synchronisation events (SEs) that drive LH pulses. The prenatal androgen (PNA) model exhibited highly variable patterns of pulse generator activity with no significant differences detected in ARNKISS neuron SEs, pulsatile LH secretion, or serum testosterone, estradiol, and progesterone concentrations. However, a machine-learning approach revealed that acyclic PNA mice retained cyclical ARNKISS neuron activity, resembling the normal estrous cycles. The frequency of ARNKISS neuron SEs was significantly increased in algorithm-identified ‘diestrous stage’ PNA mice compared to controls. Further experiments showed reduced feedback suppression of progesterone on ARNKISS neurons in PNA mice and decreased gonadotroph sensitivity to GnRH. Th…
author: Zhou, Ziyue
language: eng
keywords: endocrinology, fertility, GnRH, hypothalamus, kisspeptin, LH, neuroendocrinology, PCOS, reproduction, reproductive neuroendocrinology, women's reproductive health
license: https://www.repository.cam.ac.uk/bitstreams/c4450701-bc30-4ccd-b257-8b607a4580db/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2025-05-30
date modified: 2026-07-24T01:33:30Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.121741