Gonadotropin releasing hormone (GnRH) neurons comprise the final pathway through which the central nervous system exerts its control over the hypothalamic-pituitary-gonadal (HPG) axis. GnRH is released in a pulsatile manner, and conveyed to the anterior pituitary gland to stimulate synthesis and secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). A number of physiological factors, including gonadal steroids and energy balance, regulate this reproductive axis by modulation of GnRH pulsatility. In female mammals, ovarian steroids, i.e. estrogen and progesterone, inhibit GnRH/gonadotropin secretion via their homeostatic negative feedback actions. Despite extensive studies, the cellular and molecular mechanisms underlying these processes remain largely unknown. In addition, states of negative energy balance resulting from decreased food intake and/or increased energy expenditure, also lead to a suppression of the GnRH/gonadotropin secretion. However, the molecular mechanisms mediating this process are still poorly understood. Recent studies identified the ATP-sensitive potassium (KATP) channels in a variety of neurons in the hypothalamus, some of which have been implicated in energy homeostasis and regulation of GnRH neurons by ovarian steroids. I have postulated that KATP channels may convey the signals of ovarian steroids and negative energy balance to regulate GnRH secretion. This thesis tests this hypothesis by using molecular and integrative physiological approaches. In this thesis, the following evidence is provided: (1) KATP channels are involved in regulating activity of the GnRH pulse generator and the responsiveness of pulsatile GnRH release to central KATP channel blockade is conferred by the presence of both estrogen and progesterone, (2) Estrogen and progesterone, but not either hormone alone, upregulate KATP channel expression in the preoptic area (POA) and mediobasal hypothalamus (MBH), (3) Short-term food deprivation suppresses pulsatile GnRH release and LH level in female mice, and (4) Central KATP channel modulation is not necessary for fasting-induced suppression of GnRH/LH release in female mice. Taken together, our data demonstrated that KATP channels are involved in mediating the negative feedback actions of ovarian steroids on GnRH secretion through the regulation of KATP channel gene expression, but do not play a role in mediating the effects of negative energy balance.

Last modified

• 08/06/2018

Creator

• Wenyu Huang

DOI

• https://doi.org/10.21985/N23B0W

Subject

• Neuroscience Institute Graduate Program

Keyword

• Neuroscience
• Biology

Date created

• 2007-06-21

Resource type

• Dissertation

Rights statement

• In Copyright