Abstract
The pulsatile secretion of hormones is an efficient way of coding a large variety of chemical messages. The GnRH pulse pattern determines which gonadotropin is released when and at what concentration, prescribing a detailed set of instructions to the gonads that produce changes in the steroid hormone milieu. Although GnRH neurons possess some inherent rhythmicity, they are diffusely situated within the hypothalamus and in isolation are only capable of generating physiologically irrelevant messages, hence a synchronization module exists upstream. The identity of the neural unit comprising the GnRH pulse generator is now generally thought to include KNDy neurons in the arcuate nucleus. These neurons coexpress the neuropeptides kisspeptin, neurokinin B and dynorphin A, as well as other transmitters, and are in intimate contact with the GnRH network. The GnRH pulse generator’s function is the precise control of GnRH neuron excitability, coordinated activation, stimulation of neurosecretory events, modulation of gene transcription and the mediation of the negative feedback effect of gonadal steroids. Additionally, the GnRH pulse generator is an ideal venue for the integration of various sensory and homeostatic cues that regulate reproductive functions. In this chapter we provide a historical perspective of the elegant science that sparked interest in the central mechanisms underlying the functions of the reproductive system, explain how hypotheses surrounding GnRH pulse generation have evolved and describe the current state of knowledge within the dynamic field of GnRH pulse generator research.
Highlights
Reproduction is essential for the survival and evolution of all life forms on earth
The major hypothalamic effector within the HPG axis is the neuropeptide gonadotropin-releasing hormone (GnRH), which is secreted from axon terminals in the median eminence (ME) by a population of neurons scattered throughout the preoptic area (POA) and hypothalamus
GnRH is released into the hypothalamic-hypophyseal portal circulation enabling the hormone to rapidly reach the anterior pituitary gland, where the activation of GnRH receptors on specialized gonadotrope cells leads to the secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), into the systemic circulation
Summary
Reproduction is essential for the survival and evolution of all life forms on earth. Complex physiology underlies this process, in higher organisms reliant on sexual reproduction. The major hypothalamic effector within the HPG axis is the neuropeptide gonadotropin-releasing hormone (GnRH), which is secreted from axon terminals in the median eminence (ME) by a population of neurons scattered throughout the preoptic area (POA) and hypothalamus. This secretion occurs in a pulsatile fashion [1], the dynamics of which vary according to reproductive status [2]. GnRH is released into the hypothalamic-hypophyseal portal circulation enabling the hormone to rapidly reach the anterior pituitary gland, where the activation of GnRH receptors on specialized gonadotrope cells leads to the secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), into the systemic circulation.
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