Identified GnRH neuron electrophysiology: A decade of study

Moenter, Suzanne M.

doi:10.1016/j.brainres.2010.09.066

Cited by 58 publications

(47 citation statements)

References 169 publications

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“…Bioinformatic tools are rapidly expanding our knowledge of the underlying biology of GnRH neurons that was previously limited to in vitro studies using mouse GnRH cell lines (87,88), in vivo and in vitro slice preparations (89,90), and physiological studies in knockout models (91)(92)(93). These types of bioinformatically informed approaches have made substantial progress in revealing the role of protein interactions and coordinate signaling pathways in GnRH neuronal development and are thus leading to new and better informed candidate gene discoveries.…”

Section: Candidate Gene Approaches Reveal Novel Genetic Causes Of Igdmentioning

confidence: 99%

Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the “-Omics” Era

2015

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The neuroendocrine regulation of reproduction is an intricate process requiring the exquisite coordination of an assortment of cellular networks, all converging on the GnRH neurons. These neurons have a complex life history, migrating mainly from the olfactory placode into the hypothalamus, where GnRH is secreted and acts as the master regulator of the hypothalamic-pituitary-gonadal axis. Much of what we know about the biology of the GnRH neurons has been aided by discoveries made using the human disease model of isolated GnRH deficiency (IGD), a family of rare Mendelian disorders that share a common failure of secretion and/or action of GnRH causing hypogonadotropic hypogonadism. Over the last 30 years, research groups around the world have been investigating the genetic basis of IGD using different strategies based on complex cases that harbor structural abnormalities or single pleiotropic genes, endogamous pedigrees, candidate gene approaches as well as pathway gene analyses. Although such traditional approaches, based on well-validated tools, have been critical to establish the field, new strategies, such as next-generation sequencing, are now providing speed and robustness, but also revealing a surprising number of variants in known IGD genes in both patients and healthy controls. Thus, before the field moves forward with new genetic tools and continues discovery efforts, we must reassess what we know about IGD genetics and prepare to hold our work to a different standard. The purpose of this review is to: 1) look back at the strategies used to discover the "known" genes implicated in the rare forms of IGD; 2) examine the strengths and weaknesses of the methodologies used to validate genetic variation; 3) substantiate the role of known genes in the pathophysiology of the disease; and 4) project forward as we embark upon a widening use of these new and powerful technologies for gene discovery. (Endocrine Reviews 36: 603-621, 2015)

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Section: Candidate Gene Approaches Reveal Novel Genetic Causes Of Igdmentioning

confidence: 99%

Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the “-Omics” Era

2015

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“…These neurons signal to the pituitary via the decapeptide GnRH1 to effect the release of the gonadotropins, follicle stimulating hormone and luteinizing hormone, which in turn stimulate steroid production by the gonads. It has long been known that this release depends on coordinated, pulsatile GnRH1 release, not simply elevated levels (7,8), requiring some level of synchronization in the output of these neurons. Episodic activation of the pituitary gonadotropes has been observed in multiple vertebrate taxa, including mammals and fish (9)(10)(11)(12), however, mechanisms that underlie this required coordinated activity of GnRH1 neurons are unknown.…”

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confidence: 99%

Electrical synapses connect a network of gonadotropin releasing hormone neurons in a cichlid fish

Juntti

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Initiating and regulating vertebrate reproduction requires pulsatile release of gonadotropin-releasing hormone (GnRH1) from the hypothalamus. Coordinated GnRH1 release, not simply elevated absolute levels, effects the release of pituitary gonadotropins that drive steroid production in the gonads. However, the mechanisms underlying synchronization of GnRH1 neurons are unknown. Control of synchronicity by gap junctions between GnRH1 neurons has been proposed but not previously found. We recorded simultaneously from pairs of transgenically labeled GnRH1 neurons in adult male Astatotilapia burtoni cichlid fish. We report that GnRH1 neurons are strongly and uniformly interconnected by electrical synapses that can drive spiking in connected cells and can be reversibly blocked by meclofenamic acid. Our results suggest that electrical synapses could promote coordinated spike firing in a cellular assemblage of GnRH1 neurons to produce the pulsatile output necessary for activation of the pituitary and reproduction.transgenic | GnRH | gap junction | cichlid | electrophysiology

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“…For example, it is clear that both gamma-aminobutyric acid (GABA) and glutamate play important roles in controlling GnRH secretion, and a considerable amount of information is available on the effects of these transmitters on GnRH neural activity in mice. 153,154 However, no clear picture has emerged on their role in other species. Similarly, neuropeptide Y (NPY) appears to be important for the full preovulatory LH surge in rats 124 and rabbits, 6,7 but its physiological actions and roles in other species remain unclear.…”

Section: Neural Systems Mediating Feedback Actions Of Steroidsmentioning

confidence: 99%

Neuroendocrine Control of Gonadotropin Secretion

Goodman

2015

Knobil and Neill's Physiology of Reproduction

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Identified GnRH neuron electrophysiology: A decade of study

Cited by 58 publications

References 169 publications

Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the “-Omics” Era

Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the “-Omics” Era

Electrical synapses connect a network of gonadotropin releasing hormone neurons in a cichlid fish

Neuroendocrine Control of Gonadotropin Secretion

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