Physiology of the Adult Gonadotropin-Releasing Hormone Neuronal Network

Herbison, Allan E.

doi:10.1016/b978-0-12-397175-3.00011-9

Cited by 114 publications

(120 citation statements)

References 901 publications

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“…Menarche occurred normally after the cessation of treatment. These data suggest that MKRN3 may be involved in controlling gonadotropic axis reactivation during childhood but with no effect on the GnRH-induced LH surge leading to ovulation in females at the end of the follicular phase (20). The timing of gonadotropic axis reactivation differs between boys and girls (21).…”

Section: Discussionmentioning

confidence: 99%

Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty

Simon

Mekhail

et al. 2016

European Journal of Endocrinology

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Context and objective: Idiopathic central precocious puberty (iCPP) is defined as early activation of the hypothalamicpituitary-gonadal axis in the absence of identifiable central lesions. Mutations of the makorin RING finger 3 (MKRN3) gene are associated with iCPP. We aimed to assess the frequency of MKRN3 mutations in iCPP and to compare the phenotypes of patients with and without MKRN3 mutations. Design: An observational study was carried out on patients recruited at pediatric hospitals in France and Italy. Forty-six index CPP cases were screened for mutations in the MKRN3 coding sequence: 28 index cases of familial cases and 18 cases did not report any familial history of CPP. The endocrine phenotype was compared between MKRN3 mutated and non-mutated patients. Results: MKRN3 mutations were identified in one sporadic and 13 familial cases. We identified five new heterozygous missense mutations predicted to be deleterious for protein function and two frameshift mutations, one new and the other recurrent, predicted to result in truncated proteins. Age at puberty onset varied very little among patients with MKRN3 mutations and puberty occurred earlier in these patients than in those without MKRN3 mutations (6.0 years (5.4-6.0) vs 7.0 years (6.0-7.0), PZ0.01). Conclusions: MKRN3 mutations are common in familial iCPP. MKRN3 is one of the gatekeepers of the postnatal activation of the gonadotropic axis.

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Section: Discussionmentioning

confidence: 99%

Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty

Simon

Mekhail

et al. 2016

European Journal of Endocrinology

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“…GnIH is not expressed in mammalian brain but two related peptides, RFRP-1 and RFRP-3, are encoded by a gene orthologous to that encoding avian GnIH (Tsutsui et al 2012). Evidence that RFRPs serve a hypophysiotropic role in the control of the pituitarygonadal axis of mammalian species in general, however, is tenuous (see Herbison, 2015).…”

Section: Other "Humoral" Substances Regulating Gonadotroph Functionmentioning

confidence: 99%

“…The GnRH Neuron (birth, location, morphology, electrophysiology) Two years after the structure of GnRH was announced, the first antibody to the peptide was reported (Barry, et al 1973) and since then numerous studies of the immunohistochemical distribution of GnRH neurons in the developing and mature hypothalamus have been conducted (Herbison 2015). Based on careful examination of the embryonic mouse brain the groups of Pfaff and Wray in 1989 independently proposed that GnRH neurons are born in the olfactory placode and after entering the forebrain during early embryonic development migrate to the hypothalamus where several hundred of these cells are found diffusely distributed in the preoptic area (POA) and more caudal areas in the MBH (SchwanzelFukuda, et al 1989) (Wray, et al 1989).…”

Section: Other "Humoral" Substances Regulating Gonadotroph Functionmentioning

confidence: 99%

“…The gene encoding kisspeptin, KISS1, had been of interest to cancer biologists since 1996 when it was found to be a tumor suppressor gene, but, quite remarkably, neither the gene nor the peptide was known to the neuroendocrine community in 2003. Since then, however, it has emerged in a volcanic manner that kisspeptin is an exceptionally potent GnRH secretagogue, GPR54 (the kisspeptin receptor, KISS1R) is expressed by GnRH neurons, kisspeptin neurons target the GnRH neuronal network, and one population of kisspeptin neurons is located in the arcuate nucleus (Herbison 2015), a periventricular structure located immediately above the median eminence that was originally argued by Knobil's laboratory to be the primary structure mediating the hypothalamic control of gonadotropin secretion in the primate (Knobil 1980). As a result of the foregoing findings, the idea that kisspeptin might be a component of the GnRH pulse generator, possible the output of the black box began to develop.…”

Section: Neurobiology Of the Hypothalamic Gnrh Pulse Generatormentioning

confidence: 99%

“…One school of thought proposed that pulsatility was intrinsic to the GnRH neurons themselves and that extensive inter-cellular mechanisms orchestrated synchrony within the network. A second school argued that nonGnRH neurons in the MBH target the GnRH neuronal network directly and drive intermittent release of GnRH (Herbison 2015). The later position has gained increasing support since 2003 when, in the context of the neuroendocrine axis governing the gonad, the power of molecular human genetics to identify novel signaling pathways was dramatically revealed.…”

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Hypothalamo-pituitary-gonadal Axis

2009

Encyclopedia of Neuroscience

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IntroductionIn the fourth chapter of Geoffrey Harris' widely acclaimed 1955 monograph (Harris 1955), which now 60 years later provides the corner stone of this special issue of the journal, he succinctly and systematically presented his views, and the evidence upon which they were based, on the neural mechanisms controlling the pituitary-gonadal axis. That gonadal function was under control by the central nervous system was well established at the time of Harris' monograph, as was the recognition of the gonad-stimulating properties of pituitary gonadotropin, the relative insignificance of gonadal nerves to gonadal function and the concept of neurosecretion. The problem for Harris and his fellow neuroendocrinologists was how did the hypothalamus regulate the secretion of the anterior pituitary hormones, specifically gonadotropin in the context of this review, and what was the role of the hypopophysial portal system in this regard. After elegantly interpreting and summarizing the extant data, Harris proposed that of the hypotheses that were being debated at the time "the most likely seems to be that nerve fibres from the hypothalmus liberate some humoral substance(s) into the capillaries of the primary plexus in the median eminence and that this substance is carried by the portal vessels to excite or inhibit the cells of the pars distalis." It is to be recalled, that this idea had been proposed by Harris and Green and Harris on several occasions prior to publication of the monograph (see Harris, 1955). It is also worth noting that the evidence upon which Harris' hypothesis was based had been obtained primarily from studies of the female, most likely because ovulation was a discrete and readily detected event and, at the time, the only reliable surrogate marker of acute hypothalamic activation.The main purpose of the present chapter is to describe the essential refinements and additional complexities that have been added to the fundamental model Harris put forward in 1955 for the neuroendocrine control of gonadal function (Figure 1). The major additions Postal address: Magee-Womens Research Institute, 204 Craft Avenue; Room B311, Pittsburgh, PA 15213 USA, planttm@mwri.magee.edu. Declaration of interest: I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of my interpretation of the research reported in this review. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscriptto the neuroendocrinologist's armamentarium that have facilitated the development of the ideas of Harris are, according to an historical timeline, the introduction of radioimmunoassay to measure concentrations of pituitary and gonadal hormones in the peripheral circulation and GnRH in portal blood, the development of immunohistochemical techniques to localize neuropeptides and neurotransmitters in the hypothalamus, the application of techniques in molecular endocrinology to the study of gene expression in the hypothalamus and pituitary, the introduction of transgeni...

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The Framework Upon Which Current Research on the GnRH Neuron and its Control is Built

Plant

Herbison

2018

The GnRH Neuron and Its Control

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Physiology of the Adult Gonadotropin-Releasing Hormone Neuronal Network

Cited by 114 publications

References 901 publications

Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty

Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty

Hypothalamo-pituitary-gonadal Axis

The Framework Upon Which Current Research on the GnRH Neuron and its Control is Built

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