Epigenomic control of gonadotrophin‐releasing hormone neurone development and hypogonadotrophic hypogonadism

Autor: Wilson C. J. Chung, Megan L. Linscott
Rok vydání: 2020
Předmět:
Epigenomics
0301 basic medicine
endocrine system
medicine.medical_specialty
Kallmann syndrome
Neurogenesis
Endocrinology
Diabetes and Metabolism
Mice
Transgenic
Biology
Fibroblast growth factor
Epigenesis
Genetic
Gonadotropin-Releasing Hormone
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Endocrinology
FGF8
Anterior pituitary
Internal medicine
medicine
Animals
Humans
Receptor
Fibroblast Growth Factor
Type 1
Neurons
Endocrine and Autonomic Systems
Hypogonadism
Fibroblast growth factor receptor 1
medicine.disease
Fibroblast Growth Factors
030104 developmental biology
medicine.anatomical_structure
Fibroblast growth factor receptor
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Hypogonadotrophic hypogonadism
Signal Transduction
Hormone
Zdroj: Journal of Neuroendocrinology. 32
ISSN: 1365-2826
0953-8194
DOI: 10.1111/jne.12860
Popis: Mammalian reproductive success depends on gonadotrophin-releasing hormone (GnRH) neurones to stimulate gonadotrophin secretion from the anterior pituitary and activate gonadal steroidogenesis and gametogenesis. Genetic screening studies in patients diagnosed with Kallmann syndrome (KS), a congenital form of hypogonadotrophic hypogonadism (CHH), identified several causal mutations, including those in the fibroblast growth factor (FGF) system. This signalling pathway regulates neuroendocrine progenitor cell proliferation, fate specification and cell survival. Indeed, the GnRH neurone system was absent or abrogated in transgenic mice with reduced (ie, hypomorphic) Fgf8 and/or Fgf receptor (Fgfr) 1 expression, respectively. Moreover, we found that GnRH neurones were absent in the embryonic olfactory placode of Fgf8 hypomorphic mice, the putative birthplace of GnRH neurones. These observations, together with those made in human KS/CHH patients, indicate that the FGF8/FGFR1 signalling system is a requirement for the ontogenesis of the GnRH neuronal system and function. In this review, we discuss how epigenetic factors control the expression of genes such as Fgf8 that are known to be critical for GnRH neurone ontogenesis, fate specification, and the pathogenesis of KS/CHH.
Databáze: OpenAIRE
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