ACTH signalling and adrenal development: lessons from mouse models

Novoselova, Tatiana ORCID: https://orcid.org/0000-0002-2394-4667, King, Peter J., Guasti, Leonardo, Metherell, Louise A., Clark, Adrian and Chan, Li F. (2019) ACTH signalling and adrenal development: lessons from mouse models. Endocrine Connections, 8 (7) . R122-R130. [Article] (doi:10.1530/ec-19-0190)

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Abstract

The melanocortin-2-receptor (MC2R), also known as the ACTH receptor, is a critical component of the hypothalamic–pituitary–adrenal axis. The importance of MC2R in adrenal physiology is exemplified by the condition familial glucocorticoid deficiency (FGD), a potentially fatal disease characterised by isolated cortisol deficiency. MC2R mutations cause ~25% of cases. The discovery of a MC2R accessory protein MRAP, mutations of which account for ~20% of FGD, has provided insight into MC2R trafficking and signalling. MRAP is a single transmembrane domain accessory protein highly expressed in the adrenal gland and essential for MC2R expression and function. Mouse models helped elucidate the action of ACTH. The Mc2r-knockout (Mc2r−/−) mice was the first mouse model developed to have adrenal insufficiency with deficiencies in glucocorticoid, mineralocorticoid and catecholamines. We recently reported the generation of the Mrap−/− mice which better mimics the human FGD phenotype with isolated glucocorticoid deficiency alone. The adrenal glands of adult Mrap−/− mice were grossly dysmorphic with a thickened capsule, deranged zonation and deranged WNT4/beta-catenin and sonic hedgehog (SHH) pathway signalling. Collectively, these mouse models of FGD highlight the importance of ACTH and MRAP in adrenal progenitor cell regulation, cortex maintenance and zonation.

Item Type: Article
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 28122
Notes on copyright: © 2019 The authors.
Published by Bioscientifica Ltd.
This work is licensed under a Creative Commons Attribution 4.0 International License.
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Depositing User: Tatiana Novoselova
Date Deposited: 12 Nov 2019 10:36
Last Modified: 29 Jan 2020 12:16
URI: https://eprints.mdx.ac.uk/id/eprint/28122

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