Glucocorticoid-sensitive period of corticotroph development-Implications for mechanisms of early life stress.


Journal

Journal of neuroendocrinology
ISSN: 1365-2826
Titre abrégé: J Neuroendocrinol
Pays: United States
ID NLM: 8913461

Informations de publication

Date de publication:
Nov 2023
Historique:
revised: 19 12 2022
received: 13 06 2022
accepted: 20 12 2022
medline: 23 11 2023
pubmed: 21 1 2023
entrez: 20 1 2023
Statut: ppublish

Résumé

Corticotrophs are intermediaries in the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in stress response in vertebrates. The HPA axis displays an intricate mode of negative feedback regulation, whereby the peripheral effector, cortisol inhibits the secretion of its upstream regulator, adrenocorticotropic hormone (ACTH) from proopiomelanocortin (POMC)-expressing cells in the pituitary. While the feedback regulation of the HPA axis is well characterized in the adult organism, the effect of feedback regulation on the development of corticotrophs is poorly understood. Here, we studied the effect of glucocorticoids on the development of POMC-expressing cells in the zebrafish pituitary. The development of POMC cells showed a steady increase in numbers between 2-6 days post fertilization. Inhibition of endogenous glucocorticoid synthesis resulted in an increase in POMC cell number due to reduced developmental feedback inhibition of cortisol on POMC cells. Conversely, addition of exogenous dexamethasone at a critical developmental window led to a decrease in corticotroph cell number, mimicking greater feedback control due to increased cortisol levels. Finally, developmental dysregulation of ACTH levels resulted in impaired anxiety-like and stress-coping behaviours. Hence, we identified a sensitive developmental window for the effect of glucocorticoids on corticotrophs and demonstrate the downstream effect on stress-responsive behaviour.

Identifiants

pubmed: 36662676
doi: 10.1111/jne.13229
doi:

Substances chimiques

Adrenocorticotropic Hormone 9002-60-2
Glucocorticoids 0
Hydrocortisone WI4X0X7BPJ
Pro-Opiomelanocortin 66796-54-1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e13229

Subventions

Organisme : Israel Science Foundation
ID : 349/21
Organisme : US-Israel Bi-national Science Foundation
ID : 2017325
Organisme : Israel Ministry of Science and Technology
ID : 3-16548

Informations de copyright

© 2022 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

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Auteurs

Guy Peles (G)

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.

Amrutha Swaminathan (A)

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.

Gil Levkowitz (G)

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.

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