Androgen Receptor signaling promotes the neural progenitor cell pool in the developing cortex.
J Neurochem
; 157(4): 1153-1166, 2021 05.
Article
in En
| MEDLINE
| ID: mdl-32959393
ABSTRACT
Neural Progenitor Cells (NPCs) are multipotent cells that are able to self-renew and differentiate into neurons. The size of the initial pool of NPCs during the brain development strongly affects the number of neurons that compose cortical multi-layer during development. Gonadal hormones can influence the balance between self-renewal and differentiation processes. Herein, we investigated the role of dihydrotestosterone (DHT), the active metabolite of testosterone, in the regulation of NPC stemness and differentiation. First, we evaluated the expression of the androgen receptor (AR), the transcription factor activated by DHT that mediates the physiological effects of androgens, in NPCs. Western blot analysis showed that DHT-mediated activation of AR induces mitogenic signaling pathways (PI3K/AKT and MAPK/ERK) in NPCs, whereas luciferase activity assays demonstrated the induction of AR transcriptional activity. AR activation mediated by DHT treatment strongly increased the proliferation of NPCs and reduced their propensity to differentiate into neurons. Furthermore, the effects of AR activation were mediated, at least in part, by increased expression of Aldehyde Dehydrogenase 1 Family Member A3 enzyme (ALDH1A3). Pharmacological inhibition of ALDH activity with N,N-diethylaminobenzaldehyde (DEAB) reduced the effect of DHT on NPC proliferation in vitro. Furthermore, inhibition of AR activity by Enzalutamide reduced the NPC pool in the developing cortex of male C57/BL6 mouse embryos. These findings indicate that androgens engage an AR-dependent signaling pathway that impact on neurogenesis by increasing the NPC pool in the developing mouse cortex.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Receptors, Androgen
/
Cerebral Cortex
/
Neurogenesis
/
Neural Stem Cells
Limits:
Animals
Language:
En
Journal:
J Neurochem
Year:
2021
Document type:
Article
Affiliation country: