Microglia regulate sex hormones via brain receptor
Microglia, the immune cells of the brain, do more than clear damage. They also control hormone production through a specific receptor in the hypothalamus.
The hypothalamus controls the hormonal axis (hypothalamus-pituitary-gonads) that governs the production of sex hormones such as testosterone and estrogen. As people age, activity along this axis declines. That decline is linked to loss of muscle mass, shifts in fat storage, lower bone density, and reduced libido.
New research shows that microglia directly influence the nerve cells (GnRH neurons) that trigger this axis, through a protein called RANK. GnRH neurons provide the starting signal for the entire hormonal chain. Without sufficient input from microglia, they function less effectively.
A new link in hormonal aging
Microglia were already known to be involved in brain development and the clearance of damaged tissue. Their role in driving the hormonal axis was not. The study shows that mice in which RANK signaling in microglia was switched off displayed disrupted GnRH activity and lower levels of sex hormones.
Microglia change their state during aging. They become more active in producing inflammatory signals and less effective in their supportive tasks. If RANK signaling also diminishes in that process, it may contribute to the hormonal decline associated with growing older.
Possible therapeutic targets
The finding opens a new therapeutic direction. Until now, interventions for hormonal aging focused mainly on the hormones themselves, through hormone replacement. The role of microglia suggests it may also be possible to intervene higher up the chain, at the level of the brain cells that drive production.
Whether modulating RANK signaling in microglia can restore the hormonal axis in humans remains unknown. But the discovery adds a new cell type to the understanding of hormonal aging.
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