Progesterone, progestagens and the central nervous system.

Area of Science:

• Neuroendocrinology
• Neurosteroidology
• Molecular Psychiatry

Background:

• Gonadal steroids (oestrogen, progestagens, androgens) modulate diverse brain functions.
• Steroid receptors are found throughout the brain, including the amygdala, hippocampus, and cortex.
• Steroid action in the brain involves both genomic and non-genomic mechanisms, similar to peripheral tissues.

Purpose of the Study:

• To investigate the biochemical and metabolic properties of progestin molecules used in hormonal therapies.
• To explore the interactions between oestrogens and progestins in neuroendocrine control.
• To understand the role of neurosteroids in brain function and their clinical implications.

Main Methods:

• Review of experimental and clinical studies on sex steroid hormone therapies.
• Analysis of receptor distribution for gonadal steroids in various brain regions.
• Investigation of de novo synthesis and action of neurosteroids in the brain.

Main Results:

• Sex steroids exert genomic and non-genomic effects in the brain via specific receptors.
• Neurosteroids, including progesterone derivatives, are synthesized de novo in the brain by glial cells.
• Neurosteroids rapidly modulate neurotransmission, notably acting as allosteric modulators of GABA(A) receptors.

Conclusions:

• The brain synthesizes its own steroids (neurosteroids) from precursors like cholesterol.
• Neurosteroids play a critical role in regulating brain functions through rapid, non-classical actions.
• Modifications in neurosteroid synthesis and release are significant in controlling brain function, with potential clinical relevance.