Allopregnanolone: From molecular pathophysiology to therapeutics. A historical perspective
Steven M. Paul; Graziano Pinna; Alessandro Guidotti
Neurobiology of Stress2020
Summary (paraphrased)
Tracing three decades of research, the authors describe how allopregnanolone — synthesized in the CNS from cholesterol or from progesterone and pregnenolone — came to be recognized as a rapid, non-genomic modulator of GABA-A receptors. Shifts in brain allopregnanolone during pregnancy, the postpartum period, and protracted stress are linked to the pathophysiology of mood disorders. The review then follows the molecule's path into therapeutics, culminating in the development of allopregnanolone-based treatments for postpartum depression. It is both a history and a mechanistic synthesis, showing how central this single neurosteroid is to affective regulation.
Why it’s in the corpus
Shows the therapeutic flip side of the mechanism: if allopregnanolone deficiency drives mood pathology and its replacement treats it, then 5-AR-inhibitor-induced depletion is a coherent causal story for PFS neuropsychiatric symptoms.
Related records
- Peer-reviewed paper
Allopregnanolone: State of the art
Roberto Cosimo Melcangi; Gian Carlo Panzica · Progress in Neurobiology
Melcangi and Panzica consolidate the state of knowledge on allopregnanolone: its enzymatic synthesis via 5-alpha-reductase and 3alpha-hydroxysteroid dehydrogenase, its distribution in brain and periphery, and its potent modulation of GABA-A receptors. The…
ARLIT-0542014PFSLiterature sweep · Oct 2026 - Peer-reviewed paper
Revisiting the roles of progesterone and allopregnanolone in the nervous system: Resurgence of the progesterone receptors
M. Schumacher; C. Mattern; A. Ghoumari; J.P. Oudinet; P. Liere; F. Labombarda; R. Sitruk-Ware; A.F. De Nicola · Progress in Neurobiology
This major review reconsiders progesterone and its 5-alpha-reduced metabolite allopregnanolone as central nervous system signaling molecules rather than mere reproductive hormones. It covers their synthesis in the brain, their potentiation of GABA-A receptor…
ARLIT-0532014Literature sweep · Oct 2026 - Peer-reviewed paper
The connection of 5-alpha reductase inhibitors to the development of depression
Thiraphat Saengmearnuparp; Bannakij Lojanapiwat; Nipon Chattipakorn; Siriporn Chattipakorn · Biomedicine & Pharmacotherapy
Clinical studies indicate that former users of 5-alpha-reductase inhibitors carry a higher incidence of depressive symptoms and neuropsychiatric side effects than non-users, yet the mechanisms behind depression in former users — sometimes called…
ARLIT-0512021PFSLiterature sweep · Oct 2026