Allopregnanolone: State of the art
Roberto Cosimo Melcangi; Gian Carlo Panzica
Progress in Neurobiology2014
Summary (paraphrased)
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 review spans the molecule's roles in stress regulation, mood, sexual behavior, neuroprotection, and neuroinflammation, and flags how pharmacological blockade of its synthesis can disturb each of these domains. Written by the group that leads PFS mechanistic research, it explicitly connects allopregnanolone biology to the consequences of 5-alpha-reductase inhibition. It serves as the definitive short synthesis of why allopregnanolone matters to the post-drug syndrome question.
Why it’s in the corpus
The allopregnanolone review from the PFS research group itself — directly bridges the neurosteroid mechanism to 5-AR inhibitor effects and anchors the GABA-A pillar of the corpus.
Related records
- 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 - Peer-reviewed paper
Allopregnanolone: From molecular pathophysiology to therapeutics. A historical perspective
Steven M. Paul; Graziano Pinna; Alessandro Guidotti · Neurobiology of Stress
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…
ARLIT-0562020PFSLiterature sweep · Oct 2026