Prefrontal 5α-Reductase 2 Mediates Male-Specific Acute Stress Response

January 2025 in “ Science Advances ”

Roberto Cadeddu, Giulia Braccagni, Gabriele Floris, Caterina Branca, Eleonora Corridori, Sara Salviati, Pilar Sánchez, Luca Spiro Santovito, Jesús M. Torres, Esperanza Ortega, Graziano Pinna, Philip J. Moos, Simona Scheggi, Marco Bortolato

5α-reductase 5α-reductase 2 5α-reductase 1 allopregnanolone medial prefrontal cortex neurons glia

TLDR 5α-reductase 2 is crucial for stress response in male rats.

The study investigates the role of 5α-reductase isoenzymes in stress response, revealing that 5αR2, but not 5αR1, is upregulated in the medial prefrontal cortex of male rats under acute stress, while females show no such change. Down-regulation of 5αR2 reduces stress response in males, and similar effects are seen in 5αR2 knockout rats. 5αR1 is responsible for baseline allopregnanolone synthesis, whereas 5αR2 facilitates its production during stress. Administering allopregnanolone restores stress response in 5αR2 knockdown rats. The findings underscore 5αR2's critical role in sex-specific stress reactivity by enabling stress-induced protein translation in neurons and glia.

View this study on doi.org →

Discuss this study in the Community →

Research cited in this study

5 / 5 results

research The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli

20 citations , November 2019 in “Biomolecules”

Finasteride reduces response to stress and rewards, affecting behavior and mental health.

research The Neurosteroidogenic Enzyme 5α-Reductase Modulates the Role of D1 Dopamine Receptors in Rat Sensorimotor Gating

49 citations , September 2015 in “Psychoneuroendocrinology”

5α-reductase affects dopamine receptors linked to sensorimotor gating, which may help understand disorders like schizophrenia.

research Inhibition Of 5α-Reductase Attenuates Behavioral Effects Of D1-, But Not D2-Like Receptor Agonists In C57BL/6 Mice

42 citations , August 2012 in “Psychoneuroendocrinology”

Finasteride reduces certain behaviors caused by D1-like receptor agonists but not by D2-like receptor agonists in mice.

research Isolation Rearing-Induced Reduction of Brain 5α-Reductase Expression: Relevance to Dopaminergic Impairments

48 citations , January 2011 in “Neuropharmacology”

Isolation stress in rats reduces brain enzyme levels, affecting dopamine function.

research Steroid 5α-Reductase as a Novel Therapeutic Target for Schizophrenia and Other Neuropsychiatric Disorders

72 citations , January 2011 in “Current Pharmaceutical Design”

S5αR inhibitors might help treat schizophrenia and other mental disorders but need more research.

Related Community Posts Join

6 / 179 results

community Finasteride only reduces scalp DHT by ~40%. Why does it work?

in Finasteride/Dutasteride 37 upvotes 2 years ago

How Finasteride and Dutasteride help reduce hair loss by reducing the amount of DHT in scalp areas, as well as discussing factors such as sensitivity to DHT, 5α-reductase expression in different parts of the hair follicle, and scalp tension.

community Let this be a warning to all, if you see progress, DONT STOP THE CONSISTENCY

in Update 492 upvotes 2 years ago

A user shared their experience with hair loss treatments Minoxidil and Finasteride. They saw improvement but stopped using them, leading to significant hair loss, and are now considering restarting the treatments.

community Which compounds in Saw Palmetto are actually beneficial?

in Research/Science 4 upvotes 1 year ago

Saw palmetto's fatty acids, particularly lauric and linoleic acids, inhibit enzymes linked to hair loss, while sterols like beta-sitosterol are less effective due to poor absorption. The conversation questions which specific compounds in saw palmetto contribute to its anti-androgenic effects.

community Pirfenidone - The answer to fibrosis and baldness

in Treatment 18 upvotes 4 years ago

Pirfenidone is suggested to treat fibrosis and baldness by blocking inflammation markers and reducing collagen. It is also available as a gel for scar removal.

community 5 alpha reductase type 1 is in brain tissue producing the main endogenous gabaergic allopregnanolone, not 2. How can finasteride as a 5ar2 lower that?

in Finasteride/Dutasteride 25 upvotes 1 year ago

Finasteride and dutasteride are discussed for hair loss, with concerns about their effects on neurosteroids and potential side effects like depression. Alternatives like topical estrogen and lifestyle changes are considered, with varying opinions on mental health and hair regrowth.

community Can I still save my hairline at age of 15?

in General 532 upvotes 3 months ago

A 15-year-old is concerned about hair loss, possibly at Norwood 2 or 3, and is using shampoos and conditioners recommended by a trichologist. Suggestions include considering topical minoxidil and consulting a doctor about topical anti-DHT treatments like finasteride or RU58841, but avoiding 5-alpha-reductase inhibitors at this age.

Similar Research

6 / 1000+ results

Immunohistochemical Localization of Types 1 and 2 5α-Reductase in Human Scalp