The Pheromone Androstenol (5α-Androst-16-en-3α-ol) Is a Neurosteroid Positive Modulator of GABAA Receptors

  title={The Pheromone Androstenol (5$\alpha$-Androst-16-en-3$\alpha$-ol) Is a Neurosteroid Positive Modulator of GABAA Receptors},
  author={Rafal M. Kaminski and Herbert Ryan Marini and Pavel I Ortinski and Stefano Vicini and Michael A. Rogawski},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={694 - 703}
Androstenol is a steroidal compound belonging to the group of odorous 16-androstenes, first isolated from boar testes and also found in humans. Androstenol has pheromone-like properties in both animals and humans, but the molecular targets of its pheromonal activity are unknown. Androstenol is structurally similar to endogenous A-ring reduced neurosteroids that act as positive modulators of GABAA receptors. Here we show that androstenol has neurosteroid-like activity as a GABAA receptor… 
17β-Nitro-5α-androstan-3α-ol and its 3β-methyl derivative: Neurosteroid analogs with potent anticonvulsant and anxiolytic activities
It is concluded that nitro can serve as a bioisostere for acetyl at the 17β-position of 5α-androstan-3α-ol, such that the nitro analog fully retains the bioactivity of the endogenous neurosteroid at GABAA receptors.
The Testosterone-Derived Neurosteroid Androstanediol Is a Positive Allosteric Modulator of GABAA Receptors
Androstanediol could be a neurosteroid mediator of testosterone actions on neuronal excitability and seizure susceptibility via its activity as a GABAA receptor modulator and that androStanediol may play a key role in men with epilepsy, especially during the age-related decline in androgen levels.
Measurement of 16-Androstenes (5α-Androst-16-en-3-One, 5α-Androst-16-en-3α-ol, 5α-Androst-16-en-3β-ol) in Saliva of German Landrace and Göttingen Minipig Boars
The results show that both odorous substances were about 50 times higher in GMB than in GLB which indicates a difference in salivary 16-androstene in these two pig breeds, which supports an effect of breed.
Mass spectrometric assay and physiological–pharmacological activity of androgenic neurosteroids
  • D. Reddy
  • Biology, Medicine
    Neurochemistry International
  • 2008
Neuroactive Steroids: Receptor Interactions and Responses
Neuroactive steroids (NASs) are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids (NSs).
Neurosteroid interactions with synaptic and extrasynaptic GABAA receptors: regulation of subunit plasticity, phasic and tonic inhibition, and neuronal network excitability
This review provides a critical appraisal of recent advances in the pharmacology of endogenous neurosteroids that interact with GABAA receptors in the brain to create improved therapies for sleep, anxiety, stress, epilepsy, and other neuropsychiatric conditions.


Assessment of porcine and human 16-ene-synthase, a third activity of P450c17, in the formation of an androstenol precursor. Role of recombinant cytochrome b5 and P450 reductase.
It is demonstrated that human P450c17, as other enzymes of the classical steroidogenic pathway, is involved in the biosynthetic pathway leading to the formation of androstenol.
Comparative biosynthetic pathway of androstenol and androgens
In Vitro and In Vivo Activity of 16,17-dehydro-epipregnanolones: 17,20-Bond Torsional Energy Analysis and D-ring Conformation
The modified orientation of the 20-keto group of neuroactive steroids containing a 16-ene, provides an explanation for their decreased biological activity overall, but did not lead to an enhanced protective index.
Anticonvulsant activity of the testosterone-derived neurosteroid 3&agr;-androstanediol
  • D. Reddy
  • Biology, Medicine
  • 2004
The results suggest that testosterone-derived 3&agr;-androstanediol has powerful anticonvulsant activity that occurs largely through non-genomic mechanisms.
Antidepressant-like effect of the neurosteroid 3α-hydroxy-5α-pregnan-20-one in mice forced swim test
Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids
The results obtained with combinations of steroids and barbiturates in the ligand binding assay appear inconsistent with the two classes of compound interacting with a common site to modulate the GABAA receptor activity.
16-ene-steroids in the human testis
  • A. Smals, J. Weusten
  • Biology, Medicine
    The Journal of Steroid Biochemistry and Molecular Biology
  • 1991