Cited by 205Estrogen and related hormone effectsStress Responses and CortisolSexual Differentiation and Disorders

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An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane-3β,17β-diol

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Handa, Robert J., Pak, Toni R., Kudwa, Andrea E., Lund, Trent D., Hinds, Laura·2008·Hormones and Behavior

DOI 10.1016/j.yhbeh.2007.09.012PMC PMC2430080

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Abstract

The complexity of gonadal steroid hormone actions is reflected in their broad and diverse effects on a host of integrated systems including reproductive physiology, sexual behavior, stress responses, immune function, cognition, and neural protection. Understanding the specific contributions of androgens and estrogens in neurons that mediate these important biological processes is central to the study of neuroendocrinology. Of particular interest in recent years has been the biological role of androgen metabolites. The goal of this review is to highlight recent data delineating the specific brain targets for the dihydrotestosterone metabolite, 5alpha-androstane, 3beta,17beta-diol (3beta-Diol). Studies using both in vitro and in vivo approaches provide compelling evidence that 3beta-Diol is an important modulator of the stress response mediated by the hypothalmo-pituitary-adrenal axis. Furthermore, the actions of 3beta-Diol are mediated by estrogen receptors, and not androgen receptors, often through a canonical estrogen response element in the promoter of a given target gene. These novel findings compel us to re-evaluate the interpretation of past studies and the design of future experiments aimed at elucidating the specific effects of androgen receptor signaling pathways.

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Authors: Handa, R. J., Pak, T. R., Kudwa, A. E., Lund, T. D., & Hinds, L.
Affiliations: Colorado State University (US)
Loyola University Chicago (US)
Corresponding author: Handa, Robert J.
ORCID: Handa, Robert J.
Pak, Toni R.
Venue: Hormones and Behavior
Publisher: Elsevier BV
Published: 2008-05
Volume: 53
Issue: 5
Pages: 741-752
ISSN: 0018-506X (ISSN-L)
DOI: 10.1016/j.yhbeh.2007.09.012
PMC: PMC2430080
OpenAlex: W2042179361
Cited by: 205
References: 145
Citations by year: 2026: 6 · 2025: 4 · 2024: 9 · 2023: 2 · 2022: 6 · 2021: 18 · 2020: 18 · 2019: 4 · 2018: 8 · 2017: 11 · 2016: 12 · 2015: 11 · 2014: 14 · 2013: 12 · 2012: 10
FWCI: 7.50
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Hormones and Behavior (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Public Health Service
National Institute of Neurological Disorders and Stroke (R01NS039951, NS 033917)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
Keywords: 5α-androstane-3β,17β-diol, estrogen receptor beta, hypothalamic-pituitary-adrenal axis, stress response, estrogen response element, androgen receptor signaling, neuroendocrinology, sex steroids
MeSH terms: Androgens, Animals, Behavior, Behavior, Animal, Mental Disorders, Brain, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Promoter Regions, Genetic, Sex Characteristics, Dihydrotestosterone, Stress, Psychological, Androstane-3,17-diol, Signal Transduction, Estrogen Receptor beta

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An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane-3β,17β-diol

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