Elevated testosterone in females reveals a robust sex difference in altered androgen levels during chronic alcohol withdrawal

Melissa R. Forquer, Joel G. Hashimoto, Melissa L. Roberts, Kristine Wiren

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The endocrine disruption associated with alcohol (ethanol) abuse in both males and females is widely recognized. Ethanol intoxication and withdrawal in males results in significant reductions in androgen levels. Less is known about female alcoholics, and because the changes in testosterone concentrations remain controversial, we systematically characterized changes in sex steroids after chronic ethanol exposure and withdrawal in both sexes. Testosterone and 17β-estradiol concentrations were determined during chronic high intoxication, over a withdrawal time course, and following a period of abstinence using a genetic model of withdrawal vulnerability, the Withdrawal Seizure-Resistant (WSR) and -Prone (WSP) selected lines. In males, testosterone concentrations were significantly lower in intoxicated WSP mice after chronic ethanol exposure, and were dramatically and transiently reduced during the withdrawal period in both WSR and WSP lines. In contrast, testosterone levels were increased in intoxicated WSP females and in both WSR and WSP mice during withdrawal. Chronic ethanol exposure disrupted normal estrous cycling in WSP mice, associated with hyperandrogenemia while intoxicated. In abstinence, elevated testosterone was observed in both sexes but only in WSR mice. Estrogen levels were modestly reduced during withdrawal in both WSR and WSP lines, predominantly in males. These findings identify a mechanism based on altered androgen signaling that likely contributes to sex-specific responses during withdrawal. However, only WSR mice showed similar elevations in androgen long after withdrawal in both sexes, suggesting that genotype is an important determinant of steroid responses after abstinence. Increased androgen signaling in females as a consequence of chronic ethanol exposure may play an important and relatively uncharacterized role in sexually dimorphic responses to alcohol abuse.

Original languageEnglish (US)
Pages (from-to)161-171
Number of pages11
JournalAlcohol
Volume45
Issue number2
DOIs
StatePublished - Mar 2011

Fingerprint

Sex Characteristics
withdrawal
Androgens
Testosterone
Seizures
Ethanol
alcohol
Alcohols
seizure
Alcoholism
Steroids
Genetic Models
Alcoholics
intoxication
Estradiol
Estrogens
Genotype
abuse
alcoholism
vulnerability

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neurology
  • Toxicology
  • Health(social science)

Cite this

Elevated testosterone in females reveals a robust sex difference in altered androgen levels during chronic alcohol withdrawal. / Forquer, Melissa R.; Hashimoto, Joel G.; Roberts, Melissa L.; Wiren, Kristine.

In: Alcohol, Vol. 45, No. 2, 03.2011, p. 161-171.

Research output: Contribution to journalArticle

Forquer, Melissa R. ; Hashimoto, Joel G. ; Roberts, Melissa L. ; Wiren, Kristine. / Elevated testosterone in females reveals a robust sex difference in altered androgen levels during chronic alcohol withdrawal. In: Alcohol. 2011 ; Vol. 45, No. 2. pp. 161-171.
@article{ad760e234e8a4e12beb7a4c7ccbc5256,
title = "Elevated testosterone in females reveals a robust sex difference in altered androgen levels during chronic alcohol withdrawal",
abstract = "The endocrine disruption associated with alcohol (ethanol) abuse in both males and females is widely recognized. Ethanol intoxication and withdrawal in males results in significant reductions in androgen levels. Less is known about female alcoholics, and because the changes in testosterone concentrations remain controversial, we systematically characterized changes in sex steroids after chronic ethanol exposure and withdrawal in both sexes. Testosterone and 17β-estradiol concentrations were determined during chronic high intoxication, over a withdrawal time course, and following a period of abstinence using a genetic model of withdrawal vulnerability, the Withdrawal Seizure-Resistant (WSR) and -Prone (WSP) selected lines. In males, testosterone concentrations were significantly lower in intoxicated WSP mice after chronic ethanol exposure, and were dramatically and transiently reduced during the withdrawal period in both WSR and WSP lines. In contrast, testosterone levels were increased in intoxicated WSP females and in both WSR and WSP mice during withdrawal. Chronic ethanol exposure disrupted normal estrous cycling in WSP mice, associated with hyperandrogenemia while intoxicated. In abstinence, elevated testosterone was observed in both sexes but only in WSR mice. Estrogen levels were modestly reduced during withdrawal in both WSR and WSP lines, predominantly in males. These findings identify a mechanism based on altered androgen signaling that likely contributes to sex-specific responses during withdrawal. However, only WSR mice showed similar elevations in androgen long after withdrawal in both sexes, suggesting that genotype is an important determinant of steroid responses after abstinence. Increased androgen signaling in females as a consequence of chronic ethanol exposure may play an important and relatively uncharacterized role in sexually dimorphic responses to alcohol abuse.",
author = "Forquer, {Melissa R.} and Hashimoto, {Joel G.} and Roberts, {Melissa L.} and Kristine Wiren",
year = "2011",
month = "3",
doi = "10.1016/j.alcohol.2010.08.013",
language = "English (US)",
volume = "45",
pages = "161--171",
journal = "Alcohol",
issn = "0741-8329",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Elevated testosterone in females reveals a robust sex difference in altered androgen levels during chronic alcohol withdrawal

AU - Forquer, Melissa R.

AU - Hashimoto, Joel G.

AU - Roberts, Melissa L.

AU - Wiren, Kristine

PY - 2011/3

Y1 - 2011/3

N2 - The endocrine disruption associated with alcohol (ethanol) abuse in both males and females is widely recognized. Ethanol intoxication and withdrawal in males results in significant reductions in androgen levels. Less is known about female alcoholics, and because the changes in testosterone concentrations remain controversial, we systematically characterized changes in sex steroids after chronic ethanol exposure and withdrawal in both sexes. Testosterone and 17β-estradiol concentrations were determined during chronic high intoxication, over a withdrawal time course, and following a period of abstinence using a genetic model of withdrawal vulnerability, the Withdrawal Seizure-Resistant (WSR) and -Prone (WSP) selected lines. In males, testosterone concentrations were significantly lower in intoxicated WSP mice after chronic ethanol exposure, and were dramatically and transiently reduced during the withdrawal period in both WSR and WSP lines. In contrast, testosterone levels were increased in intoxicated WSP females and in both WSR and WSP mice during withdrawal. Chronic ethanol exposure disrupted normal estrous cycling in WSP mice, associated with hyperandrogenemia while intoxicated. In abstinence, elevated testosterone was observed in both sexes but only in WSR mice. Estrogen levels were modestly reduced during withdrawal in both WSR and WSP lines, predominantly in males. These findings identify a mechanism based on altered androgen signaling that likely contributes to sex-specific responses during withdrawal. However, only WSR mice showed similar elevations in androgen long after withdrawal in both sexes, suggesting that genotype is an important determinant of steroid responses after abstinence. Increased androgen signaling in females as a consequence of chronic ethanol exposure may play an important and relatively uncharacterized role in sexually dimorphic responses to alcohol abuse.

AB - The endocrine disruption associated with alcohol (ethanol) abuse in both males and females is widely recognized. Ethanol intoxication and withdrawal in males results in significant reductions in androgen levels. Less is known about female alcoholics, and because the changes in testosterone concentrations remain controversial, we systematically characterized changes in sex steroids after chronic ethanol exposure and withdrawal in both sexes. Testosterone and 17β-estradiol concentrations were determined during chronic high intoxication, over a withdrawal time course, and following a period of abstinence using a genetic model of withdrawal vulnerability, the Withdrawal Seizure-Resistant (WSR) and -Prone (WSP) selected lines. In males, testosterone concentrations were significantly lower in intoxicated WSP mice after chronic ethanol exposure, and were dramatically and transiently reduced during the withdrawal period in both WSR and WSP lines. In contrast, testosterone levels were increased in intoxicated WSP females and in both WSR and WSP mice during withdrawal. Chronic ethanol exposure disrupted normal estrous cycling in WSP mice, associated with hyperandrogenemia while intoxicated. In abstinence, elevated testosterone was observed in both sexes but only in WSR mice. Estrogen levels were modestly reduced during withdrawal in both WSR and WSP lines, predominantly in males. These findings identify a mechanism based on altered androgen signaling that likely contributes to sex-specific responses during withdrawal. However, only WSR mice showed similar elevations in androgen long after withdrawal in both sexes, suggesting that genotype is an important determinant of steroid responses after abstinence. Increased androgen signaling in females as a consequence of chronic ethanol exposure may play an important and relatively uncharacterized role in sexually dimorphic responses to alcohol abuse.

UR - http://www.scopus.com/inward/record.url?scp=79751535655&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79751535655&partnerID=8YFLogxK

U2 - 10.1016/j.alcohol.2010.08.013

DO - 10.1016/j.alcohol.2010.08.013

M3 - Article

C2 - 20843636

AN - SCOPUS:79751535655

VL - 45

SP - 161

EP - 171

JO - Alcohol

JF - Alcohol

SN - 0741-8329

IS - 2

ER -