The effect of aromatase inhibition on the sexual differentiation of the sheep brain

Charles Roselli, J. M. Schrunk, H. L. Stadelman, J. A. Resko, F. Stormshak

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

This study tested the hypothesis that aromatization of testosterone to estradiol is necessary for sexual differentiation of the sheep brain. Pregnant ewes (n ≤ 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is maximally sensitive to the behavior-modifying effects of exogenous testosterone (embryonic d 50-80; 147 d is term). Control (n ≤ 10) ewes received vehicle injections. Fifteen control lambs (7 males and 8 females) and 17 ATD-exposed lambs (7 males and 10 females) were evaluated for sexually dimorphic behavioral and neuroendocrine traits as adults. Prenatal ATD exposure had no significant effect on serum concentrations of androgen at birth, growth rates, expression of juvenile play behaviors, or the onset of puberty in male and female lambs. Rams exposed to ATD prenatally exhibited a modest, but significant, decrease in mounting behavior at 18 mo of age. However, prenatal ATD exposure did not interfere with defeminization of adult sexual partner preferences, receptive behavior, or the LH surge mechanism. In summary, our results indicate that aromatization is necessary for complete behavioral masculinization in sheep. However, before we can conclude that aromatization does not play a role in defeminization of the sheep brain, it will be necessary to evaluate whether intrauterine exposure of male fetuses to higher doses of ATD for a more extended period of time can disrupt normal neuroendocrine and behavioral development.

Original languageEnglish (US)
Pages (from-to)501-511
Number of pages11
JournalEndocrine
Volume29
Issue number3
DOIs
StatePublished - Jun 2006

Fingerprint

Androstatrienes
Sex Differentiation
Aromatase
Sheep
Brain
Testosterone
Aromatase Inhibitors
Birth Rate
Sexual Partners
Puberty
Androgens
Estradiol
Fetus
Inhibition (Psychology)
Pregnancy
Injections
Growth
Serum

Keywords

  • Aromatase inhibitor
  • ATD
  • Copulatory behavior
  • Fertility
  • LH surge
  • Puberty
  • Sexual maturation
  • Sexual partner preference
  • Sheep

ASJC Scopus subject areas

  • Endocrinology

Cite this

Roselli, C., Schrunk, J. M., Stadelman, H. L., Resko, J. A., & Stormshak, F. (2006). The effect of aromatase inhibition on the sexual differentiation of the sheep brain. Endocrine, 29(3), 501-511. https://doi.org/10.1385/ENDO:29:3:501

The effect of aromatase inhibition on the sexual differentiation of the sheep brain. / Roselli, Charles; Schrunk, J. M.; Stadelman, H. L.; Resko, J. A.; Stormshak, F.

In: Endocrine, Vol. 29, No. 3, 06.2006, p. 501-511.

Research output: Contribution to journalArticle

Roselli, C, Schrunk, JM, Stadelman, HL, Resko, JA & Stormshak, F 2006, 'The effect of aromatase inhibition on the sexual differentiation of the sheep brain', Endocrine, vol. 29, no. 3, pp. 501-511. https://doi.org/10.1385/ENDO:29:3:501
Roselli, Charles ; Schrunk, J. M. ; Stadelman, H. L. ; Resko, J. A. ; Stormshak, F. / The effect of aromatase inhibition on the sexual differentiation of the sheep brain. In: Endocrine. 2006 ; Vol. 29, No. 3. pp. 501-511.
@article{24205d211f5c4a068d88b6d13af5468f,
title = "The effect of aromatase inhibition on the sexual differentiation of the sheep brain",
abstract = "This study tested the hypothesis that aromatization of testosterone to estradiol is necessary for sexual differentiation of the sheep brain. Pregnant ewes (n ≤ 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is maximally sensitive to the behavior-modifying effects of exogenous testosterone (embryonic d 50-80; 147 d is term). Control (n ≤ 10) ewes received vehicle injections. Fifteen control lambs (7 males and 8 females) and 17 ATD-exposed lambs (7 males and 10 females) were evaluated for sexually dimorphic behavioral and neuroendocrine traits as adults. Prenatal ATD exposure had no significant effect on serum concentrations of androgen at birth, growth rates, expression of juvenile play behaviors, or the onset of puberty in male and female lambs. Rams exposed to ATD prenatally exhibited a modest, but significant, decrease in mounting behavior at 18 mo of age. However, prenatal ATD exposure did not interfere with defeminization of adult sexual partner preferences, receptive behavior, or the LH surge mechanism. In summary, our results indicate that aromatization is necessary for complete behavioral masculinization in sheep. However, before we can conclude that aromatization does not play a role in defeminization of the sheep brain, it will be necessary to evaluate whether intrauterine exposure of male fetuses to higher doses of ATD for a more extended period of time can disrupt normal neuroendocrine and behavioral development.",
keywords = "Aromatase inhibitor, ATD, Copulatory behavior, Fertility, LH surge, Puberty, Sexual maturation, Sexual partner preference, Sheep",
author = "Charles Roselli and Schrunk, {J. M.} and Stadelman, {H. L.} and Resko, {J. A.} and F. Stormshak",
year = "2006",
month = "6",
doi = "10.1385/ENDO:29:3:501",
language = "English (US)",
volume = "29",
pages = "501--511",
journal = "Endocrine",
issn = "1355-008X",
publisher = "Humana Press",
number = "3",

}

TY - JOUR

T1 - The effect of aromatase inhibition on the sexual differentiation of the sheep brain

AU - Roselli, Charles

AU - Schrunk, J. M.

AU - Stadelman, H. L.

AU - Resko, J. A.

AU - Stormshak, F.

PY - 2006/6

Y1 - 2006/6

N2 - This study tested the hypothesis that aromatization of testosterone to estradiol is necessary for sexual differentiation of the sheep brain. Pregnant ewes (n ≤ 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is maximally sensitive to the behavior-modifying effects of exogenous testosterone (embryonic d 50-80; 147 d is term). Control (n ≤ 10) ewes received vehicle injections. Fifteen control lambs (7 males and 8 females) and 17 ATD-exposed lambs (7 males and 10 females) were evaluated for sexually dimorphic behavioral and neuroendocrine traits as adults. Prenatal ATD exposure had no significant effect on serum concentrations of androgen at birth, growth rates, expression of juvenile play behaviors, or the onset of puberty in male and female lambs. Rams exposed to ATD prenatally exhibited a modest, but significant, decrease in mounting behavior at 18 mo of age. However, prenatal ATD exposure did not interfere with defeminization of adult sexual partner preferences, receptive behavior, or the LH surge mechanism. In summary, our results indicate that aromatization is necessary for complete behavioral masculinization in sheep. However, before we can conclude that aromatization does not play a role in defeminization of the sheep brain, it will be necessary to evaluate whether intrauterine exposure of male fetuses to higher doses of ATD for a more extended period of time can disrupt normal neuroendocrine and behavioral development.

AB - This study tested the hypothesis that aromatization of testosterone to estradiol is necessary for sexual differentiation of the sheep brain. Pregnant ewes (n ≤ 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is maximally sensitive to the behavior-modifying effects of exogenous testosterone (embryonic d 50-80; 147 d is term). Control (n ≤ 10) ewes received vehicle injections. Fifteen control lambs (7 males and 8 females) and 17 ATD-exposed lambs (7 males and 10 females) were evaluated for sexually dimorphic behavioral and neuroendocrine traits as adults. Prenatal ATD exposure had no significant effect on serum concentrations of androgen at birth, growth rates, expression of juvenile play behaviors, or the onset of puberty in male and female lambs. Rams exposed to ATD prenatally exhibited a modest, but significant, decrease in mounting behavior at 18 mo of age. However, prenatal ATD exposure did not interfere with defeminization of adult sexual partner preferences, receptive behavior, or the LH surge mechanism. In summary, our results indicate that aromatization is necessary for complete behavioral masculinization in sheep. However, before we can conclude that aromatization does not play a role in defeminization of the sheep brain, it will be necessary to evaluate whether intrauterine exposure of male fetuses to higher doses of ATD for a more extended period of time can disrupt normal neuroendocrine and behavioral development.

KW - Aromatase inhibitor

KW - ATD

KW - Copulatory behavior

KW - Fertility

KW - LH surge

KW - Puberty

KW - Sexual maturation

KW - Sexual partner preference

KW - Sheep

UR - http://www.scopus.com/inward/record.url?scp=33748509715&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748509715&partnerID=8YFLogxK

U2 - 10.1385/ENDO:29:3:501

DO - 10.1385/ENDO:29:3:501

M3 - Article

C2 - 16943590

AN - SCOPUS:33748509715

VL - 29

SP - 501

EP - 511

JO - Endocrine

JF - Endocrine

SN - 1355-008X

IS - 3

ER -