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A role for ovarian hormones in sexual differentiation of the brain

Fitch, Roslyn Holly and Denenberg, Victor H. A role for ovarian hormones in sexual differentiation of the brain.

Short Abstract:

Historically, studies of the role of endogenous hormones in developmental differentiation of the sexes have suggested that mammalian sexual differentiation is primarily mediated by testicular androgens, and that exposure to androgens in early life leads to a male brain as defined by neuroanatomy and behavior. The female brain has been assumed to develop via a hormonal default mechanism, in the absence of androgen or other hormones. The role of ovarian hormones in female sexual differentiation may be complementary to androgen-mediated masculinization because the feminizing effects of ovarian steroids are only found in the absence of perinatal androgen. Ovarian hormones have significant effects on the development of a sexually dimorphic cortical structure, the corpus callosum, which is larger in male than female rats. In the females, removal of the ovaries as late as Day 16 increases the cross-sectional area of the adult corpus callosum. Treatment with low-dose estradiol starting on Day 25 inhibits this effect. Female callosa are also enlarged by a combination of daily postnatal handling and exogenous testosterone administered prior to Day 8. The effects of androgen treatment are expressed early in development, with males and testosterone-treated females having larger callosa than control females as early as Day 30. The effects of ovariectomy do not appear until after Day 55. These findings are consistent with other evidence of a later sensitive period for ovarian feminization than androgenic masculinization.

Long Abstract:

Historically, studies of the role of endogenous hormones in developmental differentiation of the sexes have suggested that mammalian sexual differentiation is primarily mediated by testicular androgens, and that exposure to androgens in early life leads to a male brain as defined by neuroanatomy and behavior. The female brain has been assumed to develop via a hormonal default mechanism, in the absence of androgen or other hormones. The role of ovarian hormones in female sexual differentiation may be complementary to androgen-mediated masculinization because the feminizing effects of ovarian steroids are only found in the absence of perinatal androgen. Ovarian hormones have significant effects on the development of a sexually dimorphic cortical structure, the corpus callosum, which is larger in male than female rats. In the females, removal of the ovaries as late as Day 16 increases the cross-sectional area of the adult corpus callosum. Treatment with low-dose estradiol starting on Day 25 inhibits this effect. Female callosa are also enlarged by a combination of daily postnatal handling and exogenous testosterone administered prior to Day 8. The effects of androgen treatment are expressed early in development, with males and testosterone-treated females having larger callosa than control females as early as Day 30. The effects of ovariectomy do not appear until after Day 55. These findings are consistent with other evidence of a later sensitive period for ovarian feminization than androgenic masculinization.

Keywords:	Activational effects, androgens, corpus callosum, estrogen, female default hypothesis, feminization, masculinization, organizational effects, sensitive periods, sexual differentiation, testosterone
Subjects:	Biology: Evolution Psychology: Evolutionary Psychology Neuroscience: Neurochemistry
ID code:	bbs00000557
Deposited by:	Holly Fitch on 02 May 2001