There are large sex differences in the brain regions that control song in passerine birds. These sex differences develop under the control of sex steroid hormones. The long term objectives are to understand the mechanisms of sexual differentiation of brain and behavior, i.e., the cellular mechanisms by which sex steroid hormones influence neural development. The anticipated health benefit of the proposed studies is a better fundamental understanding of the synthesis of steroid hormones and their physiological effects on development of the brain and behavior. Current theories of sexual differentiation in zebra finches suggest that the male's brain synthesizes its own estrogen early in development, and this estrogen causes masculine development of the neural song system. Several methods will be used to find the sites of estrogen action during sexual differentiation: focal implants of sex steroids, lesions, and autoradiographic techniques to locate steroid receptors. The synthesis and metabolism of estrogen will be measured in homogenates of dissected regions of the brain to look for sex differences in the availability of estrogen during development. Various inhibitors of estrogen synthesis will be tested and used in an attempt to block the masculinization that occurs in males. In cultures of neurons and glia derived from various brain regions at various ages, the synthetic enzymes for estrogen and other steroids will be measured in males and females in order to look for sex differences. Estrogen receptors will also be measured in these cultures. Little is known about the role of sex steroid hormones during embryonic life, and there are good reasons to suspect that steroids act during this period to initiate the process of sexual differentiation. This idea will be tested by administering steroids or inhibitors of steroid synthesis to embryos to assess the effects of these treatments on development of brain and behavior.
| Burgoyne, Paul S; Arnold, Arthur P (2016) A primer on the use of mouse models for identifying direct sex chromosome effects that cause sex differences in non-gonadal tissues. Biol Sex Differ 7:68 |
| Itoh, Yuichiro; Arnold, Arthur P (2014) X chromosome regulation of autosomal gene expression in bovine blastocysts. Chromosoma 123:481-9 |
| Arnold, Arthur P; Chen, Xuqi; Link, Jenny C et al. (2013) Cell-autonomous sex determination outside of the gonad. Dev Dyn 242:371-9 |
| Arnold, Arthur P (2012) The end of gonad-centric sex determination in mammals. Trends Genet 28:55-61 |
| Itoh, Yuichiro; Kampf, Kathy; Arnold, Arthur P (2011) Possible differences in the two Z chromosomes in male chickens and evolution of MHM sequences in Galliformes. Chromosoma 120:587-98 |
| Naurin, Sara; Hansson, Bengt; Hasselquist, Dennis et al. (2011) The sex-biased brain: sexual dimorphism in gene expression in two species of songbirds. BMC Genomics 12:37 |
| Itoh, Yuichiro; Kampf, Kathy; Balakrishnan, Christopher N et al. (2011) Karyotypic polymorphism of the zebra finch Z chromosome. Chromosoma 120:255-64 |
| Itoh, Yuichiro; Arnold, Arthur P (2011) Zebra finch cell lines from naturally occurring tumors. In Vitro Cell Dev Biol Anim 47:280-2 |
| Arnold, Arthur P; Itoh, Yuichiro (2011) Factors causing sex differences in birds. Avian Biol Res 4: |
| McCarthy, Margaret M; Arnold, Arthur P (2011) Reframing sexual differentiation of the brain. Nat Neurosci 14:677-83 |
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