Brain development, gonadal steroid hormone receptors, sexual differentiation, reproduction, neuroprotection by gonadal steroids, non-classical mechanisms of steroid hormone action.

The main focus of our laboratory is to understand sexual differentiation of the brain as a model for how the external environment influences development of the nervous system.  In mammals, induction of the masculine neuronal phenotype depends on the presence of androgens, derived from the testes; in the absence of androgens, the phenotype of the brain is essentially feminine. Androgens, estrogens, and other steroid hormones exert effects through steroid-specific receptors; the expression of these receptors, which are ligand-dependent transcription factions, is highly regulated. Many behaviors and physiological functions such as reproduction, language, spatial learning and stress responses, are sexually differentiated. Moreover, many mental and neurological disorders are more prevalent in one gender than the other.

Histochemical, molecular, and behavioral experiments in our laboratory are aimed at understanding the role of steroid receptors in modulating specific developmental processes such as neurogenesis, neurite outgrowth, selection of neurotransmitter phenotype, and cell death and the impact of these alterations on functional sexual differentiation. In addition, we are exploring the role of gonadal hormones in neuronal survival following injury, and are investigating the impact of estrogen on mood disorders. An understanding of the specific mechanisms through which gonadal steroids impact on functional differentiation of the central nervous system may elucidate the etiology of sexually differentiated psychological and neurological disturbances. Further, this research may offer clues as to the relative contributions of environmental and biological factors in the onset of gender-based differences in mental health and disease.

Garcia-Ovejero, D., S. Veiga, L.M. Garcia-Segura, L. L. DonCarlos  Glial  expression of estrogen and androgen receptors after rat brain injury. Journal of Comparative Neurology, 450: 256-271, 2002. Garcia-Segura, L.M., I. Azcoitia, and L. L. DonCarlos  Neurprotective effects of estrogen. Progress in Neurobiology, 63: 29-60,  2001.

McAbee, M., and L. L. DonCarlos  Ontogeny of region-specific sex differences in androgen receptor messenger RNA expression in the rat forebrain. Endocrinology, 139: 1738-1745, 1998.

DonCarlos, L. L., M. McAbee, D.S. Quinn, D. Stancik    Effects of hormonal manipulations on estrogen receptor mRNA in the preoptic area of male and female neonatal rats. Developmental Brain Research, 84: 253-260, 1995.

DonCarlos, L. L., E. Monroy, and J.I. Morrell   The distribution of estrogen receptor-immunoreactive cells in the forebrain of the female guinea pig. J. Comp. Neurology. 305: 591-612, 1991.