(provided by candidate): Differences between the brains of males and females contribute to their distinct physiology and behavior. Prominent sex-specific differences in cell number and connectivity are found in the hypothalamic nuclei of many vertebrates. These dimorphisms are mediated by sex hormones. In rats, for example, sex hormones secreted by the gonad during a critical period of development determine the size of the """"""""sexually dimorphic nucleus"""""""" in the medial preoptic area of the hypothalamus, which contains more cells in males than in females. However, steroid hormones synthesized directly in the brain may also play a role in its sexual differentiation. The zebrafish provides a unique opportunity to visualize estrogen receptor activity directly in a live, developing vertebrate brain. Genetic techniques can also be used to produce adults that completely lack gonadal tissue. The overall goal of my project is to capitalize on transgenic zebrafish I have already developed to characterize estrogen-sensitive neurons in the preoptic area and hypothalamus and compare their organization in males and females. I will also explore the role gonadal hormones play in their development and in the activation of sexually dimorphic mating behaviors.
The specific aims of this proposal are: 1) to assess whether the number and projections of estrogen sensitive neurons in the preoptic area differ between male and female zebrafish;2) to determine whether inhibiting gonad differentiation and survival alters the organization of estrogen sensitive neurons in the preoptic area and the activation of mating behaviors;3) to generate transgenic zebrafish that conditionally express a dominant negative estrogen receptor. This proposal seeks to understand how estrogen hormones affect the growth and connection of cells in the brain. Abnormal estrogen activity has been implicated in the growth of certain cancers, while many environmental contaminants (such as pesticides) disrupt normal estrogen activity, which can lead to reproductive defects or cancer. Gaining a better understanding of how estrogens function in the brain may provide insights that will allow us to better combat toxic environmental contaminants and cancer.
| Gorelick, Daniel A; Pinto, Caroline Lucia; Hao, Ruixin et al. (2016) Use of Reporter Genes to Analyze Estrogen Response: The Transgenic Zebrafish Model. Methods Mol Biol 1366:315-325 |
| Gorelick, Daniel A; Iwanowicz, Luke R; Hung, Alice L et al. (2014) Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples. Environ Health Perspect 122:356-62 |
| Hao, Ruixin; Bondesson, Maria; Singh, Amar V et al. (2013) Identification of estrogen target genes during zebrafish embryonic development through transcriptomic analysis. PLoS One 8:e79020 |
| Gorelick, Daniel A; Halpern, Marnie E (2011) Visualization of estrogen receptor transcriptional activation in zebrafish. Endocrinology 152:2690-703 |
