Estrogen and androgen, two major sex steroid hormones, regulate many important functions not only during development, but also into adulthood through their specific receptors. Their intracellular distribution of these receptors in the cell has been found to be much more dynamic than previously thought. Estrogen receptor (ER) dynamism was involved in association with transcription factors including estrogen-related receptors (ERRs) and nuclear matrix, while androgen receptor (AR) trafficking between the cytoplasm to the nucleus was regulated by importin system. We found new sexually dimorphic systems in the hypothalamus expressing ERa and gastrin releasing peptide (GRP) neurons expressing AR in the spinal cord. Ventromedial nucleus of the hypothalamus in the adult showed different expression of ERa when they were different positioned within the uterus. Different expression was demonstrated by the different frequency of DNA methylation. AR activation during perinatal criticalperiod organized developing brain into a masculinized structure and sexual behavior at later adult stage. Males treated by histone deacetylase inhibition during early postnatal period reduced male sexual behavior in the adult, indicating the epigenetic role for expression of behavior. In the adulthood androgen affected dendritic spine maturation in the hippocampal pyramidal neurons associated with BDNF and PSD-95. Itching sensation was changed during estrous cycle and estrogen condition. GRP in the dorsal ganglion and spinal cord played a key role in itching mechanism in association with estrogen action.
My experiments were started from Kyoto by using immunohistochemical methods and expanded to use in situ hybridization techniques in New York where sexual behavioral studies were extensively analyzed. In Edinburgh these methods were refined and GFP live imaging in Kyoto was developed in conjunction with behavioral studies.
These seamless approach including molecular, cellular, histological and behavioral analyses offers new avenues for deep understanding of sex steroid hormones in the neuroendocrine system.