Neuroendocrine regulation of behavior is achieved through a series of actions by steroid hormones that affect genomic processes and events at the cell membrane level. The objective of the research program in our laboratory is to characterize these effects of steroids and to determine how they contribute to target cell sensitivity and, consequently, the expression of sexually dimorphic behaviors. The presence of sex and strain differences in response to the gonadal hormones testosterone, estradiol, and progesterone provides a powerful model for the elaboration of these steroidal effects and we have utilized these differences to help build increasingly refined regulatory models over the past fifteen years. The mouse has served as the primary species in our research and, more recently, we have initiated collaborative studies that involve analyses of non-human primate and sheep brains.
The current emphases of our research are on androgen and estrogen receptor regulation, the modulation of serotonin receptor and transporter function by testosterone and its metabolites, the actions of selective estrogen receptor modulators (SERM), and dehydroepiandrosterone - GABAA receptor interactions. Three of these areas, steroid receptor regulation, hormone-serotonin interactions, and the effects of the neurosteroid DHEA on GABA-A function, are tied to an ongoing effort to better understand the neurobiology of conspecific aggressive behavior. The fourth, SERM effects in the CNS, is part of our collaborative efforts with Drs. Jay Kaplan and Simon Turner in women's health and aging. A variety of techniques are employed in these studies including immunocytochemistry, Western analysis, RNase protection assays, gel mobility shift assays, and biobehavioral investigations including microinjection studies.
Guillon, C. Gary A. Koppel, Michael J. Brownstein, Michael O. Chaney, Craig F. Ferris, Shi- fang Lu , Karine M.Fabio , Marvin J. Miller, Ned D. Heindel, David C. Hunden, Robin D. G. Cooper, Stephen W. Kaldor, Jeffrey J. Skelton, Bruce A. Dressman Michael P. Clay, Mitchell I. Steinberg, Robert F. Bruns, Neal G. Simon,. (2007) Azetidinones as vasopressin V1a antagonists. J. Biorganic Med Chem.
Simon, N. G. and Ferris, C.F. (2007) Aversive emotions: Hormonal basis of aggression. In L. Squire, et al. (eds.) New Encyclopedia of Neuroscience, Elsevier.
Simon, N. and Lu, S (2006). Androgens and aggression. In R. Nelson (ed), Aggressive Behavior. Oxford Press, pp. 537-582.
Simon, N., Mo, Q., Hu, S., and Lu, S. (2006). Hormonal pathways regulating intermale and interfemale aggression. Intl. Rev. Neurobiol., 73, 99-124Ferris, C.F., Lu, S., Messenger, T., Miller, M., Koppel, G.A., Bruns, F.R., Simon, N.G. (2006) An orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior. Pharmacol, Biochem. Behav, 83, 169-174
Mo, Q., Lu, S., Simon, N.G. (2006) Dehydroepiandrosterone and its metabolites: Differential
effects on androgen receptor trafficking and transcriptional activity. J ster. Biochem. Mol. Biol., 99, 50-58
Hu, S., Kaplan, J., Adams, M., and Simon, N. (2005). ER-beta protein expression in cynomolgus monkey and CF-1 mouse brain. J. Neurobiol., 64, 298-309.
Simon, N.G., Kaplan, J.R., Hu, S., Register, T.C., and Adams, M.R.(2004) Increased aggressive behavior and decreased affiliative behavior in adult male monkeys after long-term consumption of diets rich in soy protein and isoflavones. Horm. Behav. 45, 278-284
Mo, Q., Lu, S., Hu, S., and Simon, N.G. (2004) DHEA and DHEA sulfate differentially regulate androgen receptor and its transcriptional activity. Mol. Brain Res., 126, 165-172.