Toni R. Pak, PhD

Associate Professor
Department of Cell and Molecular Physiology

1995 - University of Colorado at Boulder
BA – Environmental, Population and Organismic Biology

1997 - University of Colorado at Boulder
MA – Education (Science)

2002 - University of Colorado at Boulder,
Ph.D. – Neuroscience

Neuroendocrine regulation of puberty and the molecular mechanisms of nuclear steroid receptor transactivation.

The central theme of my research falls under the broad category of neuroendocrinology with a specific focus on the molecular signaling properties of nuclear steroid receptors and the process of sexual maturation.  Elucidating the molecular basis of nuclear steroid receptor-mediated gene expression is central to understanding how steroid hormones modulate a variety of physiological processes including social behaviors, sexual maturation, and reproductive function.  Research in my lab integrates molecular techniques with whole animal physiology in order to determine how gene expression and hormones interact to regulate the process of puberty.

There are currently three main projects in the lab.  The first one involves elucidating the molecular signaling pathway for estrogen receptor-beta (ER) by addressing the following questions: 1) how do the ERb splice variants interact with each other to modulate estrogen signaling and 2) what are the molecular mechanisms governing ERb splice variant-induced gene transcription.  Recent work has shown that ER has strong ligand-independent activity.  Insight into the cellular and molecular consequences of these ligand-independent effects will provide another dimension to our general knowledge of steroid hormone action. 

Second, a dramatic increase in gonadotropin-releasing hormone (GnRH) is one of the hallmarks of pubertal onset.  Research in this laboratory uses a transgenic rat model that expresses green fluorescent protein under the control of the GnRH promoter in order to identify candidate genes in GnRH neurons that are differentially regulated during the process of sexual maturation. 

Finally, centrally expressed nuclear steroid hormone receptors are important integrators of the internal and external factors that potentiate downstream centrally mediated behaviors.  Previous work demonstrated that ER and its splice variants modulate arginine vasopressin (AVP) promoter activity in neuronal cells; an important central mediator for social, aggressive and affiliative behaviors. Recent work has focused on determining 1) how hormones affect AVP expression during pubertal development and 2) how does “binge drinking” during puberty affect AVP expression in the brain.  In addition, recent work has begun to investigate how changes in gonadal steroid hormones at the time of puberty contribute to the sexually dimorphic patterns of alcohol consumption.

Pak TR, Chung WCJ, Roberts JL, Handa RJ (2006) Ligand-independent effects of estrogen receptor beta on mouse gonadotropin releasing hormone (GnRH) promoter activity. Endocrinology 147(4):1924-1931.

Pak TR, Chung WCJ, Lund TD, Hinds LR, Clay CM, Handa RJ (2005) The androgen metabolite, 5a-androstane-3b, 17b-diol (3bAdiol), is a potent modulator of estrogen receptor-b1-mediated gene transcription in neuronal cells. Endocrinology 146(1):147-155.

Pak TR, Lynch, G.R., Ziegler, D.M., Lunden, J.B., and Tsai, P.-S. (2003) Disruption of pubertal onset by exogenous testosterone and estrogen in two species of rodents. Am J Physiol Endocrinol Metab. 284:206-212.

Pak TR, Lynch, GR, and Tsai, P-S (2002). Estrogen accelerates gonadal recrudescence in photo-regressed male Siberian hamsters. Endocrinology143:4131-4134.

Pak TR, Lynch GR, Tsai P.-S. (2001) Testosterone and estrogen act via different pathways to inhibit puberty in the male Siberian hamster (Phodopus sungorus). Endocrinology 142:3309-3316.