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 (ERβ) 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
ERβ 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 ERβ 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.
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Publications
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. Endocrinology 143:4131-4134.
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. |
