第２回「こころ」の科学セミナー
2006年1２月１２日（火）1６:00~1７:00
総合研究棟D棟1階マルチメディアルーム
From mechanisms to behavior: a tale of two hormones
Dr. Nandini Vasudevan
Assistant Professor of Biology,
Department of Biology, Penn State University, USA
Estrogens and thyroid hormones play roles in reproduction, neuroprotection and
cardiovascular physiology. The estrogen receptor (ER), a ligand-dependent
transcription factor, regulates transcription from target genes that have estrogen
response elements (EREs). This is a slow, genomic effect that occurs in the nucleus.
However, estrogen also activates intracellular signal transduction pathways by
promoting rapid non-genomic effects at the membrane. A lack of understanding of the
receptor mediating the membrane effects of estrogen has led to genomic effects gaining
prominence. In a neuroblastoma cell line, using a novel two-pulse paradigm, preliminary
membrane effects initiated by membrane-impermeable estrogens (E-BSA) are
necessary to potentiate the later genomic transcriptional effects of estrogen.
How does estrogen’s action at the membrane increase transcription in the nucleus? We
show that protein kinase activation results in phosphorylation of transcriptionally relevant
molecules such as the ER. This is also true of rapid signaling by thyroid hormone,
possibly via the thyroid hormone receptor. We further show that these may have
relevance for synapses in primary neuronal cultures.
A second facet of our work involves the delineation of affiliative and affective
behaviors in mice that lack different isoforms of the thyroid hormone receptors. Mice
that lack TRα1 have increased anxiety while those that lack the TRβ isoforms possess
decreased anxiety. Mechanisms that underlie this difference in anxiety will be
discussed.