Our laboratory studies the regulation of steroid hormone
synthesis, by analyzing the transcriptional regulation of the steroidogenic
enzymes, and the mechanism of action of steroids in both steroidogenic
tissues and in the nervous system, where we identified the developmental
and regional expression of steroidogenic enzymes and some novel actions
of steroids on neuronal function. Steroid hormones are regulators
of a multitude of physiologic processes, and act primarily by activating
nuclear receptors, which are transcriptional regulators of various
genes. However in the nervous system, where we found steroidogenic
enzymes and synthesis of a novel class of steroid, called neurosteroids,
neurosteroids modulate ion flux through the ion gated GABA A and NMDA
receptors, and regulation of their synthesis results in changes in
behavior, learning, and memory. We delineated the ontogeny and sites
of steroidogenic enzyme expression , and showed that neurosteroids
affect neuronal development by specifically modulating either axonal
or dendritic growth and neuronal differentiation.Their actions throughout
life may maintain the integrity of neural connections, and demise
of neurosteroid synthesis may result in loss of memory associated
with some age-related neurologic diseases. Our studies thus rely on
a number of different experimental paradigms, from molecular biologic
analysis of gene structure and transcription factors to developmental
and cell biology of neuronal development and function. |
Biomedical Sciences (BMS) Graduate Program
