Gene of interest:
Aromatase (Cyp19a1)
Function:
Transforms testosterone into estradiol.
Background:
One important discovery in the development of our current understanding of steroid action in the brain
was that circulating steroids often need to be metabolized into more active molecules to exert their effects.
The aromatase enzyme is the most important enzyme who participates in such role. In the brain,
androgens are converted locally by aromatase into estradiol in order to activate male sexual behaviors.
This finding demonstrates that the brain utilizes the estradiol hormone almost exclusively with this
current understanding.
There are two modes of action of steroid hormones: intracellular and extracellular. In the classic hormone
pathway, the sex hormone binds to a receptor in the cell which then binds to hormone-receptor complex
called hormone-responsive element (HRE) resulting in regulation of gene transcription. Recent findings
demonstrate that the hormone also acts via extracellular pathway where the hormone binds to receptor on
the cell membrane which initiates signal amplification cascade. Without aromatase, none of this would
occur and therefore it is an integral gene and enzyme in the process of sexual differentiation in vertebrates.
Research interests:
Through regulation of aromatase activity, I want to determine which genes are activated during the
intracellular mode and extracellular mode. This will provide insights into the genes expressed in males and
the genes expressed in females and how they differ among the sexes. Also, it will provide insights into the
possible pathways involved in the extracellular mode of steroid action from the moment the sex hormone
binds to a membrane receptors (newly identified receptors include GPR30, STX-binding protein, ER-X)
to the moment when it activates the HRE. These findings will further investigate the myriad actions and
pathways of steroid hormones and their crucial interaction with the aromatase enzyme.
1
Chavalit Sitapradit
Biology-Physiology, Chemistry Minor,
Spring 2010
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