Medical Student Research Fellowship for Summer 2005

Mentor: Keith L. Parker
Department: Internal Medicine
Room number: J6.106
Mail Code: 8857
Phone number: 214 648-5027
E-mail: keith.parker@utsouthwestern.edu
Project title: Steroidogenic factor 1 and endocrine function

Human subjects IRB approved project number (where applicable): N/A

Animal subjects IRB approved project number (where applicable): 0803-04-02-2

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)
Animal-based and basic

Brief Description of Project:

The major focus of our laboratory is the orphan nuclear receptor steroidogenic factor 1 (SF-1). Originally isolated as an essential regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases, SF-1 has subsequently been shown by us and others to regulate the expression of multiple genes that mediate reproduction and steroidogenesis. SF-1 knockout mice lack adrenal glands and gonads, the two primary steroidogenic tissues where SF-1 is expressed. They further have impaired function of the anterior pituitary cells related to reproduction, the gonadotropes. Finally, they have marked structural abnormalities of the ventromedial hypothalamic nucleus (VMH)-a brain region that is implicated in energy homeostasis and female sexual behavior.

Ongoing experiments seek to identify the target genes by which SF-1 mediates these complex, but essential, roles in endocrine function. One major approach is to make tissue-selective knockouts of SF-1, which will facilitate the analysis of its actions at different sites in isolation. Other studies are using transgenic targeting to define inactivate genes of interest specifically within the VMH. These studies will hopefully provide new insights into the mechanisms of endocrine development and function.

Previous Research Activities or Publications with Medical Students:

Correa RV, Domenice S, Bingham NR, Rainey W, Billerbeck EC, Parker KL, and Mendonca B 2004 A microdeletion in the ligand binding domain of steroidogenic factor 1 causes XY sex reversal without adrenal insufficiency by a dominant negative mechanism. J. Clin.Endocrinol. Metab. 89, 1767-1772.

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