We are interested in understanding the mechanisms that control the development and function of the adrenal glands, ovaries, and testes. One major focus is the orphan nuclear receptor steroidogenic factor 1 (SF-1), which we first identified as a global regulator of the cytochrome P450 steroid hydroxylases. Gene knockout studies showed that SF-1 knockout mice completely lacked adrenal glands and gonads, had impaired function of the pituitary gonadotropes, and lacked a specific region of the hypothalamus, the ventromedial hypothalamic nucleus. Ongoing studies will use tissue-specific gene knockouts to define the precise roles that SF-1 plays at different levels of the endocrine axis. A second goal is to identify the SF-1 target genes whose expression is essential for adrenal and gonadal development. Our other focus is a protein recently shown to be important for cholesterol trafficking within the cell, called the steroidogenic acute regulatory protein (StAR). We have generated StAR knockout mice, which are unable to translocate cholesterol to the mitochondria, where steroidogenesis commences, and thus have severe defects in the production of all steroids. These mice will be used to gain new insights into the roles of StAR within the steroidogenic cells in an intact endocrine milieu.
RESEARCH INTERESTS
SF-1
StAR
Sexual Differentiation
Obesity
RECENT PUBLICATIONS
Sasaki G, Ishii T, Jeyasuria P, Jo Y, Bahat A, Orly J, Hasegawa T and Parker KL, "Complex role of the mitochondrial targeting signal in the function on steroidogenic acute regulatory protein revealed by bacterial artificial chromosome transgenesis in vivo" Molecular Endocrinology, 22:951-964, 2008
Lavery GG, Hauton D, Walker EA, Sherlock M, Rogoff D, Ryder JW, Shelton J, Richardson JA, White PC, Stewart PM, Parker KL and McMillan DR, "Targeted deletion of hexose-6-phosphate dehydrogenase activates the unfolded protein response pathway and induces a novel skeletal myopathy" Journal of Biological Chemistry, 283:8453-8461, 2008
Bingham NC, Anderson KE, Reuter AL, Stallings NR and Parker KL, "Selective loss of leptin receptors in the ventromedical hypothalamic nucleus results in increased adiposity and a metabolic syndrome" Endocrinology In press,
Zhao L, Kim K-W, Ikeda Y, Anderson KK, Beck L, Chase S, Tobet SA and Parker KL, "CNS-specific knockout of steroidogenic factor 1 results in increased anxiety-like behavior" Molecular Endocrinology In press,
SIGNIFICANT PUBLICATIONS
Luo, X, Ikeda, Y, and Parker KL, "A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation" Cell, 77:481-490, 1994
Ingraham HA, Lala DS, Ikeda Y, Luo X, Shen W-H, Nachtigal MW, Abbud R, Nilson JH, and Parker KL, "The nuclear receptor SF-1 acts at multiple levels of the reproductive axis" Genes Dev., 8:2302-2312, 1994
Caron KM, Soo S-C, Clark BJ, Stocco DM, Wetsel W, and Parker KL, "Targeted disruption of the mouse gene encoding the steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia" Proc. Natl. Acad. Sci. USA, 94:11540-11545, 1997
Zhao L, Bakke M, Cushman LJ, Burrows HL, Parlow AF, Camper SA, and Parker KL, "Steroidogenic factor 1 is essential for pituitary gonadotrope function" Development, 128:147-154, 2001
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