BBB seminar: Keith L. Parker
Steroidogenic factor 1: a key mediator of endocrine development
Keith L. Parker
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Knockout mice lacking steroidogenic factor 1 (SF-1) have a complex endocrine phenotype that includes adrenal and gonadal agenesis, impaired expression of gonadotropins by pituitary gonadotropes, and structural abnormalities of the ventromedial hypothalamic nucleus (VMH). These multiple defects complicate efforts to define direct versus indirect effects of SF-1 deficiency in different tissues. To make tissue-specific knockouts of SF-1, we expressed Cre recombinase driven by several different promoters, thereby specifically inactivating a modified SF-1 allele in the pituitary, VMH and the gonads. These tissue-specific SF-1 knockout mice provide novel genetic models to explore the roles of SF-1 in specific cell types. In the gonads, inactivation of SF-1 using Cre driven by the receptor for anti-mullerian hormone led to sterility in both male and female mice. The females had absence of corpora lutea and hemorrhagic cysts, suggesting that estrogen production was impaired. The males had failure of testes descent, suggesting that production of androgens and/or Insl3 was impaired. Inactivation of SF-1 in the central nervous system led to marked structural abnormalities in the VMH, associated with decreased locomotor activity, increased anxiety, and increased adiposity. These studies are defining specific roles of SF-1 in different compartments where it is expressed.
|Dr. Keith L. Parker|
Dr. Parker is one of the world leading scientists in the fields of molecular steroidogenesis and development and of function of the hypothalamic-pituitary-adrenal/gonadal axis. Through the use of mouse genetics he has dissected the functional roles of transcription factors at all three levels. His talk will be of interest to everyone interested in gene regulation, tissue-specific knockout technology, steroidogenesis, sex differentiation and genetic models for obesity linked to the hypothalamus.