We have been studying the genetics and biochemistry of the steroid sulfatase (STS) system. This microsomal enzyme is capable of desulfating a range of 3Beta-hydroxysteroid sulfates. It plays a major role in the hydrolysis of sulfated precursors for estrogen biosynthesis during pregnancy and is involved in the regulation of sulfated steroid metabolism in later life as well. Patients genetically deficient in STS have been frequently identified (about 1 in 6,000 males). They are the products of pregnancies in which estrogen production is deficient by virtue of absence of placental sulfatase activity. Due to the diminished estrogen levels, pregnancies are frequently prolonged or parturition is delayed. After birth, they develop a dermatologic condition known as ichthyosis which is associated with accumulation of cholesterol sulfate in the skin. Further metabolic studies should enhance our knowledge of the mechanisms which control the onset of labor, of the development of the epidermis, and of steroid metabolism in normal and abnormal individuals. We have also shown that steroid sulfatase synthesis is controlled by a gene located in a unique region (the dital tip of the short arm) of the human X chromosome. This gene escapes X chromosome inactivation, and this portion of the X chromosome is partially homologous to the Y chromosome and appears to engage in genetic recombination with it. We plan studies involving the cloning of the steroid sulfatase gene as well as other portions of the distal X short arm in order to gain insight into gene regulation in this portion of the genome, to investigate the possibility of X-Y recombination and to study alteration of sex chromosome segregation associated with X chromosome aneuploid states such as Turner's Syndrome and Kleinfelter's Syndrome.
Showing the most recent 10 out of 34 publications
