Grant: Project Grant

Steroid hormones are critical for the maintenance of the organism's homeostasis, adaptability to the environment, developmental and reproductive functions. Changes in the rate of steroid formation in response to genetic defects, metabolic disorders, and/or drug or environmental exposures can result in life-altering diseases. Reduced testosterone has been linked to infertility, erectile dysfunction, obesity, osteoporosis and cardiovascular diseases. Adrenal cortisol synthesis is involved in stress-response and adaptation; changes in adrenal aldosterone production can lead to changes in blood pressure and thus cardiovascular diseases. Adrenocortical tumors produce excessive amounts of cortisol, and androgen and ovarian tumors produce androgen and estrogen, all leading to endocrine disorders and potentially to pathological conditions. Changes in circulating steroids in peripheral tissues and brain have been linked to neuropsychiatric disorders. The adrenals, gonads and placenta form steroids from cholesterol. The steroids exert their functions throughout the body. Other tissues, including brain, adipose, prostate, and skin can also form steroids that fulfill local needs. For over 50 years, steroid levels have been as indicators used to diagnose various diseases, e.g. Cushing's syndrome, Addison's disease, congential adrenal hypeplasia, hypogonadism, precocious puberty, etc, and steroids have served as drugs for the treatment of endocrine, reproductive and metabolic disorders. These conditions span from early development to aging. Despite the widespread use, and abuse, of steroids, there are major gaps in our knowledge of the mechanisms regulating their production, and the effects of hormones and drugs on their synthesis and function. The goal of this project is to understand the mechanisms underlying steroid hormone biosynthesis and regulation, and thus pave the way for the development of novel pharmacological strategies to control steroid formation.