The objective of this project is to advance understanding of the mechanisms that underlie normal and abnormal puberty, and to apply this knowledge to improve existing therapy for disorders of puberty. Principal areas of clinical investigation include the mechanism of premature thelarche and of the gonadotropin- independent forms of precocious puberty the developmental changes in hypothalamic regulation of gonadotropin secretion, the behavioral changes associated with normal and abnormal pubertal development, the mechanisms of prepubertal and pubertal growth, the role of pubertal sex steroids in the acquisition of normal adult bone density, the treatment of central precocious puberty with an analog of luteinizing hormone-releasing hormone, the treatment of the McCune-Albright syndrome with an aromatase inhibitor, and the treatment of familial male isosexual precocious puberty with combined antiandrogen and aromatase inhibitor. A major focus of laboratory investigation involves cloning and structural analysis of the human gonadotropin-releasing hormone gene and studies of the regulation of this gene in transfected cells.
