This project is designed to further describe the physiology of androgens and the control of gonadal secretions in man. Two related studies are proposed. We will study the feedback relationship between testosterone, androstenedione, 17 alpha hydroxyprogesterone, and estradiol on luteinizing and follicle stimulating hormone. The steroids will be measured by competitive protein binding or immunoassay and the gonadotropins by a conveniently located collaboration with W. Odell. Our study will utilize new data on blood production rates and androgen- estrogen interconversions so that constant infusions will administer physiological amounts and the natural relationship between testicular secretions and gonadotropin described. For comparative purposes, hyper- gonadotropic subjects (anorchic castrate, Klinefelter's) will also be infused using physiological and pharmacologic amounts of natural gonadal steroids. Dihydrotestosterone infusions will allow description of the role of a pure androgen. The other project will attempt to describe and generate (in rabbits) in an organized fashion antibodies to C19 gonadal steroids. Conjugation will use thyroglobulin rather than albumin since very high incorporation ratios can be achieved. The injection of a series of similarly structured steroids conjugated at different sites should allow a careful description of general rules for development of antibodies to steroids. Some of the antibodies will be used for assay of potentially important steroids such as androstane-3 alpha, 17 beta diol, DHT, and testosterone.