The general goal of this project is to understand the structure, function, and physiology of the human glycoprotein hormones--chorionic gonadotropin, thyrotropin, luteinizing hormone, and follicle-stimulating hormone--and from that knowledge to develop diagnostic and therapeutic clinical applications. Recent research progress includes the following: demonstration of the existence in humans of a peripheral metabolic pathway that cleaves carboxyterminal peptide fragments from desialylated chorionic gonadotropin; quantitation of the kinetic parameters governing the metabolism of desialylated chorionic gonadotropin in humans; characterization of hepatic pathways for catabolism of variably sialylated serum glyco-proteins in rats; and establishment of the feasibility of large-scale epidemiologic studies of early pregnancy loss based on measurement of chorionic gonadotropin in urine specimens. Future emphasis of the project will be on the development of clinical applications for ultrasensitive assays for glycoprotein hormones, elucidation of renal mechanisms for catabolism of chrionic gonadotropin and related molecules, assessment of the role of the carbohydrate moiety of thyrotropin in adenylate cyclase activation, and characterization of a naturally occurring inhibitor of the ovarian response to follicle-stimulating hormone.
