The overall objectives of this project are to understand the endocrinology of the human glycoprotein hormones, thyroid- stimulating hormone (TSH), chorigonadotropin (hCG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and thereby to develop diagnostic and therapeutic clinical applications. Recent research advances in the current period include the following: Purification and structural characterization of a fragment of the beta subunit of hCG, called beta-core, which is the most abundant hCG-related molecule in pregnancy urine; development of a radioimmunoassay for beta-core in which LH, hCG, and beta-hCG exhibit negligible cross-reactivity, thus making feasible studies of the physiology and cancer biology of beta-core; demonstration in vivo in men of full intrinsic steroidogenic activity in highly purified desiaylated hCG; and elucidation of a potential clinical role for immunoassays which detect specific carbohydrate structures in the carboxyl-terminal region of hCG-beta. Future directions of the project will include determination of the physiological pattern of beta-core production in normal pregnancy, investigations of the biochemistry and physiology of beta-core production and metabolism, characterization of the natural evolution of the oligosaccharide structures of hCG and its subunits throughout pregnancy, and assessment of the roles of subtle defects of pituitary-thyroid axis function or of TSH structure as causes of short stature and delayed growth in childhood.
