Metabolism of hCG and hLH to multiple urinary forms

Human chorionic gonadotropin (hCG) is synthesized primarily in the placenta while human luteinizing hormone (hLH) is produced in the pituitary. Both hormones are highly homologous in structure and both appear to be altered to analogous molecular forms as the hormones are proteolytically processed, or metabolized, from tissue of origin, through the circulation, and finally to the urine. Placental hCG is excreted into urine as heterodimeric hormone, heterodimeric nicked hCG, free subunits (some nicked), and predominantly as the hCG beta core fragment. A pituitary form of heterodimeric hCG, which is partly sulfated as is pituitary hLH, was recently isolated and is likely the form of hCG observed in the urine of healthy postmenopausal women and nonpregnant premenopausal women as well. A pituitary form of the hLH beta core fragment, highly analogous in structure to that of urinary hCG beta core fragment, has been used to develop specific monoclonal antibody assays to measure urinary hLH beta core fragment which is excreted at significantly higher molar concentrations than is hLH in the urine of ovulating women 1 or 2 days after the LH surge. This fragment of LH appears in the urine of postmenopausal women as well. The development of the capability to distinguish the hCG beta core fragment from the hLH beta core fragment in urine may have useful applications in tumor marker assays, pregnancy tests, and menopause. While hCG urinary assays have been widely employed, urinary assays for hCG and hLH metabolites are much less used since the urinary molecular forms are only partly known. Our studies of hCG and hLH urinary metabolites are directed towards improvement of the utility of urinary measurements of molecules derived from these hormones. Since many of the molecular forms of these two hormones in urine differ from their forms in blood, it may be necessary to produce new immunoassays as well as novel urinary reference preparations to accurately measure these molecules within their urinary matrix.