Characterization of a small molecular size urinary immunoreactive human chorionic gonadotropin (hCG)-like substance produced by normal placenta and by hCG-secreting neoplasms.

Abstract

Urine obtained from normal pregnant women as well as from patients with hCG-secreting tumors frequently contains native hCG and free hCG subunits when separated on Sephadex G-100. In addition, a small amount of an immunoreactive, hCG-like, low molecular weight substance is usually observed in those chromatograms and represents less than 1% of the total immunoreactive hCG present. Two patients with widely metastatic hCG-secreting tumors excreted disproportionately large quantities of that low molecular weight substance, and that observation raised the possibility that this substance was a secretory and not a degradative product of the hCG molecule. The small immunoreactive hCG-like substance was subsequently characterized immunologically, biologically, and physically. The hCG fragment displayed a biphasic dose-response line in a homologous hCG RIA. The slope of the upper portion of the dose-response line was equal to that for native hCG, but the slope of the lower component of the dose-response line was significantly different from that for hCG. The immunoreactive hCG substance cross-reacted with hCG beta but not with either hCG alpha or hCG beta carboxyl-terminus. The small molecular size immunoreactive hCG-like substance bound to Concanavalin A-Sepharose 4B and eluted with 0.2 M alpha-D-methyl glucopyranoside, contained no significant intrinsic biological activity when tested in the in vitro Leydig cell bioassay and also failed to compete with labeled hCG for specific ovarian LH/hCG receptors. Consequently, that small urinary immunoreactive hCG substance behaved neither as a hCG agonist or antagonist. It exhibited a plasma half-life of 4.5 min when the appropriate Sephadex G-100 fractions were injected into immature female rats. The small molecular size immunoreactive hCG-like substance may be a secretory or breakdown product of hCG-secreting cells.