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Physiological Studies of Human Chorionic Gonadotropin (hCG), hCG, and βhCG as Measured by Specific Monoclonal Immunoradiometric Assays^*

MEHMET OZTURK, DOMINIQUE BELLET, LUC MANIL, GEORGE HENNEN, RENE FRYDMAN and JACK WANDS

Gastrointestinal Unit, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School (M.O., J. W.) Boston, Massachusetts 02114
the Departement de Biologie Clinique, Institut Gustaue Roussy (D.B., L.M.) 94805 Villejuif Cedex
Service de Gynecologie, Unite Inserm 187, Hopital Antoine Beclere (R.F.) Clamart, France
Endocrinologie Clinique et Experimentale, Universite de Liege (G.H.) Liege, Belgium

Address all correspondence and requests for reprints to: J. R. Wands, MD., Gastrointestinal Unit, Masachusetts General Hospital, Boston, Massachusetts 02114

Abstract

Several libraries of monoclonal antibodies have been produced against epitopes that reside on hCG, hCG, and. βhCG. Having characterized them physically, we explored their use in the construction of highly specific and sensitive immunoradiometric assays. There were several important immunochemical considerations with respect to developing assays that accurately detect low levels of free subunits in serum in the presence of high concentrations of the native hormone. These include physical properties and specificities of the monoclonal antibodies, choice of capture antibody on the solid phase support, assay design, and purity of hormone standards. Using such assays, we found early pregnancy (in vitro fertilization) to be characterized by the sequential appearance of hCG, followed by phCG and then cvhCG. Molar ratios of βhCG to βhCG and βhCG to hCG were highest in early gestation. However, there was a reversal of the βhCG to ahCG ratio at 12–13 weeks gestation, and an excess of free ahCG was observed thereafter. Except for values obtained in very early pregnancy, the βhCG to hCG ratio remained remarkably constant at approximately 0.5% throughout gestation. In contrast, choriocarcinoma was distinguished by absolute serum βhCG concentrations 3–100 times greater than the maximum values observed during pregnancy and, more importantly, by exceedingly high βhCG to hCG ratios. For comparison, we studied hCG, ahCG, and βhCG levels in an additional 178 patients with nontrophoblastic tumors. Ectopic production of hCG and βhCG was rare (3%), and thus far, we have been unable to demonstrate the presence of hCG in such patients. Therefore, hCG and the free subunits appear not to be useful as serological markers for nontrophoblastic tumors. (Endocrinology 120: 549–558, 1987)

Footnotes

^* This work was supported in part by NIH Grants AA-20666, HD-20469, and CA-35711 and a grant from Association pour la Recherche sur le Cancer (Villejuif, France).

Recipient of a research fellowship from Association pour la Recherche sur le Cancer.

Recipient of Research Center Scientist Development Award AA-00048 from the NIH.

Received March 20, 1986.

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