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Functional, Structural, and Distribution Analysis of the Chorionic Gonadotropin Receptor Using Murine Monoclonal Antibodies

Department of Genetics, Biology and Biochemistry (A.F., B.F., A.L.H., F.M.), Research Center for Experimental Medicine (A.F., B.F., A.L.H., F.M.), Department of Biomedical Science and Human Oncology (A.S., I.C.), University of Torino, Torino 10126, Italy; Department of Nuclear Medicine, University of Modena (B.B.), Modena 41100, Italy; and Serono International (G.G.), Geneva 1228, Switzerland

Address all correspondence and requests for reprints to: Fabio Malavasi, M.D., Department of Genetics, Biology and Biochemistry, via Santena 19, 10126 Torino, Italy. E-mail: fabio.malavasi{at}unito.it.

LH and human chorionic gonadotropin (hCG) control steroid production and gametogenesis. They also function as growth factors through interaction with a specific receptor that is a member of the seven-transmembrane receptor family coupled via G proteins to signal pathways involving cAMP and phospholipase C/inositol 3 phosphate.

For this study, monoclonal antibodies (mAbs) were raised against the human LH receptor (LHR)/hCG receptor (hCGR), using Chinese hamster ovary LHR-transfected cells as the immunogen. Two reagents were then selected on the basis of their ability to recognize the full-length transmembrane re-ceptor expressed both by Chinese hamster ovary LHR-transfected cells and by a limited number of tumor cell lines.

One of these mAbs reacts with the LHR/hCGR in tissue sections of both frozen and paraffin-embedded specimens. This unique feature allowed us to map the cytological distribution of LHR/hCGR in human breast tissues at different stages of development in physiological and benign pathological conditions. The same mAb proved to be agonistic: receptor ligation elicits signals that modulate the growth of selected breast tumor cell lines. This observation suggests that the mAb recognizes an epitope that is included in the domain of the receptor involved in the interaction with the natural ligand.

This work was supported by Associazione Italiana Ricerca Cancro, Fondo Investimenti Ricerca di Base (Ministero dell’Istruzione, dell’Università e della Ricerca), Special Project "Oncologia" Compagnia SanPaolo (Torino, Italy), and Serono International (Geneva, Switzerland). The Compagnia SanPaolo and FIRMS (International Foundation for Research in Experimental Medicine) provided valuable financial contribution. I.C. is a student of the Postgraduate School of Pathology, University of Torino, Italy.

Abbreviations: CHO, Chinese hamster ovary; CHO-LHR, CHO cells transfected with the cDNA of human LHR; GaMIgG, goat antimouse IgG; hCG, human chorionic gonadotropin; hCGR, hCG receptor; IMDM, Iscove’s MEM; LHR, LH receptor; mAb, monoclonal antibody; rLH, human recombinant LH.

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