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New Evidence for Intrinsic Follicle-Stimulating Hormone-Like Activity in Human Chorionic Gonadotropin and Luteinizing Hormone^*

ETHEL S. SIRIS, BRUCE C. NISULA, KEVIN J. CATT, KATHLEEN HORNER, STEVEN BIRKEN, ROBERT E. CANFIELD and GRIFF T. ROSS

Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20014
The Department of Medicine, College of Physicians and Surgeons of Columbia University New York, New York 10032

Abstract

In order to investigate whether the follicle-stimulating activity (FSA) of purified human CG (hCG) is an intrinsic property of the hCG molecule or reflects contamination with FSH of pituitary origin, we measured the FSH-like effects of a series of hCG preparations in an FSH radioligand-receptor assay (RRA). Preparations included crude and highly purified hCG, isolated hCGa or hCGβ subunits, and the hCG subunits recombined either with each other or with purified ovine LHa or ovine LHβ subunits. FSH-like activity in the RRA was based on the ability of test preparations to inhibit specific binding of radiolabeled FSH to rat testis homogenate. To examine for the presence of contaminating pituitary FSH, the FSH-like activity of several of the preparations was measured in the FSH RRA after incubation with a specific antiserum to ovine FSH. Purified hCG had 0.10-0.15% the potency of highly purified hFSH in the FSH RRA. Recombined hCGa plus β was essentially indistinguishable from purified native hCG, although the isolated subunits had virtually no FSH-like activity. Similar to purified hCG, the hybrid recombinants hCGaoLH/J and oLHahCGβ also had FSH-like activity. Although an excess of the FSH antiserum neutralized over 94% of the activity of a pituitary hFSH preparation in the FSH RRA, it failed to neutralize the FSH-like activity of hCG, hCGaoLHβ, or oLHahCGjS. Thus.the FSH-like effects of highly purified hCG and hCG-oLH hybrid preparations were not due to pituitary FSH contamination. We conclude that the FSH-like effects of purified hCG preparations are due to an interaction of the intact hCG molecule with the FSH receptor and that LHy8-containing hybrids also possess an intrinsic FSH-like action. (Endocrinology 102: 1356, 1978)

Footnotes

^* This study was presented in part at the 59th Annual Meeting of the Endocrine Society, Chicago, Illinois, 1977.

To whom requests for reprints should be addressed: National Institutes of Health, Building 10, Room 10B12, Bethesda, Maryland 20014.

Received July 27, 1977.

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