Primary and Secondary Biologic Activities Intrinsic to the Human Chorionic Gonadotropin Molecule

Abstract

The hypothesis that follicle-stimulating activity (FSA) and thyroid-stimulating activity (TSA) are intrinsic to the human chorionic gonadotropin (hCG) molecule is one aspect of a broad controversy nearly as old as the discovery, more than 50 years ago, that the urine of pregnant women contains gonadotropic activity. At the heart of this controversy is the observation that urine rich in hCG stimulates follicular growth, as well as interstitial repair in the ovaries of hypophysectomized rats (Evans et al., 1953; Lyons et al., 1953). The unsettled issue is whether one accounts for the FSA in pregnancy urine on the basis of follicle-stimulating hormone (hFSH) of pituitary origin, on the basis of a putative separate factor with FSA secreted by the placenta, or potentially even on the basis of the hCG molecule having intrinsic FSA. There is reason to suspect that all three may contribute, making the FSA in pregnancy urine heterogeneous in nature. Kulin et al. (1979) have recently found low, but measurable levels of pituitary hFSH-like material in pregnancy urine by radioimmunoassay. Ashitaka et al. (1970) have separated two glycoprotein fractions from pregnancy urine, one of which is richer in FSA than the other. Albert (1969) has shown that FSA is not lost when hCG is purified seven-fold, suggesting that FSA represents an intrinsic property of the hCG molecule. A controversy, similar in nature, has gone on concerning what substances account for the TSA in pregnancy urine (Lyon et al., 1953). Possible candidates include thyroid-stimulating hormone (hTSH) of pituitary origin (Burger, 1967), a putative separate factor with TSA secreted by the placenta (Akasu et al., 1955; Hennen, 1965; Hershman and Starnes, 1969; Kitagaki, 1977; Tojo et al., 1978), or the hCG molecule on the basis of its hypothetical intrinsic TSA. Again, some combination of these may actually account for the TSA in extracts of pregnancy urine.