FOLLICLE STIMULATING HORMONE-LIKE ACTIVITY IN HUMAN CHORIONIC GONADOTROPHIN PREPARATIONS

ABSTRACT The follicle stimulating hormone (FSH)-like activity of human chorionic gonadotrophin (HCG) preparations was assayed by the method based on the ovarian weight augmentation in intact immature rats. The potencies ranged from 4.8 to 7.4 IU equivalents of FSH per mg. The FSH-like potency of the Second International Standard Preparation of HCG was 8.5 IU per vial. However, when in intact immature rats the ovarian weight response to HCG preparations was compared at a wide range of doses (40 to 51 200 IU) to that obtained with a human menopausal gonadotrophin (HMG) preparation (0.5 to 128 IU of FSH) in the presence of 40 IU of HCG, significant differences were found. The assays conducted in hypophysectomised immature female rats were invalid, because of lack of parallelism. Antisera were prepared by immunising rabbits with HCG and human hypophysial gonadotrophin (HHG) preparations and the antigonadotrophin profiles (HCG-, FSH- and FSH-like neutralising potencies) of these antisera were established by the use of statistically valid bioassay procedures. The anti-HCG and anti-HHG sera neutralised the FSH activity of HMG preparations as well as the FSH-like activity of HCG preparations. However, 3 to 175 times more antiserum was required to neutralise the equivalent of 1.0 IU of FSH-like activity present in HCG than expected on the basis of the anti-FSH potency of the antisera. On the other hand, there was a high degree of correlation between the neutralising potencies of the antisera when tested against the FSH-like activity and the HCG activity of various HCG preparations. When the FSH-like activity of an HCG preparation was quantitatively neutralised with an anti-HCG serum, some 30 per cent of the HCG activity remained unneutralised, as evidenced by repeated bioassays. Although at least 2000 IU of this »FSH-free« HCG was administered to groups of intact as well as hypophysectomised immature female rats, this high dose of HCG did not induce an increase in ovarian weight beyond that elicited by 40 IU of untreated HCG. Histological examination of the ovaries indicated lack of follicle stimulation in the hypophysectomised, but not in the intact immature animals. There was an excessive stimulation of the interstitial cells in both types of animals. The data indicate that the FSH-like activity of HCG preparations is neither due to a contamination by FSH of pituitary origin, nor is it an evenly distributed intrinsic property of the HCG molecules. It is also concluded that the gonadotrophic activity of biologically pure HCG in immature hypophysectomised female rats consists of a specific stimulation of the interstitial cell apparatus. Such HCG preparations do not induce any follicle stimulation, not even when administered in excessive doses.