Preparation and properties of human chorionic gonadotropin antagonist for biological studies: antifertility effects in the female rat.
We compared the effects of treatment of clinical grade hCG powders with anhydrous HF (hydrogen fluoride) or TFMS (trifluoromethane sulfonic acid). HF treatment yielded stable product (DG-hCG), which had desirable antagonistic activity in mouse Leydig cells. Binding of HF-hCG to ovarian granulosa cell FSH receptors was less than 5% as compared to purified ovine FSH. As LH/hCG receptor specificity was not significantly compromised crude hCG could be directly used in obtaining large amounts of the antagonist. The effects of antagonist (DG-hCG) and agonists crude hCG and purified hCG were evaluated in pregnant rats. When administered between days 1 to 5 of pregnancy, crude DG-hCG inhibited serum progesterone and oestradiol levels and implantation. The effect was dose-dependent. However, both crude hCG and purified hCG elevated progesterone level and partially inhibited implantation (up to about 40%). In the post-implantation period (days 8-11) crude DG-hCG treatment induced abortion due to a decrease in circulating progesterone and oestradiol levels. The agonists, crude hCG and purified hCG, on the other hand, elevated both steroid levels in serum and induced partial termination of pregnancy (up to 50%). During the second half of pregnancy, when luteotropic support of LH becomes unnecessary in the rat, crude DG-hCG (antagonist) had no effect on parturition. However, crude or purified hCG caused delay in parturition by sustaining high level of progesterone in circulation. Our data demonstrate that the antifertility effects of crude DG-hCG are more potent and consistent than the administration of either crude or purified hCG in the pregnant rat.
D000019:Abortifacient Agents / Q000494:pharmacology*; D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000138:chemical synthesis / Q000494:pharmacology*; D010064:Embryo Implantation / Q000187:drug effects*; D004958:Estradiol / Q000097:blood; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006858:Hydrofluoric Acid / Q000494:pharmacology; D007743:Labor, Obstetric / Q000187:drug effects; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D008698:Mesylates / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D011863:Radioimmunoassay; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011974:Receptors, LH
D000019:Abortifacient Agents; D000020:Abortifacient Agents, Nonsteroidal; D006063:Chorionic Gonadotropin; C034923:HCG, deglycosylated; D008698:Mesylates; D011956:Receptors, Cell Surface; D011974:Receptors, LH; D011374:Progesterone; D004958:Estradiol; C012077:trifluoromethanesulfonic acid; D006858:Hydrofluoric Acid