Effect of sex hormones on hypoprothrombinemia induced by N-methyltetrazolethiol in rats.
N-Methyltetrazolethiol (NMTT) increased prothrombin time (PT) and decreased plasma factor VII and prothrombin levels only in vitamin K-deficient male rats. In female rats identical treatment with NMTT did not produce hypoprothrombinemia. Conventional and germ-free rats displayed no significant difference in the manifestation of hypoprothrombinemia, but the increase of PT in NMTT-treated vitamin K-deficient rats was greater in the germ-free males. Estradiol administration or castration of male rats retarded manifestation of vitamin K deficient syndromes such as increases of PT and activated partial thromboplastin time (APTT), decreases of plasma factor VII and prothrombin levels, and increases of plasma and liver descarboxyprothrombin (PIVKA) levels, and testosterone injection to the castrated rats restored these changes. In female rats testosterone treatment or castration enhanced the manifestation of hypoprothrombinemia and estradiol treatment to the castrated females retarded it. Gamma-glutamyl-carboxylase activity was increased by vitamin K-deficiency but not inhibited by testosterone or NMTT. These data suggest that estrogen protects the rat against manifestation of hypoprothrombinemia even with NMTT treatment, while androgen enhances vitamin K deficiency, and supplementation of vitamin K prevents its deficiency in NMTT-treated rats.
D000818:Animals; D001393:Azoles; D004958:Estradiol / Q000494:pharmacology; D005167:Factor VII / Q000378:metabolism; D005260:Female; D005856:Germ-Free Life; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D007020:Hypoprothrombinemias / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D009919:Orchiectomy; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000494:pharmacology; D013777:Tetrazoles; D014813:Vitamin K Deficiency / Q000097:blood
D001393:Azoles; D012739:Gonadal Steroid Hormones; D013777:Tetrazoles; C038625:1-N-methyl-5-thiotetrazole; D013739:Testosterone; D004958:Estradiol; D005167:Factor VII; D011516:Prothrombin