Direct and sex-specific stimulation by sex steroids of creatine kinase activity and DNA synthesis in rat bone.
A direct in vitro effect of 17 beta-estradiol (E2) was demonstrated on bone and cartilage cell energy metabolism. Sex-specific stimulation by E2 and testosterone was shown in diaphyseal bone of weanling rats. E2 (30 nM) caused, within 24 hr, a 70-200% increase in creatine kinase (CK; ATP:creatine N-phosphotransferase, EC 2.7.3.2) specific activity in ROS 17/2.8 rat osteogenic sarcoma cells, MC3T3-E1 mouse calvaria-derived cells, and rat fetal calvaria cells, and a 40% increase in rat epiphyseal cartilage cells. Stimulation of CK activity by E2 was dose and time dependent: in ROS 17/2.8 cells, a highly significant increase was found at 3 nM E2 and a greater than 100% increase in CK activity was found 1 hr after E2 administration. In female 20-day-old Wistar-derived rats, E2 (5 micrograms per rat) increased CK activity in diaphyseal bone by 82% within 1 hr of i.p. injection, with a maximal increase of 200% after 24 hr; neither the weakly estrogenic agonist 17 alpha-estradiol, testosterone, nor progesterone showed this effect. Conversely, in male rat diaphyseal bone, testosterone or dihydrotestosterone increased CK activity after 24 hr by approximately 100%, while E2 was ineffective. In epiphyseal cartilage, both E2 and testosterone increased CK activity. Stimulation of CK activity by sex hormones was paralleled by significant increases in [3H]thymidine incorporation into DNA. Therefore, it is possible that direct sex-specific actions of gonadal steroids may contribute to stimulating bone growth and maintaining balanced bone turnover.
Sömjen
D
D
Hard Tissues Unit, Ichilov Hospital, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Weisman
Y
Y
Harell
A
A
Berger
E
E
Kaye
A M
AM
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008297:Male; D012516:Osteosarcoma / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012739:Gonadal Steroid Hormones; D013739:Testosterone; D004958:Estradiol; D004247:DNA; D003402:Creatine Kinase