EFFECTS OF PROGESTERONE ON SERUM LEVELS OF IGF-1 AND ON FEMUR IGF-1 MESSENGER-RNA IN OVARIECTOMIZED RATS

Local and systemic insulin-like growth factors (IGFs) may be involved in the regulation of bone formation by sex hormones. The present studi es describe the in vivo effects of estradiol, progesterone, or both on IGF-I mRNA abundance in bone, serum IGF-1 levels, and bone formation. Rats were sham-operated (SHAM) or ovariectomized (OVX) at 12 weeks of age and used a week later in three experiments. First, OVX rats were treated with vehicle, estradiol, and/or medroxyprogesterone (MPA) for 3 weeks, and bone formation was assessed in the tibial metaphysis. Sec ond, OVX rats were treated in the same manner and serum IGF-1 levels m easured. Third, OVX rats were treated with an injection of vehicle, es tradiol, and/or progesterone, and 24 h later, levels of IGF-1 mRNA in the femur were analyzed, The mineralized surface, mineral apposition r ate, and bone formation I-ate (BFR) were higher in OVX than in SHAM ra ts, The BFR was decreased in estrogen-treated but increased in MPA-tre ated rats compared with vehicle-treated OVX rats. Circulating levels o f IGF-1 were higher in OVX than in SHAM rats but were not affected by sex hormones in a 3-week experiment, whereas these levels mere not dif ferent among groups in a 24-h experiment. Northern analysis detected 7 .5 and 0.8 kb IGF-1 mRNA transcripts. The abundance of IGF-1 mRNA was higher in OVX than in SHAM rats. IGF-I transcripts 7.5 and 0.8 kb were decreased by 72 and 29%, respectively, in estrogen-treated and increa sed by 44 and 43%, respectively, in progesterone-treated rats compared with vehicle-treated OVX cats, We conclude that in the short term, es trogen lowers and progesterone raises I-tone IGF-1 mRNA and these chan ges are followed by coordinated changes in bone formation rate.