Effects of progesterone on serum levels of IGF-1 and on femur IGF-1 mRNA in ovariectomized rats.


Barengolts EI, Kouznetsova T, Segalene A, Lathon P, Odvina C, Kukreja SC, Unterman TG.




J Bone Miner Res


Local and systemic insulin-like growth factors (IGFs) may be involved in the regulation of bone formation by sex hormones. The present studies describe the in vivo effects of estradiol, progesterone, or both on IGF-1 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. Second, OVX rats were treated in the same manner and serum IGF-1 levels measured. Third, OVX rats were treated with an injection of vehicle, estradiol, and/or progesterone, and 24 h later, levels of IGF-1 mRNA in the femur were analyzed. The mineralized surface, mineral opposition rate, and bone formation rate (BFR) were higher in OVX than in SHAM rats. The BFR was decreased in estrogen-treated but increased in MPA-treated rats compared with vehicle-treated OVX rats. Circulating levels of 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 were not different 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-1 transcripts 7.5 and 0.8 kb were decreased by 72 and 29%, respectively, in estrogen-treated and increased by 44 and 43%, respectively, in progesterone-treated rats compared with vehicle-treated OVX rats. We conclude that in the short term, estrogen lowers and progesterone raises bone IGF-1 mRNA and these changes are followed by coordinated changes in bone formation rate.