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

Abstract

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.

Insulin-Like Growth Factor-1 Promotes Wound Healing in Estrogen-Deprived Mice: New Insights into Cutaneous IGF-1R/ERα Cross Talk

“…This is not a new concept and has been suggested in the context of both natural cycling and menopause (Fritton et al, 2010;Della Torre et al, 2011). Indeed, serum IGF-1 reportedly increases during the estrus (low estrogen) phase of the goat reproductive cycle (Hashizume et al, 2000) and following ovariectomy in female rodents (Barengolts et al, 1996;Govoni et al, 2008) and humans (Fogle et al, 2008;Nar et al, 2009). On the basis of our observations, we hypothesize that IGF-1 may partially compensate for lack of estrogen in the skin of Ovx mice and postmenopausal women.…”

Steroidal and Gonadotropin Hormone Profile Studies of a Classical Ayurvedic Preparation of “Makardhvaja” after Chronic Administration to Male Sprague-Dawley Rats

“…Progesterone has a stimulating effect on bone building osteoblasts, resulting in increased bone building activity [16][17][18][19][20][21]. This is due to a direct stimulation of progesterone receptors in osteoblast bone cells [22,23] as well as an increased secretion of IGF-1 and other growth factors by the bone cells exposed to progesterone [24][25][26]. The most positive effect is seen when estrogen and progesterone are used in combination [27].…”

Calcium Flux During Growth in Sham-operated and Ovariectomized Rats

“…Furthermore, ovariectomy induces a high level of IGF-1 in blood at 4 weeks postsurgery. 9,16) The increase in tibia length may be related to the IGF-1 level after ovariectomy. However, there was no significant difference in the tibia length between the two groups at the end of the experiment (approx.…”