Leptin regulates estrogen receptor gene expression in ATDC5 cells through the extracellular signal regulated kinase signaling pathway

Abstract

Both estrogen and leptin play an important role in the regulation of physiological processes of endochondral bone formation in linear growth. Estrogen receptors (ERα and ERβ) are known as members of the superfamily of nuclear steroid hormone receptors and are detected in all zones of growth plate chondrocytes. They can be regulated in a ligand-independent manner. Whether leptin regulates ERs in the growth plate is still not clear. To explore this issue, chondrogenic ATDC5 cells were used in the present study. Messenger RNA and protein analyses were performed by quantitative PCR and Western blotting. We found that both ERα and ERβ were dynamically expressed during the ATDC5 cell differentiation for 21 days. Leptin (50 ng/ml) significantly upregulated ERα and ERβ mRNA and protein levels 48 h after leptin stimulation (P<0.05) at day 14. The up-regulation of ERα and ERβ mRNA by leptin was shown in a dose-dependent manner, but the most effective dose of leptin was different (100 and 1,000 ng/ml, respectively). Furthermore, we confirmed that leptin augmented the phosphorylation of ERK1/2 in a time-dependent manner. A maximum eightfold change was observed at 15 min. Finally, a specific ERK1/2 inhibitor, UO126, blocked leptin-induced ERs regulation in ATDC5 cells, indicating that ERK1/2 mediates, partly, the effects of leptin on ERs. These data demonstrate, for the first time, that leptin regulates the expression of ERs in growth plate chondrocytes via ERK signaling pathway, thereby suggesting a crosstalk between leptin and estrogen receptors in the regulation of bone formation.

Leptin stimulates aromatase in the growth plate: limiting catch-up growth efficiency

“…ADTC5 cells treated with leptin showed an increase in the gene expressions of leptin receptor, ER-α and aromatase. Similar results were previously shown by Wang et al (2012b) who showed in ATDC5 cells that leptin increased estrogen receptor mRNA expression and protein levels in a dose-dependent manner by activating ERK1/2, and that estrogen significantly up-regulated Ob-R protein and mRNA levels (Wang et al 2012a).…”

Leptin in osteoarthritis: Focus on articular cartilage and chondrocytes

“…The group of Figenschau demonstrated increased proliferation of chondrocytes and enhanced synthesis of proteoglycans and collagen after leptin incubation. Recent studies have provided evidence that treatment of chondrocytes with leptin can promote proliferation, differentiation, type X collagen production and cytoskeletal remodeling via a RhoA/RhoA kinase (ROCK) pathway [49][50][51]. In addition, Kishida et al showed a reduction of type X collagen in growth plates from ob/ob mice [52].…”

Rapid steroid hormone actions via membrane receptors

“…In humans, serum leptin concentration has been shown to fluctuate during the menstrual cycle in fertile women, peaking at day 14, or at ovulation, like estradiol [110]. Leptin has been shown to regulate ERα and ERβ expression through an ERK signaling pathway in growth zone chondrocytes [111]. In cancer, leptin has been shown to initially increase cell proliferation and ERα expression in malignant prostate cells and in ER positive breast cancer [112][113][114].…”