17β-estradiol upregulates oxytocin and the oxytocin receptor in C2C12 myotubes

Abstract

BackgroundThe endocrinology of skeletal muscle is highly complex and many issues about hormone action in skeletal muscle are still unresolved. Aim of the work is to improve our knowledge on the relationship between skeletal muscle and 17β-estradiol.MethodsThe skeletal muscle cell line C2C12 was treated with 17β-estradiol, the oxytocin peptide and a combination of the two hormones. The mRNA levels of myogenic regulatory factors, myosin heavy chain, oxytocin, oxytocin receptor and adipogenic factors were analysed in C2C12 myotubes.ResultsIt was demonstrated that C2C12 myoblasts and myotubes express oxytocin and its receptor, in particular the receptor levels physiologically increase in differentiated myotubes. Myotubes treated with 17β-estradiol overexpressed oxytocin and oxytocin receptor genes by approximately 3- and 29-fold, respectively. A decrease in the expression of fatty acid binding protein 4 (0.62-fold), a fat metabolism-associated gene, was observed in oxytocin-treated myotubes. On the contrary, fatty acid binding protein 4 was upregulated (2.66-fold) after the administration of the combination of 17β-estradiol and oxytocin. 17β-estradiol regulates oxytocin and its receptor in skeletal muscle cells and they act in a synergic way on fatty acid metabolism.DiscussionOxytocin and its receptor are physiologically regulated along differentiation. 17β-estradiol regulates oxytocin and its receptor in skeletal muscle cells. 17β-estradiol and oxytocin act in a synergic way on fatty acid metabolism. A better understanding of the regulation of skeletal muscle homeostasis by estrogens and oxytocin peptide could contribute to increase our knowledge of muscle and its metabolism.

Skeletal Muscle: A Significant Novel Neurohypophyseal Hormone-Secreting Organ

“…Studies from other laboratories highlighted the presence of functional oxytocin receptors (OT-R) in human myoblasts derived from postnatal satellite cells (Breton et al, 2002), and in C2C12 myogenic cells which respond to oxytocin by activating the calcium–CaMKK–AMPK pathway (Lee et al, 2008). A recent in vitro study showed that C2C12 myoblasts express not only OT-R but also oxytocin and that the expression of both products increases upon myogenic differentiation of the cells (Berio et al, 2017). Furthermore, myotubes treated with 17β-estradiol overexpress oxytocin and OT-R genes by approximately 3- and 29-fold, respectively (Berio et al, 2017).…”

“…A recent in vitro study showed that C2C12 myoblasts express not only OT-R but also oxytocin and that the expression of both products increases upon myogenic differentiation of the cells (Berio et al, 2017). Furthermore, myotubes treated with 17β-estradiol overexpress oxytocin and OT-R genes by approximately 3- and 29-fold, respectively (Berio et al, 2017).…”

Divergent Regulation of Myotube Formation and Gene Expression by E2 and EPA during In-Vitro Differentiation of C2C12 Myoblasts

“…Fish oil contains n-3PUFA that are known to improve muscle strength, particularly in older women [10,11]. However, while some studies find supportive effects of E2 or n-3PUFA on myoblast differentiation in-vitro [12][13][14][15][16], others have shown an inhibition [17][18][19][20][21][22].…”

Oxytocin in metabolic homeostasis: implications for obesity and diabetes management

“…Oxytocin was shown to increase glucose uptake in murine C2C12 myoblasts, through the stimulation of intracellular Ca 2+ release and activation of AMP‐activated protein kinase in a time‐dependent and dose‐dependent manner , although it could not be concluded whether these effects were associated with specific binding of oxytocin to the OTR. Down‐regulation of fatty acid binding protein 4 ( Fabp4 , also known as aP2) mRNA expression was also observed with oxytocin treatment of murine C2C12 myotubes . Although no direct links have been established between Fabp4 and glucose metabolism in muscle cells, increases of Fabp4 mRNA expression in skeletal muscle cells (bovine and murine) have been linked to the inhibition of myoblast differentiation as well as transdifferentiation of myotubes and muscle‐derived stem cells into adipocyte‐like cells .…”