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

Abstract

Catch-up growth (CUG) in childhood is defined as periods of growth acceleration, after the resolution of growth attenuation causes, bringing the children back to their original growth trajectory. Sometimes, however, CUG is incomplete, leading to permanent growth deficit and short stature. The aim of this study was to investigate the mechanisms that limit nutritional-CUG. Specifically, we focused on the crosstalk between leptin, increased by re-feeding, and sex hormones, which increase with age. studies were performed in young male Sprague Dawley rats fed or subjected to 10/36 days of 40% food restriction followed by 90-120 days of re-feeding. studies were performed on ATDC5 cells. Analyses of mRNA and protein levels were done using qPCR and Western blot, respectively. CUG was complete in body weight and humerus length in animals that were food-restricted for 10 days but not for those food-restricted for 36 days. studies showed that leptin significantly increased aromatase gene expression and protein level as well as the expression of estrogen and leptin receptors in a dose- and time-dependent manner. The effect of leptin on aromatase was direct and was mediated through the MAPK/Erk, STAT3 and PI3K pathways. The crosstalk between leptin and aromatase in the growth plate suggests that re-feeding during puberty may lead to increased estrogen level and activity, and consequently, irreversible premature epiphyseal growth plate closure. These results may have important implications for the development of novel treatment strategies for short stature in children.

Sam68 mediates leptin signaling and action in human granulosa cells: possible role in leptin resistance in PCOS

“…The results showed that leptin stimulated significantly the expression of aromatase mRNA in GCs from healthy donors ( Fig. 5A ), possibly via activation of the canonical signal transduction pathways, MAPK and PI3K, as previously shown in other cellular systems ( 36 ). However, no significant changes in aromatase mRNA was detected after of 24-h leptin treatment in GCs from PCOS women ( Fig.…”

“…Leptin is a well-characterized obesity-associated factor with biological effects on survival, growth and proliferation in different biological systems ( 43 , 44 , 45 ). Moreover, leptin has also been shown to be a potent stimulator of aromatase expression and activity in isolated adipose stromal cells ( 36 , 46 ) and luteinized granulosa cells ( 34 ). However, some studies have shown contradictory results.…”

Evolution and Future of Growth Plate Therapeutics

“…Leptin, increased in obese children, has direct effects on skeletal growth centers [13], enhancing chondrocyte proliferation and subsequent cell differentiation [14]. Leptin also increases growth plate aromatase activity [15], which along with estrogen produced through adipose tissue aromatization [16] accelerates skeletal maturation.…”

Mangiferin Relieves Lipopolysaccharide-Induced Injury by Up-Regulating miR-181a via Targeting PTEN in ATDC5 Cells

“…Additionally, for investigation of the signal pathways, the LPS + MF treated ATDC5 cells were respectively incubated with the PI3K inhibitor Wortmannin (MedChemExpress, New Jersey, USA) (10 m M , 1 h ) , P T E N i n h i b i t o r V O -O H p i c t r i h y d r a t e (MedChemExpress) (10 nM, 1 h), AKT inhibitor MK2206 (MedChemExpress) (200 nM, 30 min) and NF-kB pathway inhibitor pyrrolidine dithiocarbamate (PDTC) (Sigma) (10 mM, 30 min) reference to earlier published literatures (Xu et al, 2015a;Lu et al, 2017;Guo et al, 2018;Masarwi et al, 2018).…”