Elevated (Pro)renin Receptor Expression Contributes to Maintaining Aerobic Metabolism in Growth Hormone Deficiency

Figure 1.. Effect of SGHD and obesity on serum s(P)RR concentration in humans. (a) Serum s(P)RR concentration of the patients with SGHD (SGHD+, n = 32) or without SGHD (SGHD−, n = 40). *P < 0.05 vs SGHD−. (b, upper) BMI and (lower) serum s(P)RR concentration of the patients classified based on obesity and SGHD. *P < 0.05 vs Lean SGHD−; †P < 0.05 vs Lean SGHD+. (c–e) Change of serum (c) IGF-1 levels, (d) IGF-1 SD score, and (e) serum s(P)RR concentration, before and after GH replacement therapy (n = 16). *P < 0.05 vs before the therapy. (f) Correlation between the changes in serum s(P)RR concentration and the changes in BMI.

Figure 2.. Effect of GH receptor blockade and obesity on serum s(P)RR concentration in mice. Serum (a) IGF-1 concentration, (b) blood glucose concentration, (c) body weight, (d) WAT weight ratio to body weight, and (e) s(P)RR concentration in lean and obese mice treated with saline or pegvisomant (Peg). *P < 0.05 vs Lean + Saline mice; †P < 0.05 vs Lean + Peg mice; ‡P < 0.05 vs Obese + Saline mice.

Figure 3.. Expression of (P)RR mRNA and its processing enzyme mRNA in lean and obese mice treated with saline or pegvisomant (Peg). (a) Relative mRNA expression of (P)RR of WAT, gastrocnemius muscle, liver, and kidneys of the lean and obese mice treated with or without the pegvisomant treatment. (b) Relative mRNA expression of furin and ADAM19 of the WAT. *P < 0.05 vs Lean + Saline mice; †P < 0.05 vs Lean + Peg mice; ‡P < 0.05 vs Obese + Saline mice.

Figure 4.. Effects of hypoxia on (P)RR and PDHB expression in 3T3-L1 cells. (a) Representative Western blot image and protein levels for (P)RR and β-actin expression after normoxia or 5% hypoxia treatment of 8 hours. *P < 0.05 vs normoxia. (b) Relative mRNA expression of (P)RR after normoxia or 5% hypoxia treatment of 8 hours. (c) Relative mRNA expression of (P)RR after the 48-hour treatment with scrambled or (P)RR siRNAs. *P < 0.05 vs scrambled siRNA. (d) Representative Western blot image for (P)RR, PDHB, and β-actin after the 48-hour treatment with scrambled or (P)RR siRNAs, followed by 8-hour treatment of normoxia or 5% hypoxia.

Figure 5.. Hypothetic regulation of PDH activity by (P)RR in ATs. Under hypoxic condition and GHD, PDH activity tends to decrease through the hypoxia-induced stimulation of PDK. However, hypoxia also enhances the (P)RR expression. As (P)RR binds to PDHB and thus maintains the PDH activity, PDH activity is actually unchanged even under hypoxic conditions if the expression of (P)RR is intact. CoA, coenzyme A; TCA, tricarboxylic acid.