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

Abstract

ContextGrowth hormone deficiency (GHD) leads to obesity and may induce tissue hypoxia. As (pro)renin receptor [(P)RR] is reported to contribute to the aerobic metabolism by stabilizing pyruvate dehydrogenase (PDH), it may play a substantial role in GHD.ObjectiveWe aimed to investigate serum soluble (P)RR [s(P)RR] concentration, the origin of s(P)RR, and significance of (P)RR in GHD.Design, Setting, and ParticipantsSerum s(P)RR concentration was examined in 72 patients with pituitary diseases, including 32 patients with severe GHD (SGHD) and after GH replacement in 16 SGHD patients. Leptin-deficient ob/ob obese mice were treated with pegvisomant, a GH receptor antagonist, to explore the source of elevated serum s(P)RR in GHD. Adipocytes were cultured with 5% O2 to examine the effects of hypoxia.ResultsSerum s(P)RR concentration was higher in patients with SGHD than in those without SGHD. Obesity was the important determinant of s(P)RR concentration. Serum s(P)RR concentration significantly decreased after GH replacement in SGHD patients. (P)RR mRNA expression was increased specifically in the adipose tissue (AT) of pegvisomant-treated obese mice compared with that of control obese mice. Hypoxia in cultured adipocytes increased (P)RR expression without affecting the PDH E1 β subunit (PDHB) expression; however, with (P)RR knockdown by small interfering RNA, hypoxia significantly decreased the expression of PDHB.ConclusionGHD patients showed increased serum s(P)RR concentration, possibly caused by obesity and hypoxia. (P)RR expression in AT of GHD patients may be elevated to help maintain aerobic metabolism under hypoxia. Thus, the elevated serum s(P)RR level may reflect hypoxia in ATs.

Urinary soluble (pro)renin receptor excretion is associated with urine pH in humans

“…Serum s(P)RR concentration showed completely different features compared with urinary s(P)RR excretion, and showed significantly positive relationships with age, BMI, WC, VFA, urine Alb excretion, Hb, uric acid, Cre, Ca, BS, insulin, HbA1c, TG, and hsCRP, and significantly negative relationships with urine pH, eGFR, and HDL-cholesterol (Table 4). These data are in accordance with those of previous investigations reporting that blood s(P)RR levels are associated with obesity [30], dyslipidemia [15], renal dysfunction [15,21], and inflammation [22]. These findings suggest that blood s(P)RR concentration is affected by the expression levels of tissue RAS and/or tissue (P)RR in various organs.…”

Soluble (Pro)Renin Receptor Level in Patients with Severe Obesity Is Associated with Visceral Adiposity and Is Involved with Insulin Resistance and Renal Injury

“…Wu et al [ 19 ] reported that blood s(P)RR levels were high in a mouse model of diet-induced obesity. Furthermore, in humans, it has been reported that adult growth hormone deficient patients with visceral fat accumulation showed high blood s(P)RR levels and that these levels were related to BMI [ 25 ]. However, these reports did not sufficiently demonstrate whether obesity is associated with blood s(P)RR levels independently of other comorbid conditions.…”