Regulation of growth hormone secretion by (pro)renin receptor

Tani, Yuji; Yamada, Shozo; Inoshita, Naoko; Hirata, Yukio; Shichiri, Masayoshi

doi:10.1038/srep10878

Cited by 16 publications

(23 citation statements)

References 45 publications

(56 reference statements)

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“…Previous studies showed that (pro)renin receptor [(P)RR] contributes to tissue renin-angiotensin system-related pathogenesis, such as hypertension and diabetes [ 8–10 ]. Furthermore, there is a report that (P)RR is expressed in pituitary adenoma cells and regulates secretion of GH [ 11 ]. In addition, a recent study demonstrated an important role of (P)RR under hypoxic condition [ 12 ], in which (P)RR binds to pyruvate dehydrogenase (PDH) protein and maintains the PDH activity through inhibition of its degradation.…”

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confidence: 99%

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

Seki

Yatabe

Suda

et al. 2018

Journal of the Endocrine Society

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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.

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confidence: 99%

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

Seki

Yatabe

Suda

et al. 2018

Journal of the Endocrine Society

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“…The nuclei were counterstained using DAPI Fluoromount-G ® (SouthernBiotech). Laser scanning confocal microscopy was performed using an LSM510 confocal microscope (Carl Zeiss, Jena, Germany) as described 41 .…”

Section: Methodsmentioning

confidence: 99%

Identification of the salusin-β receptor using proteoliposomes embedded with endogenous membrane proteins

Shichiri

Nonaka²,

Lee³

et al. 2018

Sci Rep

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Although orphan G protein-coupled receptors (GPCRs) have been used as targets to discover unidentified natural ligands, increasing numbers of non-GPCRs have been found to mediate important biological functions. Bioinformatics of genome and cDNA resources predict putative bioactive peptides, demanding an alternative approach to efficiently unravel cell surface targets. In silico analysis of a full-length cDNA library previously allowed us to identify salusin-β, a parasympathomimetic/pro-atherosclerotic peptide with unique physicochemical properties. Here, we show that the β-chain of ATP synthase is a cell surface receptor for salusin-β by utilizing artificial liposomes embedded with endogenous membrane proteins directly transferred from animal tissues while retaining the ligand-binding capability. Conventional techniques using detergents identified a β-actin-profilin complex as membrane-associated salusin-β-binding proteins, but failed to identify the cell surface receptor. Since the α-chain of ATP synthase is a principal cell surface target for angiostatin, a potent endogenous angiogenesis inhibitor, we investigated whether salusin-β modulates angiogenesis. Salusin-β inhibited cell surface ATP synthase activity and prevented sarcoma cell-induced angiogenesis in an in vivo mouse air sac model. Therefore, salusin-β binds to membrane-bound ATP synthase and acts as an angiogenesis inhibitor. The current methodology allows the identification of novel cell surface targets, irrespective of the receptor structure.

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“…Tani et al (2015) reported that (P)RR, together with v-ATPase, played a stimulatory role in the secretion of growth hormone by pituitary tumor cells. Because (P)RR is widely distributed in the brain (Takahashi et al 2010a(Takahashi et al , 2015, the complex of (P)RR and v-ATPase may also play essential roles in the processing and secretion of sleep-related neuropeptides, such as orexins (Nishijima et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Elevated Plasma Levels of Soluble (Pro)Renin Receptor in Patients with Obstructive Sleep Apnea Syndrome in Parallel with the Disease Severity

Nishijima

Tajima

Yamashiro

et al. 2016

Tohoku J. Exp. Med.

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(Pro)renin receptor ((P)RR), a receptor for renin and prorenin, is implicated in the pathophysiology of diabetes mellitus, hypertension and their complications. Soluble (P)RR (s(P)RR) is composed of extracellular domain of (P)RR and thus exists in blood. We have reported that plasma concentrations of s(P)RR were elevated in male patients with obstructive sleep apnea syndrome (OSAS). The aim of the present study was to clarify the difference in plasma s(P)RR concentrations between male and female OSAS patients. Plasma s(P)RR concentrations were studied in 289 subjects (206 males and 83 females) consisting of 259 OSAS patients and 30 non-OSAS control subjects. The 259 OSAS patients were classified into mild (5 ≤ apnea hypopnea index (AHI) < 15 events/h), moderate (15 ≤ AHI < 30), and severe OSAS (AHI ≥ 30). Plasma s(P)RR levels were significantly elevated in all three OSAS groups compared to non-OSAS control subjects (AHI < 5) in the entire cohort and male subjects, whereas in female subjects, the significant elevation was found only in severe OSAS. Plasma s(P)RR levels were significantly correlated with AHI in both sexes, with a higher r value found in male subjects (male r = 0.413, p < 0.0001; female r = 0.263, p < 0.05). Importantly, when OSAS patients (26 males and 15 females) with AHI ≥ 20 underwent continuous positive airway pressure treatment, plasma s(P)RR levels were significantly decreased. In conclusion, plasma s(P)RR levels are elevated in both male and female OSAS patients in parallel with the disease severity.

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Regulation of growth hormone secretion by (pro)renin receptor

Cited by 16 publications

References 45 publications

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

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

Identification of the salusin-β receptor using proteoliposomes embedded with endogenous membrane proteins

Elevated Plasma Levels of Soluble (Pro)Renin Receptor in Patients with Obstructive Sleep Apnea Syndrome in Parallel with the Disease Severity

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