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Sökning: WFRF:(Carpentier C.) > (2010-2014) > Angiotensin II Type...

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FältnamnIndikatorerMetadata
00003512naa a2200373 4500
001oai:DiVA.org:uu-235337
003SwePub
008141030s2014 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2353372 URI
0247 a https://doi.org/10.1210/en.2014-11852 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Leblanc, Samuel4 aut
2451 0a Angiotensin II Type 2 Receptor Stimulation Improves Fatty Acid Ovarian Uptake and Hyperandrogenemia in an Obese Rat Model of Polycystic Ovary Syndrome
264 1b The Endocrine Society,c 2014
338 a print2 rdacarrier
520 a Polycystic ovary syndrome (PCOS) is mainly defined by hyperandrogenism but is also characterized by insulin resistance (IR). Studies showed that overexposure of nonadipose tissues to nonesterified fatty acids (NEFA) may explain both IR and hyperandrogenism. Recent studies indicate that treatment with an angiotensin II type 2 receptor (AT2R)-selective agonist improves diet-induced IR. We thus hypothesized that PCOS hyperandrogenism is triggered by ovarian NEFA overexposure and is improved after treatment with an AT2R agonist. Experiments were conducted in 12-week-old female JCR:LA-cp/cp rats, which are characterized by visceral obesity, IR, hyperandrogenism, and polycystic ovaries. Control JCR:LA +/? rats have a normal phenotype. Rats were treated for 8 days with saline or the selective AT2R agonist C21/M24 and then assessed for: 1) fasting testosterone, NEFA, and insulin levels; and 2) an iv 14(R,S)-[F-18]fluoro-6-thia-heptadecanoic acid test to determine NEFA ovarian tissue uptake (Km). Compared with controls, saline-treated PCOS/cp rats displayed higher insulin (100 vs 5.6 mu U/mL), testosterone (0.12 vs 0.04 nmol/L), NEFA (0.98 vs 0.48 mmol/L), and Km (20.7 vs 12.9 nmol/g.min) (all P < .0001). In PCOS/cp rats, C21/M24 did not significantly improve insulin or NEFA but normalized testosterone (P = .004) and Km(P = .009), which were strongly correlated together in all PCOS/cp rats (rho = 0.74, P = .009). In conclusion, in an obese PCOS rat model, ovarian NEFA uptake and testosterone levels are strongly associated and are both significantly reduced after short-term C21/M24 therapy. These findings provide new information on the role of NEFA in PCOS hyperandrogenemia and suggest a potential role for AT2R agonists in the treatment of PCOS.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
7001 a Battista, Marie-Claude4 aut
7001 a Noll, Christophe4 aut
7001 a Hallberg, Andersu Uppsala universitet,Avdelningen för organisk farmaceutisk kemi4 aut0 (Swepub:uu)andehall
7001 a Gallo-Payet, Nicole4 aut
7001 a Carpentier, Andre C.4 aut
7001 a Vine, Donna F.4 aut
7001 a Baillargeon, Jean-Patrice4 aut
7102 a Uppsala universitetb Avdelningen för organisk farmaceutisk kemi4 org
7730 t Endocrinologyd : The Endocrine Societyg 155:9, s. 3684-3693q 155:9<3684-3693x 0013-7227x 1945-7170
8564 u https://academic.oup.com/endo/article-pdf/155/9/3684/10827768/endo3684.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-235337
8564 8u https://doi.org/10.1210/en.2014-1185

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