Activation of the LH receptor up regulates the type 2 adiponectin receptor in human granulosa cells

详细信息    查看全文

• 作者：Edmond P. Wickham III (1)
  Tao Tao (1) (5)
  John E. Nestler (1) (3)
  Elizabeth A. McGee (2) (3) (4)
  
• 关键词：Ovary ; Granulosa ; Adiponectin ; Adiponectin receptor ; PCOS ; Progesterone
• 刊名：Journal of Assisted Reproduction and Genetics
• 出版年：2013
• 出版时间：July 2013
• 年：2013
• 卷：30
• 期：7
• 页码：963-968
• 全文大小：242KB
• 参考文献：1. Bersinger NA, Wunder DM. Adiponectin isoform distribution in serum and in follicular fluid of women undergoing treatment by ICSI. Acta Obstet Gynecol Scand. 2010;89(6):782-. CrossRef
  2. Chabrolle C, Tosca L, Crochet S, Tesseraud S, Dupont J. Expression of adiponectin and its receptor s (AdipoR1 and AdipoR2) in chicek ovary: Potential role in ovarian steroidogenesis. Domest Anim Endocrinol. 2007;33(4):480-. CrossRef
  3. Chabrolle C, Tosca T, Dupont J. Regulation of adiponectin and its receptor in rat ovary by human chorionic gonadotropihim treatment and potential involvement of adiponectin in granulosa cell steroidogenesis. Reproduction. 2007;133(4):719-1. CrossRef
  4. Chabrolle C, Tosca L, Ramé C, Lecomte P, Royère D, Dupont J. Adiponectin increases insulin-like growth factor I-induced progesterone and estradiol secretion in human granulosa cells. Fertil Steril. 2009;92(6):1988-6. CrossRef
  5. Chaudhuri C, Harada Y, Shimizu K, Gut M, Dorfman RI. Biosynthesis of Pregnenolone from 22-Hydroxycholesterol. J Biol Chem. 1962;237(3):703-.
  6. Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the polycystic ovary syndrome. Int J Obes Relat Metab Disord. 2002;26(7):883-6. CrossRef
  7. Jung M, Ramankulov A, Roigas J, Johannsen M, Ringsdorf M, Kristiansen G, et al. In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real‐time PCR. BMC Mol Biol 2007;8:e47.
  8. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005;26(3):439-1. CrossRef
  9. Kishida K, Funahashi T, Shimoura I. Molecular mechanisms of diabetes and atherosclerosis; role of adiponectin. Endocr Metab Immune Disord Drug Targets. 2012;12(2):118-1. CrossRef
  10. Ledoux S, Campos DB, Lopes FL, Dobias-Goff M, Palin MF, Murphy BD. Adiponectin induces periovulatory changes in ovarian follicular cells. Endocrinology. 2006;147(11):5178-6. CrossRef
  11. Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2009;302(2):179-8. CrossRef
  12. Li L, Yun JH, Lee JH, Song S, Choi BC, Baek KH. Association study of +45G15G(T/G) and +276(G/T) polymorphisms in the adiponectin gene in patients with polycystic ovary syndrome. Int J Mol Med. 2011;27(2):283-.
  13. Li L, Ferin M, Sauer MV, Lobo RA. Ovarian adipocytokines are associated with early in vitro human embryo development independent of the action of ovarian insulin. J Assist Reprod Genet. 2012;29:1397-404.
  14. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(?Delta Delta C (T)) method. Methods. 2001;25(4):402-. CrossRef
  15. McGee EA, Hsueh AJW. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 2000;21(2):200-4. CrossRef
  16. McGee E, Sawetawan C, Bird I, Rainey WE, Carr BR. The effects of insulin on 3 beta- hydroxysteroid dehydrogenase expression in human luteinized granulosa cells. J Soc Gynecol Investig. 1995;2(3):535-1. CrossRef
  17. Michalakis KG, Segars JH. The role of adiponectin in reproduction: from polycystic ovary syndrome to assisted reproduction. Fertil Steril. 2010;94(6):1949-7. CrossRef
  18. Nishida M, Funahashi T, Shimomura I. Pathophysiological significance of adiponectin. Med Mol Morphol. 2007;40(2):55-7. CrossRef
  19. Pajvani UB, Scherer PE. Adiponectin: systemic contributor to insulin sensitivity. Curr Diabetes Rep. 2003;3(3):207-3. CrossRef
  20. Pierre P, Froment P, Nègre D, Ramé C, Barateau V, Chabrolle C, et al. Role of adiponectin receptors, AdipoR1 and AdipoR2, in the steroidogenesis of the human granulosa tumor cell line, KGN. Hum Reprod. 2009;24(11):2890-01. CrossRef
  21. Putz DM, Goldner WS, Bar RS, Haynes WG, Sivitz WI. Adiponectin and C-reactive protein in obesity, type 2 diabetes, and monodrug therapy. Metabolism. 2004;53(11):1454-1. CrossRef
  22. Richards JS, Liu Z, Kawai T, Tabata K, Watanabe H, Suresh D, et al. Adiponectin and its receptors modulate granulosa cell and cumulus cell functions, fertility, and early embryo development in the mouse and human. Fertil Steril. 2012;98(2):471-. CrossRef
  23. Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes. 2006;55:1537-5. CrossRef
  24. Tabandeh MR, Golestanib N, Kafi M, Hosseini A, Saeb M, Sarkoohi P. Gene expression pattern of adiponectin and adiponectin receptors in dominant and atretic follicles and oocytes screened based on brilliant cresyl blue staining. Anim Reprod Sci. 2012;131(1-):30-0. CrossRef
  25. Takikawa S, Iwase A, Goto M, Harata T, Umezu T, Nakahara T, et al. Assessment of the predictive value of follicular fluid insulin, leptin and adiponectin in assisted reproductive cycles. Gynecol Endocrinol. 2010;26(7):494-. CrossRef
  26. Tishinsky JM, Dyck DJ, Robinson LE. Lifestyle factors increasing adiponectin synthesis and secretion. Vitam Horm. 2012;90:1-0. CrossRef
  27. Toulis KA, Goulis DG, Farmakiotis D, Georgopoulus NA, Katsikis I, Tarlatzis BC, et al. Adiponectin levels in women with polycystic ovary syndrome: a sytematic review and meta-analysis. Hum Reprod Update. 2009;15(3):297-07. CrossRef
  28. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86(5):1930-. CrossRef
  29. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423(6941):762-. CrossRef
  
• 作者单位：Edmond P. Wickham III (1)
  Tao Tao (1) (5)
  John E. Nestler (1) (3)
  Elizabeth A. McGee (2) (3) (4)
  
  1. Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA
  5. Department of Internal Medicine Renji Hospital, Division of Endocrinology and Metabolism, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China
  3. Institute of Women’s Health, Virginia Commonwealth University, Richmond, VA, 23298, USA
  2. Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298, USA
  4. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, 05401, USA
  

文摘

Purpose Adiponectin is a predominantly adipocyte-derived hormone which influences insulin sensitivity and energy homeostasis through at least two receptors, AdipoR1 and AdipoR2. In animal models, adiponectin may regulate ovarian steroidogenesis, folliculogenesis, and ovulation. The receptors AdipoR1 and AdipoR2 are present in the human ovary, but their regulation is unknown. In these studies, we determined the effects of LH receptor activation on the expression and function of the two adiponectin receptors in human granulosa cells. Methods Granulosa cells were obtained at the time of oocyte retrieval in women undergoing in vitro fertilization (IVF). Cells were isolated and cultured for 48?h in DMEM/F12 medium with 5?% FBS and 50 ug/ml gentamicin. Medium was changed to low serum for 12?h and cells were treated with hCG (100?ng/ml), forskolin (30 μMol/L), or FSH (1?IU/ml) for 24?h for mRNA experiments. mRNA was isolated and RT PCR was performed using Taqman assays and quantification with the delta delta CT method. For immunocytochemistry, cells were grown on chamber slides and treated with hCG for 1 to 24?h and fixed with acetone. ICC was performed with polyclonal rabbit primary antibodies followed by alexa fluor goat anti-rabbit antibody and imaging with a fluorescence microscope and Zeiss software analysis. 3β-hydroxysteroid dehydrogenase (3βHSD) enzyme activity was determined by measuring the progesterone produced when cells were provided with an excess of 22-hydroxy-cholesterol as substrate following an incubation with hCG (1?IU/ml) and/or adiponectin (10?ng/ml). Progesterone content in the media was determined by ELISA. Results Messenger RNA for the two Adiponectin receptors is differentially regulated by activation of LHR with hCG treatment. AdipoR2 was increased nearly 4-fold (p-lt;-.05), whereas AdipoR1 expression was not changed by hCG treatment. Treatment with either FSH or forskolin (an activator of cAMP) had similar effects. Basal AdipoR2 protein was fairly low in granulosa cells in culture however treatment of cells with hCG resulted in a discernible increase in immunodetectable cytoplasmic protein as early as 6?h after treatment and was maintained for at least 24?h. The number of cells positive for AdipoR2 at 6?h increased from a basal of 20?% to almost 60?% (p-lt;-.05). Adiponectin treatment of hCG-primed cells resulted in increased 3βHSD activity by approximately 60?% over hCG alone and more than 3-fold over basal levels. Conclusions AdipoR2 is regulated by the LH receptor function via a cAMP dependant mechanism. Increased expression of adipoR2 prior to and following ovulation may contribute to enhanced 3βHSD activity and increased progesterone secretion by the corpus luteum of the ovary. Dysregulation of adiponectin that may occur with PCOS may impair normal progesterone production.