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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2013

Open Access 01-12-2013 | Research

Analysis of androgen receptor and anti-Müllerian hormone pathways in human granulosa cells under luteinizing hormone treatment

Authors: Kuo-Chung Lan, Shiuh Young Chang, Fu-Jen Huang, Hsin-Jung Lin, Ching-Yuang Lin, Ko-En Huang, Hong-Yo Kang

Published in: Reproductive Biology and Endocrinology | Issue 1/2013

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Abstract

Background

The objective of this study was to determine the gene expression profiles of the androgen/androgen receptor (AR) and anti-Müllerian hormone (AMH)/ Sry-related high-mobility group box 9 (SOX9) pathways in granulosa-luteal cells from patients undergoing standard in vitro fertilization (IVF) with or without recombinant luteinizing hormone (rLH) therapy.

Methods

Levels of reproductive hormones in the pre-ovulatory follicular fluid and the expression levels of LHR (luteinizing hormone receptor), AR, SOX9, AMH, AR-associated protein 54(ARA54)and ARA70 were determined in granulosa-luteal cells by real-time reverse-transcription PCR. The effects of androgen and rLH treatments on AR and AMH expression levels were also tested in vitro using HO23 cells.

Results

We collected 35 an 70 granulosa cell samples from patients cycled with and without rLH supplementation, respectively. The clinical outcomes were similar in patients who received rLH therapy and those who did not, though the pre-ovulatory follicular fluid levels of androstenedione, testosterone, and estradiol were significantly higher and progesterone was lower in the rLH supplementation group. Moreover, granulosa-luteal cell mRNA levels of LHR, AR, AMH, and SOX9 were significantly higher in the rLH supplementation group relative to the group that did not receive rLH supplementation. In addition, we observed significant correlations between LHR and AR mRNA expression and among AR, AMH, and SOX9 mRNA expression in granulosa-luteal cells from patients undergoing standard IVF treatment.

Conclusions

Increased expression of LHR, AR, AMH, and SOX9 is characteristic of granulosa-luteal cells from IVF/ intracytoplasmic sperm injection (ICSI) patients receiving rLH supplementation.
Appendix
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Literature
1.
Filicori M, Cognigni GE, Samara A, Melappioni S, Perri T, Cantelli B, Parmegiani L, Pelusi G, DeAloysio D: The use of LH activity to drive folliculogenesis: exploring uncharted territories in ovulation induction. Hum Reprod Update. 2002, 8: 543-557. 10.1093/humupd/8.6.543.CrossRefPubMed
2.
Levy DP, Navarro JM, Schattman GL, Davis OK, Rosenwaks Z: The role of LH in ovarian stimulation: exogenous LH: let’s design the future. Hum Reprod. 2000, 15: 2258-2265. 10.1093/humrep/15.11.2258.CrossRefPubMed
3.
Mochtar MH, Van Der V, Ziech M, Van Wely M: Recombinant Luteinizing Hormone (rLH) for controlled ovarian hyperstimulation in assisted reproductive cycles. Cochrane Database Syst Rev. 2007, 18: CD005070-
4.
Kolibianakis EM, Kalogeropoulou L, Griesinger G, Papanikolaou EG, Papadimas J, Bontis J, Tarlatzis BC: Among patients treated with FSH and GnRH analogues for in vitro fertilization, is the addition of recombinant LH associated with the probability of live birth? A systematic review and meta-analysis. Hum Reprod Update. 2007, 13: 445-452. 10.1093/humupd/dmm008.CrossRefPubMed
5.
Hill MJ, Levy G, Levens ED: Does exogenous LH in ovarian stimulation improve assisted reproduction success? An appraisal of the literature. Reprod Biomed Online. 2012, 24: 261-271. 10.1016/j.rbmo.2011.12.005.CrossRefPubMed
6.
Musters AM, van Wely M, Mastenbroek S, Kaaijk EM, Repping S, van der Veen F, Mochtar MH: The effect of recombinant LH on embryo quality: a randomized controlled trial in women with poor ovarian reserve. Hum Reprod. 2012, 27: 244-250. 10.1093/humrep/der371.CrossRefPubMed
7.
Revelli A, Chiado A, Guidetti D, Bongioanni F, Rovei V, Gennarelli G: Outcome of in vitro fertilization in patients with proven poor ovarian responsiveness after early vs. mid-follicular LH exposure: a prospective, randomized, controlled study. J Assist Reprod Genet. 2012, 29: 869-875. 10.1007/s10815-012-9804-0.PubMedCentralCrossRefPubMed
8.
Sonmezer M, Iltemir Duvan C, Ozmen B, Tasci T, Ozkavukcu S, Atabekoglu CS: Outcomes after early or midfollicular phase LH supplementation in previous inadequate responders. Reprod Biomed Online. 2010, 20: 350-357. 10.1016/j.rbmo.2009.11.022.CrossRefPubMed
9.
Hill MJ, Levens ED, Levy G, Ryan ME, Csokmay JM, DeCherney AH, Whitcomb BW: The use of recombinant luteinizing hormone in patients undergoing assisted reproductive techniques with advanced reproductive age: a systematic review and meta-analysis. Fertil Steril. 2012, 97: 1108-1114. 10.1016/j.fertnstert.2012.01.130. e1101CrossRefPubMed
10.
Wong PC, Qiao J, Ho C, Ramaraju GA, Wiweko B, Takehara Y, Nadkarni PV, Cheng LC, Chen HF, Suwajanakorn S, Vuong TN: Current opinion on use of luteinizing hormone supplementation in assisted reproduction therapy: an Asian perspective. Reprod Biomed Online. 2011, 23: 81-90.CrossRefPubMed
11.
Konig TE, van der Houwen LE, Lambalk CB: Recombinant LH supplementation in women of 35 years and older undergoing IVF. Fertil Steril. 2012, 98: e10-11. 10.1016/j.fertnstert.2012.04.048. author reply e12CrossRefPubMed
12.
Alviggi C, Clarizia R, Mollo A, Ranieri A, De Placido G: Who needs LH in ovarian stimulation?. Reprod Biomed Online. 2011, 22 (Suppl 1): S33-41.CrossRefPubMed
13.
Venetis CA, Kolibianakis EM, Tarlatzi TB, Tarlatzis BC: Benefits of luteinizing hormone activity in ovarian stimulation for IVF. Reprod Biomed Online. 2009, 18 (Suppl 2): 31-36.CrossRefPubMed
14.
Lisi F: To add or not to add LH: comments on recent commentaries. Reprod Biomed Online. 2006, 12: 415-417. 10.1016/S1472-6483(10)61992-X.CrossRefPubMed
15.
Franco JG, Baruffi RL, Oliveira JB, Mauri AL, Petersen CG, Contart P, Felipe V: Effects of recombinant LH supplementation to recombinant FSH during induced ovarian stimulation in the GnRH-agonist protocol: a matched case-control study. Reprod Biol Endocrinol. 2009, 7: 58-10.1186/1477-7827-7-58.PubMedCentralCrossRefPubMed
16.
Kang HY, Tsai MY, Chang C, Huang KE: Mechanisms and clinical relevance of androgens and androgen receptor actions. Chang Gung Med J. 2003, 26: 388-402.PubMed
17.
Chang SY, Kang HY, Lan KC, Chang CY, Huang FJ, Tsai MY, Huang KE: Expression of steroid receptors, their cofactors, and aromatase in human luteinized granulosa cells after controlled ovarian hyperstimulation. Fertil Steril. 2005, 83 (Suppl 1): 1241-1247.CrossRefPubMed
18.
Rey R, Lukas-Croisier C, Lasala C, Bedecarras P: AMH/MIS: what we know already about the gene, the protein and its regulation. Mol Cell Endocrinol. 2003, 211: 21-31. 10.1016/j.mce.2003.09.007.CrossRefPubMed
19.
La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A: Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010, 16: 113-130. 10.1093/humupd/dmp036.CrossRefPubMed
20.
Knight PG, Glister C: TGF-beta superfamily members and ovarian follicle development. Reproduction. 2006, 132: 191-206. 10.1530/rep.1.01074.CrossRefPubMed
21.
Erickson GF, Magoffin DA, Dyer CA, Hofeditz C: The ovarian androgen producing cells: a review of structure/function relationships. Endocr Rev. 1985, 6: 371-399. 10.1210/edrv-6-3-371.CrossRefPubMed
22.
Filicori M, Cognigni GE, Tabarelli C, Pocognoli P, Taraborrelli S, Spettoli D, Ciampaglia W: Stimulation and growth of antral ovarian follicles by selective LH activity administration in women. J Clin Endocrinol Metab. 2002, 87: 1156-1161. 10.1210/jc.87.3.1156.CrossRefPubMed
23.
Jeppesen JV, Nielsen ME, Kristensen SG, Yding Andersen C: Concentration of activin A and follistatin in follicular fluid from human small antral follicles associated to gene expression of the corresponding granulosa cells. Mol Cell Endocrinol. 2012, 356: 48-54. 10.1016/j.mce.2011.07.051.CrossRefPubMed
24.
Nielsen ME, Rasmussen IA, Kristensen SG, Christensen ST, Mollgard K, Wreford Andersen E, Byskov AG, Yding Andersen C: In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA. Mol Hum Reprod. 2011, 17: 63-70. 10.1093/molehr/gaq073.CrossRefPubMed
25.
Eilso Nielsen M, Rasmussen IA, Fukuda M, Westergaard LG, Yding Andersen C: Concentrations of anti-Mullerian hormone in fluid from small human antral follicles show a negative correlation with CYP19 mRNA expression in the corresponding granulosa cells. Mol Hum Reprod. 2010, 16: 637-643. 10.1093/molehr/gaq001.CrossRefPubMed
26.
Sanchez F, Adriaenssens T, Romero S, Smitz J: Different follicle-stimulating hormone exposure regimens during antral follicle growth alter gene expression in the cumulus-oocyte complex in mice. Biol Reprod. 2010, 83: 514-524. 10.1095/biolreprod.109.083311.CrossRefPubMed
27.
Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, Dewailly D: Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab. 2003, 88: 5957-5962. 10.1210/jc.2003-030727.CrossRefPubMed
28.
Rose S, Laan MJ: Why match? Investigating matched case-control study designs with causal effect estimation. Int J Biostat. 2009, 5: 1-10.3923/ijb.2009.1.35.CrossRef
29.
Lisi F, Rinaldi L, Fishel S, Lisi R, Pepe GP, Picconeri MG, Campbell A: Use of recombinant LH in a group of unselected IVF patients. Reprod Biomed Online. 2002, 5: 104-108. 10.1016/S1472-6483(10)61610-0.CrossRefPubMed
30.
Lan KC, Huang FJ, Lin YC, Kung FT, Lan TH, Chang SY: Significantly superior response in the right ovary compared with the left ovary after stimulation with follicle-stimulating hormone in a pituitary down-regulation regimen. Fertil Steril. 2010, 93: 2269-2273. 10.1016/j.fertnstert.2008.12.123.CrossRefPubMed
31.
Vanttinen T, Liu J, Hyden-Granskog C, Voutilainen R: Biphasic regulation of activin A secretion by gonadotropins in cultured human ovarian granulosa-luteal cells leads to decreasing activin:inhibin ratios during continuing gonadotropin stimulation. J Endocrinol. 2002, 172: 557-563. 10.1677/joe.0.1720557.CrossRefPubMed
32.
Hosokawa K, Dantes A, Schere-Levy C, Barash A, Yoshida Y, Kotsuji F, Vlodavsky I, Amsterdam A: Induction of Ad4BP/SF-1, steroidogenic acute regulatory protein, and cytochrome P450scc enzyme system expression in newly established human granulosa cell lines. Endocrinology. 1998, 139: 4679-4687. 10.1210/en.139.11.4679.PubMed
33.
Matzuk MM, Burns KH, Viveiros MM, Eppig JJ: Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science. 2002, 296: 2178-2180. 10.1126/science.1071965.CrossRefPubMed
34.
McKenzie LJ, Pangas SA, Carson SA, Kovanci E, Cisneros P, Buster JE, Amato P, Matzuk MM: Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. Hum Reprod. 2004, 19: 2869-2874. 10.1093/humrep/deh535.CrossRefPubMed
35.
Brannian J, Eyster K, Mueller BA, Bietz MG, Hansen K: Differential gene expression in human granulosa cells from recombinant FSH versus human menopausal gonadotropin ovarian stimulation protocols. Reprod Biol Endocrinol. 2010, 8: 25-10.1186/1477-7827-8-25.PubMedCentralCrossRefPubMed
36.
Macklon NS, Fauser BC: Follicle-stimulating hormone and advanced follicle development in the human. Arch Med Res. 2001, 32: 595-600. 10.1016/S0188-4409(01)00327-7.CrossRefPubMed
37.
Westergaard LG, Erb K, Laursen SB, Rasmussen PE, Rex S, Westergaard CG, Andersen CY: Concentrations of gonadotrophins and steroids in pre-ovulatory follicular fluid and serum in relation to stimulation protocol and outcome of assisted reproduction treatment. Reprod Biomed Online. 2004, 8: 516-523. 10.1016/S1472-6483(10)61097-8.CrossRefPubMed
38.
Smitz J, Andersen AN, Devroey P, Arce JC: Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients. Hum Reprod. 2007, 22: 676-687.CrossRefPubMed
39.
Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, Kramer P, Fauser BC, Themmen AP: Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod. 2004, 10: 77-83. 10.1093/molehr/gah015.CrossRefPubMed
40.
Wunder DM, Guibourdenche J, Birkhauser MH, Bersinger NA: Anti-Mullerian hormone and inhibin B as predictors of pregnancy after treatment by in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2008, 90: 2203-2210. 10.1016/j.fertnstert.2007.10.078.CrossRefPubMed
41.
Andersen CY, Lossl K: Increased intrafollicular androgen levels affect human granulosa cell secretion of anti-Mullerian hormone and inhibin-B. Fertil Steril. 2008, 89: 1760-1765. 10.1016/j.fertnstert.2007.05.003.CrossRefPubMed
42.
Billig H, Furuta I, Hsueh AJ: Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis. Endocrinology. 1993, 133: 2204-2212. 10.1210/en.133.5.2204.PubMed
43.
Jonard S, Dewailly D: The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest. Hum Reprod Update. 2004, 10: 107-117. 10.1093/humupd/dmh010.CrossRefPubMed
44.
de Santa BP, Moniot B, Poulat F, Berta P: Expression and subcellular localization of SF-1, SOX9, WT1, and AMH proteins during early human testicular development. Dev Dyn. 2000, 217: 293-298. 10.1002/(SICI)1097-0177(200003)217:3<293::AID-DVDY7>3.0.CO;2-P.CrossRef
45.
De Santa BP, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, Scherer G, Poulat F, Berta P: Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Mullerian hormone gene. Mol Cell Biol. 1998, 18: 6653-6665.CrossRef
Metadata
Title
Analysis of androgen receptor and anti-Müllerian hormone pathways in human granulosa cells under luteinizing hormone treatment
Authors
Kuo-Chung Lan
Shiuh Young Chang
Fu-Jen Huang
Hsin-Jung Lin
Ching-Yuang Lin
Ko-En Huang
Hong-Yo Kang
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2013
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-11-11

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