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研究生:葉伊婷
研究生(外文):Yi-Ting Yeh
論文名稱:卵泡促素與乙型轉型生長因子調節苯環化酶表現
論文名稱(外文):Molecular mechanism of follicle-stimulating hormone (FSH) and transforming growth factor (TGFb1) regulation of aromatase expression
指導教授:黃娟娟黃娟娟引用關係
指導教授(外文):Jiuan-Jiuan Hwang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:英文
論文頁數:56
中文關鍵詞:苯環化&苯環化&苯環化&苯環化&苯環化&
外文關鍵詞:aromataseTGFbeta1FSH
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雌激素在生殖系統及非生殖系統皆具有重要的功能。在女性,雌激素主要是在卵巢顆粒細胞製造,而其是由 Cyp19 基因所轉錄的苯環化酶(aromatase)催化生成,此酵素的表現主要受到腦垂體賀爾蒙-卵泡促素(FSH)的調節。過去已知,卵巢的細胞激素乙型轉型生長因子(TGFb1)有加強 FSH 刺激苯環化酶活性表現的作用。而本研究的主要目的乃利用卵巢顆粒細胞初級培養系統,進一步探討 FSH 與TGFb1 如何調控大鼠卵巢顆粒細胞苯環化酶的表現及功能。針對此,我們首先探究 FSH 及 TGFb1 調控卵巢顆粒細胞苯環化酶表現的時間效應,並探討其中參與的訊息傳遞路徑;更進而探討轉錄調節因子 CRTC2 及轉錄因子 LRH-1 參與其中的角色功能。
我們的研究結果發現 FSH 在短時間內即可誘導苯環化酶表現,而此效應會受到鈣離子調節的 calcineurin 抑制劑(CNI)所抑制,但不受 PKA 及 PI3K 抑制劑(PKAI 和wortmannin)的影響。而 FSH 與 TGFb1 的共同誘導作用發生在長時間,且其效應受CNI、PKAI 及 wortmannin 所抑制。已知 Cyp19 基因的近端啟動子區域包含了CREB結合位 CLS,以及兩個供給轉錄因子 LRH-1 及 SF-1 的結合位NRE。有趣的是,我們研究室近期的實驗發現,CNI 會抑制 FSH 與 TGFb1 所誘導的 CRTC2 之活性,CRTC2是 CREB 的轉錄協同活化因子。而在本篇研究中,我們利用染色質免疫沉澱法証實FSH 在短時間的作用下加強了 CRTC2 對 Cyp19 基因的結合力,而 FSH 與 TGFb1 的長時間共同作用下亦可增強 CRTC2 對 Cyp19 基因的結合力。進一步,我們也發現 LRH-1 參與 FSH 與 TGFb1 共同強化苯環化酶表現之調節,而此可歸因於 FSH 與TGFb1 作用經由 Ca2+/calcineurin 及 cAMP/PKA 和 PI3K/Akt 訊息傳遞路徑增進 LRH-1的表現。
總結而論,本研究在卵巢顆粒細胞提出了幾項新事證。首次證實 FSH 在短時間可透過 Ca2+/calcineurin 的傳遞路徑促進苯環化酶表現,而 TGFb1 協同 FSH 在長時間的作用下透過Ca2+/calcineurin、cAMP/PKA 和 PI3K/Akt 訊息傳遞路徑來加強苯環化酶表現。我們進而證實 CREB 的轉錄協同活化因子 CRTC2 及轉錄因子 LRH-1 皆在FSH 與 TGFb1 促進苯環化酶表現的作用中扮演了重要的影響角色。
Estrogens exert important functions in reproductive and nonreproductive systems. In females, estrogens are largely produced in ovarian granulosa cells through Cyp19 gene-encoded aromatase that is dominantly regulated by the pituitary FSH. And, intraovarian cytokine TGFb1 enhances FSH-stimulated aromatase activity. The purpose of this study was to investigate the molecular mechanism of FSH and TGFb1 regulation of aromatase expression and activity in rat ovarian granulosa cells using primary cell culture system. There were two specific aims: (1) to determine the temporal profile of FSH and TGFb1 induction of aromatase expression and the involved signaling mechanisms, and (2) to investigate the potential involvement of transcription regulators CRTC2 and LRH-1.
In this study, FSH exerted short-term induction of aromatase expression, and this was blocked by the inhibitor of Ca2+-dependent calcineurin (CNI) but not the inhibitor of PKA (PKAI) and PI3K (wortmannin). And, FSH plus TGFb1 displayed long-term induction of aromatase expression and activity, and these effects were suppressed by CNI, PKAI and wortmannin. Proximal promoter region of Cyp19 gene contains a CLS site for CREB and two potential NRE sites for LRH-1/SF-1. Interestingly, we recently demonstrated that CNI blocked the FSH and TGFb1-induced activation of CRTC2, a CREB transcription coactivator. Here, ChIP assay showed that FSH acutely increased CRTC2 binding to Cyp19 gene, and FSH plus TGFb1 further increased this binding activity chronically. Furthermore, we demonstrated that LRH-1 is involved in FSH plus TGFb1 chronic induction of aromatase expression, and this is partly attributed to the upregulation of LRH-1 through Ca2+/calcineurin, and cAMP/PKA and PI3K/Akt pathways.
In conclusion, we demonstrate novel findings in ovarian granulosa cells that FSH acts acutely through Ca2+/calcineurin pathway to increase aromatase expression, and TGFb1 chronic enhancement of FSH effect involves the cAMP/PKA, PI3K/Akt and Ca2+/calcineurin signaling. Furthermore, the CREB transcription coregulator CRTC2 and transcription factor LRH-1 are crucially involved in FSH and TGFb1-regulated aromatase expression.

English abstract 1
Chinese abstract 2
?? Introduction
A. General ovarian physiology 3
B. Role of follicle-stimulating hormone (FSH) in the ovary 3
C. Role of transforming growth factor ? (TGF?? in the ovary 4
D. Biological functions of estrogen and the regulation of its biosynthesis 6
E. Goal of the study 10

Ⅱ. Materials and Methods
A. Materials 12
B. Animals 12
C. Isolation of rat granulosa cells 12
D. Cell culture and treatment 13
E. Crystal violet assay 13
F. Enzyme-linked immunoassay 13
G. Immunoblotting 14
H. Reverse transcription-polymerase chain reaction (RT-PCR) 15
I. Chromatin immunoprecipitation (ChIP) assay 15
J. Statistics 17

Ⅲ. Results
A. FSH and TGF?? regulation of aromatase expression and activity 18
B. Potential involvement of cAMP/PKA and PI3K/Akt pathway in FSH and TGF??-induced aromatase expression and activity 19
C. Potential involvement of Ca2+/calcineurin pathway, and CREB coactivator CRTC2 in FSH and TGF??-induced aromatase expression and activity 19
D. Potential involvement of LRH-1 transcription factor in FSH and TGF??-induced aromatase expression and activity 21

Ⅳ. Discussion 39
Ⅴ. References 44


Adashi EY & Hsueh AJ 1982 Estrogens augment the stimulation of ovarian aromatase activity by follicle-stimulating hormone in cultured rat granulosa cells. J Biol Chem 257 6077-6083.
Alam H, Maizels ET, Park Y, Ghaey S, Feiger ZJ, Chandel NS & Hunzicker-Dunn M 2004 Follicle-stimulating hormone activation of hypoxia-inducible factor-1 by the phosphatidylinositol 3-kinase/AKT/Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follicular differentiation. J Biol Chem 279 19431-19440.
Anderson E 2002 The role of oestrogen and progesterone receptors in human mammary development and tumorigenesis. Breast Cancer Res 4 197-201.
Balthazart J, Cornil CA, Taziaux M, Charlier TD, Baillien M & Ball GF 2006 Rapid changes in production and behavioral action of estrogens. Neuroscience 138 783-791.
Boerboom D, Pilon N, Behdjani R, Silversides DW & Sirois J 2000 Expression and regulation of transcripts encoding two members of the NR5A nuclear receptor subfamily of orphan nuclear receptors, steroidogenic factor-1 and NR5A2, in equine ovarian cells during the ovulatory process. Endocrinology 141 4647-4656.
Brown KA, McInnes KJ, Hunger NI, Oakhill JS, Steinberg GR & Simpson ER 2009 Subcellular localization of cyclic AMP-responsive element binding protein-regulated transcription coactivator 2 provides a link between obesity and breast cancer in postmenopausal women. Cancer Res 69 5392-5399.
Bulun SE, Lin Z, Imir G, Amin S, Demura M, Yilmaz B, Martin R, Utsunomiya H, Thung S, Gurates B, et al. 2005 Regulation of aromatase expression in estrogen-responsive breast and uterine disease: from bench to treatment. Pharmacol Rev 57 359-383.
Bulun SE, Lin Z, Zhao H, Lu M, Amin S, Reierstad S & Chen D 2009 Regulation of aromatase expression in breast cancer tissue. Ann N Y Acad Sci 1155 121-131.
Bulun SE, Sebastian S, Takayama K, Suzuki T, Sasano H & Shozu M 2003 The human CYP19 (aromatase P450) gene: update on physiologic roles and genomic organization of promoters. J Steroid Biochem Mol Biol 86 219-224.
Carlone DL & Richards JS 1997a Evidence that functional interactions of CREB and SF-1 mediate hormone regulated expression of the aromatase gene in granulosa cells and constitutive expression in R2C cells. J Steroid Biochem Mol Biol 61 223-231.
Carlone DL & Richards JS 1997b Functional interactions, phosphorylation, and levels of 3',5'-cyclic adenosine monophosphate-regulatory element binding protein and steroidogenic factor-1 mediate hormone-regulated and constitutive expression of aromatase in gonadal cells. Mol Endocrinol 11 292-304.
Chen D, Reierstad S, Lu M, Lin Z, Ishikawa H & Bulun SE 2009 Regulation of breast cancer-associated aromatase promoters. Cancer Lett 273 15-27.
Chen YJ, Hsiao PW, Lee MT, Mason JI, Ke FC & Hwang JJ 2007 Interplay of PI3K and cAMP/PKA signaling, and rapamycin-hypersensitivity in TGFbeta1 enhancement of FSH-stimulated steroidogenesis in rat ovarian granulosa cells. J Endocrinol 192 405-419.
Clyne CD, Speed CJ, Zhou J & Simpson ER 2002 Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. J Biol Chem 277 20591-20597.
Conkright MD, Canettieri G, Screaton R, Guzman E, Miraglia L, Hogenesch JB & Montminy M 2003 TORCs: transducers of regulated CREB activity. Mol Cell 12 413-423.
Corbin CJ, Trant JM & Conley AJ 2001 Porcine gonadal and placental isozymes of aromatase cytochrome P450: sub-cellular distribution and support by NADPH-cytochrome P450 reductase. Mol Cell Endocrinol 172 115-124.
Czajka-Oraniec I & Simpson ER Aromatase research and its clinical significance. Endokrynol Pol 61 126-134.
Czajka-Oraniec I, Zgliczynski W, Kurylowicz A, Mikula M & Ostrowski J 2008 Association between gynecomastia and aromatase (CYP19) polymorphisms. Eur J Endocrinol 158 721-727.
del Castillo-Olivares A & Gil G 2000 Alpha 1-fetoprotein transcription factor is required for the expression of sterol 12alpha -hydroxylase, the specific enzyme for cholic acid synthesis. Potential role in the bile acid-mediated regulation of gene transcription. J Biol Chem 275 17793-17799.
Diel P 2002 Tissue-specific estrogenic response and molecular mechanisms. Toxicol Lett 127 217-224.
Doody KJ, Lorence MC, Mason JI & Simpson ER 1990 Expression of messenger ribonucleic acid species encoding steroidogenic enzymes in human follicles and corpora lutea throughout the menstrual cycle. J Clin Endocrinol Metab 70 1041-1045.
Drummond AE 2006 The role of steroids in follicular growth. Reprod Biol Endocrinol 4 16.
Drummond AE & Findlay JK 1999 The role of estrogen in folliculogenesis. Mol Cell Endocrinol 151 57-64.
Duggavathi R, Volle DH, Mataki C, Antal MC, Messaddeq N, Auwerx J, Murphy BD & Schoonjans K 2008 Liver receptor homolog 1 is essential for ovulation. Genes Dev 22 1871-1876.
Eimerl S & Orly J 2002 Regulation of steroidogenic genes by insulin-like growth factor-1 and follicle-stimulating hormone: differential responses of cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, and 3beta-hydroxysteroid dehydrogenase/isomerase in rat granulosa cells. Biol Reprod 67 900-910.
Erickson GF, Garzo VG & Magoffin DA 1989 Insulin-like growth factor-I regulates aromatase activity in human granulosa and granulosa luteal cells. J Clin Endocrinol Metab 69 716-724.
Falender AE, Lanz R, Malenfant D, Belanger L & Richards JS 2003 Differential expression of steroidogenic factor-1 and FTF/LRH-1 in the rodent ovary. Endocrinology 144 3598-3610.
Fitzpatrick SL & Richards JS 1991 Regulation of cytochrome P450 aromatase messenger ribonucleic acid and activity by steroids and gonadotropins in rat granulosa cells. Endocrinology 129 1452-1462.
Flores JA, Leong DA & Veldhuis JD 1992 Is the calcium signal induced by follicle-stimulating hormone in swine granulosa cells mediated by adenosine cyclic 3',5'-monophosphate-dependent protein kinase? Endocrinology 130 1862-1866.
Fujiki Y, Rathnam P & Saxena BB 1980 Studies on the disulfide bonds in human pituitary follicle-stimulating hormone. Biochim Biophys Acta 624 428-435.
Gillies RJ, Didier N & Denton M 1986 Determination of cell number in monolayer cultures. Anal Biochem 159 109-113.
Gonzalez-Robayna IJ, Falender AE, Ochsner S, Firestone GL & Richards JS 2000 Follicle-Stimulating hormone (FSH) stimulates phosphorylation and activation of protein kinase B (PKB/Akt) and serum and glucocorticoid-lnduced kinase (Sgk): evidence for A kinase-independent signaling by FSH in granulosa cells. Mol Endocrinol 14 1283-1300.
Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, Galardi C, Wilson JG, Lewis MC, Roth ME, et al. 2000 A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell 6 517-526.
Hagiwara M, Brindle P, Harootunian A, Armstrong R, Rivier J, Vale W, Tsien R & Montminy MR 1993 Coupling of hormonal stimulation and transcription via the cyclic AMP-responsive factor CREB is rate limited by nuclear entry of protein kinase A. Mol Cell Biol 13 4852-4859.
Heldin CH, Landstrom M & Moustakas A 2009 Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition. Curr Opin Cell Biol 21 166-176.
Hickey GJ, Chen SA, Besman MJ, Shively JE, Hall PF, Gaddy-Kurten D & Richards JS 1988 Hormonal regulation, tissue distribution, and content of aromatase cytochrome P450 messenger ribonucleic acid and enzyme in rat ovarian follicles and corpora lutea: relationship to estradiol biosynthesis. Endocrinology 122 1426-1436.
Hickey GJ, Krasnow JS, Beattie WG & Richards JS 1990 Aromatase cytochrome P450 in rat ovarian granulosa cells before and after luteinization: adenosine 3',5'-monophosphate-dependent and independent regulation. Cloning and sequencing of rat aromatase cDNA and 5' genomic DNA. Mol Endocrinol 4 3-12.
Hinshelwood MM, Corbin CJ, Tsang PC & Simpson ER 1993 Isolation and characterization of a complementary deoxyribonucleic acid insert encoding bovine aromatase cytochrome P450. Endocrinology 133 1971-1977.
Hinshelwood MM, Shelton JM, Richardson JA & Mendelson CR 2005 Temporal and spatial expression of liver receptor homologue-1 (LRH-1) during embryogenesis suggests a potential role in gonadal development. Dev Dyn 234 159-168.
Hirshfield AN 1991 Development of follicles in the mammalian ovary. Int Rev Cytol 124 43-101.
Hunzicker-Dunn M & Maizels ET 2006 FSH signaling pathways in immature granulosa cells that regulate target gene expression: branching out from protein kinase A. Cell Signal 18 1351-1359.
Hwang JJ, Lin SW, Teng CH, Ke FC & Lee MT 1996 Relaxin modulates the ovulatory process and increases secretion of different gelatinases from granulosa and theca-interstitial cells in rats. Biol Reprod 55 1276-1283.
Ikushima H & Miyazono K TGFbeta signalling: a complex web in cancer progression. Nat Rev Cancer 10 415-424.
Ingman WV, Robker RL, Woittiez K & Robertson SA 2006 Null mutation in transforming growth factor beta1 disrupts ovarian function and causes oocyte incompetence and early embryo arrest. Endocrinology 147 835-845.
Inoue K, Nakamura K, Abe K, Hirakawa T, Tsuchiya M, Matsuda H, Miyamoto K & Minegishi T 2002 Effect of transforming growth factor beta on the expression of luteinizing hormone receptor in cultured rat granulosa cells. Biol Reprod 67 610-615.
Jones ME, Thorburn AW, Britt KL, Hewitt KN, Misso ML, Wreford NG, Proietto J, Oz OK, Leury BJ, Robertson KM, et al. 2001 Aromatase-deficient (ArKO) mice accumulate excess adipose tissue. J Steroid Biochem Mol Biol 79 3-9.
Kaivo-oja N, Jeffery LA, Ritvos O & Mottershead DG 2006 Smad signalling in the ovary. Reprod Biol Endocrinol 4 21.
Katzenellenbogen BS 1996 Estrogen receptors: bioactivities and interactions with cell signaling pathways. Biol Reprod 54 287-293.
Kim JW, Havelock JC, Carr BR & Attia GR 2005 The orphan nuclear receptor, liver receptor homolog-1, regulates cholesterol side-chain cleavage cytochrome p450 enzyme in human granulosa cells. J Clin Endocrinol Metab 90 1678-1685.
Kim JW, Peng N, Rainey WE, Carr BR & Attia GR 2004 Liver receptor homolog-1 regulates the expression of steroidogenic acute regulatory protein in human granulosa cells. J Clin Endocrinol Metab 89 3042-3047.
Kitawaki J, Noguchi T, Amatsu T, Maeda K, Tsukamoto K, Yamamoto T, Fushiki S, Osawa Y & Honjo H 1997 Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in human endometriotic and adenomyotic tissues but not in normal endometrium. Biol Reprod 57 514-519.
Klee CB, Ren H & Wang X 1998 Regulation of the calmodulin-stimulated protein phosphatase, calcineurin. J Biol Chem 273 13367-13370.
Knight PG & Glister C 2006 TGF-beta superfamily members and ovarian follicle development. Reproduction 132 191-206.
Lanzino M, Catalano S, Genissel C, Ando S, Carreau S, Hamra K & McPhaul MJ 2001 Aromatase messenger RNA is derived from the proximal promoter of the aromatase gene in Leydig, Sertoli, and germ cells of the rat testis. Biol Reprod 64 1439-1443.
Liu DL, Liu WZ, Li QL, Wang HM, Qian D, Treuter E & Zhu C 2003 Expression and functional analysis of liver receptor homologue 1 as a potential steroidogenic factor in rat ovary. Biol Reprod 69 508-517.
Luo Y, Liang CP & Tall AR 2001 The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor. J Biol Chem 276 24767-24773.
Massague J & Chen YG 2000 Controlling TGF-beta signaling. Genes Dev 14 627-644.
Massague J & Gomis RR 2006 The logic of TGFbeta signaling. FEBS Lett 580 2811-2820.
Massague J & Wotton D 2000 Transcriptional control by the TGF-beta/Smad signaling system. EMBO J 19 1745-1754.
McGee EA & Hsueh AJ 2000 Initial and cyclic recruitment of ovarian follicles. Endocr Rev 21 200-214.
Michael MD, Michael LF & Simpson ER 1997 A CRE-like sequence that binds CREB and contributes to cAMP-dependent regulation of the proximal promoter of the human aromatase P450 (CYP19) gene. Mol Cell Endocrinol 134 147-156.
Moustakas A & Heldin CH 2005 Non-Smad TGF-beta signals. J Cell Sci 118 3573-3584.
Moustakas A & Heldin CH 2009 The regulation of TGFbeta signal transduction. Development 136 3699-3714.
O'Donnell L, Robertson KM, Jones ME & Simpson ER 2001 Estrogen and spermatogenesis. Endocr Rev 22 289-318.
Orisaka M, Tajima K, Tsang BK & Kotsuji F 2009 Oocyte-granulosa-theca cell interactions during preantral follicular development. J Ovarian Res 2 9.
Oz OK, Hirasawa G, Lawson J, Nanu L, Constantinescu A, Antich PP, Mason RP, Tsyganov E, Parkey RW, Zerwekh JE, et al. 2001 Bone phenotype of the aromatase deficient mouse. J Steroid Biochem Mol Biol 79 49-59.
Pacher P, Sharma K, Csordas G, Zhu Y & Hajnoczky G 2008 Uncoupling of ER-mitochondrial calcium communication by transforming growth factor-beta. Am J Physiol Renal Physiol 295 F1303-1312.
Park Y, Maizels ET, Feiger ZJ, Alam H, Peters CA, Woodruff TK, Unterman TG, Lee EJ, Jameson JL & Hunzicker-Dunn M 2005 Induction of cyclin D2 in rat granulosa cells requires FSH-dependent relief from FOXO1 repression coupled with positive signals from Smad. J Biol Chem 280 9135-9148.
Peng N, Kim JW, Rainey WE, Carr BR & Attia GR 2003 The role of the orphan nuclear receptor, liver receptor homologue-1, in the regulation of human corpus luteum 3beta-hydroxysteroid dehydrogenase type II. J Clin Endocrinol Metab 88 6020-6028.
Ratoosh SL, Lifka J, Hedin L, Jahsen T & Richards JS 1987 Hormonal regulation of the synthesis and mRNA content of the regulatory subunit of cyclic AMP-dependent protein kinase type II in cultured rat ovarian granulosa cells. J Biol Chem 262 7306-7313.
Robertson KM, Simpson ER, Lacham-Kaplan O & Jones ME 2001 Characterization of the fertility of male aromatase knockout mice. J Androl 22 825-830.
Sadate-Ngatchou PI, Pouchnik DJ & Griswold MD 2004 Follicle-stimulating hormone induced changes in gene expression of murine testis. Mol Endocrinol 18 2805-2816.
Saragueta PE, Lanuza GM & Baranao JL 2002 Autocrine role of transforming growth factor beta1 on rat granulosa cell proliferation. Biol Reprod 66 1862-1868.
Screaton RA, Conkright MD, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR, 3rd, Takemori H, et al. 2004 The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell 119 61-74.
Sen A, Bettegowda A, Jimenez-Krassel F, Ireland JJ & Smith GW 2007 Cocaine- and amphetamine-regulated transcript regulation of follicle-stimulating hormone signal transduction in bovine granulosa cells. Endocrinology 148 4400-4410.
Silandre D, Delalande C, Durand P & Carreau S 2007 Three promoters PII, PI.f, and PI.tr direct the expression of aromatase (cyp19) gene in male rat germ cells. J Mol Endocrinol 39 169-181.
Simpson ER 2003 Sources of estrogen and their importance. J Steroid Biochem Mol Biol 86 225-230.
Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD, et al. 1994a Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 15 342-355.
Simpson ER, Mahendroo MS, Nichols JE & Bulun SE 1994b Aromatase gene expression in adipose tissue: relationship to breast cancer. Int J Fertil Menopausal Stud 39 Suppl 2 75-83.
Simpson ER, Misso M, Hewitt KN, Hill RA, Boon WC, Jones ME, Kovacic A, Zhou J & Clyne CD 2005 Estrogen--the good, the bad, and the unexpected. Endocr Rev 26 322-330.
Sirianni R, Seely JB, Attia G, Stocco DM, Carr BR, Pezzi V & Rainey WE 2002 Liver receptor homologue-1 is expressed in human steroidogenic tissues and activates transcription of genes encoding steroidogenic enzymes. J Endocrinol 174 R13-17.
Stocco C 2004 In vivo and in vitro inhibition of cyp19 gene expression by prostaglandin F2alpha in murine luteal cells: implication of GATA-4. Endocrinology 145 4957-4966.
Stocco C 2008 Aromatase expression in the ovary: hormonal and molecular regulation. Steroids 73 473-487.
Stocco C, Kwintkiewicz J & Cai Z 2007 Identification of regulatory elements in the Cyp19 proximal promoter in rat luteal cells. J Mol Endocrinol 39 211-221.
ten Dijke P & Hill CS 2004 New insights into TGF-beta-Smad signalling. Trends Biochem Sci 29 265-273.
Toda K, Takeda K, Okada T, Akira S, Saibara T, Kaname T, Yamamura K, Onishi S & Shizuta Y 2001 Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to 17beta-oestradiol. J Endocrinol 170 99-111.
Walker WH & Cheng J 2005 FSH and testosterone signaling in Sertoli cells. Reproduction 130 15-28.
Webb R, Garnsworthy PC, Gong JG & Armstrong DG 2004 Control of follicular growth: local interactions and nutritional influences. J Anim Sci 82 E-Suppl E63-74.
Woods DC & Johnson AL 2005 Regulation of follicle-stimulating hormone-receptor messenger RNA in hen granulosa cells relative to follicle selection. Biol Reprod 72 643-650.
Yamada-Mouri N, Hirata S & Kato J 1996 Existence and expression of the untranslated first exon of aromatase mRNA in the rat brain. J Steroid Biochem Mol Biol 58 163-166.
Ying SY, Becker A, Ling N, Ueno N & Guillemin R 1986 Inhibin and beta type transforming growth factor (TGF beta) have opposite modulating effects on the follicle stimulating hormone (FSH)-induced aromatase activity of cultured rat granulosa cells. Biochem Biophys Res Commun 136 969-975.
Younglai EV, Wu YJ, Kwan TK & Kwan CY 2005 Non-genomic action of estradiol and progesterone on cytosolic calcium concentrations in primary cultures of human granulosa-lutein cells. Hum Reprod 20 2383-2390.
Zeleznik AJ, Saxena D & Little-Ihrig L 2003 Protein kinase B is obligatory for follicle-stimulating hormone-induced granulosa cell differentiation. Endocrinology 144 3985-3994.




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3. 登革病毒感染時CLEC5A在調節蝕骨細胞活性中扮演的角色
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