跳到主要內容

臺灣博碩士論文加值系統

(3.231.230.177) 您好!臺灣時間:2021/07/28 21:59
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:孫蘇琴
研究生(外文):Su-Chin Sun
論文名稱:甲狀腺刺激素受體在卵巢中的配體種類與生理功能的探討
論文名稱(外文):Characterization of the endogenous ligand pair and physiological roles of thyroid-stimulating hormone receptor in the ovary
指導教授:羅清維
指導教授(外文):Ching-Wei Luo
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生命科學暨基因體科學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:88
中文關鍵詞:甲狀腺刺激素受體thyrostimulin卵巢生殖週期G蛋白偶合受體
外文關鍵詞:TSHRthyrostimulinovaryovarian cycleGPCR
相關次數:
  • 被引用被引用:0
  • 點閱點閱:172
  • 評分評分:
  • 下載下載:7
  • 收藏至我的研究室書目清單書目收藏:0
甲狀腺刺激素受體 (thyroid stimulating hormone receptor, TSHR) 屬於G蛋白偶合受體的成員之一,主要表現在甲狀腺濾泡細胞上,負責調控甲狀腺素的分泌,以控制生長發育。除了甲狀腺刺激素 (TSH) 之外, 最近新發現的醣蛋白激素:thyrostimulin (A2/B5) 也可作為TSHR的配體。A2/B5是由��2及��5兩個次單元所形成的異源二聚體,但目前對於其作用的組織與調控的生理功能並不清楚。有趣的是,我們在小鼠卵巢微陣列分析資料中發現TSHR mRNA表現量在生殖週期中有著週期性的波動,此現象也可由即時聚合�○s鎖反應分析超排卵的大鼠卵巢得到驗證。接著,我們以大鼠作為動物模式,用雷射顯微擷取法或針頭穿刺法來分離卵巢濾泡中不同種的細胞,發現TSHR mRNA在顆粒細胞中有最高的表現量。我們利用TSHR mRNA表現量最高的卵巢顆粒細胞進行原代培養 (primary culture) 實驗,發現不論在未成熟或成熟雌鼠的顆粒細胞中,同時加入A2/B5和性腺刺激素可以促使cAMP的增加,也會快速活化下游訊息c-fos mRNA的表現量。此外,我們也發現雌性素會抑制TSHR mRNA的表現;另外,FSH和hCG在短時間內會快速增加cAMP的濃度,而這樣的作用似乎會使TSHR mRNA的表現量上升。另一方面,我們也利用聚合�○s鎖反應檢測TSHR的2對配體基因在卵巢細胞中的表現,發現A2及B5的 mRNA在卵巢濾泡的各種細胞中都有表現,且在卵細胞中含量最高;但TSH-�狾b相同條件下卻沒有被偵測到。此外,我們也利用免疫組織化學分析法,證實TSHR與A2/B5蛋白質的表現位置與其mRNA所在位置相同。因此,我們猜測:A2/B5可能以paracrine或autocrine的方法來活化TSHR產生訊息傳遞,進而影響生殖週期的進行。
進一步,我們想要探討TSHR到底在卵巢的發育生長中扮演什麼樣的生理角色。為了獲得具有功能的A2/B5醣蛋白激素,我們將帶有FLAG標籤的A2/B5載體送入人類HEK 293T細胞中,進行穩定株選殖並收取分泌的培養液以純化A2/B5蛋白。藉由偵測二級訊號cAMP的濃度變化,我們證實所純化的A2/B5蛋白具有活化TSHR的能力。為了探討TSHR在卵巢中的訊息傳遞路徑,我們首先利用卵巢的細胞株NIH:OVCAR-3作為測試,發現此細胞株不但有TSHR mRNA的表現,在A2/B5的刺激下也可以促使cAMP的上升,且會引起c-fos mRNA的快速增加,證實TSHR蛋白確實會表現在卵巢細胞中,並具有引起訊息傳遞的功能。在未來,我們想更進一步釐清A2/B5和TSHR在卵巢中的交互作用對調控卵巢生理功能或卵巢癌症生長上的重要性。
Thyroid-stimulating hormone receptor (TSHR) is mainly expressed on the thyroid follicular cells to regulate the secretion of thyroid hormones for the control of body growth and development. In addition to TSH, a newly discovered glycoprotein hormone A2/B5, a heterodimer composed of α2 and β5 subunits, can also act as the cognate ligand to activate TSHR. However, the targeted tissues and exact functions of A2/B5 remain unclear. Of interest, we currently observed the ovarian expression of TSHR is periodically regulated by gonadotropins. Such a phenomenon was also confirmed by real-time PCR in a superovulatory rat model. Further, using laser capture microdissection and needle puncturing of immature rat ovaries to isolate different ovarian cell types, we demonstrated the TSHR gene can be expressed in all cell types with granulosa cells showing the highest levels. In primary culture of either immature or mature granulosa cells, which show the highest TSHR gene expression, we demonstrated the treatment of A2/B5 can induce the cAMP production and the c-fos gene response effectively in the presence of gonadotropins. We also demonstrated that the expression of TSHR gene was down-regulated by estrogen. In contrast, the TSHR gene showed up-regulation by cAMP triggered by gonadotropins. In addition, we also characterized the expression of A2, B5 and TSH-β genes in all ovarian cell types. The A2 and B5 genes are ubiquitous in all ovarian cells with oocytes showing the highest B5 levels. In contrast, the TSH-β gene was undetectable in the ovary. In addition to their mRNA levels, the ovarian locations of TSHR and B5 were also confirmed by immunohistochemical analyses. Therefore, we concluded that A2/B5 may play a paracrine and/or autocrine factor to activate ovarian TSHR.
Further, we would like to explore the physiological roles of TSHR in the regulation of ovarian growth and development. To obtain the active A2/B5 protein, a construct containing the FLAG-tagged human A2/B5 genes was transfected into HEK-293T cells for conditioned media collection and recombinant protein purification. The bioactivity of purified A2/B5 protein was confirmed by the TSHR-triggered cAMP elevation. To identify the potential functions of TSHR signaling in the ovary, an ovary-derived cell line, NIH:OVCAR-3, was chosen for primary tests. We demonstrated treatment of A2/B5 can rapidly induce the c-fos mRNA expression, indicative of the existence of functional TSHR on NIH:OVCAR-3 cells. Future studies will be carried on to elucidate the physiological roles of TSHR in the mediation of ovarian development and tumorigenesis.
目錄
中文摘要 1
Abstract 3
第壹章 緒論 5
1-1 G蛋白偶合受體 (G protein-coupled receptor) 5
1-2 GPCRs的訊息傳遞 5
1-3 甲狀腺刺激素受體 (thyroid-stimulating hormone receptor) 6
1-4 醣蛋白激素家族 (glycoprotein hormone family) 7
1-4-1 TSH特性與生理角色 8
1-4-2 FSH特性與生理角色 9
1-4-3 LH特性與生理角色 10
1-4-4 CG特性與生理角色 11
1-4-5 A2/B5特性與生理角色 12
1-5 卵巢的發育 12
1-6 研究動機 14
第貳章 實驗材料與方法 16
2-1 核醣核酸之萃取 (RNA extraction) 16
2-2 互補去氧核醣核酸之製備 (cDNA preparation) 16
2-3 聚合�○s鎖反應 (polymerase chain reaction, PCR) 17
2-4 小量質體DNA萃取 (plasmid DNA isolation) 18
2-5 DNA瓊脂膠體電泳 (DNA agarose gel electrophoresis) 18
2-6 膠體DNA之回收與純化 18
2-7 細胞培養 (cell culture) 19
2-7-1 細胞轉染 (cell transfection) 19
2-7-2 細胞內冷光�� (luciferase) 與β-半乳糖���� (β-galactosidase) 含量之偵測 19
2-7-3 細胞培養液收集 (conditioned medium collection)和濃縮 20
2-7-4 單一細胞株 (cell line) 建立與選殖 20
2-7-5 具FLAG標記重組蛋白質的純化 21
2-8 蛋白質聚丙醯胺膠體電泳 (sodium dodecyl sulfate polyacrylamide gel electrophoresis, SDS-PAGE) 之分析 21
2-8-1 SDS-polyacryamide gel 製備 22
2-8-2 樣品配製與電泳分離 23
2-8-3 西方墨點法 23
2-9 模擬大鼠之卵巢生殖週期 24
2-10 組織脫水與石蠟包埋 (tissue processing and paraffin embedding) 24
2-11 免疫組織化學法 (Immunohistochemistry, IHC) 25
2-11-1 免疫組織化學法 25
2-11-2 抗體中和試驗法 (antibody neutralization) 26
2-11-3 Avidin-biotin blocking kit 27
2-12 卵巢濾泡細胞分離 27
2-12-1 雷射顯微擷取 (Laser Capture Microdissection, LCM) 27
2-12-2 針頭穿刺 (needle puncture) 28
2-13 卵巢顆粒細胞的原代培養 (primary culture of ovarian granulosa cells) 29
2-13-1 顆粒細胞製備與培養 29
2-13-2 實驗設計 29
2-14 cAMP酵素免疫偵測法 30
2-15 黃體素酵素免疫偵測法 30
2-16 定量聚合�○s鎖反應 (Quantitative real-time polymerase chain reaction) 31
2-16-1 TagMan real-time PCR 31
2-16-2 SYBR GREEN real-time PCR 32
2-17 統計分析 32
2-18 緩衝溶液配製 33
第參章 實驗結果 35
3-1 TSHR在組織中的表現 35
3-1-1 TSHR在卵巢中的表現 35
3-1-2 TSHR在卵巢中的分佈 36
3-2 卵巢中TSHR配體種類的探討 36
3-2-1 TSHR配體種類的確認 36
3-2-2 A2和B5在卵巢中的分佈 37
3-3 製備A2/B5重組蛋白 37
3-3-1 選擇適合表現A2/B5重組蛋白的哺乳動物細胞株 37
3-3-2 報導質體的選擇 38
3-3-3 建立穩定表現A2/B5重組蛋白的單一細胞株 38
3-3-4 大量表現且純化A2/B5重組蛋白 39
3-4 TSHR在卵巢中的功能與調節機制分析 40
3-4-1 利用顆粒細胞原代培養分析TSHR對卵巢生理功能的影響 40
3-4-2 性腺刺激素對TSHR mRNA的影響 41
3-4-3 雌性素對TSHR mRNA的調控 41
3-5 TSHR在人類卵巢細胞株NIH:OVCAR-3中的功能探討 42
第肆章 討論 43
4-1 TSHR在卵巢中的表現與分佈 43
4-2 A2/B5醣蛋白激素的生理角色 44
4-3 TSHR在卵巢中的調控機制 45
4-4 TSHR在卵巢癌症細胞中的調控 47
4-5 未來目標與展望 48
參考文獻 70
附圖 76
附表 79
圖目錄
圖 一、TSHR在卵巢與輸卵管中的表現 50
圖 二、分析TSHR在卵巢生殖週期中表現量的差異 51
圖 三、TSHR在卵巢細胞中的分佈 52
圖 四、TSHR蛋白質在卵巢中的分佈 53
圖 五、探討TSHR的配體A2/B5和TSH在卵巢中的表現情形 54
圖 六、 利用雷射顯微擷取法分離卵巢細胞 55
圖 七、A2和B5在卵巢細胞中的分佈 56
圖 八、A2/B5在卵巢中的分佈 57
圖 九、A2/B5重組蛋白在不同哺乳動物細胞株的表現情形 58
圖 十、偵測不同報導質體的效率 59
圖 十一、建立持續表現A2/B5重組蛋白細胞株 60
圖 十二、 No 3細胞株表現的A 2/B5重組蛋白活性測試 61
圖 十三、純化A2/B5重組蛋白 62
圖 十四、偵測純化後A2/B5重組蛋白的活性 63
圖 十五、利用卵巢顆粒細胞原代培養分析A2/B5刺激對cAMP的影響 64
圖 十六、利用卵巢顆粒細胞原代培養分析A2/B5刺激對黃體素的影響 65
圖 十七、利用卵巢顆粒細胞原代培養分析A2/B5刺激對c-fos的影響 66
圖 十八、性腺刺激素對TSHR mRNA表現量的影響 67
圖 十九、雌性素對TSHR mRNA表現量的影響 68
圖 二十、利用人類卵巢細胞株NIH:OVACAR-3探討TSHR的生理功能 69
Aghajanova, L., Lindeberg, M., Carlsson, I. B., Stavreus-Evers, A., Zhang, P., Scott, J. E., et al. (2009). Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue. Reprod Biomed Online, 18(3), 337-347.
Alfthan, H., & Stenman, U. H. (1996). Pathophysiological importance of various molecular forms of human choriogonadotropin. Mol Cell Endocrinol, 125(1-2), 107-120.
Atri, M., Leduc, C., Gillett, P., Bret, P. M., Reinhold, C., Kintzen, G., et al. (1996). Role of endovaginal sonography in the diagnosis and management of ectopic pregnancy. Radiographics, 16(4), 755-774; discussion 775.
Baenziger, J. U., & Green, E. D. (1988). Pituitary glycoprotein hormone oligosaccharides: structure, synthesis and function of the asparagine-linked oligosaccharides on lutropin, follitropin and thyrotropin. Biochim Biophys Acta, 947(2), 287-306.
Ben-Ze'ev, A., & Amsterdam, A. (1987). In vitro regulation of granulosa cell differentiation. Involvement of cytoskeletal protein expression. J Biol Chem, 262(11), 5366-5376.
Binkley, S. A. (1995). New York: Harper Collins College Publishers, chapter 17, 18. Endocrinology.
Bockaert, J., & Pin, J. P. (1999). Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J, 18(7), 1723-1729.
Channing, C. P., Schaerf, F. W., Anderson, L. D., & Tsafriri, A. (1980). Ovarian follicular and luteal physiology. Int Rev Physiol, 22, 117-201.
Chen, C. R., Chazenbalk, G. D., Wawrowsky, K. A., McLachlan, S. M., & Rapoport, B. (2006). Evidence that human thyroid cells express uncleaved, single-chain thyrotropin receptors on their surface. Endocrinology, 147(6), 3107-3113.
Combarnous, Y., Guillou, F., Martinat, N., & Cahoreau, C. (1984). [Origin of the FSH + LH double activity of equine chorionic gonadotropin (eCG/PMSG)]. Ann Endocrinol (Paris), 45(4-5), 261-268.
Dalrymple, M. B., Pfleger, K. D., & Eidne, K. A. (2008). G protein-coupled receptor dimers: functional consequences, disease states and drug targets. Pharmacol Ther, 118(3), 359-371.
De Felice, M., Postiglione, M. P., & Di Lauro, R. (2004). Minireview: thyrotropin receptor signaling in development and differentiation of the thyroid gland: insights from mouse models and human diseases. Endocrinology, 145(9), 4062-4067.
de Kretser, D. M., & Phillips, D. J. (1998). Mechanisms of protein feedback on gonadotropin secretion. J Reprod Immunol, 39(1-2), 1-12.
Dos Santos, S., Bardet, C., Bertrand, S., Escriva, H., Habert, D., & Querat, B. (2009). Distinct expression patterns of glycoprotein hormone-{alpha}2 (GPA2) and -{beta}5 (GPB5) in a basal chordate suggest independent developmental functions. Endocrinology.
Filicori, M. (1999). The role of luteinizing hormone in folliculogenesis and ovulation induction. Fertil Steril, 71(3), 405-414.
Gilbert, S. F. (2006). Developmental Biology, Eighth Edition.
Goff, A. K., Leung, P. C., & Armstrong, D. T. (1979). Stimulatory action of follicle-stimulating hormone and androgens on the responsiveness of rat granulosa cells to gonadotropins in vitro. Endocrinology, 104(4), 1124-1129.
Hepler, J. R., & GilMAN, A. M. (1992). G protein. Trends Biochem. Sic., 17, 383-387.
Hershman, J. M. (1999). Human chorionic gonadotropin and the thyroid: hyperemesis gravidarum and trophoblastic tumors. Thyroid, 9(7), 653-657.
Hsueh, A. J., Adashi, E. Y., Jones, P. B., & Welsh, T. H., Jr. (1984). Hormonal regulation of the differentiation of cultured ovarian granulosa cells. Endocr Rev, 5(1), 76-127.
Hsueh, A. J., Billig, H., & Tsafriri, A. (1994). Ovarian follicle atresia: a hormonally controlled apoptotic process. Endocr Rev, 15(6), 707-724.
Jalili, T., Takeishi, Y., & Walsh, R. A. (1999). Signal transduction during cardiac hypertrophy: the role of G alpha q, PLC beta I, and PKC. Cardiovasc Res, 44(1), 5-9.
Kaipia, A., & Hsueh, A. J. (1997). Regulation of ovarian follicle atresia. Annu Rev Physiol, 59, 349-363.
Keay, S. D., Vatish, M., Karteris, E., Hillhouse, E. W., & Randeva, H. S. (2004). The role of hCG in reproductive medicine. BJOG, 111(11), 1218-1228.
Knecht, M. (1988). Plasminogen activator is associated with the extracellular matrix of ovarian granulosa cells. Mol Cell Endocrinol, 56(1-2), 1-9.
Kumar, R. S., Ijiri, S., Kight, K., Swanson, P., Dittman, A., Alok, D., et al. (2000). Cloning and functional expression of a thyrotropin receptor from the gonads of a vertebrate (bony fish): potential thyroid-independent role for thyrotropin in reproduction. Mol Cell Endocrinol, 167(1-2), 1-9.
Kurose, H. (2003). Galpha12 and Galpha13 as key regulatory mediator in signal transduction. Life Sci, 74(2-3), 155-161.
Lamminen, T., Jiang, M., Manna, P. R., Pakarinen, P., Simonsen, H., Herrera, R. J., et al. (2002). Functional study of a recombinant form of human LHbeta-subunit variant carrying the Gly(102)Ser mutation found in Asian populations. Mol Hum Reprod, 8(10), 887-892.
Lejeune, H., Sanchez, P., Chuzel, F., Langlois, D., & Saez, J. M. (1998). Time-course effects of human recombinant luteinizing hormone on porcine Leydig cell specific differentiated functions. Mol Cell Endocrinol, 144(1-2), 59-69.
Lim, A. S., & Tsakok, M. F. (1997). Age-related decline in fertility: a link to degenerative oocytes? Fertil Steril, 68(2), 265-271.
Luo, C. W., Kawamura, K., Klein, C., & Hsueh, A. J. (2004). Paracrine regulation of ovarian granulosa cell differentiation by stanniocalcin (STC) 1: mediation through specific STC1 receptors. Mol Endocrinol, 18(8), 2085-2096.
Macdonald, L. E., Wortley, K. E., Gowen, L. C., Anderson, K. D., Murray, J. D., Poueymirou, W. T., et al. (2005). Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5. Proc Natl Acad Sci U S A, 102(7), 2496-2501.
Marians, R. C., Ng, L., Blair, H. C., Unger, P., Graves, P. N., & Davies, T. F. (2002). Defining thyrotropin-dependent and -independent steps of thyroid hormone synthesis by using thyrotropin receptor-null mice. Proc Natl Acad Sci U S A, 99(24), 15776-15781.
McAllister, J. M., Mason, J. I., Byrd, W., Trant, J. M., Waterman, M. R., & Simpson, E. R. (1990). Proliferating human granulosa-lutein cells in long term monolayer culture: expression of aromatase, cholesterol side-chain cleavage, and 3 beta-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab, 71(1), 26-33.
Mizutori, Y., Chen, C. R., McLachlan, S. M., & Rapoport, B. (2008). The thyrotropin receptor hinge region is not simply a scaffold for the leucine-rich domain but contributes to ligand binding and signal transduction. Mol Endocrinol, 22(5), 1171-1182.
Nagasaki, H., Wang, Z., Jackson, V. R., Lin, S., Nothacker, H. P., & Civelli, O. (2006). Differential expression of the thyrostimulin subunits, glycoprotein alpha2 and beta5 in the rat pituitary. J Mol Endocrinol, 37(1), 39-50.
Nagayama, Y., Kaufman, K. D., Seto, P., & Rapoport, B. (1989). Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor. Biochem Biophys Res Commun, 165(3), 1184-1190.
Nakabayashi, K., Matsumi, H., Bhalla, A., Bae, J., Mosselman, S., Hsu, S. Y., et al. (2002). Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor. J Clin Invest, 109(11), 1445-1452.
Naylor, S. L., Chin, W. W., Goodman, H. M., Lalley, P. A., Grzeschik, K. H., & Sakaguchi, A. Y. (1983). Chromosome assignment of genes encoding the alpha and beta subunits of glycoprotein hormones in man and mouse. Somatic Cell Genet, 9(6), 757-770.
Neves, S. R., Ram, P. T., & Iyengar, R. (2002). G protein pathways. Science, 296(5573), 1636-1639.
Okada, S. L., Ellsworth, J. L., Durnam, D. M., Haugen, H. S., Holloway, J. L., Kelley, M. L., et al. (2006). A glycoprotein hormone expressed in corticotrophs exhibits unique binding properties on thyroid-stimulating hormone receptor. Mol Endocrinol, 20(2), 414-425.
Okajima, Y., Nagasaki, H., Suzuki, C., Suga, H., Ozaki, N., Arima, H., et al. (2008). Biochemical roles of the oligosaccharide chains in thyrostimulin, a heterodimeric hormone of glycoprotein hormone subunits alpha 2 (GPA2) and beta 5 (GPB5). Regul Pept, 148(1-3), 62-67.
Pierce, J. G., & Parsons, T. F. (1981). Glycoprotein hormones: structure and function. Annu Rev Biochem, 50, 465-495.
Rapoport, B., Chazenbalk, G. D., Jaume, J. C., & McLachlan, S. M. (1998). The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. Endocr Rev, 19(6), 673-716.
Richards, J. S. (1980). Maturation of ovarian follicles: actions and interactions of pituitary and ovarian hormones on follicular cell differentiation. Physiol Rev, 60(1), 51-89.
Rocha, A., Gomez, A., Galay-Burgos, M., Zanuy, S., Sweeney, G. E., & Carrillo, M. (2007). Molecular characterization and seasonal changes in gonadal expression of a thyrotropin receptor in the European sea bass. Gen Comp Endocrinol, 152(1), 89-101.
Skinner, M. K., & Dorrington, J. H. (1984). Control of fibronectin synthesis by rat granulosa cells in culture. Endocrinology, 115(5), 2029-2031.
Song, L., McGee, J. A., & Walsh, E. J. (2006). Consequences of combined maternal, fetal and persistent postnatal hypothyroidism on the development of auditory function in Tshrhyt mutant mice. Brain Res, 1101(1), 59-72.
Sudo, S., Kuwabara, Y., Park, J. I., Hsu, S. Y., & Hsueh, A. J. (2005). Heterodimeric fly glycoprotein hormone-alpha2 (GPA2) and glycoprotein hormone-beta5 (GPB5) activate fly leucine-rich repeat-containing G protein-coupled receptor-1 (DLGR1) and stimulation of human thyrotropin receptors by chimeric fly GPA2 and human GPB5. Endocrinology, 146(8), 3596-3604.
Sunahara, R. K., Dessauer, C. W., & Gilman, A. G. (1996). Complexity and diversity of mammalian adenylyl cyclases. Annu Rev Pharmacol Toxicol, 36, 461-480.
Szkudlinski, M. W., Fremont, V., Ronin, C., & Weintraub, B. D. (2002). Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships. Physiol Rev, 82(2), 473-502.
Tando, Y., & Kubokawa, K. (2009). Expression of the gene for ancestral glycoprotein hormone beta subunit in the nerve cord of amphioxus. Gen Comp Endocrinol, 162(3), 329-339.
Thotakura, N. R., & Blithe, D. L. (1995). Glycoprotein hormones: glycobiology of gonadotrophins, thyrotrophin and free alpha subunit. Glycobiology, 5(1), 3-10.
Ulloa-Aguirre, A., & Timossi, C. (1998). Structure-function relationship of follicle-stimulating hormone and its receptor. Hum Reprod Update, 4(3), 260-283.
Van Look, P. F., & Baird, D. T. (1980). Regulatory mechanisms during the menstrual cycle. Eur J Obstet Gynecol Reprod Biol, 11(2), 121-144.
Vassart, G., & Dumont, J. E. (1992). The thyrotropin receptor and the regulation of thyrocyte function and growth. Endocr Rev, 13(3), 596-611.
Wang, C. J., Hsu, S. H., Hung, W. T., & Luo, C. W. (2009). Establishment of a chimeric reporting system for the universal detection and high-throughput screening of G protein-coupled receptors. Biosens Bioelectron.
Welt, C. K., Martin, K. A., Taylor, A. E., Lambert-Messerlian, G. M., Crowley, W. F., Jr., Smith, J. A., et al. (1997). Frequency modulation of follicle-stimulating hormone (FSH) during the luteal-follicular transition: evidence for FSH control of inhibin B in normal women. J Clin Endocrinol Metab, 82(8), 2645-2652.
Wilson, J. D., Griffin, J. E., Leshin, M., & George, F. W. (1981). Role of gonadal hormones in development of the sexual phenotypes. Hum Genet, 58(1), 78-84.
Ying, S. Y. (1988). Inhibins, activins, and follistatins: gonadal proteins modulating the secretion of follicle-stimulating hormone. Endocr Rev, 9(2), 267-293.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊