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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭應誠(Ing-Cherng Guo) | |
| dc.contributor.author | Yun-Ru Chen | en |
| dc.contributor.author | 陳韻如 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:43:13Z | - |
| dc.date.available | 2006-07-21 | |
| dc.date.copyright | 2006-07-21 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-17 | |
| dc.identifier.citation | 參考文獻
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De Vos, J., et al., JAK2 tyrosine kinase inhibitor tyrphostin AG490 downregulates the mitogen-activated protein kinase(MAPK) and signal transducer and activator of transcription(STAT) pathways and induces apoptosis in myeloma cells. Br J Haematol, 2000. 109(4): p. 823-8. 29. Morris, A.J. and C.C. Malbon, Physiological regulation of G protein-linked signaling. Physiol Rev, 1999. 79(4): p. 1373-430. 30. Rosenberg, D., et al., Role of the PKA-regulated transcription factor CREB in development and tumorigenesis of endocrine tissues. Ann N Y Acad Sci, 2002. 968: p. 65-74. 31. Palfreyman, J.W. and D. Schulster, Proceedings: Cyclic AMP and corticosteroid output of isolated adrenal cells stimulated by cholera toxin. J Endocrinol, 1975. 64(3): p. 68P. 32. Syin, C., et al., The H89 cAMP-dependent protein kinase inhibitor blocks Plasmodium falciparum development in infected erythrocytes. Eur J Biochem, 2001. 268(18): p. 4842-9. 33. Suy, S., et al., Association of Grb2 with Sos and Ras with Raf-1 upon gamma irradiation of breast cancer cells. Oncogene, 1997. 15(1): p. 53-61. 34. Gyles, S.L., et al., ERKs regulate cyclic AMP-induced steroid synthesis through transcription of the steroidogenic acute regulatory(StAR) gene. J Biol Chem, 2001. 276(37): p. 34888-95. 35. Favata, M.F., et al., Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem, 1998. 273(29): p. 18623-32. 36. Tworoger, S.S. and S.E. Hankinson, Prolactin and breast cancer risk. Cancer Lett, 2006. 37. Kaluzny, M. and M. Bolanowski, [Hyperprolactinemia: etiology, clinical symptoms, and therapy]. Postepy Hig Med Dosw(Online), 2005. 59: p. 20-7. 38. Silva, E.J., et al., Prolactin induces adrenal hypertrophy. Braz J Med Biol Res, 2004. 37(2): p. 193-9. 39. Yamaji, T., et al., Hyperprolactinemia in Cushing's disease and Nelson's syndrome. J Clin Endocrinol Metab, 1984. 58(5): p. 790-5. 40. Meijer, J.C., et al., Hypothalamic corticotrophin releasing factor activity in dogs with pituitary-dependent hyperadrenocorticism. J Endocrinol, 1978. 79(2): p. 209-13. 41. Cobb, V.J., et al., Forskolin treatment directs steroid production towards the androgen pathway in the NCI-H295R adrenocortical tumour cell line. Endocr Res, 1996. 22(4): p. 545-50. 42. Hsu, H.T., et al., Leptin Interferes with ACTH/cAMP Signaling Possibly through a Janus kinase 2-Phosphatidylinositol 3-kinase/Akt-Phosphodiesterase 3-Cyclic AMP Pathway to Down-Regulate Cholesterol Side-Chain Cleavage Cytochrome P450 Enzyme in Human Adrenocortical NCI-H295 Cell Line. J Clin Endocrinol Metab, 2006. 43. Albertson, B.D., et al., New evidence for a direct effect of prolactin on rat adrenal steroidogenesis. Endocr Res, 1987. 13(3): p. 317-33. 44. Tafaro, E., et al., Does adrenal cortex influence prolactin secretion? Evaluation in hirsute women. Boll Soc Ital Biol Sper, 1983. 59(12): p. 1872-6. 45. Tuckey, R.C., Cholesterol side-chain cleavage by mitochondria from the human placenta. Studies using hydroxycholesterols as substrates. J Steroid Biochem Mol Biol, 1992. 42(8): p. 883-90. 46. Piccoletti, R., et al., Rapid stimulation of mitogen-activated protein kinase of rat liver by prolactin. Biochem J, 1994. 303( Pt 2): p. 429-33. 47. Das, R. and B.K. Vonderhaar, Activation of raf-1, MEK, and MAP kinase in prolactin responsive mammary cells. Breast Cancer Res Treat, 1996. 40(2): p. 141-9. 48. Ihle, J.N., Janus kinases in cytokine signalling. Philos Trans R Soc Lond B Biol Sci, 1996. 351(1336): p. 159-66. 49. Stofega, M.R., et al., Mutation of the SHP-2 binding site in growth hormone(GH) receptor prolongs GH-promoted tyrosyl phosphorylation of GH receptor, JAK2, and STAT5B. Mol Endocrinol, 2000. 14(9): p. 1338-50. 50. Strauss, J.F., 3rd, et al., The steroidogenic acute regulatory protein(StAR): a window into the complexities of intracellular cholesterol trafficking. Recent Prog Horm Res, 1999. 54: p. 369-94; discussion 394-5. 51. Sugawara, T. and S. Fujimoto, The potential function of steroid sulphatase activity in steroid production and steroidogenic acute regulatory protein expression. Biochem J, 2004. 380(Pt 1): p. 153-60. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33486 | - |
| dc.description.abstract | 泌乳素(Prolactin, PRL)由198個胺基酸所構成的內泌素，為腦垂腺前葉泌乳素分泌細胞(Lactotrophs)所分泌。正常的生理值下，泌乳素在調節乳腺發育、泌乳與卵巢功能上扮演重要的角色。高泌乳素血症(Hyperprolactinemia, HPRL)發生原因常為腦垂腺腺瘤，導致大量泌乳素存在於血液中，除引起女性月經失調、溢乳或不孕，也易導致腎上腺功能過高等症狀。腎上腺皮質是體內類固醇內泌素首要的合成器官，分泌類固醇的種類為醣皮質醇(Glucocorticoid)、鹽皮質醇(Mineralocorticoid)、性類固醇(Sex hormone)等三類，維持許多生理功能的運作如醣類、水分與電解質之平衡。腎上腺皮質細胞表現泌乳素受體的發現，暗示泌乳素可能直接影響腎上腺皮質細胞類固醇生成，也提供了高泌乳素血症引發腎上腺功能過高症狀的解釋。本實驗的目的在了解泌乳素對腎上腺類固醇生合成的直接作用及其機制。
以人類腎上腺皮質細胞株(NCI-H295)作為試驗模式，收集以PRL藥物處理後之細胞培養液，以酵素免疫分析法發現，PRL在極短的時間內即可以增加孕酮(Progesterone, P4)和皮質醇(cortisol, F)的分泌，因此PRL必參與急性調節的作用。以西方點墨法(Western blotting)與反轉錄聚合酶鏈反應(Reverse Transcription-PCR, RT-PCR)偵測，分別發現PRL能夠有效增加P450scc蛋白質表現以及StAR mRNA表現。 使用JAK2抑制劑AG490 、MEK/ERK1/2抑制劑U0126、PKA抑制劑H89，皆有效阻止PRL對類固醇生成的急性調節作用。此外，JAK2與PKA抑制劑能減弱PRL對P450scc表現的慢性刺激作用，但是三者皆能抑制PRL對類固醇生成的刺激作用。顯然，PRL經由JAK2與PKA傳訊途徑調節P450scc表現，但是經由MEK/ERK1/2傳訊途徑調節不明因子，而刺激腎上腺皮質類固醇的生成。 | zh_TW |
| dc.description.abstract | Prolactin (PRL) is a 23 kDa protein hormone closely related to growth hormone. It is secreted by lactotrophs in the anterior pituitary and primarily functions to enhance breast development during pregnancy and to induce lactation. Hyperprolactinemia, a condition of abnormal elevation in the serum PRL level caused by differential physiologic conditions, is frequently associated with hirsutism, hypogonadism, and amenorrhea due to anomalous adrenal and gonadal functions. Since the expression of PRL receptor has been detected by immunohistochemistry and RT-PCR in the human adrenal glands, it is speculated that PRL has a direct effect on adrenals. In this study, we want to investigate the function of PRL on adrenal steroid biosynthesis and its mechanism.
We used the human adrenocortical NCI-H295 cell line as the model. After treated with PRL, the culture medium was collected and detected by ELISA. The administration of PRL stimulated progesterone (P4) and crotisol (F) secretion of the cells in several minutes. The induction of P450scc protein amount and StAR mRNA amount were detected with Western Blotting and RT-PCR, respectively. Specific inhibitors of JAK2, MEK/ERK1/2 and PKA were used to study the signal pathways of PRL. The acute induction on steroid secretion was reduced by all three inhibitors. Interestingly, both inhibitors of JAK2 and PKA reduced PRL-induced P450scc protein amount, but MEK/ERK1/2 inhibitor did not. Obviously, PRL activates P450scc expression via signaling pathway of JAK2 and PKA and an unknown steroidogenic protein via MEK/ERK1/2 to stimulate adrenal steroidogenesis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:43:13Z (GMT). No. of bitstreams: 1 ntu-95-R93629021-1.pdf: 524248 bytes, checksum: 04dddb0656347d41e5548455848028eb (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 目錄
中文摘要 ……………………………………………………………………… 1 英文摘要 ……………………………………………………………………… 2 序論 …………………………………………………………………………… 3 第ㄧ章 腎上腺皮質類固醇生合成 一、腎上腺皮質類固醇的種類 …………………………………………… 3 二、腎上腺類固醇生合成途徑 …………………………………………… 3 三、類固醇生成急性調控蛋白與膽固醇側鏈截切酵素 ………………… 4 四、腎上腺類固醇生成的調控 …………………………………………… 5 第二章 泌乳素 ㄧ、泌乳素 ………………………………………………………………… 6 二、生理功能 ……………………………………………………………… 7 三、泌乳素接受體 ………………………………………………………… 7 第三章 訊息傳遞路徑 ㄧ、JAK/STAT Pathway ………………………………………………… 8 二、cAMP/PKA Pathway ………………………………………………… 9 三、MEK/ERK1/2 Pathway ……………………………………………… 9 第四章 泌乳素與腎上腺 ㄧ、高泌乳素血症 ……………………………………………………… 10 二、泌乳素對腎上腺的直接作用 ……………………………………… 10 研究動機與目的 ………………………………………………………………12 材料與方法 ㄧ、細胞培養 …………………………………………………………… 13 二、藥品 ………………………………………………………………… 13 三、競爭型酵素免疫分析法 …………………………………………… 13 四、反轉錄聚合酶連鎖反應 …………………………………………… 15 五、西方墨染法 ………………………………………………………… 16 六、統計分析 …………………………………………………………… 18 結果 ㄧ、泌乳素對腎上腺皮質細胞類固醇分泌的影響 …………………… 19 二、泌乳素對腎上腺皮質細胞P450scc與StAR表現的影響 ……… 20 三、JAK2 抑制劑對泌乳素刺激腎上腺類固醇分泌的影響 ………… 21 四、MEK/ERK1/2抑制劑對泌乳素刺激腎上腺類固醇分泌的影響 … 21 五、PKA抑制劑對泌乳素刺激腎上腺類固醇分泌的影響 ………………22 六、PI3K抑制劑對泌乳素刺激腎上腺類固醇分泌的影響 …………… 22 七、抑制劑對泌乳素刺激腎上腺皮質細胞P450scc表現的影響 …… 23 討論…………………………………………………………………………… 24 結論…………………………………………………………………………… 29 參考文獻……………………………………………………………………… 30 附圖…………………………………………………………………………… 35 圖次 圖一、腎上腺類固醇的生合成途徑………………………………………… 35 圖二、StAR與P450scc蛋白在類固醇生合成中所扮演的角色………… 36 圖三、泌乳素之訊息傳遞假想圖…………………………………………… 37 圖四、泌乳素對腎上腺皮質細胞分泌P4的影響…………………………… 38 圖五、泌乳素對腎上腺皮質細胞分泌Cortisol的影響…………………… 39 圖六、泌乳素對腎上腺皮質細胞P450scc與StAR表現的影響………… 40 圖七、JAK2 抑制劑AG490抑制泌乳素刺激的P4分泌………………… 41 圖八、JAK2 抑制劑AG490抑制泌乳素刺激的Cortisol分泌…………… 42 圖九、MEK/ERK1/2抑制劑U0126抑制泌乳素刺激的P4分泌………… 43 圖十、MEK/ERK1/2抑制劑U0126抑制泌乳素刺激的Cortisol分泌…… 44 圖十一、PKA抑制劑H89抑制泌乳素刺激的P4分泌……………………… 45 圖十二、PKA抑制劑H89抑制泌乳素刺激的Cortisol分泌……………… 46 圖十三、PI3K抑制劑Wortmannin對泌乳素刺激的P4分泌…………… 47 圖十四、PI3K抑制劑Wortmannin對泌乳素刺激的Cortisol分泌…… 48 圖十五、JAK2 抑制劑抑制泌乳素刺激的P450scc蛋白質表現………… 49 圖十六、PKA抑制劑抑制泌乳素刺激的P450scc蛋白質表現…………… 50 圖十七、MEK/ERK1/2抑制劑對泌乳素刺激的p450scc蛋白質表現…… 51 圖十八、參與泌乳素刺激腎上腺皮質細胞之訊息傳遞途徑……………… 52 圖十九、泌乳素刺激腎上腺皮質細胞訊息傳遞途徑假設圖……………… 53 | |
| dc.language.iso | zh-TW | |
| dc.subject | 類固醇生成急性調控蛋白 | zh_TW |
| dc.subject | 腎上腺 | zh_TW |
| dc.subject | 膽固醇側鏈截切酵素 | zh_TW |
| dc.subject | 訊息傳遞途徑 | zh_TW |
| dc.subject | 泌乳素 | zh_TW |
| dc.subject | 類固醇生合成 | zh_TW |
| dc.subject | Prolactin | en |
| dc.subject | StAR | en |
| dc.subject | P450scc | en |
| dc.subject | Signal Pathway | en |
| dc.subject | Steroidogenesis | en |
| dc.subject | Adrenal | en |
| dc.title | 泌乳素在腎上腺類固醇生合成的直接效果與機制 | zh_TW |
| dc.title | Direct Effect of Prolactin on Adrenal Steroidogenesis and It's Mechanism | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳兩新(Leang-shin Wu),邱智賢(Chih-Hsien Chiu) | |
| dc.subject.keyword | 泌乳素,腎上腺,類固醇生合成,訊息傳遞途徑,膽固醇側鏈截切酵素,類固醇生成急性調控蛋白, | zh_TW |
| dc.subject.keyword | Prolactin,Adrenal,Steroidogenesis,Signal Pathway,P450scc,StAR, | en |
| dc.relation.page | 53 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-18 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 獸醫學研究所 | zh_TW |
| 顯示於系所單位： | 獸醫學系 | |
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