[1] LIU YX, CHEN JY, TANG XL, et al. The 20 kDa and 22 kDa forms of human growth hormone (hGH) exhibit different intracellular signalling profiles and properties[J].Gen Comp Endocrinol, 2017, 248(7): 49
[2] STRASBURGER CJ, DATTANI MT. New growth hormone assays: potential benefits[J].Acta Paediatr Suppl, 1997, 86(S423): 5
[3] DEHKHODA F, LEE CMM, MEDINA J, et al. The growth hormone receptor: mechanism of receptor activation, cell signaling, and physiological aspects[J].Front Endocrinol (Lausanne), 2018, 13(9): 35
[4] LEUNG DW, SPENCER SA, CACHIANES G, et al. Growth hormone receptor and serum binding protein: purification, cloning and expression[J].Nature, 1987, 330(6148): 537
[5] DE-VOSAM, ULTSCH M, KOSSIAKOFF AA. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex[J].Science, 1992, 255(5042): 306
[6] CUNNINGHAM BC, ULTSCH M, DE-VOS AM, et al. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule[J].Science, 1991, 254(5033): 821
[7] GENT J, VANKERKHOF P, ROZA M, et al. Ligand-independent growth hormone receptor dimerization occurs in the endoplasmic reticulum and is required for ubiquitin system-dependent endocytosis[J].Proc Natl Acad Sci USA, 2002, 99(15): 9858
[8] BROWN RJ, ADAMS JJ, PELEKANOS RA, et al. Model for growth hormone receptor activation based on subunit rotation within a receptor dimer[J].Nat Struct Mol Biol, 2005, 12(9): 814
[9] GENT J, EIJNDEN MVD, KERKHOF PV, et al. Dimerization and signal transduction of the growth hormone receptor[J].Mol Endocrinol, 2003, 17(5): 967
[10] LIU Y, ZHANG Y, JIANG J, et al. GHR/PRLR heteromultimer is composed of ghr homodimers and PRLR homodimers[J].Mol Endocrinol, 2016, 30(5): 504
[11] SOTIROPOULOS A, MOUTOUSSAMY S, RENAUDIE F, et al. Differential activation of Stat 3 and Stat 5 by distinct regions of the growth hormone receptor[J].Mol Endocrinol, 1996, 10(8): 998
[12] CHILTON BS, HEWETSON A. Prolactin and growth hormone signaling[J].Curr Top Dev Biol, 2005, 68(8): 1
[13] ZHOU Y, XU BC, MAHESHWARI HG, et al. A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse)[J].Proc Natl Acad Sci USA, 1997, 94(24): 13215
[14] ARGETSINGER LS, CAMPBELL GS, YANG X, et al. Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase[J].Cell, 1993, 74(2): 237
[15] FRANK SJ. Classical and novel GH receptor signaling pathways[J].Mol Cell Endocrinol, 2020, 518(12): 110999
[16] NEUBAUER H, CUMANO A, MÜLLER M, et al. Jak 2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis[J].Cell, 1998, 93(3): 397
[17] SOS BC, HARRIS C, NORDSTROM SM, et al. Abrogation of growth hormone secretion rescues fatty liver in mice with hepatocyte-specific deletion of JAK 2[J].J Clin Invest, 2011, 121(4): 1412
[18] SMIT LS, MEYER DJ, BILLESTRUP N, et al. The role of the growth hormone (GH) receptor and JAK1 and JAK2 kinases in the activation of Stats 1, 3, and 5 by GH[J].Mol Endocrinol, 1996, 10(5): 519
[19] HAN Y, LEAMAN DW, WATLING D, et al. Participation of JAK and STAT proteins in growth hormone-induced signaling[J].J Biol Chem, 1996, 271(10): 5947
[20] GRONOWSKI AM, ROTWEIN P. Rapid changes in nuclear protein tyrosine phosphorylation after growth hormone treatment in vivo. Identification of phosphorylated mitogen-activated protein kinase and STAT91[J].J Biol Chem, 1994, 269(11): 7874
[21] CAMPBELL GS, MEYER DJ, RAZ R, et al. Activation of acute phase response factor (APRF)/Stat 3 transcription factor by growth hormone[J].J Biol Chem, 1995, 270(8): 3974
[22] BARCLAY JL, KERR LM, ARTHUR L, et al. In vivo targeting of the growth hormone receptor (GHR) Box 1 sequence demonstrates that the GHR does not signal exclusively through JAK 2[J].Mol Endocrinol, 2010, 24(1): 204
[23] ROWLAND JE, LICHANSKA AM, KERR LM, et al. In vivo analysis of growth hormone receptor signaling domains and their associated transcripts[J].Mol Cell Biol, 2005, 25(1): 66
[24] HWA V. STAT5B deficiency: impacts on human growth and immunity[J].Growth Horm IGF Res, 2016, 28: 16
[25] ZHANG Y, LAZ EV, WAXMAN DJ. Dynamic, sex-differential STAT5 and BCL6 binding to sex-biased, growth hormone-regulated genes in adult mouse liver[J].Mol Cell Biol, 2012, 32(4): 880
[26] CARTER-SU C, KING AP, ARGETSINGER LS, et al. Signalling pathway of GH[J].Endocr J, 1996, 43(10):S65
[27] ZEHORAI E, YAO Z, PLOTNIKOV A, et al. The subcellular localization of MEK and ERK——a novel nuclear translocation signal (NTS) paves a way to the nucleus[J].Mol Cell Endocrinol, 2010, 314(2): 213
[28] GURLAND G, ASHCOM G, COCHRAN BH, et al. Rapid events in growth hormone action. Induction of c-fos and c-jun transcription in 3T3-F442A preadipocytes[J].Endocrinology, 1990, 127(6): 3187
[29] HODGE C, LIAO J, STOFEGA M, et al. Growth hormone stimulates phosphorylation and activation of elk-1 and expression of c-fos, egr-1, and jun B through activation of extracellular signal-regulated kinases 1 and 2[J].J Biol Chem, 1998, 273(47): 31327
[30] CUI TX, KWOK R, SCHWARTZ J. Cooperative regulation of endogenous cAMP-response element binding protein and CCAAT/enhancer-binding protein beta in GH-stimulated c-fos expression[J].J Endocrinol, 2008, 196(1): 89
[31] KOUZARIDES T. Chromatin modifications and their function[J].Cell, 2007, 128(4): 693
[32] HANSBERG-PASTOR V, PIÑA-MEDINA AG, GONZÁLEZ-ARENAS A, et al. C/EBPβ isoforms expression in the rat brain during the estrous cycle[J].Int J Endocrinol, 2015, 2015(4): 674915
[33] ARGETSINGER LS, HSU GW, MYERS-Jr MG, et al. Growth hormone, interferon-gamma, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1[J].J Biol Chem, 1995, 270(24): 14685
[34] ARGETSINGER LS, NORSTEDT G, BILLESTRUP N, et al. Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling[J].J Biol Chem, 1996, 271(46): 29415
[35] ALESSI DR, JAMES SR, DOWNES CP, et al. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha[J].Curr Biol, 1997, 7(4): 261
[36] PIWIEN-PILIPUK G, VAN-MATER D, ROSS SE, et al. Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3[J].J Biol Chem, 2001, 276(22): 19664
[37] MEYER DJ, CAMPBELL GS, COCHRAN BH, et al. Growth hormone induces a DNA binding factor related to the interferon-stimulated 91-kDa transcription factor[J].J Biol Chem, 1994, 269(7): 4701
[38] DURBIN JE, HACKENMILLER R, SIMON MC, et al. Targeted disruption of the mouse Stat 1 gene results in compromised innate immunity to viral disease[J].Cell, 1996, 84(3): 443
[39] CHIA DJ. Minireview: mechanisms of growth hormone-mediated gene regulation[J].Mol Endocrinol, 2014, 28(7): 1012
[40] NIELSEN C, GORMSEN LC, JESSEN N, et al. Growth hormone signaling in vivo in human muscle and adipose tissue: impact of insulin, substrate background, and growth hormone receptor blockade[J].J Clin Endocrinol Metab, 2008, 93(7): 2842
[41] VESTERGAARD PF, VENDELBO MH, PEDERSEN SB, et al. GH signaling in skeletal muscle and adipose tissue in healthy human subjects: impact of gender and age[J].Eur J Endocrinol, 2014, 171(5): 623
[42] OBERBAUER AM. The regulation of IGF-1 gene transcription and splicing during development and aging[J].Front Endocrinol (Lausanne), 2013,26(3): 4
[43] ROTWEIN P. Regulation of gene expression by growth hormone[J].Mol Cell Endocrinol, 2020, 507(5): 110788
[44] ALZHANOV D, MUKHERJEE A, ROTWEIN P. Identifying growth hormone-regulated enhancers in the IGF 1 locus[J].Physiol Genomics, 2015, 47(11): 559
[45] MUKHERJEE A, ALZHANOV D, ROTWEIN P. Defining human insulin-like growth factor I gene regulation[J].Am J Physiol Endocrinol Metab, 2016, 311(2): E519
[46] CHIA DJ, ROTWEIN P. Defining the epigenetic actions of growth hormone: acute chromatin changes accompany GH-activated gene transcription[J].Mol Endocrinol, 2010, 24(10): 2038
[47] OUNI M, BELOT MP, CASTELL AL, et al. The P 2 promoter of the IGF 1 gene is a major epigenetic locus for GH responsiveness[J].Pharmacogenomics J, 2016, 16(1): 102
[48] WU S, MORRISON A, SUN H, et al. Nuclear factor-kappaB (NF-kappaB) p65 interacts with Stat5b in growth plate chondrocytes and mediates the effects of growth hormone on chondrogenesis and on the expression of insulin-like growth factor-1 and bone morphogenetic protein-2[J].J Biol Chem, 2011, 286(28): 24726
[49] UMAYAHARA Y, BILLIARD JJIC. CCAAT/enhancer-binding protein delta is a critical regulator of insulin-like growth factor-I gene transcription in osteoblasts[J].J Biol Chem, 1999, 274(15): 10609
[50] ZHU T, LING L, LOBIE PE. Identification of a JAK2-independent pathway regulating growth hormone (GH)-stimulated p44/42 mitogen-activated protein kinase activity. GH activation of Ral and phospholipase D is Src-dependent[J].J Biol Chem, 2002, 277(47): 45592
[51] ZHU T, GOH EL, LEROITH D, et al. Growth hormone stimulates the formation of a multiprotein signaling complex involving p130(Cas) and CrkII. Resultant activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK)[J].J Biol Chem, 1998, 273(50): 33864
[52] WANG X, HE K, GERHART M, et al. Metalloprotease-mediated GH receptor proteolysis and GHBP shedding. Determination of extracellular domain stem region cleavage site[J].J Biol Chem, 2002, 277(52): 50510
[53] ZHANG Y, WANG X, LOESCH K, et al. TIMP3 modulates GHR abundance and GH sensitivity[J].Mol Endocrinol, 2016, 30(6): 587
[54] GUAN R, ZHANG Y, JIANG J, et al. Phorbol ester- and growth factor-induced growth hormone (GH) receptor proteolysis and GH-binding protein shedding: relationship to GH receptor down-regulation[J].Endocrinology, 2001, 142(3): 1137
[55] WANG X, JIANG J, WARRAM J, et al. Endotoxin-induced proteolytic reduction in hepatic growth hormone (GH) receptor: a novel mechanism for GH insensitivity[J].Mol Endocrinol, 2008, 22(6): 1427
[56] DAVEY HW, MCLACHLAN MJ, WILKINS RJ, et al. STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in the liver[J].Mol Cell Endocrinol, 1999, 158(1-2): 111
[57] UNGUREANU D, SAHARINEN P, JUNTTILA I, et al. Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak 2 on Y1007 and interaction with SOCS-1[J].Mol Cell Biol, 2002, 22(10): 3316
[58] CHHABRA Y, WONG HY, NIKOLAJSEN LF, et al. A growth hormone receptor SNP promotes lung cancer by impairment of SOCS 2-mediated degradation[J].Oncogene, 2018, 37(4): 489
[59] PASQUALI C, CURCHOD ML, WÄLCHLI S, et al. Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor[J].Mol Endocrinol, 2003, 17(11): 2228
[60] RAM PA, WAXMAN DJ. Interaction of growth hormone-activated STATs with SH2-containing phosphotyrosine phosphatase SHP-1 and nuclear JAK2 tyrosine kinase[J].J Biol Chem, 1997, 272(28): 17694
[61] STOFEGA MR, HERRINGTON J, BILLESTRUP N, 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[J].Mol Endocrinol, 2000, 14(9): 1338
[62] PILECKA I, PATRIGNANI C, PESCINI R, et al. Protein-tyrosine phosphatase H1 controls growth hormone receptor signaling and systemic growth[J].J Biol Chem, 2007, 282(48): 35405
[63] RUI L, MATHEWS LS, HOTTA K, et al. Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2 involved in growth hormone signaling[J].Mol Cell Biol, 1997, 17(11): 6633
[64] RUI L, CARTER-SU C. Identification of SH2-bbeta as a potent cytoplasmic activator of the tyrosine kinase Janus kinase 2[J].Proc Natl Acad Sci USA, 1999, 96(13): 7172
[65] SU HW, LANNING NJ, MORRIS DL, et al. Phosphorylation of the adaptor protein SH2B1β regulates its ability to enhance growth hormone-dependent macrophage motility[J].J Cell Sci, 2013, 126(Pt 8): 1733
[66] HUANG Y, KIM SO, YANG N, et al. Physical and functional interaction of growth hormone and insulin-like growth factor-I signaling elements[J].Mol Endocrinol, 2004, 18(6): 1471
[67] GAN Y, ZHANG Y, DIGIROLAMO DJ, et al. Deletion of IGF-I receptor (IGF-IR) in primary osteoblasts reduces GH-induced STAT5 signaling[J].Mol Endocrinol, 2010, 24(3): 644
[68] GAN Y, ZHANG Y, BUCKELS A, et al. IGF-1R modulation of acute GH-induced STAT5 signaling: role of protein tyrosine phosphatase activity[J].Mol Endocrinol, 2013, 27(11): 1969
[69] STRASBURGER CJ, WU Z, PFLAUM CD, et al. Immunofunctional assay of human growth hormone (hGH) in serum: a possible consensus for quantitative hGH measurement[J].J Clin Endocrinol Metab, 1996, 81(7): 2613
[70] 中华人民共和国药典2020年版. 四部[S].2020: 530
ChP 2020. Vol Ⅳ[S].2020: 530
[71] USP 2021-NF 39[S/OL].[2021-05-01]. https://online.uspnf.com/uspnf/search?query=Somatropinbioidentitytests
[72] 梁誉龄,高学军,李湛军,等. 重组人生长激素体内生物活性测定中美药典方法对比研究[J].中国药事, 2020, 34(6): 658
LIANG YL,GAO XJ, LI ZJ, et al. A comparative study on Chinese Pharmacopeia and U. S. Pharmacopeia methods for rhGH in vivo bioactivty[J].Chin Pharm Aff, 2020, 34(6): 658
[73] BELLINI MH, BARTOLINI P. In vivo bioassay for the potency determination of human growth hormone in dwarf “little” mice[J].Endocrinology, 1993, 132(5): 2051
[74] TANAKA T, SHIU RP, GOUT PW, et al. A new sensitive and specific bioassay for lactogenic hormones: measurement of prolactin and growth hormone in human serum[J].J Clin Endocrinol Metab, 1980, 51(5): 1058
[75] FUH G, CUNNINGHAM BC, FUKUNAGA R, et al. Rational design of potent antagonists to the human growth hormone receptor[J].Science, 1992, 256(5064): 1677
[76] WADA M, UCHIDA H, IKEDA M, et al. The 20-kilodalton (kDa) human growth hormone (hGH) differs from the 22-kDa hGH in the complex formation with cell surface hGH receptor and hGH-binding protein circulating in human plasma[J].Mol Endocrinol, 1998, 12(1): 146
[77] ISHIKAWA M, NIMURA A, HORIKAWA R, et al. A novel specific bioassay for serum human growth hormone[J].J Clin Endocrinol Metab, 2000, 85(11): 4274
[78] IKEDA M, WADA M, FUJITA Y, et al. A novel bioassay based on human growth hormone (hGH) receptor mediated cell proliferation: measurement of 20K-hGH and its modified forms[J].Growth Horm IGF Res, 2000, 10(5): 248
[79] WANG L, YU C, WANG J. Development of reporter gene assays to determine the bioactivity of biopharmaceuticals[J].Biotechnol Adv, 2020, 39: 107466
[80] ANDERSSON R, SANDELIN A. Determinants of enhancer and promoter activities of regulatory elements[J].Nat Rev Genet, 2020, 21(2): 71
[81] YAO W, YU L, FAN W, et al. A cell-based strategy for bioactivity determination of long-acting Fc-fusion recombinant human growth hormone[J].Molecules, 2019, 24(7): 1389
[82] YANG Y, ZHOU Y, YU L, et al. A novel reporter gene assay for recombinant human erythropoietin (rHuEPO) pharmaceutical products[J].J Pharm Biomed Anal, 2014, 100(11): 316
[83] DECKER T, KOVARIK P, MEINKE A. GAS elements: a few nucleotides with a major impact on cytokine-induced gene expression[J].J Interferon Cytokine Res, 1997, 17(3): 121
