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Gonadotropin-Releasing Hormone and Gonadal Steroids Regulate Transcription Factor mRNA Expression in Primary Pituitary and Immortalized Gonadotrope Cells

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Abstract

Hormonal regulation of pituitary gonadotropin gene expression has been attributed to gonadotropin-releasing hormone (GnRH)-mediated stimulation of immediate early gene expression and gonadal steroid interactions with their respective nuclear receptors. A number of orphan nuclear receptors including steroidogenic factor 1, liver receptor homologue 1, dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1, and chicken ovalbumin upstream promoter-transcription factors I/II as well as the GATA family members, GATA2 and GATA4, have also been implicated in transcriptional regulation of the gonadotropin genes. We hypothesized that hormonally mediated changes in these latter transcription factors may provide an additional mechanism for mediating hormonal effects beyond the more classically appreciated pathways. In these studies, we demonstrate significant regulation of orphan nuclear receptor and GATA messenger RNA levels by GnRH, dihydrotestosterone, estradiol, and progesterone in both cultured primary pituitary cells and gonadotrope-derived cell line, LβT2. These results advance our understanding of the complex mechanisms by which GnRH and steroid hormones achieve precise regulation of anterior pituitary function.

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References

  1. Burger LL, Haisenleder DJ, Marshall JC. GnRH pulse frequency differentially regulates steroidogenic factor 1 (SF1), dosage-sensitive sex reversal-AHC critical region on the X chromosome gene 1 (DAX1), and serum response factor (SRF): potential mechanism for GnRH pulse frequency regulation of LH beta transcription in the rat. Endocrine. 2011;39(3):212–219.

    Article  CAS  PubMed  Google Scholar 

  2. Cesnjaj M, Catt KJ, Stojilkovic SS. Coordinate actions of calcium and protein kinase-C in the expression of primary response genes in pituitary gonadotrophs. Endocrinology. 1994;135(2):692–701.

    Article  CAS  PubMed  Google Scholar 

  3. Kaiser UB, Halvorson LM, Chen MT. Sp1, steroidogenic factor 1 (SF-1), and early growth response protein 1 (Egr-1) binding sites form a tripartite gonadotropin-releasing hormone response element in the rat luteinizing hormone-beta gene promoter: an integral role for SF-1. Mol Endocrinol. 2000;14(8):1235–1245.

    CAS  PubMed  Google Scholar 

  4. Liu F, Austin DA, Mellon PL, Olefsky JM, Webster NJ. GnRH activates ERK1/2 leading to the induction of c-fos and LHbeta protein expression in LbetaT2 cells. Mol Endocrinol. 2002; 16(3):419–434.

    CAS  PubMed  Google Scholar 

  5. Padmanabhan V, Dalkin A, Yasin M, Haisenleder DJ, Marshall JC, Landefeld TD. Are immediate early genes involved in gonadotropin-releasing hormone receptor gene regulation? Characterization of changes in GnRH receptor (GnRH-R), c-fos, and c-jun messenger ribonucleic acids during the ovine estrous cycle. Biol Reprod. 1995;53(2):263–269.

    Article  CAS  PubMed  Google Scholar 

  6. Tremblay JJ, Drouin J. Egr-1 is a downstream effector of GnRH and synergizes by direct interaction with Ptx1 and SF-1 to enhance luteinizing hormone beta gene transcription. Mol Cell Biol. 1999; 19(4):2567–2576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wolfe MW, Call GB. Early growth response protein 1 binds to the luteinizing hormone-beta promoter and mediates gonadotropin-releasing hormone-stimulated gene expression. Mol Endocrinol. 1999;13(5):752–763.

    CAS  PubMed  Google Scholar 

  8. Jorgensen JS, Quirk CC, Nilson JH. Multiple and overlapping combinatorial codes orchestrate hormonal responsiveness and dictate cell-specific expression of the genes encoding luteinizing hormone. Endocr Rev. 2004;25(4):521–542.

    Article  CAS  PubMed  Google Scholar 

  9. Saunders BD, Sabbagh E, Chin WW, Kaiser UB. Differential use of signal transduction pathways in the gonadotropin-releasing hormone-mediated regulation of gonadotropin subunit gene expression. Endocrinology. 1998;139(4):1835–1843.

    Article  CAS  PubMed  Google Scholar 

  10. Weck J, Fallest PC, Pitt LK, Shupnik MA. Differential gonadotropin-releasing hormone stimulation of rat luteinizing hormone subunit gene transcription by calcium influx and mitogen-activated protein kinase-signaling pathways. Mol Endocrinol. 1998;12(3):451–457.

    Article  CAS  PubMed  Google Scholar 

  11. Curtin D, Jenkins S, Farmer N, et al. Androgen suppression of GnRH-stimulated rat LHbeta gene transcription occurs through Sp1 sites in the distal GnRH-responsive promoter region. Mol Endocrinol. 2001;15(11):1906–1917.

    CAS  PubMed  Google Scholar 

  12. Jorgensen JS, Nilson JH. AR suppresses transcription of the LHbeta subunit by interacting with steroidogenic factor-1. Mol Endocrinol. 2001;15(9):1505–1516.

    CAS  PubMed  Google Scholar 

  13. Jorgensen JS, Nilson JH. AR suppresses transcription of the alpha glycoprotein hormone subunit gene through protein-protein interactions with cJun and activation transcription factor 2. Mol Endocrinol. 2001;15(9):1496–1504.

    CAS  PubMed  Google Scholar 

  14. Thackray VG, Hunnicutt JL, Memon AK, Ghochani Y, Mellon PL. Progesterone inhibits basal and gonadotropin-releasing hormone induction of luteinizing hormone beta-subunit gene expression. Endocrinology. 2009;150(5):2395–2403.

    Article  CAS  PubMed  Google Scholar 

  15. Thackray VG, McGillivray SM, Mellon PL. Androgens, progestins, and glucocorticoids induce follicle-stimulating hormone beta-subunit gene expression at the level of the gonadotrope. Mol Endocrinol. 2006;20(9):2062–2079.

    Article  CAS  PubMed  Google Scholar 

  16. Thackray VG, Mellon PL. Synergistic induction of folliclestimulating hormone beta-subunit gene expression by gonadal steroid hormone receptors and Smad proteins. Endocrinology. 2008;149(3):1091–1102.

    Article  CAS  PubMed  Google Scholar 

  17. Asa SL, Bamberger AM, Cao B, Wong M, Parker KL, Ezzat S. The transcription activator steroidogenic factor-1 is preferentially expressed in the human pituitary gonadotroph. J Clin Endocrinol Metab. 1996;81(6):2165–2170.

    CAS  PubMed  Google Scholar 

  18. Luo X, Ikeda Y, Parker KL. A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell. 1994;77(4):481–490.

    Article  CAS  PubMed  Google Scholar 

  19. Zhao L, Bakke M, Krimkevich Y, et al. Steroidogenic factor 1 (SF1) is essential for pituitary gonadotrope function. Development. 2001;128(2):147–154.

    CAS  PubMed  Google Scholar 

  20. Barnhart KM, Mellon PL. The orphan nuclear receptor, steroidogenic factor-1, regulates the glycoprotein hormone alpha-subunit gene in pituitary gonadotropes. Mol Endocrinol. 1994;8(7):878–885.

    CAS  PubMed  Google Scholar 

  21. Dorn C, Ou Q, Svaren J, Crawford PA, Sadovsky Y. Activation of luteinizing hormone response-1 and steroidogenic factor-1. J Biol Chem. 1999;274(20):13870–13876.

    Article  CAS  PubMed  Google Scholar 

  22. Duval DL, Nelson SE, Clay CM. A binding site for steroidogenic factor-1 is part of complex enhancer that mediates expression of the murine gonadotropin-releasing hormone receptor gene. Biol Reprod. 1997;56(1):160–168.

    Article  CAS  PubMed  Google Scholar 

  23. Halvorson LM, Kaiser UB, Chin WW. Stimulation of luteinizing hormone beta gene promoter activity by the orphan nuclear receptor, steroidogenic factor-1. J Biol Chem. 1996;271(12): 6645–6650.

    Article  CAS  PubMed  Google Scholar 

  24. Keri RA, Nilson JH. A steroidogenic factor-1 binding site is required for activity of the luteinizing hormone beta subunit promoter in gonadotropes of transgenic mice. J Biol Chem. 1996; 271(18):10782–10785.

    Article  CAS  PubMed  Google Scholar 

  25. Ngan ES, Cheng PK, Leung PC, Chow BK. Steroidogenic factor-1 interacts with a gonadotrope-specific element within the first exon of the human gonadotropin-releasing hormone receptor gene to mediate gonadotrope-specific expression. Endocrinology. 1999;140(6):2452–2462.

    Article  CAS  PubMed  Google Scholar 

  26. Zhao L, Bakke M, Parker KL. Pituitary-specific knockout of steroidogenic factor 1. Mol Cell Endocrinol. 2001;185(1–2): 27–32.

    Article  CAS  PubMed  Google Scholar 

  27. Fortin J, Kumar V, Zhou X, et al. NR5A2 regulates Lhb and Fshb transcription in gonadotrope-like cells in vitro, but is dispensable for gonadotropin synthesis and fertility in vivo. PLoS One. 2013;8(3):e59058.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zheng W, Yang J, Jiang Q, He Z, Halvorson LM. Liver receptor homologue-regulates gonadotrope function. J Mol Endocrinol. 2007;38(1–2):207–219.

    Article  CAS  PubMed  Google Scholar 

  29. Pare JF, Malenfant D, Courtemanche C, et al. The fetoprotein transcription factor (FTF) gene is essential to embryogenesis and cholesterol homeostasis and is regulated by a DR4 element. J Biol Chem. 2004;279(20):21206–21216.

    Article  CAS  PubMed  Google Scholar 

  30. Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell. 2006; 126(4):789–799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Falender AE, Lanz R, Malenfant D, Belanger L, Richards JS. Differential expression of steroidogenic factor-1 and FTF/LRH-1 in the rodent ovary. Endocrinology. 2003;144(8):3598–3610.

    Article  CAS  PubMed  Google Scholar 

  32. Hinshelwood MM, Repa JJ, Shelton JM, Richardson JA, Mangelsdorf DJ, Mendelson CR. Expression of LRH-1 and SF-1 in the mouse ovary: localization in different cell types correlates with differing function. Mol Cell Endocrinol. 2003;207(1–2):39–45.

    Article  CAS  PubMed  Google Scholar 

  33. Peng N, Kim JW, Rainey WE, Carr BR, Attia GR. 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. 2003;88(12):6020–6028.

    Article  CAS  PubMed  Google Scholar 

  34. Clyne CD, Kovacic A, Speed CJ, Zhou J, Pezzi V, Simpson ER. Regulation of aromatase expression by the nuclear receptor LRH-1 in adipose tissue. Mol Cell Endocrinol. 2004;215(1–2):39–44.

    Article  CAS  PubMed  Google Scholar 

  35. Saxena D, Escamilla-Hernandez R, Little-Ihrig L, Zeleznik AJ. Liver receptor homolog-1 and steroidogenic factor-1 have similar actions on rat granulosa cell steroidogenesis. Endocrinology. 2007;148(2):726–734.

    Article  CAS  PubMed  Google Scholar 

  36. Petit FG, Jamin SP, Kurihara I, et al. Deletion of the orphan nuclear receptor COUP-TFII in uterus leads to placental deficiency. Proc Natl Acad Sci USA. 2007;104(15):6293–6298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Qin J, Tsai MJ, Tsai SY. Essential roles of COUP-TFII in Leydig cell differentiation and male fertility. PLoS One. 2008;3(9): e3285.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Qiu Y, Pereira FA, DeMayo FJ, Lydon JP, Tsai SY, Tsai MJ. Null mutation of mCOUP-TFI results in defects in morphogenesis of the glossopharyngeal ganglion, axonal projection, and arborization. Genes Dev. 1997;11(15):1925–1937.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yamaguchi H, Zhou C, Lin SC, Durand B, Tsai SY, Tsai MJ. The nuclear orphan receptor COUP-TFI is important for differentiation of oligodendrocytes. Dev Biol. 2004;266(2):238–251.

    Article  CAS  PubMed  Google Scholar 

  40. Wang LH, Tsai SY, Cook RG, Beattie WG, Tsai MJ, O’Malley BW. COUP transcription factor is a member of the steroid receptor superfamily. Nature. 1989;340(6229):163–166.

    Article  CAS  PubMed  Google Scholar 

  41. Raccurt M, Smallwood S, Mertani HC, et al. Cloning, expression and regulation of chicken ovalbumin upstream promoter transcription factors (COUP-TFII and EAR-2) in the rat anterior pituitary gland. Neuroendocrinology. 2005;82(5–6): 233–244.

    Article  CAS  PubMed  Google Scholar 

  42. Zheng W, Horton CD, Kim J, Halvorson LM. The orphan nuclear receptors COUP-TFI and COUP-TFII regulate expression of the gonadotropin LHbeta gene. Mol Cell Endocrinol. 2010;330(1–2):59–71.

    Article  CAS  PubMed  Google Scholar 

  43. Bakke M, Lund J. Mutually exclusive interactions of two nuclear orphan receptors determine activity of a cyclic adenosine 3’,5’-monophosphate-responsive sequence in the bovine CYP17 gene. Mol Endocrinol. 1995;9(3):327–339.

    CAS  PubMed  Google Scholar 

  44. Cooney AJ, Leng X, Tsai SY, O’Malley BW, Tsai MJ. Multiple mechanisms of chicken ovalbumin upstream promoter transcription factor-dependent repression of transactivation by the vitamin D, thyroid hormone, and retinoic acid receptors. J Biol Chem. 1993;268(6):4152–4160.

    CAS  PubMed  Google Scholar 

  45. Shibata H, Nawaz Z, Tsai SY, O’Malley BW, Tsai MJ. Gene silencing by chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) is mediated by transcriptional corepressors, nuclear receptor-corepressor (N-CoR) and silencing mediator for retinoic acid receptor and thyroid hormone receptor (SMRT). Mol Endocrinol. 1997;11(6):714–724.

    Article  CAS  PubMed  Google Scholar 

  46. Muscatelli F, Strom TM, Walker AP, et al. Mutations in the DAX–1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Nature. 1994; 372(6507):672–676.

    Article  CAS  PubMed  Google Scholar 

  47. Ehrlund A, Treuter E. Ligand-independent actions of the orphan receptors/corepressors DAX-1 and SHP in metabolism, reproduction and disease. J Steroid Biochem Mol Biol. 2012;130(3–5): 169–179.

    Article  CAS  PubMed  Google Scholar 

  48. Guo W, Burris TP, McCabe ER. Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/gonadal axis. Biochem MolMed. 1995;56(1):8–13.

    CAS  Google Scholar 

  49. Ikeda Y, Takeda Y, Shikayama T, Mukai T, Hisano S, Morohashi KI. Comparative localization of Dax-1 and Ad4BP/SF-1 during development of the hypothalamic–pituitary–gonadal axis suggests their closely related and distinct functions. Dev Dyn. 2001; 220(4):363–376.

    Article  CAS  PubMed  Google Scholar 

  50. Habiby RL, Boepple P, Nachtigall L, Sluss PM, Crowley WF Jr, Jameson JL. Adrenal hypoplasia congenita with hypogonadotropic hypogonadism: evidence that DAX-1 mutations lead to combined hypothalmic and pituitary defects in gonadotropin production. J Clin Invest. 1996;98(4):1055–1062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Chanda D, Park JH, Choi HS. Molecular basis of endocrine regulation by orphan nuclear receptor small heterodimer partner. Endocr J. 2008;55(2):253–268.

    Article  CAS  PubMed  Google Scholar 

  52. Volle DH, Duggavathi R, Magnier BC, et al. The small heterodimer partner is a gonadal gatekeeper of sexual maturation in male mice. Genes Dev. 2007;21(3):303–315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. LaVoie HA. The role of GATA in mammalian reproduction. Exp Biol Med. 2003;228(11):1282–1290.

    Article  CAS  Google Scholar 

  54. Dasen JS, O’Connell SM, Flynn SE, et al. Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell. 1999;97(5):587–598.

    Article  CAS  PubMed  Google Scholar 

  55. Lo A, Zheng W, Gong Y, Crochet JR, Halvorson LM. GATA transcription factors regulate LHbeta gene expression. J Mol Endocrinol. 2011;47(1):45–58.

    Article  CAS  PubMed  Google Scholar 

  56. Pincas H, Amoyel K, Counis R, Laverriere JN. Proximal cisacting elements, including steroidogenic factor 1, mediate the efficiency of a distal enhancer in the promoter of the rat gonadotropin-releasing hormone receptor gene. Mol Endocrinol. 2001;15(2):319–337.

    Article  CAS  PubMed  Google Scholar 

  57. Steger DJ, Hecht JH, Mellon PL. GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the placenta and pituitary gland. Mol Cell Biol. 1994;14(8):5592–5602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Charles MA, Saunders TL, Wood WM, et al. Pituitary-specific Gata2 knockout: effects on gonadotrope and thyrotrope function. Mol Endocrinol. 2006;20(6):1366–1377.

    Article  CAS  PubMed  Google Scholar 

  59. Grafer CM, Halvorson LM. Androgen receptor drives transcription of rat PACAP in gonadotrope cells. Mol Endocrinol. 2013; 27(8):1343–1356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lawson MA, Li D, Glidewell-Kenney CA, Lopez FJ. Androgen responsiveness of the pituitary gonadotrope cell line LbetaT2. J Endocrinol. 2001;170(3):601–607.

    Article  CAS  PubMed  Google Scholar 

  61. Schreihofer DA, Stoler MH, Shupnik MA. Differential expression and regulation of estrogen receptors (ERs) in rat pituitary and cell lines: estrogen decreases ERalpha protein and estrogen responsiveness. Endocrinology. 2000;141(6):2174–2184.

    Article  CAS  PubMed  Google Scholar 

  62. Turgeon JL, Waring DW. Differential expression and regulation of progesterone receptor isoforms in rat and mouse pituitary cells and LbetaT2 gonadotropes. J Endocrinol. 2006; 190(3):837–846.

    Article  CAS  PubMed  Google Scholar 

  63. Jiang Q, Jeong KH, Horton CD, Halvorson LM. Pituitary homeobox 1 (Pitx1) stimulates rat LHbeta gene expression via two functional DNA-regulatory regions. J Mol Endocrinol. 2005;35(1):145–158.

    Article  CAS  PubMed  Google Scholar 

  64. Tremblay JJ, Lanctot C, Drouin J. The pan-pituitary activator of transcription, Ptx1 (pituitary homeobox 1), acts in synergy with SF-1 and Pit1 and is an upstream regulator of the Lim-homeodomain gene Lim3/Lhx3. Mol Endocrinol. 1998;12(3): 428–441.

    Article  CAS  PubMed  Google Scholar 

  65. Quirk CC, Lozada KL, Keri RA, Nilson JH. A single Pitx1 binding site is essential for activity of the LHbeta promoter in transgenic mice. Mol Endocrinol. 2001;15(5):734–746.

    CAS  PubMed  Google Scholar 

  66. Zheng W, Jimenez-Linan M, Rubin BS, Halvorson LM. Anterior pituitary gene expression with aging in the female rat. Biol Reprod. 2007;76(6):1091–1102.

    Article  CAS  PubMed  Google Scholar 

  67. Shupnik MA, Gharib SD, Chin WW. Divergent effects of estradiol on gonadotropin gene transcription in pituitary fragments. Mol Endocrinol. 1989;3(3):474–480.

    Article  CAS  PubMed  Google Scholar 

  68. Luo M, Koh M, Feng J, Wu Q, Melamed P. Cross talk in hormonally regulated gene transcription through induction of estrogen receptor ubiquitylation. Mol Cell Biol. 2005;25(16):7386–7398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kowase T, Walsh HE, Darling DS, Shupnik MA. Estrogen enhances gonadotropin-releasing hormone-stimulated transcription of the luteinizing hormone subunit promoters via altered expression of stimulatory and suppressive transcription factors. Endocrinology. 2007;148(12):6083–6091.

    Article  CAS  PubMed  Google Scholar 

  70. Tremblay JJ, Viger RS. Nuclear receptor Dax-1 represses the transcriptional cooperation between GATA-4 and SF-1 in Sertoli cells. Biol Reprod. 2001;64(4):1191–1199.

    Article  CAS  PubMed  Google Scholar 

  71. Johansson L, Thomsen JS, Damdimopoulos AE, Spyrou G, Gustafsson JA, Treuter E. The orphan nuclear receptor SHP inhibits agonist-dependent transcriptional activity of estrogen receptors ERalpha and ERbeta. J Biol Chem. 1999;274(1):345–353.

    Article  CAS  PubMed  Google Scholar 

  72. Zhang H, Thomsen JS, Johansson L, Gustafsson JA, Treuter E. DAX-1 functions as an LXXLL-containing corepressor for activated estrogen receptors. J Biol Chem. 2000;275(51): 39855–39859.

    Article  CAS  PubMed  Google Scholar 

  73. Eertmans F, De Wever O, Dhooge W, et al. Estrogen receptor signaling is an unstable feature of the gonadotropic LbetaT2 cell line. Mol Cell Endocrinol. 2007;273(1–2):16–24.

    Article  CAS  PubMed  Google Scholar 

  74. An BS, Poon SL, So WK, Hammond GL, Leung PC. Rapid effect of GNRH1 on follicle-stimulating hormone beta gene expression in LbetaT2 mouse pituitary cells requires the progesterone receptor. Biol Reprod. 2009;81(2):243–249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zheng W, Grafer CM, Halvorson LM. Interaction of gonadal steroids and gonadotropin-releasing hormone on pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP receptor expression in cultured rat anterior pituitary cells. Reprod Sci. 2013;21(1):41–51.

    Article  CAS  PubMed  Google Scholar 

  76. Murayama C, Miyazaki H, Miyamoto A, Shimizu T. Involvement of Ad4BP/SF-1, DAX-1, and COUP-TFII transcription factor on steroid production and luteinization in ovarian theca cells. Mol Cell Biochem. 2008;314(1–2):51–58.

    Article  CAS  PubMed  Google Scholar 

  77. Martin LJ, Taniguchi H, Robert NM, Simard J, Tremblay JJ, Viger RS. GATA factors and the nuclear receptors, steroidogenic factor 1/liver receptor homolog 1, are key mutual partners in the regulation of the human 3beta-hydroxysteroid dehydrogenase type 2 promoter. Mol Endocrinol. 2005;19(9):2358–2370.

    Article  CAS  PubMed  Google Scholar 

  78. Tremblay JJ, Viger RS. GATA factors differentially activate multiple gonadal promoters through conserved GATA regulatory elements. Endocrinology. 2001;142(3):977–986.

    Article  CAS  PubMed  Google Scholar 

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Zheng, W., Grafer, C.M., Kim, J. et al. Gonadotropin-Releasing Hormone and Gonadal Steroids Regulate Transcription Factor mRNA Expression in Primary Pituitary and Immortalized Gonadotrope Cells. Reprod. Sci. 22, 285–299 (2015). https://doi.org/10.1177/1933719114565031

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