Reproduction - GnRH signaling

print

Select Species:

Click on a target from the pathway image to view related information. Zoom     View Legend

photo_map
 


Gonadotropin releasing hormone signaling

Gonadotropin-releasing hormone (GnRH) is the first key hormone of reproduction in vertebrates. GnRH is released from the hypothalamus in a pulsatile manner and stimulates pituitary gonadotropes to synthesize and release Luteinizing hormone beta (LH-beta) and Follicle stimulating hormone, beta polypeptide (FSH-beta). The gonadotropins (LH-beta and FSH-beta) stimulate sex hormone production and gametogenesis. GnRH regulates the hypothalamo-pituitary axis [1], [2].

The binding of GnRH to Gonadotropin-releasing hormone receptor (GnRHR) is a critical factor for receptor activation, initiation and propagation of intracellular signaling. GnRHR is a G-protein coupled receptor. GnRHR interacts with multiple G-proteins such as G-protein alpha-q/11 and G-protein alpha-s [3], [4], [5].

G-protein alpha-q/11 activated by the GnRHR stimulates Ca2+-independent of Phospholipase C beta (PLC beta). PLC beta cleaves Phosphatidylinositol 4,5-bisphosphate (Ptdins(4,5)P2) to generate Inositol-1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG) [6], [7]. DAG and IP3 stimulate Protein kinase C, type delta (PKC-delta) and epsilon (PKC-epsilon) and mobilize intracellular Ca2+, respectively [6], [8], [9]. GnRH stimulates rapid Ca2+ mobilization from internal IP3-sensitive stores, followed by external Ca2+ influx via nifedipine-sensitive L-type voltage-sensitive Ca2+ channels (L-type Ca(II) channel, alpha 1C subunit) [2], [10].

The PKC-delta and PKC-epsilon are then able to bind to and activate V-raf-1 murine leukemia viral oncogene homolog 1 (c-Raf-1)/ Mitogen-activated protein kinase kinase 1 and 2 (MEK1 and MEK1)/ Mitogen activated protein kinases 3 and 1 (Erk (MAPK1/3)) cascade [11], [12]. In addition, Erk (MAPK1/3) activation is partially dependent on Proto-oncogene tyrosine-protein kinase (c-Src)/ v-Ha-ras Harvey rat sarcoma viral oncogene homolog (H-Ras) cascade in Dynamin-dependent manner [12], [13]. Erk (MAPK1/3) also activated by PTK2B protein tyrosine kinase 2 beta (Pyk2(FAK2))/ c-Src / Growth factor receptor bound protein 2 (Grb2)/ Son of sevenless homolog (SOS)/ H-Ras/ c-Raf-1 pathway. Pyk2(FAK2) probably activated by c-Src [14]. Erk (MAPK1/3) activated by GnRH subsequently phosphorylates ELK1 member of ETS oncogene family (Elk-1). Elk-1 regulates expression of Early growth response 1 (EGR1) [15] and FBJ osteosarcoma oncogene (c-Fos) [16].

GnRH stimulates expression of Dual specificity phosphatase 1 and 2 (MKP-1 and MKP-2). GnRH activates MKP-2 most likely through Erk (MAPK1/3)/ Elk-1/ EGR1 pathway. MKP-1 and MKP-2 serve as negative feedback regulators that modulate Erk (MAPK1/3) and JNK activity [17].

GnRH stimulates Mitogen-activated protein kinases (JNK(MAPK8-10)) activity by a pathway that includes sequential activation of PKC-epsilon / c-Src/ Cell division cycle 42 (CDC42)/ Mitogen-activated protein kinase kinase kinase 1 (MEKK1) [18]. Activated JNK phosphorylates jun oncogene (c-Jun), thereby regulate expression of Secretogranin II [19], LH-beta [20], Activating transcription factor 3 (ATF-3) and Glycoprotein hormone alpha-subunit gene promoter (CG alpha) [21]. In addition, ATF-3 stimulates expression of CG alpha [21], Secretogranin II [19] and inhibits expression of Secretogranin 1 [22].

Furthermore, MEKK1 can activate Mitogen-activated protein kinase p38 (most likely p38alpha (MAPK14)) [23]. p38 and Erk (MAPK1/3) can regulate Adenylate cyclase activating polypeptide 1 (PACAP), FSH-beta and GnRHR transcription via activation of Activator protein-1 (AP-1) factors [24], [25], [26]. p38 phosphorylates EGR1 [14]. Erk (MAPK1/3) and Protein kinase A (PKA) also activate EGR1 through activation cAMP responsive element binding protein (CREB1) and Elk-1 [15]. EGR1 regulates expression of PER1 [27], ATF-3, Secretogranin 1 [22] and LH-beta [28]

GnRH also activates Activating transcription factor 2 (ATF-2) probably through p38 and Erk (MAPK1/3), thus regulating expression of ATF-3 [22].

Activation of G-protein alpha-s further activates the Adenylate cyclase / Cyclic adenosine monophosphate (cAMP)/ PKA/ CREB1 [29]. In addition, Ca2+ (via intermediate, presumably - Ca2+/calmodulin-dependent protein kinase II (CaMK II) activates CREB1. CREB1 also activated by PKC / MEK1/2/ ERK1/2/ Ribosomal protein S6 kinase (p90RSK) cascade [30]. CREB1 regulates expression of Secretogranin II [19], [29], Nuclear receptor subfamily 4 group A member 1 (Nur77) [31], LH-beta, FSH-beta [32], Follistatin [33], ATF-3 [22], PACAP [26] and EGR1 [15]. Nur77 activated by cAMP/ PKA regulates expression of FSH-beta [31], [34].

Moreover, Ca2+/calmodulin-dependent protein kinase I (CaMK I) activates Myocyte enhancer factor 2D (MEF2D) by phosphorylation of Histone deacetylase 5 and 4 (HDAC5 and HDAC4). MEF2D regulates expression of FSH-beta [34].

References:

  1. Dobkin-Bekman M, Naidich M, Pawson AJ, Millar RP, Seger R, Naor Z
    Activation of mitogen-activated protein kinase (MAPK) by GnRH is cell-context dependent. Molecular and cellular endocrinology 2006 Jun 27;252(1-2):184-90
  2. Naor Z
    Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor. Frontiers in neuroendocrinology 2009 Jan;30(1):10-29
  3. Liu F, Usui I, Evans LG, Austin DA, Mellon PL, Olefsky JM, Webster NJ
    Involvement of both G(q/11) and G(s) proteins in gonadotropin-releasing hormone receptor-mediated signaling in L beta T2 cells. The Journal of biological chemistry 2002 Aug 30;277(35):32099-108
  4. Krsmanovic LZ, Mores N, Navarro CE, Arora KK, Catt KJ
    An agonist-induced switch in G protein coupling of the gonadotropin-releasing hormone receptor regulates pulsatile neuropeptide secretion. Proceedings of the National Academy of Sciences of the United States of America 2003 Mar 4;100(5):2969-74
  5. White CD, Coetsee M, Morgan K, Flanagan CA, Millar RP, Lu ZL
    A crucial role for Galphaq/11, but not Galphai/o or Galphas, in gonadotropin-releasing hormone receptor-mediated cell growth inhibition. Molecular endocrinology (Baltimore, Md.) 2008 Nov;22(11):2520-30
  6. Naor Z, Azrad A, Limor R, Zakut H, Lotan M
    Gonadotropin-releasing hormone activates a rapid Ca2+-independent phosphodiester hydrolysis of polyphosphoinositides in pituitary gonadotrophs. The Journal of biological chemistry 1986 Sep 25;261(27):12506-12
  7. Oh DY, Song JA, Moon JS, Moon MJ, Kim JI, Kim K, Kwon HB, Seong JY
    Membrane-proximal region of the carboxyl terminus of the gonadotropin-releasing hormone receptor (GnRHR) confers differential signal transduction between mammalian and nonmammalian GnRHRs. Molecular endocrinology (Baltimore, Md.) 2005 Mar;19(3):722-31
  8. Harris D, Reiss N, Naor Z
    Differential activation of protein kinase C delta and epsilon gene expression by gonadotropin-releasing hormone in alphaT3-1 cells. Autoregulation by protein kinase C. The Journal of biological chemistry 1997 May 23;272(21):13534-40
  9. Maccario H, Junoy B, Poulin B, Boyer B, Enjalbert A, Drouva SV
    Protein kinase Cdelta as gonadotropin-releasing hormone target isoenzyme in the alphaT3-1 gonadotrope cell line. Neuroendocrinology 2004;79(4):204-20
  10. Naor Z, Capponi AM, Rossier MF, Ayalon D, Limor R
    Gonadotropin-releasing hormone-induced rise in cytosolic free Ca2+ levels: mobilization of cellular and extracellular Ca2+ pools and relationship to gonadotropin secretion. Molecular endocrinology (Baltimore, Md.) 1988 Jun;2(6):512-20
  11. Navratil AM, Bliss SP, Berghorn KA, Haughian JM, Farmerie TA, Graham JK, Clay CM, Roberson MS
    Constitutive localization of the gonadotropin-releasing hormone (GnRH) receptor to low density membrane microdomains is necessary for GnRH signaling to ERK. The Journal of biological chemistry 2003 Aug 22;278(34):31593-602
  12. Bonfil D, Chuderland D, Kraus S, Shahbazian D, Friedberg I, Seger R, Naor Z
    Extracellular signal-regulated kinase, Jun N-terminal kinase, p38, and c-Src are involved in gonadotropin-releasing hormone-stimulated activity of the glycoprotein hormone follicle-stimulating hormone beta-subunit promoter. Endocrinology 2004 May;145(5):2228-44
  13. Benard O, Naor Z, Seger R
    Role of dynamin, Src, and Ras in the protein kinase C-mediated activation of ERK by gonadotropin-releasing hormone. The Journal of biological chemistry 2001 Feb 16;276(7):4554-63
  14. Maudsley S, Naor Z, Bonfil D, Davidson L, Karali D, Pawson AJ, Larder R, Pope C, Nelson N, Millar RP, Brown P
    Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene. Molecular endocrinology (Baltimore, Md.) 2007 May;21(5):1216-33
  15. Mayer SI, Willars GB, Nishida E, Thiel G
    Elk-1, CREB, and MKP-1 regulate Egr-1 expression in gonadotropin-releasing hormone stimulated gonadotrophs. Journal of cellular biochemistry 2008 Dec 1;105(5):1267-78
  16. Kang SK, Tai CJ, Nathwani PS, Choi KC, Leung PC
    Stimulation of mitogen-activated protein kinase by gonadotropin-releasing hormone in human granulosa-luteal cells. Endocrinology 2001 Feb;142(2):671-9
  17. Zhang T, Roberson MS
    Role of MAP kinase phosphatases in GnRH-dependent activation of MAP kinases. Journal of molecular endocrinology 2006 Feb;36(1):41-50
  18. Levi NL, Hanoch T, Benard O, Rozenblat M, Harris D, Reiss N, Naor Z, Seger R
    Stimulation of Jun N-terminal kinase (JNK) by gonadotropin-releasing hormone in pituitary alpha T3-1 cell line is mediated by protein kinase C, c-Src, and CDC42. Molecular endocrinology (Baltimore, Md.) 1998 Jun;12(6):815-24
  19. Xie J, Roberson MS
    3', 5'-cyclic adenosine 5'-monophosphate response element-dependent transcriptional regulation of the secretogranin II gene promoter depends on gonadotropin-releasing hormone-induced mitogen-activated protein kinase activation and the transactivator activating transcription factor 3. Endocrinology 2008 Feb;149(2):783-92
  20. Yokoi T, Ohmichi M, Tasaka K, Kimura A, Kanda Y, Hayakawa J, Tahara M, Hisamoto K, Kurachi H, Murata Y
    Activation of the luteinizing hormone beta promoter by gonadotropin-releasing hormone requires c-Jun NH2-terminal protein kinase. The Journal of biological chemistry 2000 Jul 14;275(28):21639-47
  21. Xie J, Bliss SP, Nett TM, Ebersole BJ, Sealfon SC, Roberson MS
    Transcript profiling of immediate early genes reveals a unique role for activating transcription factor 3 in mediating activation of the glycoprotein hormone alpha-subunit promoter by gonadotropin-releasing hormone. Molecular endocrinology (Baltimore, Md.) 2005 Oct;19(10):2624-38
  22. Mayer SI, Dexheimer V, Nishida E, Kitajima S, Thiel G
    Expression of the transcriptional repressor ATF3 in gonadotrophs is regulated by Egr-1, CREB, and ATF2 after gonadotropin-releasing hormone receptor stimulation. Endocrinology 2008 Dec;149(12):6311-25
  23. Roberson MS, Zhang T, Li HL, Mulvaney JM
    Activation of the p38 mitogen-activated protein kinase pathway by gonadotropin-releasing hormone. Endocrinology 1999 Mar;140(3):1310-8
  24. Ellsworth BS, White BR, Burns AT, Cherrington BD, Otis AM, Clay CM
    c-Jun N-terminal kinase activation of activator protein-1 underlies homologous regulation of the gonadotropin-releasing hormone receptor gene in alpha T3-1 cells. Endocrinology 2003 Mar;144(3):839-49
  25. Wang Y, Fortin J, Lamba P, Bonomi M, Persani L, Roberson MS, Bernard DJ
    Activator protein-1 and smad proteins synergistically regulate human follicle-stimulating hormone beta-promoter activity. Endocrinology 2008 Nov;149(11):5577-91
  26. Grafer CM, Thomas R, Lambrakos L, Montoya I, White S, Halvorson LM
    GnRH stimulates expression of PACAP in the pituitary gonadotropes via both the PKA and PKC signaling systems. Molecular endocrinology (Baltimore, Md.) 2009 Jul;23(7):1022-32
  27. Olcese J, Sikes HE, Resuehr D
    Induction of PER1 mRNA expression in immortalized gonadotropes by gonadotropin-releasing hormone (GnRH): involvement of protein kinase C and MAP kinase signaling. Chronobiology international 2006;23(1-2):143-50
  28. Ferris HA, Walsh HE, Stevens J, Fallest PC, Shupnik MA
    Luteinizing hormone beta promoter stimulation by adenylyl cyclase and cooperation with gonadotropin-releasing hormone 1 in transgenic mice and LBetaT2 Cells. Biology of reproduction 2007 Dec;77(6):1073-80
  29. Song SB, Rhee M, Roberson MS, Maurer RA, Kim KE
    Gonadotropin-releasing hormone-induced stimulation of the rat secretogranin II promoter involves activation of CREB. Molecular and cellular endocrinology 2003 Jan 31;199(1-2):29-36
  30. Zhang Q, Bratton GR, Agarwal RK, Calise D, Kugel G, Wan Y, Kumar AM
    Lead-induced cell signaling cascades in GT1-7 cells. Brain research bulletin 2003 Jul 15;61(2):207-17
  31. Hamid T, Malik MT, Millar RP, Kakar SS
    Protein kinase A serves as a primary pathway in activation of Nur77 expression by gonadotropin-releasing hormone in the LbetaT2 mouse pituitary gonadotroph tumor cell line. International journal of oncology 2008 Nov;33(5):1055-64
  32. Ciccone NA, Lacza CT, Hou MY, Gregory SJ, Kam KY, Xu S, Kaiser UB
    A composite element that binds basic helix loop helix and basic leucine zipper transcription factors is important for gonadotropin-releasing hormone regulation of the follicle-stimulating hormone beta gene. Molecular endocrinology (Baltimore, Md.) 2008 Aug;22(8):1908-23
  33. Winters SJ, Ghooray D, Fujii Y, Moore JP Jr, Nevitt JR, Kakar SS
    Transcriptional regulation of follistatin expression by GnRH in mouse gonadotroph cell lines: evidence for a role for cAMP signaling. Molecular and cellular endocrinology 2007 Jun 15;271(1-2):45-54
  34. Lim S, Luo M, Koh M, Yang M, bin Abdul Kadir MN, Tan JH, Ye Z, Wang W, Melamed P
    Distinct mechanisms involving diverse histone deacetylases repress expression of the two gonadotropin beta-subunit genes in immature gonadotropes, and their actions are overcome by gonadotropin-releasing hormone. Molecular and cellular biology 2007 Jun;27(11):4105-20

  1. Dobkin-Bekman M, Naidich M, Pawson AJ, Millar RP, Seger R, Naor Z
    Activation of mitogen-activated protein kinase (MAPK) by GnRH is cell-context dependent. Molecular and cellular endocrinology 2006 Jun 27;252(1-2):184-90
  2. Naor Z
    Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor. Frontiers in neuroendocrinology 2009 Jan;30(1):10-29
  3. Liu F, Usui I, Evans LG, Austin DA, Mellon PL, Olefsky JM, Webster NJ
    Involvement of both G(q/11) and G(s) proteins in gonadotropin-releasing hormone receptor-mediated signaling in L beta T2 cells. The Journal of biological chemistry 2002 Aug 30;277(35):32099-108
  4. Krsmanovic LZ, Mores N, Navarro CE, Arora KK, Catt KJ
    An agonist-induced switch in G protein coupling of the gonadotropin-releasing hormone receptor regulates pulsatile neuropeptide secretion. Proceedings of the National Academy of Sciences of the United States of America 2003 Mar 4;100(5):2969-74
  5. White CD, Coetsee M, Morgan K, Flanagan CA, Millar RP, Lu ZL
    A crucial role for Galphaq/11, but not Galphai/o or Galphas, in gonadotropin-releasing hormone receptor-mediated cell growth inhibition. Molecular endocrinology (Baltimore, Md.) 2008 Nov;22(11):2520-30
  6. Naor Z, Azrad A, Limor R, Zakut H, Lotan M
    Gonadotropin-releasing hormone activates a rapid Ca2+-independent phosphodiester hydrolysis of polyphosphoinositides in pituitary gonadotrophs. The Journal of biological chemistry 1986 Sep 25;261(27):12506-12
  7. Oh DY, Song JA, Moon JS, Moon MJ, Kim JI, Kim K, Kwon HB, Seong JY
    Membrane-proximal region of the carboxyl terminus of the gonadotropin-releasing hormone receptor (GnRHR) confers differential signal transduction between mammalian and nonmammalian GnRHRs. Molecular endocrinology (Baltimore, Md.) 2005 Mar;19(3):722-31
  8. Harris D, Reiss N, Naor Z
    Differential activation of protein kinase C delta and epsilon gene expression by gonadotropin-releasing hormone in alphaT3-1 cells. Autoregulation by protein kinase C. The Journal of biological chemistry 1997 May 23;272(21):13534-40
  9. Maccario H, Junoy B, Poulin B, Boyer B, Enjalbert A, Drouva SV
    Protein kinase Cdelta as gonadotropin-releasing hormone target isoenzyme in the alphaT3-1 gonadotrope cell line. Neuroendocrinology 2004;79(4):204-20
  10. Naor Z, Capponi AM, Rossier MF, Ayalon D, Limor R
    Gonadotropin-releasing hormone-induced rise in cytosolic free Ca2+ levels: mobilization of cellular and extracellular Ca2+ pools and relationship to gonadotropin secretion. Molecular endocrinology (Baltimore, Md.) 1988 Jun;2(6):512-20
  11. Navratil AM, Bliss SP, Berghorn KA, Haughian JM, Farmerie TA, Graham JK, Clay CM, Roberson MS
    Constitutive localization of the gonadotropin-releasing hormone (GnRH) receptor to low density membrane microdomains is necessary for GnRH signaling to ERK. The Journal of biological chemistry 2003 Aug 22;278(34):31593-602
  12. Bonfil D, Chuderland D, Kraus S, Shahbazian D, Friedberg I, Seger R, Naor Z
    Extracellular signal-regulated kinase, Jun N-terminal kinase, p38, and c-Src are involved in gonadotropin-releasing hormone-stimulated activity of the glycoprotein hormone follicle-stimulating hormone beta-subunit promoter. Endocrinology 2004 May;145(5):2228-44
  13. Benard O, Naor Z, Seger R
    Role of dynamin, Src, and Ras in the protein kinase C-mediated activation of ERK by gonadotropin-releasing hormone. The Journal of biological chemistry 2001 Feb 16;276(7):4554-63
  14. Maudsley S, Naor Z, Bonfil D, Davidson L, Karali D, Pawson AJ, Larder R, Pope C, Nelson N, Millar RP, Brown P
    Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene. Molecular endocrinology (Baltimore, Md.) 2007 May;21(5):1216-33
  15. Mayer SI, Willars GB, Nishida E, Thiel G
    Elk-1, CREB, and MKP-1 regulate Egr-1 expression in gonadotropin-releasing hormone stimulated gonadotrophs. Journal of cellular biochemistry 2008 Dec 1;105(5):1267-78
  16. Kang SK, Tai CJ, Nathwani PS, Choi KC, Leung PC
    Stimulation of mitogen-activated protein kinase by gonadotropin-releasing hormone in human granulosa-luteal cells. Endocrinology 2001 Feb;142(2):671-9
  17. Zhang T, Roberson MS
    Role of MAP kinase phosphatases in GnRH-dependent activation of MAP kinases. Journal of molecular endocrinology 2006 Feb;36(1):41-50
  18. Levi NL, Hanoch T, Benard O, Rozenblat M, Harris D, Reiss N, Naor Z, Seger R
    Stimulation of Jun N-terminal kinase (JNK) by gonadotropin-releasing hormone in pituitary alpha T3-1 cell line is mediated by protein kinase C, c-Src, and CDC42. Molecular endocrinology (Baltimore, Md.) 1998 Jun;12(6):815-24
  19. Xie J, Roberson MS
    3', 5'-cyclic adenosine 5'-monophosphate response element-dependent transcriptional regulation of the secretogranin II gene promoter depends on gonadotropin-releasing hormone-induced mitogen-activated protein kinase activation and the transactivator activating transcription factor 3. Endocrinology 2008 Feb;149(2):783-92
  20. Yokoi T, Ohmichi M, Tasaka K, Kimura A, Kanda Y, Hayakawa J, Tahara M, Hisamoto K, Kurachi H, Murata Y
    Activation of the luteinizing hormone beta promoter by gonadotropin-releasing hormone requires c-Jun NH2-terminal protein kinase. The Journal of biological chemistry 2000 Jul 14;275(28):21639-47
  21. Xie J, Bliss SP, Nett TM, Ebersole BJ, Sealfon SC, Roberson MS
    Transcript profiling of immediate early genes reveals a unique role for activating transcription factor 3 in mediating activation of the glycoprotein hormone alpha-subunit promoter by gonadotropin-releasing hormone. Molecular endocrinology (Baltimore, Md.) 2005 Oct;19(10):2624-38
  22. Mayer SI, Dexheimer V, Nishida E, Kitajima S, Thiel G
    Expression of the transcriptional repressor ATF3 in gonadotrophs is regulated by Egr-1, CREB, and ATF2 after gonadotropin-releasing hormone receptor stimulation. Endocrinology 2008 Dec;149(12):6311-25
  23. Roberson MS, Zhang T, Li HL, Mulvaney JM
    Activation of the p38 mitogen-activated protein kinase pathway by gonadotropin-releasing hormone. Endocrinology 1999 Mar;140(3):1310-8
  24. Ellsworth BS, White BR, Burns AT, Cherrington BD, Otis AM, Clay CM
    c-Jun N-terminal kinase activation of activator protein-1 underlies homologous regulation of the gonadotropin-releasing hormone receptor gene in alpha T3-1 cells. Endocrinology 2003 Mar;144(3):839-49
  25. Wang Y, Fortin J, Lamba P, Bonomi M, Persani L, Roberson MS, Bernard DJ
    Activator protein-1 and smad proteins synergistically regulate human follicle-stimulating hormone beta-promoter activity. Endocrinology 2008 Nov;149(11):5577-91
  26. Grafer CM, Thomas R, Lambrakos L, Montoya I, White S, Halvorson LM
    GnRH stimulates expression of PACAP in the pituitary gonadotropes via both the PKA and PKC signaling systems. Molecular endocrinology (Baltimore, Md.) 2009 Jul;23(7):1022-32
  27. Olcese J, Sikes HE, Resuehr D
    Induction of PER1 mRNA expression in immortalized gonadotropes by gonadotropin-releasing hormone (GnRH): involvement of protein kinase C and MAP kinase signaling. Chronobiology international 2006;23(1-2):143-50
  28. Ferris HA, Walsh HE, Stevens J, Fallest PC, Shupnik MA
    Luteinizing hormone beta promoter stimulation by adenylyl cyclase and cooperation with gonadotropin-releasing hormone 1 in transgenic mice and LBetaT2 Cells. Biology of reproduction 2007 Dec;77(6):1073-80
  29. Song SB, Rhee M, Roberson MS, Maurer RA, Kim KE
    Gonadotropin-releasing hormone-induced stimulation of the rat secretogranin II promoter involves activation of CREB. Molecular and cellular endocrinology 2003 Jan 31;199(1-2):29-36
  30. Zhang Q, Bratton GR, Agarwal RK, Calise D, Kugel G, Wan Y, Kumar AM
    Lead-induced cell signaling cascades in GT1-7 cells. Brain research bulletin 2003 Jul 15;61(2):207-17
  31. Hamid T, Malik MT, Millar RP, Kakar SS
    Protein kinase A serves as a primary pathway in activation of Nur77 expression by gonadotropin-releasing hormone in the LbetaT2 mouse pituitary gonadotroph tumor cell line. International journal of oncology 2008 Nov;33(5):1055-64
  32. Ciccone NA, Lacza CT, Hou MY, Gregory SJ, Kam KY, Xu S, Kaiser UB
    A composite element that binds basic helix loop helix and basic leucine zipper transcription factors is important for gonadotropin-releasing hormone regulation of the follicle-stimulating hormone beta gene. Molecular endocrinology (Baltimore, Md.) 2008 Aug;22(8):1908-23
  33. Winters SJ, Ghooray D, Fujii Y, Moore JP Jr, Nevitt JR, Kakar SS
    Transcriptional regulation of follistatin expression by GnRH in mouse gonadotroph cell lines: evidence for a role for cAMP signaling. Molecular and cellular endocrinology 2007 Jun 15;271(1-2):45-54
  34. Lim S, Luo M, Koh M, Yang M, bin Abdul Kadir MN, Tan JH, Ye Z, Wang W, Melamed P
    Distinct mechanisms involving diverse histone deacetylases repress expression of the two gonadotropin beta-subunit genes in immature gonadotropes, and their actions are overcome by gonadotropin-releasing hormone. Molecular and cellular biology 2007 Jun;27(11):4105-20

Target Details

Click on a target from the pathway image to view related information.