Gene Symbol: Lhb
Description: luteinizing hormone beta
Alias: Gm29035, LH-B, LSH-B, LSH-beta, lutropin subunit beta, leutropin, luteinizing hormone subunit beta, lutropin beta chain
Species: mouse
Products:     Lhb

Top Publications

  1. Ellsworth B, Butts D, Camper S. Mechanisms underlying pituitary hypoplasia and failed cell specification in Lhx3-deficient mice. Dev Biol. 2008;313:118-29 pubmed
  2. Davis S, Mortensen A, Camper S. Birthdating studies reshape models for pituitary gland cell specification. Dev Biol. 2011;352:215-27 pubmed publisher
    ..We propose that signals intrinsic to Rathke's pouch are necessary for cell specification between e11.5 and e13.5 and that cell-cell communication likely plays an important role in regulating this process...
  3. Ferris H, Walsh H, Stevens J, Fallest P, Shupnik M. Luteinizing hormone beta promoter stimulation by adenylyl cyclase and cooperation with gonadotropin-releasing hormone 1 in transgenic mice and LBetaT2 Cells. Biol Reprod. 2007;77:1073-80 pubmed
    Rat luteinizing hormone beta (Lhb) gene transcription is stimulated by hypothalamic gonadotropin-releasing hormone 1 (GnRH1), and this response may be modulated by other signaling pathways such as cAMP...
  4. Wang Y, Martin J, Bai C. Direct and indirect requirements of Shh/Gli signaling in early pituitary development. Dev Biol. 2010;348:199-209 pubmed publisher
    ..Our results therefore suggest both cell-autonomous and non-cell-autonomous requirements for Gli2 in regulation of pituitary progenitor specification, proliferation and differentiation. ..
  5. Andrade J, Quinn J, Becker R, Shupnik M. AMP-activated protein kinase is a key intermediary in GnRH-stimulated LH? gene transcription. Mol Endocrinol. 2013;27:828-39 pubmed publisher
    ..These studies indicate a novel role for AMPK in GnRH-stimulated transcription in pituitary gonadotropes and a potential common mechanism for GnRH and metabolic modulation of fertility. ..
  6. Ellsworth B, Egashira N, Haller J, Butts D, Cocquet J, Clay C, et al. FOXL2 in the pituitary: molecular, genetic, and developmental analysis. Mol Endocrinol. 2006;20:2796-805 pubmed
    ..These data place FOXL2 in the hierarchy of pituitary developmental control and suggest a role in regulation of Cga gene expression...
  7. Japón M, Rubinstein M, Low M. In situ hybridization analysis of anterior pituitary hormone gene expression during fetal mouse development. J Histochem Cytochem. 1994;42:1117-25 pubmed
  8. Charles M, Suh H, Hjalt T, Drouin J, Camper S, Gage P. PITX genes are required for cell survival and Lhx3 activation. Mol Endocrinol. 2005;19:1893-903 pubmed
    ..Thus, the combined dosage of these PITX family members is vital for pituitary development, and their persistent coexpression in the adult pituitary suggests a continued role in maintenance of pituitary function. ..
  9. Brinkmeier M, Potok M, Cha K, Gridley T, Stifani S, Meeldijk J, et al. TCF and Groucho-related genes influence pituitary growth and development. Mol Endocrinol. 2003;17:2152-61 pubmed
    ..Thus, we demonstrate that Tcf4 and Aes influence pituitary growth and development, and place Tcf4 and Tle3 in the genetic hierarchy with Prop1. ..

More Information


  1. Arriola D, Mayo S, Skarra D, Benson C, Thackray V. FOXO1 transcription factor inhibits luteinizing hormone ? gene expression in pituitary gonadotrope cells. J Biol Chem. 2012;287:33424-35 pubmed
    ..In this study we investigated whether FOXO1 is expressed in gonadotropes and if it can modulate LH ?-subunit (Lhb) gene expression...
  2. Treier M, Gleiberman A, O Connell S, Szeto D, McMahon J, McMahon A, et al. Multistep signaling requirements for pituitary organogenesis in vivo. Genes Dev. 1998;12:1691-704 pubmed
  3. Zhao L, Zevallos S, Rizzoti K, Jeong Y, Lovell Badge R, Epstein D. Disruption of SoxB1-dependent Sonic hedgehog expression in the hypothalamus causes septo-optic dysplasia. Dev Cell. 2012;22:585-96 pubmed publisher
    ..These data indicate that reduced levels of Shh expression in the hypothalamus cause SOD. ..
  4. Bilodeau S, Roussel Gervais A, Drouin J. Distinct developmental roles of cell cycle inhibitors p57Kip2 and p27Kip1 distinguish pituitary progenitor cell cycle exit from cell cycle reentry of differentiated cells. Mol Cell Biol. 2009;29:1895-908 pubmed publisher
  5. Ma X, Dong Y, Matzuk M, Kumar T. Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility. Proc Natl Acad Sci U S A. 2004;101:17294-9 pubmed
    ..Thus, LHbeta null mice represent a model to study the consequences of an isolated deficiency of LH ligand in reproduction, while retaining normal LH-responsiveness in target cells. ..
  6. Davis S, Camper S. Noggin regulates Bmp4 activity during pituitary induction. Dev Biol. 2007;305:145-60 pubmed
    ..This work demonstrates the importance of attenuating the activity of Bmp signaling during pituitary induction in order to maintain the proper balance of signaling factors necessary for pituitary organogenesis. ..
  7. Wang G, Hardy M. Development of leydig cells in the insulin-like growth factor-I (igf-I) knockout mouse: effects of igf-I replacement and gonadotropic stimulation. Biol Reprod. 2004;70:632-9 pubmed
  8. Pope C, McNeilly J, Coutts S, Millar M, Anderson R, McNeilly A. Gonadotrope and thyrotrope development in the human and mouse anterior pituitary gland. Dev Biol. 2006;297:172-81 pubmed
    ..The mechanism(s) responsible for the different molecular regulation of alpha-GSU gene expression in gonadotropes and thyrotropes in the developing human fetal pituitary now requires investigation...
  9. Raetzman L, Cai J, Camper S. Hes1 is required for pituitary growth and melanotrope specification. Dev Biol. 2007;304:455-66 pubmed
    ..These results demonstrate that Notch signaling plays multiple roles in pituitary development, influencing precursor number, organ size, cell differentiation and ultimately cell fate. ..
  10. Dong Y, Zhang L, Zhang S, Bai Y, Chen H, Sun X, et al. Phosphatase of regenerating liver 2 (PRL2) is essential for placental development by down-regulating PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) and activating Akt protein. J Biol Chem. 2012;287:32172-9 pubmed publisher
    ..This study provides the first evidence that PRL2 is required for extra-embryonic development and associates the oncogenic properties of PRL2 with its ability to negatively regulate PTEN, thereby activating the PI3K-Akt pathway. ..
  11. Haston S, Pozzi S, Carreno G, Manshaei S, Panousopoulos L, González Meljem J, et al. MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma. Development. 2017;144:2141-2152 pubmed publisher
  12. Russell L, Montgomery C, Cacheiro N, Johnson D. Complementation analyses for 45 mutations encompassing the pink-eyed dilution (p) locus of the mouse. Genetics. 1995;141:1547-62 pubmed
    ..The alleles specifying mottling or darker pigment (generically, pm and px, respectively) probably do not represent deletions of p-coding sequences but could be small rearrangements involving proximal regulatory elements. ..
  13. Voss J, Rosenfeld M. Anterior pituitary development: short tales from dwarf mice. Cell. 1992;70:527-30 pubmed
  14. Haisenleder D, Ferris H, Shupnik M. The calcium component of gonadotropin-releasing hormone-stimulated luteinizing hormone subunit gene transcription is mediated by calcium/calmodulin-dependent protein kinase type II. Endocrinology. 2003;144:2409-16 pubmed
    ..These data show for the first time that Ca/CaMK II activation plays an important role in the transmission of GnRH signals from the plasma membrane to the LH subunit genes. ..
  15. Sun Y, Bak B, Schoenmakers N, van Trotsenburg A, Oostdijk W, Voshol P, et al. Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement. Nat Genet. 2012;44:1375-81 pubmed publisher
    ..Collectively, our observations delineate a new X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling. ..
  16. Dasen J, O Connell S, Flynn S, Treier M, Gleiberman A, Szeto D, et al. Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell. 1999;97:587-98 pubmed
  17. Davis S, Mortensen A, Keisler J, Zacharias A, Gage P, Yamamura K, et al. ?-catenin is required in the neural crest and mesencephalon for pituitary gland organogenesis. BMC Dev Biol. 2016;16:16 pubmed publisher
    ..catenin in the Wnt1 expression domain, including the neural crest, plays a critical role in regulation of pituitary gland growth, development, and vascularization. ..
  18. Suh H, Gage P, Drouin J, Camper S. Pitx2 is required at multiple stages of pituitary organogenesis: pituitary primordium formation and cell specification. Development. 2002;129:329-37 pubmed
    ..The model developed for PITX gene function in pituitary development provides a better understanding of the etiology of Rieger syndrome and may extend to other PITX-sensitive developmental processes. ..
  19. Eckstrum K, Weis K, Baur N, Yoshihara Y, Raetzman L. Icam5 Expression Exhibits Sex Differences in the Neonatal Pituitary and Is Regulated by Estradiol and Bisphenol A. Endocrinology. 2016;157:1408-20 pubmed publisher
    ..analysis of pituitaries at postnatal day (PND)1, 3 genes were differentially expressed between males and females: Lhb, Fshb, and intracellular adhesion molecule-5 (Icam5)...
  20. Zhao E, McNeilly J, McNeilly A, Fischer Colbrie R, Basak A, Seong J, et al. Secretoneurin stimulates the production and release of luteinizing hormone in mouse L{beta}T2 gonadotropin cells. Am J Physiol Endocrinol Metab. 2011;301:E288-97 pubmed publisher
    ..However, SN did not activate the GnRH receptor. These data indicate that SN activates the protein kinase A (PKA) and cAMP-induced ERK signaling pathways in the LH-secreting mouse L?T2 pituitary cell line. ..
  21. Mortensen A, Schade V, Lamonerie T, Camper S. Deletion of OTX2 in neural ectoderm delays anterior pituitary development. Hum Mol Genet. 2015;24:939-53 pubmed publisher
    ..Otx2 expression early in head development is important for establishing normal craniofacial features including development of the brain, eyes and pituitary gland. ..
  22. Cha K, Douglas K, Potok M, Liang H, Jones S, Camper S. WNT5A signaling affects pituitary gland shape. Mech Dev. 2004;121:183-94 pubmed
    ..This study suggests that the primary role of Wnt5a in the developing pituitary gland is in establishment of the shape of the gland. ..
  23. Cogliati T, Delgado Romero P, Norwitz E, Guduric Fuchs J, Kaiser U, Wray S, et al. Pubertal impairment in Nhlh2 null mice is associated with hypothalamic and pituitary deficiencies. Mol Endocrinol. 2007;21:3013-27 pubmed
  24. Oury F, Ferron M, Huizhen W, Confavreux C, Xu L, LaCombe J, et al. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. J Clin Invest. 2013;123:2421-33 pubmed
    ..This study uncovers the existence of a second endocrine axis that is necessary for optimal male fertility in the mouse and suggests that osteocalcin modulates reproductive function in humans...
  25. Panneerdoss S, Chang Y, Buddavarapu K, Chen H, Shetty G, Wang H, et al. Androgen-responsive microRNAs in mouse Sertoli cells. PLoS ONE. 2012;7:e41146 pubmed publisher
  26. Shibusawa N, Yamada M, Hirato J, Monden T, Satoh T, Mori M. Requirement of thyrotropin-releasing hormone for the postnatal functions of pituitary thyrotrophs: ontogeny study of congenital tertiary hypothyroidism in mice. Mol Endocrinol. 2000;14:137-46 pubmed
    ..Moreover, reflecting its name, TRH has more critical effects on the pituitary thyrotrophs than on other pituitary hormone-producing cells. ..
  27. Stefaneanu L, Powell Braxton L, Won W, Chandrashekar V, Bartke A. Somatotroph and lactotroph changes in the adenohypophyses of mice with disrupted insulin-like growth factor I gene. Endocrinology. 1999;140:3881-9 pubmed
    ..In conclusion, IGF-I plays no role in differentiation of pituitary cells, affects the size of somatotrophs in females, and is a stimulator of lactotrophs in both genders. ..
  28. Wolfe M, Call G. Early growth response protein 1 binds to the luteinizing hormone-beta promoter and mediates gonadotropin-releasing hormone-stimulated gene expression. Mol Endocrinol. 1999;13:752-63 pubmed
    ..Finally, GnRH not only induced expression of Egr1, but also its corepressor, NGFI-A (Egr1) binding protein (Nab1), which can repress Egr1- induced transcription of the eLH beta promoter. ..
  29. Nagaraja A, Agno J, Kumar T, Matzuk M. Luteinizing hormone promotes gonadal tumorigenesis in inhibin-deficient mice. Mol Cell Endocrinol. 2008;294:19-28 pubmed publisher
    ..Inha(-/-)Lhb(-/-) mice have increased survival and delayed tumor progression, and these observations correlate with lower serum ..
  30. Steyn F, Wan Y, Clarkson J, Veldhuis J, Herbison A, Chen C. Development of a methodology for and assessment of pulsatile luteinizing hormone secretion in juvenile and adult male mice. Endocrinology. 2013;154:4939-45 pubmed publisher
    ..In addition, we observed a decrease in the clearance (increased half-life) and a decrease in the regularity (approximate entropy) of LH release. This method will be of wide general utility within the field of reproductive biology. ..
  31. Strauss B, Pittman R, Pixley M, Nilson J, Boime I. Expression of the beta subunit of chorionic gonadotropin in transgenic mice. J Biol Chem. 1994;269:4968-73 pubmed
    ..Additionally, a different subset of CG beta genes (CG beta 1 and beta 2) is active in the mouse brain. ..
  32. Sutton A, Keri R. The pleiotropic effects of excessive luteinizing hormone secretion in transgenic mice. Semin Reprod Med. 2007;25:360-7 pubmed
    ..Thus, mice with altered LH signaling provide valuable tools in understanding normal reproduction and various pathological conditions. ..
  33. Stubbs L, Carver E, Ashworth L, Lopez Molina L. Location of the DBP transcription factor gene in human and mouse. Mamm Genome. 1996;7:65-7 pubmed
  34. Burrows H, Birkmeier T, Seasholtz A, Camper S. Targeted ablation of cells in the pituitary primordia of transgenic mice. Mol Endocrinol. 1996;10:1467-77 pubmed
    ..Instead, commitment to individual differentiated pituitary cell fates must occur autonomously or before the expression of currently known differentiation markers. ..
  35. Kumar T. Functional analysis of LHbeta knockout mice. Mol Cell Endocrinol. 2007;269:81-4 pubmed
    ..Thus, LHbeta null mice provide a useful model to study the consequences of an isolated deficiency of LH ligand in reproduction, while retaining normal LH-responsiveness in target cells. ..
  36. Matsumoto S, Yamazaki C, Masumoto K, Nagano M, Naito M, Soga T, et al. Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2. Proc Natl Acad Sci U S A. 2006;103:4140-5 pubmed
    ..Our current findings demonstrated that physiological activation of PKR2 is essential for normal development of the OB and sexual maturation...
  37. Kourides I, Barker P, Gurr J, Pravtcheva D, Ruddle F. Assignment of the genes for the alpha and beta subunits of thyrotropin to different mouse chromosomes. Proc Natl Acad Sci U S A. 1984;81:517-9 pubmed
    ..Mouse beta-subunit gene sequences always segregated with chromosome 3 (concordant in 15 hybrids). Thus, the genes for at least one of the glycoprotein hormones, thyrotropin, are on different chromosomes. ..
  38. Feng J, Lawson M, Melamed P. A proteomic comparison of immature and mature mouse gonadotrophs reveals novel differentially expressed nuclear proteins that regulate gonadotropin gene transcription and RNA splicing. Biol Reprod. 2008;79:546-61 pubmed publisher
    ..Transgelin 3 overexpression reduced transcript levels of Fshb, and its knockdown elevated Lhb and Cga transcript levels, indicating an ongoing repressive effect on these more highly expressed genes, possibly ..
  39. Lim S, Luo M, Koh M, Yang M, bin Abdul Kadir M, Tan J, et al. 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. Mol Cell Biol. 2007;27:4105-20 pubmed
  40. Weiss J, Axelrod L, Whitcomb R, Harris P, Crowley W, Jameson J. Hypogonadism caused by a single amino acid substitution in the beta subunit of luteinizing hormone. N Engl J Med. 1992;326:179-83 pubmed
  41. Vasilyev V, Lawson M, Dipaolo D, Webster N, Mellon P. Different signaling pathways control acute induction versus long-term repression of LHbeta transcription by GnRH. Endocrinology. 2002;143:3414-26 pubmed
  42. Nasonkin I, Ward R, Raetzman L, Seasholtz A, Saunders T, Gillespie P, et al. Pituitary hypoplasia and respiratory distress syndrome in Prop1 knockout mice. Hum Mol Genet. 2004;13:2727-35 pubmed
    ..Prop1-null mice are an excellent model for MPHD and may be useful for testing the efficacy of pharmaceutical intervention for neonatal respiratory distress. ..
  43. Vesper A, Raetzman L, Camper S. Role of prophet of Pit1 (PROP1) in gonadotrope differentiation and puberty. Endocrinology. 2006;147:1654-63 pubmed
    ..We hypothesize that variation in PROP1 expression could affect the growth spurt and the onset of puberty in humans...
  44. Saunders A, Seldin M. The syntenic relationship of proximal mouse chromosome 7 and the myotonic dystrophy gene region on human chromosome 19q. Genomics. 1990;6:324-32 pubmed
    ..Their order from the centromere was Prkcg, [Apoe, Atpa-2, Ckmm, D19S19h, Ercc-2], Cyp2b, Mag, Lhb. Two other murine loci, D7Rp2 and Ngfg, were also positioned within this interval...
  45. Raivio T, Huhtaniemi I, Anttila R, Siimes M, Hagenäs L, Nilsson C, et al. The role of luteinizing hormone-beta gene polymorphism in the onset and progression of puberty in healthy boys. J Clin Endocrinol Metab. 1996;81:3278-82 pubmed
    ..Our results also suggest that the variant LH not only affects the course of puberty, but is already involved in the regulation of the GH-insulin-like growth factor I axis during childhood. ..
  46. Giacobini P, Wray S. Prenatal expression of cholecystokinin (CCK) in the central nervous system (CNS) of mouse. Neurosci Lett. 2008;438:96-101 pubmed publisher
    ..In addition, we provide evidence that regions of the CNS known to integrate hormonal and sensory information associated with reproduction and the GnRH-1 system, expressed CCK already during prenatal development. ..
  47. Moran T, Goldberg L, Serviss S, Raetzman L. Numb deletion in POMC-expressing cells impairs pituitary intermediate lobe cell adhesion, progenitor cell localization, and neuro-intermediate lobe boundary formation. Mol Endocrinol. 2011;25:117-27 pubmed publisher
    ..Unexpectedly, Notch activity appears normal in conditional knockout mice. Thus, Numb is critical for maintaining cell-cell interactions in the pituitary intermediate lobe that are essential for proper cell placement. ..
  48. Stephens S, Tolson K, Rouse M, Poling M, HASHIMOTO PARTYKA M, Mellon P, et al. Absent Progesterone Signaling in Kisspeptin Neurons Disrupts the LH Surge and Impairs Fertility in Female Mice. Endocrinology. 2015;156:3091-7 pubmed publisher
    ..Our novel findings demonstrate that progesterone signaling specifically in kisspeptin cells is essential for the positive feedback induction of normal LH surges, ovulation, and normal fertility in females. ..
  49. Calderon M, Ploegman A, Bailey B, Jung D, Navratil A, Ellsworth B. Loss of Foxm1 Results in Reduced Somatotrope Cell Number during Mouse Embryogenesis. PLoS ONE. 2015;10:e0128942 pubmed publisher
    ..5 embryos suggesting there may be subtle changes in pituitary proliferation not detected with our proliferation makers. Consistent with this, Foxm1 null mice have reductions in both the somatotrope and gonadotrope cell populations. ..
  50. Gridelet V, Tsampalas M, Berndt S, Hagelstein M, Charlet Renard C, Conrath V, et al. Evidence for cross-talk between the LH receptor and LH during implantation in mice. Reprod Fertil Dev. 2013;25:511-22 pubmed publisher
    ..In support of this hypothesis, we identified a bioactive LH signal at the time of murine blastocyst implantation. ..
  51. Bowen R, Verdile G, Liu T, Parlow A, Perry G, Smith M, et al. Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition. J Biol Chem. 2004;279:20539-45 pubmed
    ..Suppression of the age-related increase in serum gonadotropins using anti-gonadotropin agents may represent a novel therapeutic strategy for AD. ..
  52. Raetzman L, Ward R, Camper S. Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia. Development. 2002;129:4229-39 pubmed
    ..Thus, Lhx4 and Prop1 have critical, but mechanistically different roles in specification and expansion of specialized anterior pituitary cells. ..
  53. Grattan D, Jasoni C, Liu X, Anderson G, Herbison A. Prolactin regulation of gonadotropin-releasing hormone neurons to suppress luteinizing hormone secretion in mice. Endocrinology. 2007;148:4344-51 pubmed
    ..This is likely to occur, at least in part, through the direct regulation of a subpopulation of GnRH neurons. ..
  54. Wu S, Wilson M, Busby E, Isaac E, Sherwood N. Disruption of the single copy gonadotropin-releasing hormone receptor in mice by gene trap: severe reduction of reproductive organs and functions in developing and adult mice. Endocrinology. 2010;151:1142-52 pubmed publisher
    ..In terms of gonadal morphology, adult gene trap-Gnrhr null mice demonstrate a complete cessation of reproduction and serve as an important model for understanding GnRH/GnRHR physiology. ..
  55. Bentley C, Zidehsarai M, Grindley J, Parlow A, Barth Hall S, Roberts V. Pax6 is implicated in murine pituitary endocrine function. Endocrine. 1999;10:171-7 pubmed
  56. Quirk C, Seachrist D, Nilson J. Embryonic expression of the luteinizing hormone beta gene appears to be coupled to the transient appearance of p8, a high mobility group-related transcription factor. J Biol Chem. 2003;278:1680-5 pubmed
    ..Taken together, our data indicate that p8 is a stage-specific component of the gonadotrope transcriptome that may play a functional role in the initiation of LH beta gene expression during embryonic cellular differentiation. ..
  57. Million Passe C, White C, King M, Quirk P, Iovanna J, Quirk C. Loss of the protein NUPR1 (p8) leads to delayed LHB expression, delayed ovarian maturation, and testicular development of a sertoli-cell-only syndrome-like phenotype in mice. Biol Reprod. 2008;79:598-607 pubmed publisher
    ..NUPR1, also known as p8 and com1, plays a role in temporal expression of the beta subunit of luteinizing hormone, LHB, during gonadotroph development. At Embryonic Day (e) 16...
  58. Pitteloud N, Zhang C, Pignatelli D, Li J, Raivio T, Cole L, et al. Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2007;104:17447-52 pubmed
    ..Homozygous loss-of-function PROK2 mutations cause both KS and nIHH...
  59. Risma K, Hirshfield A, Nilson J. Elevated luteinizing hormone in prepubertal transgenic mice causes hyperandrogenemia, precocious puberty, and substantial ovarian pathology. Endocrinology. 1997;138:3540-7 pubmed
    ..Based on these studies we conclude that chronic prepubertal elevation of serum LH results in gonadotropin-dependent hyperandrogenemia, leading to abnormal sexual development and significant ovarian pathology. ..
  60. Cheung L, Okano H, Camper S. Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes. Mol Cell Endocrinol. 2017;439:213-223 pubmed publisher
    ..In addition, despite changes in pituitary hormone expression, hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants may be a cause of non-endocrine short stature in humans. ..
  61. Liew S, Drummond A, Jones M, Findlay J. The lack of estrogen and excess luteinizing hormone are responsible for the female ArKO mouse phenotype. Mol Cell Endocrinol. 2010;327:56-64 pubmed publisher
    ..The data indicate that the absence of estrogen in concert with elevated levels of circulating gonadotrophins, principally LH, is responsible for the abnormal reproductive phenotype of the female ArKO mouse. ..
  62. Pearl C, Boime I. Sulfation of LH does not affect intracellular trafficking. Mol Cell Endocrinol. 2009;309:76-81 pubmed publisher
    ..These data suggest that the metabolic role for sulfated N-linked oligosaccharides is not for intracellular trafficking but for the extracellular bioactivity of LH. ..
  63. Kumar T, Matzuk M. Cloning of the mouse gonadotropin beta-subunit-encoding genes, II. Structure of the luteinizing hormone beta-subunit-encoding genes. Gene. 1995;166:335-6 pubmed
    ..This confirms an important role of LH, together with follicle-stimulating hormone (FSH), in regulating several aspects of reproduction. ..
  64. Mantamadiotis T, Kretz O, Ridder S, Bleckmann S, Bock D, Grone H, et al. Hypothalamic 3',5'-cyclic adenosine monophosphate response element-binding protein loss causes anterior pituitary hypoplasia and dwarfism in mice. Mol Endocrinol. 2006;20:204-11 pubmed
    ..These findings show that CREB is required for the efficient production of GHRH in hypothalamus, in addition to its previously reported role in pituitary GH production and somatotroph expansion. ..
  65. Xie H, Hoffmann H, Meadows J, Mayo S, Trang C, Leming S, et al. Homeodomain Proteins SIX3 and SIX6 Regulate Gonadotrope-specific Genes During Pituitary Development. Mol Endocrinol. 2015;29:842-55 pubmed publisher
    ..whereas Six6 is expressed in a mature gonadotrope cell line and represses the specific β-subunits of LH and FSH (LHb and FSHb) that are expressed later in development...
  66. Wang H, Graham I, Hastings R, Gunewardena S, Brinkmeier M, Conn P, et al. Gonadotrope-specific deletion of Dicer results in severely suppressed gonadotropins and fertility defects. J Biol Chem. 2015;290:2699-714 pubmed publisher
    ..Thus, DICER-dependent microRNAs confer a new layer of transcriptional and post-transcriptional regulation in gonadotropes to orchestrate the hypothalamus-pituitary-gonadal axis physiology. ..
  67. Breen K, Thackray V, Hsu T, Mak McCully R, Coss D, Mellon P. Stress levels of glucocorticoids inhibit LH?-subunit gene expression in gonadotrope cells. Mol Endocrinol. 2012;26:1716-31 pubmed
  68. Marcinkiewicz M, Day R, Seidah N, Chretien M. Ontogeny of the prohormone convertases PC1 and PC2 in the mouse hypophysis and their colocalization with corticotropin and alpha-melanotropin. Proc Natl Acad Sci U S A. 1993;90:4922-6 pubmed
    ..It is expected that beta-endorphin processing will follow that of alpha MSH. ..
  69. Wright M, Rochelle J, Tomlinson M, Seldin M, Williams A. Gene structure, chromosomal localization, and protein sequence of mouse CD53 (Cd53): evidence that the transmembrane 4 superfamily arose by gene duplication. Int Immunol. 1993;5:209-16 pubmed
  70. Vaccari S, Weeks J, Hsieh M, Menniti F, Conti M. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol Reprod. 2009;81:595-604 pubmed publisher
  71. Zhang Z, Florez S, Gutierrez Hartmann A, Martin J, Amendt B. MicroRNAs regulate pituitary development, and microRNA 26b specifically targets lymphoid enhancer factor 1 (Lef-1), which modulates pituitary transcription factor 1 (Pit-1) expression. J Biol Chem. 2010;285:34718-28 pubmed publisher
  72. Ingman W, Robertson S. Transforming growth factor-beta1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunction. Endocrinology. 2007;148:4032-43 pubmed
  73. Salisbury T, Binder A, Grammer J, Nilson J. Maximal activity of the luteinizing hormone beta-subunit gene requires beta-catenin. Mol Endocrinol. 2007;21:963-71 pubmed
    GnRH regulates expression of LHB via transcriptional regulation of early growth response 1 (EGR1), an immediate early gene that encodes a zinc-finger DNA-binding protein...
  74. Scully K, Skowronska Krawczyk D, Krawczyk M, Merkurjev D, Taylor H, Livolsi A, et al. Epithelial cell integrin β1 is required for developmental angiogenesis in the pituitary gland. Proc Natl Acad Sci U S A. 2016;113:13408-13413 pubmed
  75. OLAH M, Milloh H, Wenger T. The role of endocannabinoids in the regulation of luteinizing hormone and prolactin release. Differences between the effects of AEA and 2AG. Mol Cell Endocrinol. 2008;286:S36-40 pubmed publisher
  76. Aujla P, Bogdanovic V, Naratadam G, Raetzman L. Persistent expression of activated notch in the developing hypothalamus affects survival of pituitary progenitors and alters pituitary structure. Dev Dyn. 2015;244:921-34 pubmed publisher
  77. Johnson D, Stubbs L, DeLoia J. The mouse cyclin E maps to chromosome 7. Mamm Genome. 1996;7:245 pubmed
  78. Gaston Massuet C, Andoniadou C, Signore M, Sajedi E, Bird S, Turner J, et al. Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development. Dev Biol. 2008;324:322-33 pubmed publisher
    ..Our research has revealed a role for Six3 in normal pituitary development, which has likely been conserved during evolution as SIX3 is also expressed in the pituitary gland of the human embryo. ..
  79. Beuschlein F, Looyenga B, Bleasdale S, Mutch C, Bavers D, Parlow A, et al. Activin induces x-zone apoptosis that inhibits luteinizing hormone-dependent adrenocortical tumor formation in inhibin-deficient mice. Mol Cell Biol. 2003;23:3951-64 pubmed
  80. Balla A, Danilovich N, Yang Y, Sairam M. Dynamics of ovarian development in the FORKO immature mouse: structural and functional implications for ovarian reserve. Biol Reprod. 2003;69:1281-93 pubmed
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