Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1988 Dec;8(12):5470–5476. doi: 10.1128/mcb.8.12.5470

Expression and regulation of the pituitary- and placenta-specific human glycoprotein hormone alpha-subunit gene is restricted to the pituitary in transgenic mice.

N Fox 1, D Solter 1
PMCID: PMC365650  PMID: 2468998

Abstract

Expression of the glycoprotein hormone alpha subunit occurs in both the pituitary and placenta in humans. However, this study found that expression of this subunit is restricted to the pituitary in mice. An interspecies analysis of human alpha-subunit gene regulation was undertaken, using the transgenic-mouse approach. In mice transgenic for a genomic clone containing the complete human alpha-subunit gene and several kilobases of 5'- and 3'-flanking sequences, cell-type-specific expression and hormonal regulation of the human alpha-subunit transgene occurred in the mouse pituitary, whereas no expression of the transgene was detectable in the mouse placenta. These findings provide strong evidence that a common trans-acting factor(s) regulates glycoprotein hormone alpha-subunit gene expression in the human and mouse pituitaries; however, this factor(s) or a unique factor(s), though functional in the human placenta, is either nonfunctional or absent in the mouse placenta.

Full text

PDF

Images in this article

5472Image
on p.5472
5473Image
on p.5473
5474Image
on p.5474
5474Image
on p.5474

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander D. C., Miller W. L. Regulation of ovine follicle-stimulating hormone beta-chain mRNA by 17 beta-estradiol in vivo and in vitro. J Biol Chem. 1982 Mar 10;257(5):2282–2286. [PubMed] [Google Scholar]
  2. Alonso S., Minty A., Bourlet Y., Buckingham M. Comparison of three actin-coding sequences in the mouse; evolutionary relationships between the actin genes of warm-blooded vertebrates. J Mol Evol. 1986;23(1):11–22. doi: 10.1007/BF02100994. [DOI] [PubMed] [Google Scholar]
  3. Boorstein W. R., Vamvakopoulos N. C., Fiddes J. C. Human chorionic gonadotropin beta-subunit is encoded by at least eight genes arranged in tandem and inverted pairs. Nature. 1982 Dec 2;300(5891):419–422. doi: 10.1038/300419a0. [DOI] [PubMed] [Google Scholar]
  4. Bremner W. J., Matsumoto A. M., Sussman A. M., Paulsen C. A. Follicle-stimulating hormone and human spermatogenesis. J Clin Invest. 1981 Oct;68(4):1044–1052. doi: 10.1172/JCI110327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carr F. E., Chin W. W. Absence of detectable chorionic gonadotropin subunit messenger ribonucleic acids in the rat placenta throughout gestation. Endocrinology. 1985 Mar;116(3):1151–1157. doi: 10.1210/endo-116-3-1151. [DOI] [PubMed] [Google Scholar]
  6. Chada K., Magram J., Costantini F. An embryonic pattern of expression of a human fetal globin gene in transgenic mice. Nature. 1986 Feb 20;319(6055):685–689. doi: 10.1038/319685a0. [DOI] [PubMed] [Google Scholar]
  7. Chen H. C., Hodgen G. D. Primate chorionic gonadotropins: antigenic similarities to the unique carboxyl-terminal peptide of HCGbeta subunit. J Clin Endocrinol Metab. 1976 Dec;43(6):1414–1417. doi: 10.1210/jcem-43-6-1414. [DOI] [PubMed] [Google Scholar]
  8. Chin W. W., Kronenberg H. M., Dee P. C., Maloof F., Habener J. F. Nucleotide sequence of the mRNA encoding the pre-alpha-subunit of mouse thyrotropin. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5329–5333. doi: 10.1073/pnas.78.9.5329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chin W. W., Shupnik M. A., Ross D. S., Habener J. F., Ridgway E. C. Regulation of the alpha and thyrotropin beta-subunit messenger ribonucleic acids by thyroid hormones. Endocrinology. 1985 Mar;116(3):873–878. doi: 10.1210/endo-116-3-873. [DOI] [PubMed] [Google Scholar]
  10. Darnell R. B., Boime I. Differential expression of the human gonadotropin alpha gene in ectopic and eutopic cells. Mol Cell Biol. 1985 Nov;5(11):3157–3167. doi: 10.1128/mcb.5.11.3157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Delegeane A. M., Ferland L. H., Mellon P. L. Tissue-specific enhancer of the human glycoprotein hormone alpha-subunit gene: dependence on cyclic AMP-inducible elements. Mol Cell Biol. 1987 Nov;7(11):3994–4002. doi: 10.1128/mcb.7.11.3994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Deutsch P. J., Jameson J. L., Habener J. F. Cyclic AMP responsiveness of human gonadotropin-alpha gene transcription is directed by a repeated 18-base pair enhancer. Alpha-promoter receptivity to the enhancer confers cell-preferential expression. J Biol Chem. 1987 Sep 5;262(25):12169–12174. [PubMed] [Google Scholar]
  13. Edmonds M., Molitch M., Pierce J. G., Odell W. D. Secretion of alpha subunits of luteinizing hormone (LH) by the anterior pituitary. J Clin Endocrinol Metab. 1975 Sep;41(3):551–555. doi: 10.1210/jcem-41-3-551. [DOI] [PubMed] [Google Scholar]
  14. Fetherston J., Boime I. Synthesis of bovine lutropin in cell-free lysates containing pituitary microsomes. J Biol Chem. 1982 Jul 25;257(14):8143–8147. [PubMed] [Google Scholar]
  15. Fiddes J. C., Goodman H. M. Isolation, cloning and sequence analysis of the cDNA for the alpha-subunit of human chorionic gonadotropin. Nature. 1979 Oct 4;281(5730):351–356. doi: 10.1038/281351a0. [DOI] [PubMed] [Google Scholar]
  16. Fiddes J. C., Goodman H. M. The gene encoding the common alpha subunit of the four human glycoprotein hormones. J Mol Appl Genet. 1981;1(1):3–18. [PubMed] [Google Scholar]
  17. Franklyn J. A., Lynam T., Docherty K., Ramsden D. B., Sheppard M. C. Effect of hypothyroidism on pituitary cytoplasmic concentrations of messenger RNA encoding thyrotrophin beta and alpha subunits, prolactin and growth hormone. J Endocrinol. 1986 Jan;108(1):43–47. doi: 10.1677/joe.0.1080043. [DOI] [PubMed] [Google Scholar]
  18. Godine J. E., Chin W. W., Habener J. F. Luteinizing and follicle-stimulating hormones. Cell-free translations of messenger RNAs coding for subunit precursors. J Biol Chem. 1980 Sep 25;255(18):8780–8783. [PubMed] [Google Scholar]
  19. Gordon J. W., Chesa P. G., Nishimura H., Rettig W. J., Maccari J. E., Endo T., Seravalli E., Seki T., Silver J. Regulation of Thy-1 gene expression in transgenic mice. Cell. 1987 Jul 31;50(3):445–452. doi: 10.1016/0092-8674(87)90498-3. [DOI] [PubMed] [Google Scholar]
  20. Gurr J. A., Kourides I. A. Ratios of alpha to beta TSH mRNA in normal and hypothyroid pituitaries and TSH-secreting tumors. Endocrinology. 1984 Aug;115(2):830–832. doi: 10.1210/endo-115-2-830. [DOI] [PubMed] [Google Scholar]
  21. Jameson J. L., Deutsch P. J., Gallagher G. D., Jaffe R. C., Habener J. F. trans-acting factors interact with a cyclic AMP response element to modulate expression of the human gonadotropin alpha gene. Mol Cell Biol. 1987 Sep;7(9):3032–3040. doi: 10.1128/mcb.7.9.3032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jameson J. L., Jaffe R. C., Gleason S. L., Habener J. F. Transcriptional regulation of chorionic gonadotropin alpha- and beta-subunit gene expression by 8-bromo-adenosine 3',5'-monophosphate. Endocrinology. 1986 Dec;119(6):2560–2567. doi: 10.1210/endo-119-6-2560. [DOI] [PubMed] [Google Scholar]
  23. Jameson J. L., Lindell C. M., Hsu D. W., Habener J. F., Ridgway E. C. Expression of chorionic gonadotropin-beta-like messenger ribonucleic acid in an alpha-subunit-secreting pituitary adenoma. J Clin Endocrinol Metab. 1986 Jun;62(6):1271–1278. doi: 10.1210/jcem-62-6-1271. [DOI] [PubMed] [Google Scholar]
  24. Julier C., Weil D., Couillin P., Côté J. C., Nguyen V. C., Foubert C., Boué A., Thirion J. P., Kaplan J. C., Junien C. The beta chorionic gonadotropin-beta luteinizing gene cluster maps to human chromosome 19. Hum Genet. 1984;67(2):174–177. doi: 10.1007/BF00272995. [DOI] [PubMed] [Google Scholar]
  25. Kelsey G. D., Povey S., Bygrave A. E., Lovell-Badge R. H. Species- and tissue-specific expression of human alpha 1-antitrypsin in transgenic mice. Genes Dev. 1987 Apr;1(2):161–171. doi: 10.1101/gad.1.2.161. [DOI] [PubMed] [Google Scholar]
  26. Kourides I. A., Landon M. B., Hoffman B. J., Weintraub B. D. Excess free alpha relative to beta subunits of the glycoprotein hormones in normal and abnormal human pituitary glands. Clin Endocrinol (Oxf) 1980 Apr;12(4):407–416. doi: 10.1111/j.1365-2265.1980.tb02728.x. [DOI] [PubMed] [Google Scholar]
  27. Kourides I. A., Weintraub B. D., Ridgway E. C., Maloof F. Pituitary secretion of free alpha and beta subunit of human thyrotropin in patients with thyroid disorders. J Clin Endocrinol Metab. 1975 May;40(5):872–885. doi: 10.1210/jcem-40-5-872. [DOI] [PubMed] [Google Scholar]
  28. Landefeld T. D., Kepa J., Karsch F. J. Regulation of alpha subunit synthesis by gonadal steroid feedback in the sheep anterior pituitary. J Biol Chem. 1983 Feb 25;258(4):2390–2393. [PubMed] [Google Scholar]
  29. Landefeld T., Kepa J., Karsch F. Estradiol feedback effects on the alpha-subunit mRNA in the sheep pituitary gland: correlation with serum and pituitary luteinizing hormone concentrations. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1322–1326. doi: 10.1073/pnas.81.5.1322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Matsumoto A. M., Bremner W. J. Stimulation of sperm production by human chorionic gonadotropin after prolonged gonadotropin suppression in normal men. J Androl. 1985 May-Jun;6(3):137–143. doi: 10.1002/j.1939-4640.1985.tb00829.x. [DOI] [PubMed] [Google Scholar]
  31. Naylor S. L., Chin W. W., Goodman H. M., Lalley P. A., Grzeschik K. H., Sakaguchi A. Y. Chromosome assignment of genes encoding the alpha and beta subunits of glycoprotein hormones in man and mouse. Somatic Cell Genet. 1983 Nov;9(6):757–770. doi: 10.1007/BF01539478. [DOI] [PubMed] [Google Scholar]
  32. Nilson J. H., Nejedlik M. T., Virgin J. B., Crowder M. E., Nett T. M. Expression of alpha subunit and luteinizing hormone beta genes in the ovine anterior pituitary. Estradiol suppresses accumulation of mRNAS for both alpha subunit and luteinizing hormone beta. J Biol Chem. 1983 Oct 25;258(20):12087–12090. [PubMed] [Google Scholar]
  33. Papavasiliou S. S., Zmeili S., Herbon L., Duncan-Weldon J., Marshall J. C., Landefeld T. D. Alpha and luteinizing hormone beta messenger ribonucleic acid (RNA) of male and female rats after castration: quantitation using an optimized RNA dot blot hybridization assay. Endocrinology. 1986 Aug;119(2):691–698. doi: 10.1210/endo-119-2-691. [DOI] [PubMed] [Google Scholar]
  34. Parlow A. F. Biologic detection of FSH in unconcentrated serum of intact male mice and the unexpected effects of orchidectomy of FSH and LH. Endocrinology. 1970 Aug;87(2):271–275. doi: 10.1210/endo-87-2-271. [DOI] [PubMed] [Google Scholar]
  35. Parlow A. F., Kovacic N., Bhalla R. C. Biologic characterization of artificial luteinizing hormones, prepared by hybridization of sub-units of hCG with bovine LH or TSH subunits. J Clin Endocrinol Metab. 1972 Aug;35(2):319–322. doi: 10.1210/jcem-35-2-319. [DOI] [PubMed] [Google Scholar]
  36. Pierce J. G., Parsons T. F. Glycoprotein hormones: structure and function. Annu Rev Biochem. 1981;50:465–495. doi: 10.1146/annurev.bi.50.070181.002341. [DOI] [PubMed] [Google Scholar]
  37. Policastro P. F., Daniels-McQueen S., Carle G., Boime I. A map of the hCG beta-LH beta gene cluster. J Biol Chem. 1986 May 5;261(13):5907–5916. [PubMed] [Google Scholar]
  38. Policastro P., Ovitt C. E., Hoshina M., Fukuoka H., Boothby M. R., Boime I. The beta subunit of human chorionic gonadotropin is encoded by multiple genes. J Biol Chem. 1983 Oct 10;258(19):11492–11499. [PubMed] [Google Scholar]
  39. Prentice L. G., Ryan R. J. LH and its subunits in human pituitary, serum and urine. J Clin Endocrinol Metab. 1975 Feb;40(2):303–312. doi: 10.1210/jcem-40-2-303. [DOI] [PubMed] [Google Scholar]
  40. Reichert L. E., Jr, Midgley A. R., Jr, Niswender G. D., Ward D. N. Formation of a hybrid molecule from subunits of human bovine luteinizing hormone. Endocrinology. 1970 Sep;87(3):534–541. doi: 10.1210/endo-87-3-534. [DOI] [PubMed] [Google Scholar]
  41. Ruddon R. W., Hanson C. A., Bryan A. H., Putterman G. J., White E. L., Perini F., Meade K. S., Aldenderfer P. H. Synthesis and secretion of human chorionic gonadotropin subunits by cultured human malignant cells. J Biol Chem. 1980 Feb 10;255(3):1000–1007. [PubMed] [Google Scholar]
  42. Schanbacher B. D., Ford J. J. Gonadotropin secretion in cryptorchid and castrate rams and the acute effects of exogenous steroid treatment. Endocrinology. 1977 Feb;100(2):387–393. doi: 10.1210/endo-100-2-387. [DOI] [PubMed] [Google Scholar]
  43. Shupnik M. A., Chin W. W., Habener J. F., Ridgway E. C. Transcriptional regulation of the thyrotropin subunit genes by thyroid hormone. J Biol Chem. 1985 Mar 10;260(5):2900–2903. [PubMed] [Google Scholar]
  44. Shupnik M. A., Chin W. W., Ross D. S., Downing M. F., Habener J. F., Ridgway E. C. Regulation by thyroxine of the mRNA encoding the alpha subunit of mouse thyrotropin. J Biol Chem. 1983 Dec 25;258(24):15120–15124. [PubMed] [Google Scholar]
  45. Silver B. J., Bokar J. A., Virgin J. B., Vallen E. A., Milsted A., Nilson J. H. Cyclic AMP regulation of the human glycoprotein hormone alpha-subunit gene is mediated by an 18-base-pair element. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2198–2202. doi: 10.1073/pnas.84.8.2198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Soares V. da C., Gubits R. M., Feigelson P., Costantini F. Tissue-specific and hormonally regulated expression of a rat alpha 2u globulin gene in transgenic mice. Mol Cell Biol. 1987 Oct;7(10):3749–3758. doi: 10.1128/mcb.7.10.3749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  48. Sugino H., Bousfield G. R., Moore W. T., Jr, Ward D. N. Structural studies on equine glycoprotein hormones. Amino acid sequence of equine chorionic gonadotropin beta-subunit. J Biol Chem. 1987 Jun 25;262(18):8603–8609. [PubMed] [Google Scholar]
  49. Talmadge K., Boorstein W. R., Fiddes J. C. The human genome contains seven genes for the beta-subunit of chorionic gonadotropin but only one gene for the beta-subunit of luteinizing hormone. DNA. 1983;2(4):281–289. doi: 10.1089/dna.1983.2.281. [DOI] [PubMed] [Google Scholar]
  50. Talmadge K., Vamvakopoulos N. C., Fiddes J. C. Evolution of the genes for the beta subunits of human chorionic gonadotropin and luteinizing hormone. Nature. 1984 Jan 5;307(5946):37–40. doi: 10.1038/307037a0. [DOI] [PubMed] [Google Scholar]
  51. Tepper M. A., Roberts J. L. Evidence for only one beta-luteinizing hormone and no beta-chorionic gonadotropin gene in the rat. Endocrinology. 1984 Jul;115(1):385–391. doi: 10.1210/endo-115-1-385. [DOI] [PubMed] [Google Scholar]
  52. Townes T. M., Lingrel J. B., Chen H. Y., Brinster R. L., Palmiter R. D. Erythroid-specific expression of human beta-globin genes in transgenic mice. EMBO J. 1985 Jul;4(7):1715–1723. doi: 10.1002/j.1460-2075.1985.tb03841.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Tramu G., Pillez A., Leonardelli J. An efficient method of antibody elution for the successive or simultaneous localization of two antigens by immunocytochemistry. J Histochem Cytochem. 1978 Apr;26(4):322–324. doi: 10.1177/26.4.207771. [DOI] [PubMed] [Google Scholar]
  54. Virgin J. B., Silver B. J., Thomason A. R., Nilson J. H. The gene for the beta subunit of bovine luteinizing hormone encodes a gonadotropin mRNA with an unusually short 5'-untranslated region. J Biol Chem. 1985 Jun 10;260(11):7072–7077. [PubMed] [Google Scholar]
  55. Wurzel J. M., Curatola L. M., Gurr J. A., Goldschmidt A. M., Kourides I. A. The luteotropic activity of rat placenta is not due to a chorionic gonadotropin. Endocrinology. 1983 Nov;113(5):1854–1857. doi: 10.1210/endo-113-5-1854. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES