Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Oct 1;88(19):8749–8753. doi: 10.1073/pnas.88.19.8749

Expression of the rat growth hormone-releasing hormone gene in placenta is directed by an alternative promoter.

S González-Crespo 1, A Boronat 1
PMCID: PMC52587  PMID: 1924334

Abstract

Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that plays a critical role in controlling the synthesis and secretion of growth hormone by the anterior pituitary. GHRH has also been detected in other nonneural extrahypothalamic tissues, including rat placenta, although its role in the hormonal control of pregnancy and/or fetal development has not yet been defined. Here we present the isolation and characterization of cDNA clones corresponding to rat placental GHRH. The placental GHRH mRNA codes for a pre-pro-GHRH identical to that found in the hypothalamus, suggesting that the mature placental GHRH is identical to its hypothalamic counterpart. Nevertheless, the placental and the hypothalamic GHRH mRNAs differ in the region corresponding to the untranslated exon 1 because of the use of an alternative promoter in the placenta located 10 kilobases upstream from the hypothalamic promoter. A combined mechanism involving the use of tissue-specific alternative promoters and the differential splicing of exon 1 generates the mature GHRH transcript in placenta and hypothalamus. Multiple transcription initiation sites have been found in the placental GHRH mRNA, which correlates to the lack of a consensus TATA box in the promoter region.

Full text

PDF
8749

Images in this article

8750Image
on p.8750
8750Image
on p.8750
8751Image
on p.8751
8751Image
on p.8751
8751Image
on p.8751

Selected References

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

  1. Baird A., Wehrenberg W. B., Böhlen P., Ling N. Immunoreactive and biologically active growth hormone-releasing factor in the rat placenta. Endocrinology. 1985 Oct;117(4):1598–1601. doi: 10.1210/endo-117-4-1598. [DOI] [PubMed] [Google Scholar]
  2. Barinaga M., Bilezikjian L. M., Vale W. W., Rosenfeld M. G., Evans R. M. Independent effects of growth hormone releasing factor on growth hormone release and gene transcription. Nature. 1985 Mar 21;314(6008):279–281. doi: 10.1038/314279a0. [DOI] [PubMed] [Google Scholar]
  3. Barinaga M., Yamonoto G., Rivier C., Vale W., Evans R., Rosenfeld M. G. Transcriptional regulation of growth hormone gene expression by growth hormone-releasing factor. Nature. 1983 Nov 3;306(5938):84–85. doi: 10.1038/306084a0. [DOI] [PubMed] [Google Scholar]
  4. Bernards A., de la Monte S. M. The ltk receptor tyrosine kinase is expressed in pre-B lymphocytes and cerebral neurons and uses a non-AUG translational initiator. EMBO J. 1990 Jul;9(7):2279–2287. doi: 10.1002/j.1460-2075.1990.tb07399.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berry S. A., Pescovitz O. H. Identification of a rat GHRH-like substance and its messenger RNA in rat testis. Endocrinology. 1988 Jul;123(1):661–663. doi: 10.1210/endo-123-1-661. [DOI] [PubMed] [Google Scholar]
  6. Billestrup N., Swanson L. W., Vale W. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6854–6857. doi: 10.1073/pnas.83.18.6854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bosman F. T., Van Assche C., Nieuwenhuyzen Kruseman A. C., Jackson S., Lowry P. J. Growth hormone releasing factor (GRF) immunoreactivity in human and rat gastrointestinal tract and pancreas. J Histochem Cytochem. 1984 Nov;32(11):1139–1144. doi: 10.1177/32.11.6436365. [DOI] [PubMed] [Google Scholar]
  8. Brar A. K., Brinster R. L., Frohman L. A. Immunohistochemical analysis of human growth hormone-releasing hormone gene expression in transgenic mice. Endocrinology. 1989 Aug;125(2):801–809. doi: 10.1210/endo-125-2-801. [DOI] [PubMed] [Google Scholar]
  9. Brazeau P., Ling N., Böhlen P., Esch F., Ying S. Y., Guillemin R. Growth hormone releasing factor, somatocrinin, releases pituitary growth hormone in vitro. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7909–7913. doi: 10.1073/pnas.79.24.7909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bruhn T. O., Mason R. T., Vale W. W. Presence of growth hormone-releasing factor-like immunoreactivity in rat duodenum. Endocrinology. 1985 Oct;117(4):1710–1712. doi: 10.1210/endo-117-4-1710. [DOI] [PubMed] [Google Scholar]
  11. Böhlen P., Wehrenberg W. B., Esch F., Ling N., Brazeau P., Guillemin R. Rat hypothalamic growth hormone-releasing factor: isolation, sequence analysis and total synthesis. Biochem Biophys Res Commun. 1984 Dec 28;125(3):1005–1012. doi: 10.1016/0006-291x(84)91383-4. [DOI] [PubMed] [Google Scholar]
  12. Christofides N. D., Stephanou A., Suzuki H., Yiangou Y., Bloom S. R. Distribution of immunoreactive growth hormone-releasing hormone in the human brain and intestine and its production by tumors. J Clin Endocrinol Metab. 1984 Oct;59(4):747–751. doi: 10.1210/jcem-59-4-747. [DOI] [PubMed] [Google Scholar]
  13. Dorin R. I., Takahashi H., Nakai Y., Fukata J., Naitoh Y., Imura H. Regulation of human corticotropin-releasing hormone gene expression by 3',5'-cyclic adenosine monophosphate in a transformed mouse corticotroph cell line. Mol Endocrinol. 1989 Oct;3(10):1537–1544. doi: 10.1210/mend-3-10-1537. [DOI] [PubMed] [Google Scholar]
  14. Frohman M. A., Downs T. R., Chomczynski P., Frohman L. A. Cloning and characterization of mouse growth hormone-releasing hormone (GRH) complementary DNA: increased GRH messenger RNA levels in the growth hormone-deficient lit/lit mouse. Mol Endocrinol. 1989 Oct;3(10):1529–1536. doi: 10.1210/mend-3-10-1529. [DOI] [PubMed] [Google Scholar]
  15. Gick G. G., Zeytin F. N., Brazeau P., Ling N. C., Esch F. S., Bancroft C. Growth hormone-releasing factor regulates growth hormone mRNA in primary cultures of rat pituitary cells. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1553–1555. doi: 10.1073/pnas.81.5.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. González-Crespo S., Monfar M., Boronat A. The proximal 5'-flanking region of the gene encoding human growth hormone-releasing factor contains an inserted Alu sequence. Gene. 1990 Sep 14;93(2):321–322. doi: 10.1016/0378-1119(90)90244-l. [DOI] [PubMed] [Google Scholar]
  17. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  18. Gubler U., Monahan J. J., Lomedico P. T., Bhatt R. S., Collier K. J., Hoffman B. J., Böhlen P., Esch F., Ling N., Zeytin F. Cloning and sequence analysis of cDNA for the precursor of human growth hormone-releasing factor, somatocrinin. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4311–4314. doi: 10.1073/pnas.80.14.4311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Guillemin R., Brazeau P., Böhlen P., Esch F., Ling N., Wehrenberg W. B. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982 Nov 5;218(4572):585–587. doi: 10.1126/science.6812220. [DOI] [PubMed] [Google Scholar]
  20. Hann S. R., King M. W., Bentley D. L., Anderson C. W., Eisenman R. N. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas. Cell. 1988 Jan 29;52(2):185–195. doi: 10.1016/0092-8674(88)90507-7. [DOI] [PubMed] [Google Scholar]
  21. Ingraham H. A., Evans G. A. Characterization of two atypical promoters and alternate mRNA processing in the mouse Thy-1.2 glycoprotein gene. Mol Cell Biol. 1986 Aug;6(8):2923–2931. doi: 10.1128/mcb.6.8.2923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lewin M. J., Reyl-Desmars F., Ling N. Somatocrinin receptor coupled with cAMP-dependent protein kinase on anterior pituitary granules. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6538–6541. doi: 10.1073/pnas.80.21.6538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Linder P., Prat A. Baker's yeast, the new work horse in protein synthesis studies: analyzing eukaryotic translation initiation. Bioessays. 1990 Nov;12(11):519–526. doi: 10.1002/bies.950121103. [DOI] [PubMed] [Google Scholar]
  24. Losa M., Wolfram G., Mojto J., Schopohl J., Spiess Y., Huber R., Müller O. A., von Werder K. Presence of growth hormone-releasing hormone-like immunoreactivity in human tumors: characterization of immunological and biological properties. J Clin Endocrinol Metab. 1990 Jan;70(1):62–68. doi: 10.1210/jcem-70-1-62. [DOI] [PubMed] [Google Scholar]
  25. Luu The V., Labrie C., Zhao H. F., Couët J., Lachance Y., Simard J., Leblanc G., Côté J., Bérubé D., Gagné R. Characterization of cDNAs for human estradiol 17 beta-dehydrogenase and assignment of the gene to chromosome 17: evidence of two mRNA species with distinct 5'-termini in human placenta. Mol Endocrinol. 1989 Aug;3(8):1301–1309. doi: 10.1210/mend-3-8-1301. [DOI] [PubMed] [Google Scholar]
  26. Margioris A. N., Brockmann G., Bohler H. C., Jr, Grino M., Vamvakopoulos N., Chrousos G. P. Expression and localization of growth hormone-releasing hormone messenger ribonucleic acid in rat placenta: in vitro secretion and regulation of its peptide product. Endocrinology. 1990 Jan;126(1):151–158. doi: 10.1210/endo-126-1-151. [DOI] [PubMed] [Google Scholar]
  27. Mayo K. E., Cerelli G. M., Lebo R. V., Bruce B. D., Rosenfeld M. G., Evans R. M. Gene encoding human growth hormone-releasing factor precursor: structure, sequence, and chromosomal assignment. Proc Natl Acad Sci U S A. 1985 Jan;82(1):63–67. doi: 10.1073/pnas.82.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mayo K. E., Cerelli G. M., Rosenfeld M. G., Evans R. M. Characterization of cDNA and genomic clones encoding the precursor to rat hypothalamic growth hormone-releasing factor. Nature. 1985 Apr 4;314(6010):464–467. doi: 10.1038/314464a0. [DOI] [PubMed] [Google Scholar]
  29. Mayo K. E., Hammer R. E., Swanson L. W., Brinster R. L., Rosenfeld M. G., Evans R. M. Dramatic pituitary hyperplasia in transgenic mice expressing a human growth hormone-releasing factor gene. Mol Endocrinol. 1988 Jul;2(7):606–612. doi: 10.1210/mend-2-7-606. [DOI] [PubMed] [Google Scholar]
  30. Mayo K. E., Vale W., Rivier J., Rosenfeld M. G., Evans R. M. Expression-cloning and sequence of a cDNA encoding human growth hormone-releasing factor. Nature. 1983 Nov 3;306(5938):86–88. doi: 10.1038/306086a0. [DOI] [PubMed] [Google Scholar]
  31. Meigan G., Sasaki A., Yoshinaga K. Immunoreactive growth hormone-releasing hormone in rat placenta. Endocrinology. 1988 Aug;123(2):1098–1102. doi: 10.1210/endo-123-2-1098. [DOI] [PubMed] [Google Scholar]
  32. Prats H., Kaghad M., Prats A. C., Klagsbrun M., Lélias J. M., Liauzun P., Chalon P., Tauber J. P., Amalric F., Smith J. A. High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1836–1840. doi: 10.1073/pnas.86.6.1836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rivier J., Spiess J., Thorner M., Vale W. Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature. 1982 Nov 18;300(5889):276–278. doi: 10.1038/300276a0. [DOI] [PubMed] [Google Scholar]
  34. Shibasaki T., Kiyosawa Y., Masuda A., Nakahara M., Imaki T., Wakabayashi I., Demura H., Shizume K., Ling N. Distribution of growth hormone-releasing hormone-like immunoreactivity in human tissue extracts. J Clin Endocrinol Metab. 1984 Aug;59(2):263–268. doi: 10.1210/jcem-59-2-263. [DOI] [PubMed] [Google Scholar]
  35. Smale S. T., Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. doi: 10.1016/0092-8674(89)90176-1. [DOI] [PubMed] [Google Scholar]
  36. Spada A., Vallar L., Giannattasio G. Presence of an adenylate cyclase dually regulated by somatostatin and human pancreatic growth hormone (GH)-releasing factor in GH-secreting cells. Endocrinology. 1984 Sep;115(3):1203–1209. doi: 10.1210/endo-115-3-1203. [DOI] [PubMed] [Google Scholar]
  37. Spanopoulou E., Giguere V., Grosveld F. Transcriptional unit of the murine Thy-1 gene: different distribution of transcription initiation sites in brain. Mol Cell Biol. 1988 Sep;8(9):3847–3856. doi: 10.1128/mcb.8.9.3847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Spiess J., Rivier J., Vale W. Characterization of rat hypothalamic growth hormone-releasing factor. Nature. 1983 Jun 9;303(5917):532–535. doi: 10.1038/303532a0. [DOI] [PubMed] [Google Scholar]
  39. Suhr S. T., Rahal J. O., Mayo K. E. Mouse growth-hormone-releasing hormone: precursor structure and expression in brain and placenta. Mol Endocrinol. 1989 Nov;3(11):1693–1700. doi: 10.1210/mend-3-11-1693. [DOI] [PubMed] [Google Scholar]
  40. van den Heuvel J. J., Bergkamp R. J., Planta R. J., Raué H. A. Effect of deletions in the 5'-noncoding region on the translational efficiency of phosphoglycerate kinase mRNA in yeast. Gene. 1989 Jun 30;79(1):83–95. doi: 10.1016/0378-1119(89)90094-2. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES