Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Jul;82(1):287–292. doi: 10.1172/JCI113585

Characterization and gestational regulation of corticotropin-releasing hormone messenger RNA in human placenta.

D M Frim 1, R L Emanuel 1, B G Robinson 1, C M Smas 1, G K Adler 1, J A Majzoub 1
PMCID: PMC303507  PMID: 3260606

Abstract

Corticotropin-releasing hormone (CRH), a hypothalamic neuropeptide involved in the regulation of ACTH secretion, has been detected by RIA in extracts of human placenta. We wished to determine whether this immunoreactive substance is a product of CRH gene expression in the placenta. We have found authentic human CRH (hCRH) mRNA in human placental tissue that is similar in size to hypothalamic CRH mRNA. Furthermore, the transcriptional initiation site for placental hCRH mRNA is identical to that previously predicted for hypothalamic hCRH mRNA, 23-26 nucleotides downstream from a canonical promoter element. Placental hCRH mRNA increases more than 20-fold in the 5 wk preceding parturition, in parallel with a rise in placental hCRH peptide content. These data strongly suggest that the hCRH gene is expressed in the placenta and that this expression changes dramatically during gestation.

Full text

PDF
287

Images in this article

Selected References

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

  1. Adler G. K., Smas C. M., Majzoub J. A. Expression and dexamethasone regulation of the human corticotropin-releasing hormone gene in a mouse anterior pituitary cell line. J Biol Chem. 1988 Apr 25;263(12):5846–5852. [PubMed] [Google Scholar]
  2. Affolter H. U., Reisine T. Corticotropin releasing factor increases proopiomelanocortin messenger RNA in mouse anterior pituitary tumor cells. J Biol Chem. 1985 Dec 15;260(29):15477–15481. [PubMed] [Google Scholar]
  3. Arbiser J. L., Morton C. C., Bruns G. A., Majzoub J. A. Human corticotropin releasing hormone gene is located on the long arm of chromosome 8. Cytogenet Cell Genet. 1988;47(3):113–116. doi: 10.1159/000132525. [DOI] [PubMed] [Google Scholar]
  4. Campbell E. A., Linton E. A., Wolfe C. D., Scraggs P. R., Jones M. T., Lowry P. J. Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition. J Clin Endocrinol Metab. 1987 May;64(5):1054–1059. doi: 10.1210/jcem-64-5-1054. [DOI] [PubMed] [Google Scholar]
  5. Caruthers M. H., Beaucage S. L., Efcavitch J. W., Fisher E. F., Matteucci M. D., Stabinsky Y. New chemical methods for synthesizing polynucleotides. Nucleic Acids Symp Ser. 1980;(7):215–223. [PubMed] [Google Scholar]
  6. Chambon P., Dierich A., Gaub M. P., Jakowlev S., Jongstra J., Krust A., LePennec J. P., Oudet P., Reudelhuber T. Promoter elements of genes coding for proteins and modulation of transcription by estrogens and progesterone. Recent Prog Horm Res. 1984;40:1–42. doi: 10.1016/b978-0-12-571140-1.50005-0. [DOI] [PubMed] [Google Scholar]
  7. Chen C. L., Chang C. C., Krieger D. T., Bardin C. W. Expression and regulation of proopiomelanocortin-like gene in the ovary and placenta: comparison with the testis. Endocrinology. 1986 Jun;118(6):2382–2389. doi: 10.1210/endo-118-6-2382. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Fisher D. A. The unique endocrine milieu of the fetus. J Clin Invest. 1986 Sep;78(3):603–611. doi: 10.1172/JCI112616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goland R. S., Wardlaw S. L., Stark R. I., Brown L. S., Jr, Frantz A. G. High levels of corticotropin-releasing hormone immunoactivity in maternal and fetal plasma during pregnancy. J Clin Endocrinol Metab. 1986 Nov;63(5):1199–1203. doi: 10.1210/jcem-63-5-1199. [DOI] [PubMed] [Google Scholar]
  12. Jingami H., Matsukura S., Numa S., Imura H. Effects of adrenalectomy and dexamethasone administration on the level of prepro-corticotropin-releasing factor messenger ribonucleic acid (mRNA) in the hypothalamus and adrenocorticotropin/beta-lipotropin precursor mRNA in the pituitary in rats. Endocrinology. 1985 Oct;117(4):1314–1320. doi: 10.1210/endo-117-4-1314. [DOI] [PubMed] [Google Scholar]
  13. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  14. Liggins G. C. Adrenocortical-related maturational events in the fetus. Am J Obstet Gynecol. 1976 Dec 1;126(7):931–941. doi: 10.1016/0002-9378(76)90680-3. [DOI] [PubMed] [Google Scholar]
  15. Liotta A., Osathanondh R., Ryan K. J., Krieger D. T. Presence of corticotropin in human placenta: demonstration of in vitro synthesis. Endocrinology. 1977 Nov;101(5):1552–1558. doi: 10.1210/endo-101-5-1552. [DOI] [PubMed] [Google Scholar]
  16. Majzoub J. A., Carrazana E. J., Shulman J. S., Baker K. J., Emanuel R. L. Defective regulation of vasopressin gene expression in Brattleboro rats. Am J Physiol. 1987 May;252(5 Pt 1):E637–E642. doi: 10.1152/ajpendo.1987.252.5.E637. [DOI] [PubMed] [Google Scholar]
  17. Majzoub J. A., Rich A., van Boom J., Habener J. F. Vasopressin and oxytocin mRNA regulation in the rat assessed by hybridization with synthetic oligonucleotides. J Biol Chem. 1983 Dec 10;258(23):14061–14064. [PubMed] [Google Scholar]
  18. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  19. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Parnes J. R., Robinson R. R., Seidman J. G. Multiple mRNA species with distinct 3' termini are transcribed from the beta 2-microglobulin gene. 1983 Mar 31-Apr 6Nature. 302(5907):449–452. doi: 10.1038/302449a0. [DOI] [PubMed] [Google Scholar]
  21. Petraglia F., Sawchenko P. E., Rivier J., Vale W. Evidence for local stimulation of ACTH secretion by corticotropin-releasing factor in human placenta. Nature. 1987 Aug 20;328(6132):717–719. doi: 10.1038/328717a0. [DOI] [PubMed] [Google Scholar]
  22. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sasaki A., Liotta A. S., Luckey M. M., Margioris A. N., Suda T., Krieger D. T. Immunoreactive corticotropin-releasing factor is present in human maternal plasma during the third trimester of pregnancy. J Clin Endocrinol Metab. 1984 Oct;59(4):812–814. doi: 10.1210/jcem-59-4-812. [DOI] [PubMed] [Google Scholar]
  24. Sasaki A., Shinkawa O., Margioris A. N., Liotta A. S., Sato S., Murakami O., Go M., Shimizu Y., Hanew K., Yoshinaga K. Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor, and delivery. J Clin Endocrinol Metab. 1987 Feb;64(2):224–229. doi: 10.1210/jcem-64-2-224. [DOI] [PubMed] [Google Scholar]
  25. Sawchenko P. E., Swanson L. W., Vale W. W. Co-expression of corticotropin-releasing factor and vasopressin immunoreactivity in parvocellular neurosecretory neurons of the adrenalectomized rat. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1883–1887. doi: 10.1073/pnas.81.6.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Seeburg P. H., Adelman J. P. Characterization of cDNA for precursor of human luteinizing hormone releasing hormone. Nature. 1984 Oct 18;311(5987):666–668. doi: 10.1038/311666a0. [DOI] [PubMed] [Google Scholar]
  27. Shambaugh G., 3rd, Kubek M., Wilber J. F. Thyrotropin-releasing hormone activity in the human placenta. J Clin Endocrinol Metab. 1979 Mar;48(3):483–486. doi: 10.1210/jcem-48-3-483. [DOI] [PubMed] [Google Scholar]
  28. Shibahara S., Morimoto Y., Furutani Y., Notake M., Takahashi H., Shimizu S., Horikawa S., Numa S. Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene. EMBO J. 1983;2(5):775–779. doi: 10.1002/j.1460-2075.1983.tb01499.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shibasaki T., Odagiri E., Shizume K., Ling N. Corticotropin-releasing factor-like activity in human placental extracts. J Clin Endocrinol Metab. 1982 Aug;55(2):384–386. doi: 10.1210/jcem-55-2-384. [DOI] [PubMed] [Google Scholar]
  30. Suda T., Tomori N., Tozawa F., Mouri T., Demura H., Shizume K. Distribution and characterization of immunoreactive corticotropin-releasing factor in human tissues. J Clin Endocrinol Metab. 1984 Nov;59(5):861–866. doi: 10.1210/jcem-59-5-861. [DOI] [PubMed] [Google Scholar]
  31. Suggs S. V., Wallace R. B., Hirose T., Kawashima E. H., Itakura K. Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6613–6617. doi: 10.1073/pnas.78.11.6613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thompson R. C., Seasholtz A. F., Herbert E. Rat corticotropin-releasing hormone gene: sequence and tissue-specific expression. Mol Endocrinol. 1987 May;1(5):363–370. doi: 10.1210/mend-1-5-363. [DOI] [PubMed] [Google Scholar]
  34. Vale W., Spiess J., Rivier C., Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science. 1981 Sep 18;213(4514):1394–1397. doi: 10.1126/science.6267699. [DOI] [PubMed] [Google Scholar]
  35. Watkins W. B., Yen S. S. Somatostatin in cytotrophoblast of the immature human placenta: localization by immunoperoxidase cytochemistry. J Clin Endocrinol Metab. 1980 May;50(5):969–971. doi: 10.1210/jcem-50-5-969. [DOI] [PubMed] [Google Scholar]
  36. de Fencl M., Tulchinsky D. Total cortisol in amniotic fluid and fetal lung maturation. N Engl J Med. 1975 Jan 16;292(3):133–136. doi: 10.1056/NEJM197501162920304. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES