Abstract
In animal models, parathyroid hormone-related protein (PTHrP) increases placental calcium transport and inhibits contraction of uterine smooth muscle. The present studies were undertaken to characterize the expression of PTHrP in human uteroplacental tissues. PTHrP mRNA was identified by Northern analysis as a single species (approximately 1.8 kilobases) in human amnion, chorion, placenta, decidua, and myometrium. The most abundant signal was seen in amnion, where it was 10-400 times that in the other uteroplacental tissues. PTHrP mRNA abundance was decreased in amnion (but not in the other tissues) following the onset of labor (P less than 0.001). PTHrP mRNA in amnion appeared to be translated to a bioactive peptide, as PTHrP bioactivity and immunoreactive PTHrP in amnion correlated closely with PTHrP mRNA content (r = 0.86 and 0.95, respectively; P less than 0.05 and P less than 0.01). Amniotic fluid contained PTHrP, 21 +/- 6 pmol/liter (n = 10) at 16 weeks and 41 +/- 9 pmol/liter (n = 7) at 38 weeks (P = 0.05). These concentrations equaled or exceeded those found in plasma of patients with hypercalcemia secondary to PTHrP. After rupture of the fetal membranes, PTHrP mRNA in amnion was decreased by 78% (P less than 0.0001). This decrease appeared to be specific for PTHrP mRNA, as glyceraldehyde-3-phosphate dehydrogenase mRNA was unchanged following rupture of membranes. Like PTHrP mRNA, PTHrP bioactivity and immunoreactive PTHrP in amnion decreased significantly following rupture of membranes (P less than 0.03 and P less than 0.01, respectively). Since PTHrP is a potent antagonist of uterine muscle contraction, the decrease of PTHrP following rupture of the fetal membranes may play a key role in the onset of labor.
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- Abbas S. K., Pickard D. W., Illingworth D., Storer J., Purdie D. W., Moniz C., Dixit M., Caple I. W., Ebeling P. R., Rodda C. P. Measurement of parathyroid hormone-related protein in extracts of fetal parathyroid glands and placental membranes. J Endocrinol. 1990 Feb;124(2):319–325. doi: 10.1677/joe.0.1240319. [DOI] [PubMed] [Google Scholar]
- Broadus A. E., Mangin M., Ikeda K., Insogna K. L., Weir E. C., Burtis W. J., Stewart A. F. Humoral hypercalcemia of cancer. Identification of a novel parathyroid hormone-like peptide. N Engl J Med. 1988 Sep 1;319(9):556–563. doi: 10.1056/NEJM198809013190906. [DOI] [PubMed] [Google Scholar]
- Burtis W. J., Brady T. G., Orloff J. J., Ersbak J. B., Warrell R. P., Jr, Olson B. R., Wu T. L., Mitnick M. E., Broadus A. E., Stewart A. F. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. N Engl J Med. 1990 Apr 19;322(16):1106–1112. doi: 10.1056/NEJM199004193221603. [DOI] [PubMed] [Google Scholar]
- Care A. D., Abbas S. K., Pickard D. W., Barri M., Drinkhill M., Findlay J. B., White I. R., Caple I. W. Stimulation of ovine placental transport of calcium and magnesium by mid-molecule fragments of human parathyroid hormone-related protein. Exp Physiol. 1990 Jul;75(4):605–608. doi: 10.1113/expphysiol.1990.sp003437. [DOI] [PubMed] [Google Scholar]
- 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]
- Ferguson J. E., 2nd, Vick D. J., Hogge J. S., Hogge W. A. Transcervical chorionic villus sampling and amniocentesis: a comparison of reliability, culture findings, and fetal outcome. Am J Obstet Gynecol. 1990 Sep;163(3):926–931. doi: 10.1016/0002-9378(90)91098-w. [DOI] [PubMed] [Google Scholar]
- Lafond J., Auger D., Fortier J., Brunette M. G. Parathyroid hormone receptor in human placental syncytiotrophoblast brush border and basal plasma membranes. Endocrinology. 1988 Dec;123(6):2834–2840. doi: 10.1210/endo-123-6-2834. [DOI] [PubMed] [Google Scholar]
- Moseley J. M., Hayman J. A., Danks J. A., Alcorn D., Grill V., Southby J., Horton M. A. Immunohistochemical detection of parathyroid hormone-related protein in human fetal epithelia. J Clin Endocrinol Metab. 1991 Sep;73(3):478–484. doi: 10.1210/jcem-73-3-478. [DOI] [PubMed] [Google Scholar]
- Nickols G. A., Nana A. D., Nickols M. A., DiPette D. J., Asimakis G. K. Hypotension and cardiac stimulation due to the parathyroid hormone-related protein, humoral hypercalcemia of malignancy factor. Endocrinology. 1989 Aug;125(2):834–841. doi: 10.1210/endo-125-2-834. [DOI] [PubMed] [Google Scholar]
- Okazaki T., Casey M. L., Okita J. R., MacDonald P. C., Johnston J. M. Initiation of human parturition. XII. Biosynthesis and metabolism of prostaglandins in human fetal membranes and uterine decidua. Am J Obstet Gynecol. 1981 Feb 15;139(4):373–381. [PubMed] [Google Scholar]
- Orloff J. J., Wu T. L., Stewart A. F. Parathyroid hormone-like proteins: biochemical responses and receptor interactions. Endocr Rev. 1989 Nov;10(4):476–495. doi: 10.1210/edrv-10-4-476. [DOI] [PubMed] [Google Scholar]
- Pandian M. R., Morgan C. H., Carlton E., Segre G. V. Modified immunoradiometric assay of parathyroid hormone-related protein: clinical application in the differential diagnosis of hypercalcemia. Clin Chem. 1992 Feb;38(2):282–288. [PubMed] [Google Scholar]
- Shew R. L., Yee J. A., Kliewer D. B., Keflemariam Y. J., McNeill D. L. Parathyroid hormone-related protein inhibits stimulated uterine contraction in vitro. J Bone Miner Res. 1991 Sep;6(9):955–959. doi: 10.1002/jbmr.5650060909. [DOI] [PubMed] [Google Scholar]
- Skinner K. A., Challis J. R. Changes in the synthesis and metabolism of prostaglandins by human fetal membranes and decidua at labor. Am J Obstet Gynecol. 1985 Feb 15;151(4):519–523. doi: 10.1016/0002-9378(85)90281-9. [DOI] [PubMed] [Google Scholar]
- Suva L. J., Winslow G. A., Wettenhall R. E., Hammonds R. G., Moseley J. M., Diefenbach-Jagger H., Rodda C. P., Kemp B. E., Rodriguez H., Chen E. Y. A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression. Science. 1987 Aug 21;237(4817):893–896. doi: 10.1126/science.3616618. [DOI] [PubMed] [Google Scholar]
- Thiede M. A., Daifotis A. G., Weir E. C., Brines M. L., Burtis W. J., Ikeda K., Dreyer B. E., Garfield R. E., Broadus A. E. Intrauterine occupancy controls expression of the parathyroid hormone-related peptide gene in preterm rat myometrium. Proc Natl Acad Sci U S A. 1990 Sep;87(18):6969–6973. doi: 10.1073/pnas.87.18.6969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weir E. C., Brines M. L., Ikeda K., Burtis W. J., Broadus A. E., Robbins R. J. Parathyroid hormone-related peptide gene is expressed in the mammalian central nervous system. Proc Natl Acad Sci U S A. 1990 Jan;87(1):108–112. doi: 10.1073/pnas.87.1.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winquist R. J., Baskin E. P., Vlasuk G. P. Synthetic tumor-derived human hypercalcemic factor exhibits parathyroid hormone-like vasorelaxation in renal arteries. Biochem Biophys Res Commun. 1987 Nov 30;149(1):227–232. doi: 10.1016/0006-291x(87)91628-7. [DOI] [PubMed] [Google Scholar]