Abstract
The parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHRP) genes are members of a gene family. Whereas PTH is a classical peptide hormone, mounting evidence suggests that the PTHRP may have predominately local actions. We report here that the PTHRP gene is expressed in rat myometrium, with a major peak in PTHRP mRNA expression occurring in the 48 hr immediately preceding parturition. A similar peak in peptide content was found in tissue extracts by biological and immunological assays, but the PTHRP could not be detected in the peripheral circulation or in uterine vein plasma during late gestation. By in situ hybridization histochemistry, PTHRP mRNA was demonstrated in both the longitudinal and circular layers of smooth muscle but was absent in the endometrium. The rise in myometrial PTHRP mRNA in late gestation was dependent upon intrauterine occupancy; it was greatly reduced or absent in nongravid uterine horns. These findings indicate that the expression of the PTHRP gene in preterm myometrium is under the control of a local stimulus and suggest that the PTHRP may play a paracrine or autocrine role in the uterus during the antepartum period, possibly involving myometrial contractility.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Budayr A. A., Halloran B. P., King J. C., Diep D., Nissenson R. A., Strewler G. J. High levels of a parathyroid hormone-like protein in milk. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7183–7185. doi: 10.1073/pnas.86.18.7183. [DOI] [PMC free article] [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]
- Burtis W. J., Wu T., Bunch C., Wysolmerski J. J., Insogna K. L., Weir E. C., Broadus A. E., Stewart A. F. Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. J Biol Chem. 1987 May 25;262(15):7151–7156. [PubMed] [Google Scholar]
- Card J. P., Fitzpatrick-McElligott S., Gozes I., Baldino F., Jr Localization of vasopressin-, vasoactive intestinal polypeptide-, peptide histidine isoleucine- and somatostatin-mRNA in rat suprachiasmatic nucleus. Cell Tissue Res. 1988 May;252(2):307–315. doi: 10.1007/BF00214373. [DOI] [PubMed] [Google Scholar]
- Carsten M. E., Miller J. D. A new look at uterine muscle contraction. Am J Obstet Gynecol. 1987 Nov;157(5):1303–1315. doi: 10.1016/s0002-9378(87)80320-4. [DOI] [PubMed] [Google Scholar]
- Civitelli R., Martin T. J., Fausto A., Gunsten S. L., Hruska K. A., Avioli L. V. Parathyroid hormone-related peptide transiently increases cytosolic calcium in osteoblast-like cells: comparison with parathyroid hormone. Endocrinology. 1989 Sep;125(3):1204–1210. doi: 10.1210/endo-125-3-1204. [DOI] [PubMed] [Google Scholar]
- Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
- Drucker D. J., Asa S. L., Henderson J., Goltzman D. The parathyroid hormone-like peptide gene is expressed in the normal and neoplastic human endocrine pancreas. Mol Endocrinol. 1989 Oct;3(10):1589–1595. doi: 10.1210/mend-3-10-1589. [DOI] [PubMed] [Google Scholar]
- FEASTER J. P., HANSARD S. L., OUTLER J. C., DAVIS G. K. Placental transfer of calcium in the rat. J Nutr. 1956 Mar 10;58(3):399–406. doi: 10.1093/jn/58.3.399. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- 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]
- Fuchs A. R. Uterine activity in late pregnancy and during parturition in the rat. Biol Reprod. 1969 Dec;1(4):344–353. doi: 10.1095/biolreprod1.4.344. [DOI] [PubMed] [Google Scholar]
- Goldman M. E., Chorev M., Reagan J. E., Nutt R. F., Levy J. J., Rosenblatt M. Evaluation of novel parathyroid hormone analogs using a bovine renal membrane receptor binding assay. Endocrinology. 1988 Sep;123(3):1468–1475. doi: 10.1210/endo-123-3-1468. [DOI] [PubMed] [Google Scholar]
- Habener J. F., Rosenblatt M., Potts J. T., Jr Parathyroid hormone: biochemical aspects of biosynthesis, secretion, action, and metabolism. Physiol Rev. 1984 Jul;64(3):985–1053. doi: 10.1152/physrev.1984.64.3.985. [DOI] [PubMed] [Google Scholar]
- Ikeda K., Lu C., Weir E. C., Mangin M., Broadus A. E. Regulation of parathyroid hormone-related peptide gene expression by cycloheximide. J Biol Chem. 1990 Apr 5;265(10):5398–5402. [PubMed] [Google Scholar]
- Ikeda K., Lu C., Weir E. C., Mangin M., Broadus A. E. Transcriptional regulation of the parathyroid hormone-related peptide gene by glucocorticoids and vitamin D in a human C-cell line. J Biol Chem. 1989 Sep 25;264(27):15743–15746. [PubMed] [Google Scholar]
- Ikeda K., Weir E. C., Mangin M., Dannies P. S., Kinder B., Deftos L. J., Brown E. M., Broadus A. E. Expression of messenger ribonucleic acids encoding a parathyroid hormone-like peptide in normal human and animal tissues with abnormal expression in human parathyroid adenomas. Mol Endocrinol. 1988 Dec;2(12):1230–1236. doi: 10.1210/mend-2-12-1230. [DOI] [PubMed] [Google Scholar]
- Lu C., Ikeda K., Deftos L. J., Gazdar A. F., Mangin M., Broadus A. E. Glucocorticoid regulation of parathyroid hormone-related peptide gene transcription in a human neuroendocrine cell line. Mol Endocrinol. 1989 Dec;3(12):2034–2040. doi: 10.1210/mend-3-12-2034. [DOI] [PubMed] [Google Scholar]
- Mangin M., Ikeda K., Dreyer B. E., Broadus A. E. Identification of an up-stream promoter of the human parathyroid hormone-related peptide gene. Mol Endocrinol. 1990 Jun;4(6):851–858. doi: 10.1210/mend-4-6-851. [DOI] [PubMed] [Google Scholar]
- Mangin M., Ikeda K., Dreyer B. E., Broadus A. E. Isolation and characterization of the human parathyroid hormone-like peptide gene. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2408–2412. doi: 10.1073/pnas.86.7.2408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mangin M., Webb A. C., Dreyer B. E., Posillico J. T., Ikeda K., Weir E. C., Stewart A. F., Bander N. H., Milstone L., Barton D. E. Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy. Proc Natl Acad Sci U S A. 1988 Jan;85(2):597–601. doi: 10.1073/pnas.85.2.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Merendino J. J., Jr, Insogna K. L., Milstone L. M., Broadus A. E., Stewart A. F. A parathyroid hormone-like protein from cultured human keratinocytes. Science. 1986 Jan 24;231(4736):388–390. doi: 10.1126/science.2417317. [DOI] [PubMed] [Google Scholar]
- Mok L. L., Ajiwe E., Martin T. J., Thompson J. C., Cooper C. W. Parathyroid hormone-related protein relaxes rat gastric smooth muscle and shows cross-desensitization with parathyroid hormone. J Bone Miner Res. 1989 Jun;4(3):433–439. doi: 10.1002/jbmr.5650040319. [DOI] [PubMed] [Google Scholar]
- Mok L. L., Nickols G. A., Thompson J. C., Cooper C. W. Parathyroid hormone as a smooth muscle relaxant. Endocr Rev. 1989 Nov;10(4):420–436. doi: 10.1210/edrv-10-4-420. [DOI] [PubMed] [Google Scholar]
- Moseley J. M., Kubota M., Diefenbach-Jagger H., Wettenhall R. E., Kemp B. E., Suva L. J., Rodda C. P., Ebeling P. R., Hudson P. J., Zajac J. D. Parathyroid hormone-related protein purified from a human lung cancer cell line. Proc Natl Acad Sci U S A. 1987 Jul;84(14):5048–5052. doi: 10.1073/pnas.84.14.5048. [DOI] [PMC free article] [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]
- Parnham M. J., Sneddon J. M., Williams K. I. Evidence for a possible foetal control of prostaglandin release from the pregnant rat uterus in vitro. J Endocrinol. 1975 Jun;65(3):429–437. doi: 10.1677/joe.0.0650429. [DOI] [PubMed] [Google Scholar]
- Rodan S. B., Insogna K. L., Vignery A. M., Stewart A. F., Broadus A. E., D'Souza S. M., Bertolini D. R., Mundy G. R., Rodan G. A. Factors associated with humoral hypercalcemia of malignancy stimulate adenylate cyclase in osteoblastic cells. J Clin Invest. 1983 Oct;72(4):1511–1515. doi: 10.1172/JCI111108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rodan S. B., Wesolowski G., Ianacone J., Thiede M. A., Rodan G. A. Production of parathyroid hormone-like peptide in a human osteosarcoma cell line: stimulation by phorbol esters and epidermal growth factor. J Endocrinol. 1989 Jul;122(1):219–227. doi: 10.1677/joe.0.1220219. [DOI] [PubMed] [Google Scholar]
- Rodda C. P., Kubota M., Heath J. A., Ebeling P. R., Moseley J. M., Care A. D., Caple I. W., Martin T. J. Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcaemia of malignancy. J Endocrinol. 1988 May;117(2):261–271. doi: 10.1677/joe.0.1170261. [DOI] [PubMed] [Google Scholar]
- Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
- Stewart A. F., Elliot J., Burtis W. J., Wu T., Insogna K. L. Synthetic parathyroid hormone-like protein-(1-74): biochemical and physiological characterization. Endocrinology. 1989 Feb;124(2):642–648. doi: 10.1210/endo-124-2-642. [DOI] [PubMed] [Google Scholar]
- Stewart A. F., Insogna K. L., Goltzman D., Broadus A. E. Identification of adenylate cyclase-stimulating activity and cytochemical glucose-6-phosphate dehydrogenase-stimulating activity in extracts of tumors from patients with humoral hypercalcemia of malignancy. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1454–1458. doi: 10.1073/pnas.80.5.1454. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stewart A. F., Wu T., Goumas D., Burtis W. J., Broadus A. E. N-terminal amino acid sequence of two novel tumor-derived adenylate cyclase-stimulating proteins: identification of parathyroid hormone-like and parathyroid hormone-unlike domains. Biochem Biophys Res Commun. 1987 Jul 31;146(2):672–678. doi: 10.1016/0006-291x(87)90581-x. [DOI] [PubMed] [Google Scholar]
- Strewler G. J., Stern P. H., Jacobs J. W., Eveloff J., Klein R. F., Leung S. C., Rosenblatt M., Nissenson R. A. Parathyroid hormonelike protein from human renal carcinoma cells. Structural and functional homology with parathyroid hormone. J Clin Invest. 1987 Dec;80(6):1803–1807. doi: 10.1172/JCI113275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suva L. J., Mather K. A., Gillespie M. T., Webb G. C., Ng K. W., Winslow G. A., Wood W. I., Martin T. J., Hudson P. J. Structure of the 5' flanking region of the gene encoding human parathyroid-hormone-related protein (PTHrP). Gene. 1989 Apr 15;77(1):95–105. doi: 10.1016/0378-1119(89)90363-6. [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., Rodan G. A. Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue. Science. 1988 Oct 14;242(4876):278–280. doi: 10.1126/science.3175653. [DOI] [PubMed] [Google Scholar]
- Thiede M. A., Strewler G. J., Nissenson R. A., Rosenblatt M., Rodan G. A. Human renal carcinoma expresses two messages encoding a parathyroid hormone-like peptide: evidence for the alternative splicing of a single-copy gene. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4605–4609. doi: 10.1073/pnas.85.13.4605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thiede M. A. The mRNA encoding a parathyroid hormone-like peptide is produced in mammary tissue in response to elevations in serum prolactin. Mol Endocrinol. 1989 Sep;3(9):1443–1447. doi: 10.1210/mend-3-9-1443. [DOI] [PubMed] [Google Scholar]
- Vasicek T. J., McDevitt B. E., Freeman M. W., Fennick B. J., Hendy G. N., Potts J. T., Jr, Rich A., Kronenberg H. M. Nucleotide sequence of the human parathyroid hormone gene. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2127–2131. doi: 10.1073/pnas.80.8.2127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walters C. A., Daly D. C., Chapitis J., Kuslis S. T., Prior J. C., Kusmik W. F., Riddick D. H. Human myometrium: a new potential source of prolactin. Am J Obstet Gynecol. 1983 Nov 15;147(6):639–644. doi: 10.1016/0002-9378(83)90441-6. [DOI] [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]
- Wright B. S., Tyler G. A., O'Brien R., Caporale L. H., Rosenblatt M. Immunoprecipitation of the parathyroid hormone receptor. Proc Natl Acad Sci U S A. 1987 Jan;84(1):26–30. doi: 10.1073/pnas.84.1.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yasuda T., Banville D., Hendy G. N., Goltzman D. Characterization of the human parathyroid hormone-like peptide gene. Functional and evolutionary aspects. J Biol Chem. 1989 May 5;264(13):7720–7725. [PubMed] [Google Scholar]