Abstract
Objective
A recent study on the distribution of angiotensin II (ANG II), ANG II (AT) receptors, and human placental lactogen in human placental tissues from term pregnancies showed positive correlations among these indices, suggesting an important role for ANG II in placental endocrinology. However, nothing is known about the ontogenesis of this functional role for ANG II during pregnancy. Therefore, the aim of this study was to investigate the placental AT receptor expression at various trimesters of pregnancy. We also studied the ontogenesis of phospholipase C—linked Gαq/11 protein, which is known to transduce ANG II type-1 (AT1) receptor signal.
Methods
Western blot analysis of placental membrane proteins was performed using a chemiluminescence kit and specific antibodies against AT1 receptor and Gαq/11 protein. Northern blot analyses of AT1 receptor and Gαq/11 mRNA expression were accomplished using random primed [32P]dCTP-labeled specific probes.
Results
The autoradiography of AT1 receptor mRNAs (2.4 kb) and proteins (83 kDa) showed a progressive 4.8-fold and 2.6-fold increase, respectively, during pregnancy, with maximal levels at term. We also observed progressive 1.8-fold and 4.5-fold increases of Gαq/11 protein (43 kDa) and mRNAs (4.5, 6.0, and 7.1 kb), respectively, during pregnancy, with maximal levels observed at term.
Conclusion
Our results demonstrate that both the human placental AT1 receptor content and the Gαq/11 protein level increase during pregnancy, and suggest that the AT1 receptor pathway may play a role in human placental physiology.
Similar content being viewed by others
References
Soubrier F, Panthier JJ, Corvol P, Rougeon F. Molecular cloning and nucleotide sequence of human renin cDNA fragment. Nucleic Acids Res 1983;11:7181–90.
Skinner SL, Lumbers ER, Symards EM. Renin concentration in human fetal and maternal tissues. Am J Obstet Gynecol 1968;101:529–33.
Shaw KJ, Do YS, Anderson PW, Shinagavva T, Dubeau L, Hsueh WA. Human decidua is a major source of renin. J Clin Invest 1989;83:2085–92.
Symards EM, Stanley MA, Skinner SL. Production of renin by in vitro cultures ot human chorion and uterine muscle. Nature 1968;217:1152–3.
Acker CM, Galen FX, Devaux C, et al. Human chorionic cells in primary culture: A model for renin biosynthesis. J Clin Endocrinol Metab 1982;55:902–9.
Lenz T, James GD, Laragh JH, Sealy JE. Proremn secretion from human placenta perfused in vitro. Am J Phvsiol 1991;260:E876–82.
Egan DA, Grzegorczyk V, Tncanco KA, Rueter A, Holleman WH, Marcotte PA. Human placental chorionic renin: Production, purification and characterization. Biochim Biophys Acta 1988;965:68–75.
Craven DJ, Wanen AY, Symards EM. Generation of angiotensin I by human chorion-decidua in vitro. Am J Obstet Gynecol 1983;145:744–8.
Taira H, Mizutani S, Narita O, Tomoda Y. Angiotensin 1-converting enzyme in human placenta. Placenta 1985;6:543–9.
Tulenko TN. Regional sensitivity to vasoactive polypeptides in the human umbilicoplacental vasculature. Am J Obstet Gynecol 1979;135:629–36.
Cooke SF, Craven DJ, Symards EM. A study of angiotensin II binding sites in human placenta, chorion and amnion. Am J Obstet Gynecol 1981;140:689–92.
Tence M, Petit A. Characterization of angiotensin II binding sites in the human term placenta. Mol Cell Endocrinol 1989;63:111–9.
Kalenga MK, de Gasparo M, de Hertogh R, Whitebread S, Vankrieken L, Thomas K. Les recepteurs de l’angiotensine II dans le placenta humain sont de type AT1. Reprod Nutr Dev 1991;31:257–67.
Petit A, Guillon G, Tence M, et al. Angiotensin II stimulates both inositol phosphate production and human placental lactogen release from human trophoblastic cells. J Clin Endocrinol Metab 1989:69:280–6.
Petit A, Guillon G, Pantaloni C, et al. An islet-activating protein-sensitive G-protein is involved in dopamine inhibition of both angiotensin-stimulated inositol phosphate production and human placental lactogen release in human trophoblastic cells. J Clin Endocrinol Metab 1990;71:1573–80.
Taylor SN, Chae HZ, Rhee SG, Exton JH. Activation of the b 1 isoenzyme of phospholipase C by a subunit of the Gq class of proteins. Nature 1991;350:516–8.
Zelezna B, Richards EM, Tang W, Lu D, Sumners C, Raizada MK. Characterization of a polyclonal anti-peptide antibody to the angiotensin II type-1 (AT1) receptor. Biochem Biophys Res Commun 1992;183:781–8.
Forcier I, St-Louis J, Brochu M. Angiotensin II receptor subtypes in the adrenals of pregnant rats. Mol Cell Endocrinol 1995;114:177–86.
Phillips MI, Shen L, Richards EM, Raizada MK. Immunohistochemical mapping of angiotensin AT1 receptors in the brain. Regul Pept 1993;44:95–107.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–75.
Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970;227:680–5.
Petit A, Geoffroy P, Bessette P, Prévost J, Bélisle S. Expression of human placental G proteins dunng pregnancy. J Soc Gynecol Invest 1995;2:678–85.
Maniatis T, Fritsch EF, Sambrook J. Transformation of Escherichia coli by plasmid DNA. In: Molecular cloning. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory, 1982:249–51.
Sasaki K, Yamano Y, Bardhan S, et al. Cloning and expression of a complementary DNA encoding a bovine adrenal angiotensin II type-1 receptor. Nature 1991;351:230–3.
Strathmann M, Simon MI. G protein diversity: A distinct class of α subunits is present in vertebrates and invertebrates. Proc Natl Acad Sci USA 1990;87:9113–7.
Promega protocols and applications guide. 2nd ed. Madison, Wisconsin: Promega Corporation, 1991:106.
Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol chloroform extraction. Anal Biochem 1987;162:156–9.
Maniatis T, Fritsch EF, Sambrook J. Extraction, purification and analysis of mRNA from eucaryotic cells. In: Molecular cloning. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory, 1982:203.
Bergsma DJ, Ellis C, Kumar C, et al. Cloning and characterization of human angiotensin 11 type-1 receptor. Biochem Biophys Res Commun 1992;183:989–95.
Komsh K, Kuroda S, Inada Y, Fujisawa Y. Novel subtype of human angiotensin II type-1 receptor: cDNA cloning and expression. Biochem Biophys Res Commun 1994;199:467–74.
Hepler JR, Oilman AG. G proteins. Trends Biochem Sci 1992;17:383–7.
Haugen TB, Paulssen RH, Hansson V. Cell-specific expression of Gq/11 protein and mRNA in rat seminiferous tubules. FEBS Lett 1993;329:96–8.
Blank JL, Ross AH, Exton JH. Purification and characterization of two G proteins that activate the β1 isoenzyme of phosphoinosidde-specific phospholipase C. Identification as members of the Gq class. J Biol Chem 1991:266:18206–16.
Offermanns S, Heiler EH, Spicher K, Schultz G. Gq and G11 are concurrently activated by bombesin and vasopressin in Swiss 3T3 cells. FEBS Lett 1994;349:201–4.
Taylor SJ, Exton JH. Two α subumts of the Gq class of G proteins stimulate phosphoinositide phospholipase C β-1 activity. FEBS Lett 1991;286:214–6.
Wu D, Lee CH, Rhee SG, Simon MI. Activation of phospholipase C by the α subunits of the Gq and G11 proteins in trans-fected Cos-7 cells. J Biol Chem 1992;267:1811–7.
Hepler JR, Kozasa T, Smrcka AV, et al. Purification from Sf9 cells and characterization of recombinant Gqα and G11α. Activation of purified phospholipase C isoenzymes by Gq subunits. J Biol Chem 1993;268:14367–75.
Kalenga MK, DeHertogh R, Whitebread S, Vankrieken L, Thomas K, de Gasparo M. Distribution des concentrations de l’angiotensin II (A II), des récepteurs A II, de l’hPL, de la prolactine et des stéroides dans les annexes foetales humaines. Rev Fr Gynecol Obstet 1991;86:585–91.
MacLeod JN, Lee AK, Liebhaber SA, Cooke NE. Developmental control and alternative splicing of the placentally expressed transcripts from the human growth hormone gene cluster. J Biol Chem 1992;267:14219–26.
Kalenga MK, de Gasparo M, Thomas K, DeHertogh R. Angiotensin II induces human placental lactogen and pregnancy-specific beta 1-glycoprotein secretion via an angiotensin AT, receptor. Eur j Pharmacol 1994;268:231–6.
Kalenga MK, de Gasparo M, Thomas K, DeHertogh R. Angiotensin-II stimulates estradiol secretion from human placental explants through AT1 receptor activation. J Clin Endocrinol Metab 1995;80:1233–7.
Grudzinskas JG, Gordon YB, Jeffrey D, Chard T. Specific sensitive determination of pregnancy-specific β1-glycoprotein by radioimmunoassay. A new pregnancy test. Lancet 1977;i:331–5.
Westergaard JG, Teisner B, Hau J, Grudzinskas JG. Placental protein measurements in complicated pregnancies. I. Intrauterine growth retardation. Br J Obstet Gynaecol 1984;91:1216–23.
Tatannov YS. Trophoblastic-specific beta 1-glycoprotein as a marker for pregnancy and malignancy. Gynecol Obstet Invest 1978;9:65–97.
Sorenson S. Pregnancy-specific β1-glycoprotein (SP1): Purification, characterization, quantification, and clinical applications in malignancies (a review). Tumour Biol 1984;5:275–302.
Yoshizawa I, Takanashi K, Watenabe K, et al. The physiological role of estradiol 17-sulfate during pregnancy. J Steroid Biochem Mol Biol 1992;41:567–70.
Bocco JL, Panzetta G, Flury A, Patrito LC. Expression of pregnancy specific beta 1-glycoprotein gene in human placenta and hydatidiform mole. Biochem Int 1989;18:999–1008.
Streydio C, Vassart G. Expression of human pregnancy specific beta 1 glycoprotein (PSG) genes during placental development. Biochem Biophys Res Commun 1990;166:1265–73.
Author information
Authors and Affiliations
Additional information
Some of these results were presented at the 42nd Annual Meeting of the Society for Gynecologic Investigation, March 15–18, 1995, Chicago, Illinois.
Rights and permissions
About this article
Cite this article
Petit, A., Geoffroy, P. & Bélisle, S. Expression of Angiotensin II Type-I Receptor and Phospholipase C-Linked Gαq/11 Protein in the Human Placenta. Reprod. Sci. 3, 316–321 (1996). https://doi.org/10.1016/S1071-5576(96)00035-4
Published:
Issue Date:
DOI: https://doi.org/10.1016/S1071-5576(96)00035-4