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Chapter 14 - The Role of Hormones in Hypertensive Disorders of Pregnancy

from Section II - Hormones and Gestational Disorders

Published online by Cambridge University Press:  09 November 2022

By
Leslie Myatt  and
James M. Roberts
Edited by
Felice Petraglia ,
Mariarosaria Di Tommaso  and
Federico Mecacci
Felice Petraglia
Affiliation:
Università degli Studi, Florence
Mariarosaria Di Tommaso
Affiliation:
Università degli Studi, Florence
Federico Mecacci
Affiliation:
Università degli Studi, Florence
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Summary

Hypertensive disorders of pregnancy including preeclampsia affect 5–7 percent of pregnancies and cause significant morbidity and mortality. The effects extend beyond pregnancy, being associated with increased risk of later life cardiovascular disease in the mother and programming of cardio-metabolic disease in the offspring. The profound changes in maternal metabolic and cardiovascular systems during pregnancy are mediated by altered production of hormones from the ovary, heart, brain, pineal gland, adrenal gland, and thyroid together with production and release of steroid and peptide hormones from the placenta. Production of these hormones is altered in hypertensive pregnancies, but distinction of cause from effect has been difficult to determine. Recent attention has focused on altered placental production of pro- and anti-angiogenic factors that may damage both the vasculature and renal systems. Although there is still debate as to the initiating factors for placenta dysfunction, syncytiotrophoblast stress has been postulated but without clear demonstration of cause versus effect.

Type
Chapter
Information
Hormones and Pregnancy
Basic Science and Clinical Implications
 , pp. 151 - 163
Publisher: Cambridge University Press
Print publication year: 2022

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References

Staff, AC, Redman, CW, Williams, D, et al. Pregnancy and long-term maternal cardiovascular health: Progress through harmonization of research cohorts and biobanks. Hypertension. 2016, 67:251–260.CrossRefGoogle ScholarPubMed
Stojanovska, V, Scherjon, SA, and Plosch, T. Preeclampsia as modulator of offspring health. Biol Reprod. 2016, 94:53.Google Scholar
Piering, WF, Garancis, JG, Becker, CG, et al. Preeclampsia related to a functioning extrauterine placenta: Report of a case and 25-year follow-up. Am J Kidney Dis. 1993, 21:310–313.Google Scholar
Brittain, PC, and Bayliss, P. Partial hydatidiform molar pregnancy presenting with severe preeclampsia prior to twenty weeks gestation: A case report and review of the literature. Mil Med. 1995, 160:42–44.CrossRefGoogle ScholarPubMed
Chesley, LC. Hypertensive disorders of pregnancy. In. New York: Appleton-Century-Crofts, 1978.Google Scholar
Roberts, JM, Taylor, RN, Musci, TJ, et al. Preeclampsia: An endothelial cell disorder. Am J Obstet Gynecol. 1989, 161:1200–1204.CrossRefGoogle ScholarPubMed
Redman, CW, Sacks, GP, and Sargent, IL. Preeclampsia: An excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol. 1999, 180:499–506.Google Scholar
Redman, CWG, Staff, AC, and Roberts, JM. Syncytiotrophoblast stress in preeclampsia: The convergence point for multiple pathways. Am J Obstet Gynecol. 2020, 08:08.Google Scholar
Salas, SP, Marshall, G, Gutierrez, BL, et al. Time course of maternal plasma volume and hormonal changes in women with preeclampsia or fetal growth restriction. Hypertension. 2006, 47:203–208.CrossRefGoogle ScholarPubMed
Duvekot, JJ, Cheriex, EC, Pieters, FA, et al. Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a primary fall in systemic vascular tone. Am J Obstet Gynecol. 1993, 169:1382–1392.Google Scholar
Oelkers, WK. Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Steroids. 1996, 61:166–171.CrossRefGoogle ScholarPubMed
Van Buren, GA, Yang, DS, and Clark, KE. Estrogen-induced uterine vasodilatation is antagonized by L-nitroarginine methyl ester, an inhibitor of nitric oxide synthesis. Am J Obstet Gynecol. 1992, 167:828–833.CrossRefGoogle ScholarPubMed
Johnson, ML, Grazul-Bilska, AT, Redmer, DA, et al. Effects of estradiol-17beta on expression of mRNA for seven angiogenic factors and their receptors in the endometrium of ovariectomized (OVX) ewes. Endocrine. 2006, 30:333–342.CrossRefGoogle ScholarPubMed
Miller, VM, and Vanhoutte, PM. Progesterone and modulation of endothelium-dependent responses in canine coronary arteries. Am J Physiol. 1991, 261:R1022–1027.Google Scholar
Berkane, N, Liere, P, Oudinet, JP, et al. From pregnancy to preeclampsia: A key role for estrogens. Endocr Rev. 2017, 38:123–144.CrossRefGoogle ScholarPubMed
Magness, RR, Sullivan, JA, Li, Y, et al. Endothelial vasodilator production by uterine and systemic arteries. VI. Ovarian and pregnancy effects on eNOS and NO(x). Am J Physiol Heart Circ Physiol. 2001, 280:H1692–1698.Google Scholar
Nelson, SH, Steinsland, OS, Wang, Y, et al. Increased nitric oxide synthase activity and expression in the human uterine artery during pregnancy. Circ Res. 2000, 87:406–411.CrossRefGoogle ScholarPubMed
Salom, JB, Burguete, MC, Perez-Asensio, FJ, et al. Relaxant effects of 17-beta-estradiol in cerebral arteries through Ca(2+) entry inhibition. J Cereb Blood Flow Metab. 2001, 21:422–429.CrossRefGoogle ScholarPubMed
Bausero, P, Ben-Mahdi, M, Mazucatelli, J, et al. Vascular endothelial growth factor is modulated in vascular muscle cells by estradiol, tamoxifen, and hypoxia. Am J Physiol Heart Circ Physiol. 2000, 279:H2033–2042.Google Scholar
Mueller, MD, Vigne, JL, Minchenko, A, et al. Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta. Proc Natl Acad Sci U S A. 2000, 97:10972–10977.CrossRefGoogle ScholarPubMed
Shimodaira, M, Nakayama, T, Sato, I, et al. Estrogen synthesis genes CYP19A1, HSD3B1, and HSD3B2 in hypertensive disorders of pregnancy. Endocrine. 2012, 42:700–707.Google Scholar
Sharifzadeh, F, Kashanian, M, and Fatemi, F. A comparison of serum androgens in pre-eclamptic and normotensive pregnant women during the third trimester of pregnancy. Gynecol Endocrinol. 2012, 28:834–836.Google Scholar
Kumar, P, Luo, Y, Tudela, C, et al. The c-Myc-regulated microRNA-17~92 (miR-17~92) and miR-106a~363 clusters target hCYP19A1 and hGCM1 to inhibit human trophoblast differentiation. Mol Cell Biol. 2013, 33:1782–1796.Google Scholar
Stamilio, DM, Sehdev, HM, Morgan, MA, et al. Can antenatal clinical and biochemical markers predict the development of severe preeclampsia? Am J Obstet Gynecol. 2000;182:589–594.Google Scholar
Steier, JA, Ulstein, M, and Myking, OL. Human chorionic gonadotropin and testosterone in normal and preeclamptic pregnancies in relation to fetal sex. Obstet Gynecol. 2002, 100:552–556.Google Scholar
Kumar, S, Gordon, GH, Abbott, DH, et al. Androgens in maternal vascular and placental function: implications for preeclampsia pathogenesis. Reproduction. 2018, 156:R155–R167.Google Scholar
Shao, X, Liu, Y, Liu, M, et al. Testosterone represses estrogen signaling by upregulating miR-22: A mechanism for imbalanced steroid hormone production in preeclampsia. Hypertension. 2017, 69:721–730.CrossRefGoogle ScholarPubMed
Laivuori, H, Kaaja, R, Rutanen, EM, et al. Evidence of high circulating testosterone in women with prior preeclampsia. J Clin Endocrinol Metab. 1998, 83:344–347.Google Scholar
Pion, R, Jaffe, R, Eriksson, G, et al. Studies on the metabolism of C-21 steroids in the human foeto-placental unit. I. Formation of a beta-unsaturated 3-ketones in midterm placentas perfused in situ with pregnenolone and 17-alpha-hydroxypregnenolone. Acta Endocrinol (Copenh). 1965, 48:234–248.Google Scholar
Rosing, U, and Carlstrom, K. Serum levels of unconjugated and total oestrogens and dehydroepiandrosterone, progesterone and urinary oestriol excretion in pre-eclampsia. Gynecol Obstet Invest. 1984, 18:199–205.CrossRefGoogle ScholarPubMed
Tamimi, R, Lagiou, P, Vatten, LJ, et al. Pregnancy hormones, pre-eclampsia, and implications for breast cancer risk in the offspring. Cancer Epidemiol Biomarkers Prev. 2003, 12:647–650.Google ScholarPubMed
Schoof, E, Girstl, M, Frobenius, W, et al. Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation. Eur J Endocrinol. 2001, 145:187–192.Google Scholar
Aufdenblatten, M, Baumann, M, Raio, L, et al. Prematurity is related to high placental cortisol in preeclampsia. Pediatr Res. 2009, 65:198–202.Google Scholar
Cole, LA. Biological functions of hCG and hCG-related molecules. Reprod Biol Endocrinol. 2010, 8:102.Google Scholar
Zygmunt, M, Herr, F, Keller-Schoenwetter, S, et al. Characterization of human chorionic gonadotropin as a novel angiogenic factor. J Clin Endocrinol Metab. 2002, 87:5290–5296.Google Scholar
Barjaktarovic, M, Korevaar, TIM, Jaddoe, VWV, et al. Human chorionic gonadotropin and risk of pre-eclampsia: prospective population-based cohort study. Ultrasound Obstet Gynecol. 2019, 54:477–483.Google Scholar
Levine, RJ, Lam, C, Qian, C, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006, 355:992–1005.CrossRefGoogle ScholarPubMed
Levine, RJ, Maynard, SE, Qian, C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004, 350:672–683.Google Scholar
Campbell, EA, Linton, EA, Wolfe, CD, et al. Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition. J Clin Endocrinol Metab. 1987, 64:1054–1059.Google Scholar
Chau, K, Hennessy, A, and Makris, A. Placental growth factor and pre-eclampsia. J Hum Hypertens. 2017, 31:782–786.CrossRefGoogle ScholarPubMed
Thadhani, R, Hagmann, H, Schaarschmidt, W, et al. Removal of soluble fms-like tyrosine kinase-1 by dextran sulfate apheresis in preeclampsia. J Am Soc Nephrol. 2016, 27:903–913.Google Scholar
Salustiano, EM, De Pinho, JC, Provost, K, et al. Maternal serum hormonal factors in the pathogenesis of preeclampsia. Obstet Gynecol Surv. 2013, 68:141–150.Google Scholar
Conrad, KP. Emerging role of relaxin in the maternal adaptations to normal pregnancy: Implications for preeclampsia. Semin Nephrol. 2011, 31:15–32.Google Scholar
Conrad, KP, and Baker, VL. Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies. Am J Physiol Regul Integr Comp Physiol. 2013, 304:R69–72.Google Scholar
Post Uiterweer, ED, Koster, MPH, Jeyabalan, A, et al. Circulating pregnancy hormone relaxin as a first trimester biomarker for preeclampsia. Pregnancy Hypertens. 2020, 22:47–53.Google Scholar
Korevaar, TIM, Medici, M, Visser, TJ, et al. Thyroid disease in pregnancy: New insights in diagnosis and clinical management. Nat Rev Endocrinol. 2017, 13:610–622.CrossRefGoogle ScholarPubMed
Berta, E, Lengyel, I, Halmi, S, et al. Hypertension in thyroid disorders. Front Endocrinol. 2019, 10:482.CrossRefGoogle ScholarPubMed
Wilson, KL, Casey, BM, McIntire, DD, et al. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol. 2012, 119:315–320.Google Scholar
Gant, NF, Daley, GL, Chand, S, et al. A study of angiotensin II pressor response throughout primigravid pregnancy. J Clin Invest. 1973, 52:2682–2689.Google Scholar
Yang, J, Shang, JY, Zhang, SL, et al. The role of the renin-angiotensin-aldosterone system in preeclampsia: genetic polymorphisms and microRNA. J Mol Endocrinol. 2013, 50:R53–R66.Google Scholar
Xia, Y, Kellems, RE, Xia, Y, et al. Angiotensin receptor agonistic autoantibodies and hypertension: Preeclampsia and beyond. Circ Res. 2013, 113:78–87.Google Scholar
Chang, Y, and Wei, W. Angiotensin II in inflammation, immunity and rheumatoid arthritis. Clin Exper Immunol. 2015, 179:137–145.Google Scholar
Chen, T-H, Wang, J-F, Chan, P, et al. Angiotensin II stimulates hypoxia-inducible factor 1alpha accumulation in glomerular mesangial cells. Ann NY Acad Sci. 2005, 1042:286–293.CrossRefGoogle ScholarPubMed
Zhou, CC, Ahmad, S, Mi, T, et al. Angiotensin II induces soluble fms-Like tyrosine kinase-1 release via calcineurin signaling pathway in pregnancy. Circ Res. 2007, 100:88–95.Google Scholar
Carey, RM. Update on angiotensin AT2 receptors. Curr Opin Nephrol Hypertens. 2017, 26:91–96.Google Scholar
Wu, C, Lu, H, Cassis, LA, et al. Molecular and pathophysiological features of angiotensinogen: A mini review. N Am J Med Sci. 2011, 4:183–190.Google Scholar
Ichihara, A, and Yatabe, MS. The (pro)renin receptor in health and disease. Nat Rev Nephrol. 2019, 15:693–712.Google Scholar
Gathiram, P, and Moodley, J. The role of the renin-angiotensin-aldosterone system in preeclampsia: A review. Curr Hypertens Rep. 2020, 22:89.Google Scholar
Hladunewich, MA, Kingdom, J, Odutayo, A, et al. Postpartum assessment of the renin angiotensin system in women with previous severe, early-onset preeclampsia. J Clin Endocrinol Metab. 2011, 96:3517–3524.CrossRefGoogle ScholarPubMed
Saxena, AR, Karumanchi, SA, Brown, NJ, et al. Increased sensitivity to angiotensin II is present postpartum in women with a history of hypertensive pregnancy. Hypertension. 2010, 55:1239–1245.CrossRefGoogle ScholarPubMed
Vinnakota, S, and Chen, HH. The importance of natriuretic peptides in cardiometabolic diseases. J Endocr Soc. 2020, 4:bvaa052.Google Scholar
Thomsen, JK, Fogh-Andersen, N, and Jaszczak, P. Atrial natriuretic peptide, blood volume, aldosterone, and sodium excretion during twin pregnancy. Acta Obstet. Gynecologica Scand. 1994, 73:14–20.Google Scholar
Yoshimura, T, Yoshimura, M, Yasue, H, et al. Plasma concentration of atrial natriuretic peptide and brain natriuretic peptide during normal human pregnancy and the postpartum period. J Endocrinol. 1994, 140:393–397.Google Scholar
Adam, Malatyalio, Gbreve, lu, Alvur, Kokcu, et al. Plasma atrial natriuretic peptide levels in preeclampsia and eclampsia. J Matern Fetal Investig. 1998, 8:85–88.Google Scholar
Franz, MB, Andreas, M, Schiessl, B, et al. NT-proBNP is increased in healthy pregnancies compared to non-pregnant controls. Acta Obstet Gynecol Scand. 2009, 88:234–237.Google Scholar
Li, H, Zhang, Y, and Wu, Q. Role of corin in the regulation of blood pressure. Curr Opin Nephrol Hyperten. 2017, 26:67–73.Google Scholar
Yan, W, Sheng, N, Seto, M, et al. Corin, a mosaic transmembrane serine protease encoded by a novel cDNA from human heart. J Biol Chem. 1999, 274:14926–14935.Google Scholar
Cui, Y, Wang, W, Dong, N, et al. Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy. Nature. 2012, 484:246–250.CrossRefGoogle ScholarPubMed
Stepanian, A, Alcais, A, de Prost, D, et al. Highly significant association between two common single nucleotide polymorphisms in CORIN gene and preeclampsia in caucasian women. PLoS ONE. 2014, 9.Google Scholar
Degrelle, SA, Chissey, A, Stepanian, A, et al. Placental overexpression of soluble CORIN in preeclampsia. Am J Pathol. 2020, 190:970–976.Google Scholar
Jadli, A, Ghosh, K, and Shetty, S. Is peripheral blood corin level clinically relevant for prediction of pre-eclampsia? Ultrasound Obstet Gynecol. 2015, 46:380.Google Scholar
Degrelle, SA, Chissey, A, Stepanian, A, et al. Placental overexpression of soluble CORIN in preeclampsia. Am J Pathol. 190:970–976.Google Scholar
Baird, RC, Li, S, Wang, H, et al. Pregnancy-associated cardiac hypertrophy in corin-deficient mice: Observations in a transgenic model of preeclampsia. Can J Cardiol. 2019, 35:68–76.Google Scholar
Rotondo, F, Butz, H, Syro, LV, et al. Arginine vasopressin (AVP): A review of its historical perspectives, current research and multifunctional role in the hypothalamo-hypophysial system. Pituitary. 2016, 19:345–355.CrossRefGoogle ScholarPubMed
Christ-Crain, M. Vasopressin and Copeptin in health and disease. Rev Endocr Metab Disord. 2019, 20:283–294.CrossRefGoogle ScholarPubMed
Santillan, MK, Santillan, DA, Scroggins, SM, et al. Vasopressin in preeclampsia: A novel very early human pregnancy biomarker and clinically relevant mouse model. Hypertension. 2014, 64:852–859.Google Scholar
Scroggins, SM, Santillan, DA, Lund, JM, et al. Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia. Clin Sci. 2018, 132:419–436.Google Scholar
Bellos, I, Pergialiotis, V, Papapanagiotou, A, et al. Association between serum copeptin levels and preeclampsia risk: A meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2020, 250:66–73.CrossRefGoogle ScholarPubMed
Asvold, BO, Vatten, LJ, Romundstad, PR, et al. Angiogenic factors in maternal circulation and the risk of severe fetal growth restriction. Am J Epidemiol. 2011, 173:630–639.Google Scholar
Palei, AC, Warrington, JP, and Granger, JP. The effect of placental ischemia-induced hypertension on circulating copeptin levels of pregnant rats. FASEB J. 2016, 30.Google Scholar
Matsuura, T, Shinohara, K, Iyonaga, T, et al. Prior exposure to placental ischemia causes increased salt sensitivity of blood pressure via vasopressin production and secretion in postpartum rats. J Hyperten. 2019, 37:1657–1667.Google Scholar
Yousif, D, Bellos, I, Penzlin, AI, et al. Autonomic dysfunction in preeclampsia: A systematic review. Front Neurol. 2019, 10:816.Google Scholar
Palacios, C, Kostiuk, LK, and Peña-Rosas, JP. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2019, 7:Cd008873.Google Scholar
Langston-Cox, A, Marshall, SA, Lu, D, et al. Melatonin for the management of preeclampsia: A review. Antioxidants. 2021, 10:376.CrossRefGoogle ScholarPubMed
Kapustin, RV, Drobintseva, AO, Alekseenkova, EN, et al. Placental protein expression of kisspeptin-1 (KISS1) and the kisspeptin-1 receptor (KISS1R) in pregnancy complicated by diabetes mellitus or preeclampsia. Arch Gynecol Obstet. 2020, 301:437–445.Google Scholar
Roberts, JM, Rich-Edwards, JW, McElrath, TF, et al. Subtypes of preeclampsia: Recognition and determining clinical usefulness. Hypertension. 2021, 77:1430–1441.Google Scholar

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