Comparison of steroid hormones in three different preeclamptic models

Shin,Ye Young; An,Sung-Min; Jeong,Jea Sic; Yang,Seung Yun; Lee,Geun-Shik; Hong,Eui-Ju; Jeung,Eui-Bae; Kim,Seung Chul; An,Beum-Soo

doi:10.3892/mmr.2021.11891

Comparison of steroid hormones in three different preeclamptic models

Authors:
- Ye Young Shin
- Sung-Min An
- Jea Sic Jeong
- Seung Yun Yang
- Geun-Shik Lee
- Eui-Ju Hong
- Eui-Bae Jeung
- Seung Chul Kim
- Beum-Soo An
View Affiliations

Affiliations: Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Gyeongsangnam 50463, Republic of Korea, College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea, Department of Obstetrics and Gynecology, Biomedical Research Institute, Pusan National University School of Medicine, Busan 49241, Republic of Korea
Published online on: February 2, 2021 https://doi.org/10.3892/mmr.2021.11891
Article Number: 252
Copyright: © Shin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Preeclampsia (PE) is a complication of pregnancy and is characterized by hypertension and proteinuria, threatening both the mother and the fetus. However, the etiology of PE has not yet been fully understood. Since the imbalance of steroid hormones is associated with the pathogenesis of PE, investigating steroidogenic mechanisms under various PE conditions is essential to understand the entire spectrum of pregnancy disorders. Therefore, the current study established three PE in vitro and in vivo models, and compared the levels of steroid hormones and steroidogenic enzymes within them. In cellular PE models induced by hypoxia, N‑nitro‑L‑arginine methyl ester hydrocholride (L‑NAME) and catechol‑o‑methyltransferase inhibitor, the levels of steroid hormones, including pregnenolone (P5), progesterone (P4), dehydroepiandrosterone (DHEA) and testosterone tended to decrease during steroidogenesis. Injection of L‑NAME in pregnant rats led to a reduction in the levels of estradiol and P4 through regulation of cholesterol side‑chain cleavage enzyme (CYP11A1) and 3β‑hydroxysteroid dehydrogenase/δ5 4‑isomerase type 1 (HSD3B1), whereas rats treated with COMT‑I exhibited elevated levels of P5 and DHEA by regulation of the CYP11A1 and aromatase cytochrome P450 (CYP19A1) in the placenta and plasma. The reduced uterine perfusion pressure operation decreased CYP11A1 and increased CYP19A1 expression in placental tissues, whereas steroid hormone levels were not altered. In conclusion, the results of the present study suggest that the induction of PE conditions dysregulates the steroid hormones via regulation of steroidogenic enzymes, depending on specific PE symptoms. These findings can contribute to the development of novel diagnostic and therapeutic modalities for PE, by monitoring and supplying appropriate levels of steroid hormones.

View Figures

View References

1	Li J, LaMarca B and Reckelhoff JF: A model of preeclampsia in rats: The reduced uterine perfusion pressure (RUPP) model. Am J Physiol Heart Circ Physiol. 303:H1–H8. 2012. View Article : Google Scholar : PubMed/NCBI
2	Dragun D and Haase-Fielitz A: Low catechol-O-methyltransferase and 2-methoxyestradiol in preeclampsia: More than a unifying hypothesis. Nephrol Dial Transplant. 24:31–32. 2009. View Article : Google Scholar : PubMed/NCBI
3	Fushima T, Sekimoto A, Minato T, Ito T, Oe Y, Kisu K, Sato E, Funamoto K, Hayase T, Kimura Y, et al: Reduced uterine perfusion pressure (RUPP) model of preeclampsia in mice. PLoS One. 11:e01554262016. View Article : Google Scholar : PubMed/NCBI
4	Talebianpoor MS and Mirkhani H: The effect of tempol administration on the aortic contractile responses in rat preeclampsia model. ISRN Pharmacol. 2012:1872082012. View Article : Google Scholar : PubMed/NCBI
5	AbdAlla S, Lother H, el Massiery A and Quitterer U: Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med. 7:1003–1009. 2001. View Article : Google Scholar : PubMed/NCBI
6	McKinney D, Boyd H, Langager A, Oswald M, Pfister A and Warshak CR: The impact of fetal growth restriction on latency in the setting of expectant management of preeclampsia. Am J Obstet Gynecol. 214:395.e1–e7. 2016. View Article : Google Scholar
7	Sato K, Iemitsu M, Matsutani K, Kurihara T, Hamaoka T and Fujita S: Resistance training restores muscle sex steroid hormone steroidogenesis in older men. FASEB J. 28:1891–1897. 2014. View Article : Google Scholar : PubMed/NCBI
8	Shin YY, Jeong JS, Park MN, Lee JE, An SM, Cho WS, Kim SC, An BS and Lee KS: Regulation of steroid hormones in the placenta and serum of women with preeclampsia. Mol Med Rep. 17:2681–2688. 2018.PubMed/NCBI
9	Pennington KA, Schlitt JM, Jackson DL, Schulz LC and Schust DJ: Preeclampsia: Multiple approaches for a multifactorial disease. Dis Model Mech. 5:9–18. 2012. View Article : Google Scholar : PubMed/NCBI
10	Hertig A, Liere P, Chabbert-Buffet N, Fort J, Pianos A, Eychenne B, Cambourg A, Schumacher M, Berkane N, Lefevre G, et al: Steroid profiling in preeclamptic women: Evidence for aromatase deficiency. Am J Obstet Gynecol. 203:477.e1–e9. 2010. View Article : Google Scholar
11	Lowe DT: Nitric oxide dysfunction in the pathophysiology of preeclampsia. Nitric Oxide. 4:441–458. 2000. View Article : Google Scholar : PubMed/NCBI
12	Kanasaki K, Palmsten K, Sugimoto H, Ahmad S, Hamano Y, Xie L, Parry S, Augustin HG, Gattone VH, Folkman J, et al: Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia. Nature. 453:1117–1121. 2008. View Article : Google Scholar : PubMed/NCBI
13	Suzuki H, Ohkuchi A, Shirasuna K, Takahashi H, Usui R and Matsubara S: Animal models of preeclampsia: Insight into possible biomarker candidates for predicting preeclampsia. Med J Obstet Gynecol. 2:10312014.
14	Gilbert JS, Babcock SA and Granger JP: Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble fms-like tyrosine kinase-1 expression. Hypertension. 50:1142–1147. 2007. View Article : Google Scholar : PubMed/NCBI
15	Kumasawa K: Animal models in preeclampsia. Preeclampsia. Springer Nature Singapore; pp. 141–155. 2018, View Article : Google Scholar
16	Zeisler H, Jirecek S, Hohlagschwandtner M, Knofler M, Tempfer C and Livingston JC: Concentrations of estrogens in patients with preeclampsia. Wien Klin Wochenschr. 114:458–461. 2002.PubMed/NCBI
17	Sun MN and Zi Y: Effects of preeclampsia-like symptoms at early gestational stage on feto-placental outcomes in a mouse model. Chin Med J (Engl). 123:707–712. 2010.PubMed/NCBI
18	Yang H, Ahn C and Jeung EB: Differential expression of calcium transport genes caused by COMT inhibition in the duodenum, kidney and placenta of pregnant mice. Mol Cell Endocrinol. 401:45–55. 2015. View Article : Google Scholar : PubMed/NCBI
19	Nathan HL, Duhig K, Hezelgrave NL, Chappell LC and Shennan AH: Blood pressure measurement in pregnancy. Obstetr Gynaecol. 17:91–98. 2015.
20	Spradley FT, Tan AY, Joo WS, Daniels G, Kussie P, Karumanchi SA and Granger JP: Placental growth factor administration abolishes placental ischemia-induced hypertension. Hypertension. 67:740–747. 2016. View Article : Google Scholar : PubMed/NCBI
21	Berg A, Fasmer KE, Mauland KK, Ytre-Hauge S, Hoivik EA, Husby JA, Tangen IL, Trovik J, Halle MK, Woie K, et al: Tissue and imaging biomarkers for hypoxia predict poor outcome in endometrial cancer. Oncotarget. 7:69844–69856. 2016. View Article : Google Scholar : PubMed/NCBI
22	Yasujima M, Abe K, Kohzuki M, Tanno M, Kasai Y, Sato M, Omata K, Kudo K, Takeuchi K, Hiwatari M, et al: Effect of atrial natriuretic factor on angiotensin II-induced hypertension in rats. Hypertension. 8:748–753. 1986. View Article : Google Scholar : PubMed/NCBI
23	Costa RA, Hoshida MS, Alves EA, Zugaib M and Francisco RP: Preeclampsia and superimposed preeclampsia: The same disease? The role of angiogenic biomarkers. Hypertens Pregnancy. 35:139–149. 2016. View Article : Google Scholar : PubMed/NCBI
24	Tal R: The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis. Biol Reprod. 87:1342012. View Article : Google Scholar : PubMed/NCBI
25	Gaspar JM and Velloso LA: Hypoxia inducible factor as a central regulator of metabolism-implications for the development of obesity. Front Neurosci. 12:8132018. View Article : Google Scholar : PubMed/NCBI
26	Olson N and Van Der Vliet A: Interactions between nitric oxide and hypoxia-inducible factor signaling pathways in inflammatory disease. Nitric Oxide. 25:125–137. 2011. View Article : Google Scholar : PubMed/NCBI
27	Arendt KW and Garovic VD: Association of deficiencies of catechol-O-methyltransferase and 2-methoxyestradiol with preeclampsia. Expert Rev Obstetr Gynecol. 4:379–381. 2009. View Article : Google Scholar
28	Zheng L, Huang J, Su Y, Wang F, Kong H and Xin H: Vitexin ameliorates preeclampsia phenotypes by inhibiting TFPI-2 and HIF-1α/VEGF in al-NAME induced rat model. Drug Dev Res. 80:1120–1127. 2019. View Article : Google Scholar : PubMed/NCBI
29	Kulkarni K: HIF-1 alpha: A master regulator of trophoblast differentiation and placental development. Browse Theses Dissertations. 943:2009, https://corescholar.libraries.wright.edu/etd_all/943September 3–2020
30	Saravani M, Rokni M, Mehrbani M, Amirkhosravi A, Faramarz S, Fatemi I, Esmaeili Tarzi M and Nematollahi MH: The evaluation of VEGF and HIF-1α gene polymorphisms and multiple sclerosis susceptibility. J Gene Med. 21:e31322019. View Article : Google Scholar : PubMed/NCBI
31	Mizukami Y, Li J, Zhang X, Zimmer MA, Iliopoulos O and Chung DC: Hypoxia-inducible factor-1-independent regulation of vascular endothelial growth factor by hypoxia in colon cancer. Cancer Res. 64:1765–1772. 2004. View Article : Google Scholar : PubMed/NCBI
32	Pant V, Yadav BK and Sharma J: A cross sectional study to assess the sFlt-1:PlGF ratio in pregnant women with and without preeclampsia. BMC Pregnancy Childbirth. 19:2662019. View Article : Google Scholar : PubMed/NCBI
33	Schrier RW: Renal and Electrolyte Disorders. Lippincott Williams & Wilkins; Philadelphia, PA: 2010
34	Banek CT, Bauer AJ, Gingery A and Gilbert JS: Timing of ischemic insult alters fetal growth trajectory, maternal angiogenic balance, and markers of renal oxidative stress in the pregnant rat. Am J Physiol Regul Integr Comp Physiol. 303:R658–R664. 2012. View Article : Google Scholar : PubMed/NCBI
35	Salari S, Eskandari M, Nanbakhsh F and Dabiri A: Evaluation of androgen and progesterone levels in women with preeclampsia. Iranian J Med Sci. 30:186–189. 2015.
36	Kaludjerovic J and Ward WE: The interplay between estrogen and fetal adrenal cortex. J Nutr Metab. 2012:8379012012. View Article : Google Scholar : PubMed/NCBI
37	Furukawa S, Tsuji N and Sugiyama A: Morphology and physiology of rat placenta for toxicological evaluation. J Toxicol Pathol. 32:1–17. 2019. View Article : Google Scholar : PubMed/NCBI
38	Buster JE: Gestational changes in steroid hormone biosynthesis, secretion, metabolism, and action. Clin Perinatol. 10:527–552. 1983. View Article : Google Scholar : PubMed/NCBI
39	Hu XQ, Song R and Zhang L: Effect of oxidative stress on the estrogen-NOS-NO-KCa channel pathway in uteroplacental dysfunction: Its implication in pregnancy complications. Oxid Med Cell Longev. 2019:91942692019. View Article : Google Scholar : PubMed/NCBI
40	Vonnahme KA, Wilson ME and Ford SP: Relationship between placental vascular endothelial growth factor expression and placental/endometrial vascularity in the pig. Biol Reprod. 64:1821–1825. 2001. View Article : Google Scholar : PubMed/NCBI
41	Maliqueo M, Echiburú B and Crisosto N: Sex steroids modulate uterine-placental vasculature: Implications for obstetrics and neonatal outcomes. Front Physiol. 7:1522016. View Article : Google Scholar : PubMed/NCBI
42	Kanasaki K and Kanasaki M: Angiogenic defects in preeclampsia: What is known, and how are such defects relevant to preeclampsia pathogenesis? Hypertension Res Pregnancy. 1:57–65. 2013. View Article : Google Scholar
43	Liu D, Iruthayanathan M, Hosman LL, Wang Y, Yang L, Wang Y and Dillon JS: Dehydroepiandrosterone stimulates endothelial proliferation and angiogenesis through extracellular signal-regulated kinase 1/2-mediated mechanisms. Endocrinology. 149:889–898. 2007. View Article : Google Scholar : PubMed/NCBI
44	Barnabas O, Wang H and Gao XM: Role of estrogen in angiogenesis in cardiovascular diseases. J Geriatr Cardiol. 10:377–382. 2013.PubMed/NCBI