Prenatal testosterone exposure induces hypertension in adult females via androgen receptor-dependent protein kinase Cδ-mediated mechanism

Hypertension

Volumn 65, Issue 3, 2015, Pages 683-690

  Blesson, Chellakkan S ^a   Chinnathambi, Vijayakumar ^b   Hankins, Gary D ^b   Yallampalli, Chandra ^a   Sathishkumar, Kunju ^b  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b University of Texas Medical Branch School of Medicine   (United States)

Author keywords

blood pressure; polycystic ovary syndrome; protein kinase C; testosterone; vasoconstriction

Indexed keywords

BINDING PROTEIN; FLUTAMIDE; ISOENZYME; LUCIFERASE; MESSENGER RNA; PHORBOL DIBUTYRATE; PROTEIN KINASE C DELTA; ROTTLERIN; TESTOSTERONE; TESTOSTERONE PROPIONATE; ANDROGEN RECEPTOR;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTERIAL PRESSURE; ARTERY CONSTRICTION; ARTICLE; BINDING SITE; BLOOD PRESSURE; CELL CULTURE; CHROMATIN IMMUNOPRECIPITATION; COMPARATIVE STUDY; CONTROLLED STUDY; ENHANCER REGION; ENZYME ACTIVITY; FEMALE; GENE EXPRESSION; GENETIC ANALYSIS; HORMONAL REGULATION; HYPERANDROGENISM; HYPERTENSION; IN VITRO STUDY; INTRON; NONHUMAN; PRENATAL DRUG EXPOSURE; PRENATAL EXPOSURE; PRIORITY JOURNAL; PROMOTER REGION; RAT; REAL TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TESTOSTERONE BLOOD LEVEL; TRANSCRIPTION INITIATION SITE; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; UPREGULATION; VASOCONSTRICTION; ANIMAL; DISEASE MODEL; DOSE RESPONSE; DRUG EFFECTS; MESENTERIC ARTERY; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PREGNANCY; SPRAGUE DAWLEY RAT;

ANIMALS; BLOOD PRESSURE; CELLS, CULTURED; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FLUTAMIDE; HYPERANDROGENISM; HYPERTENSION; MESENTERIC ARTERIES; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS; PROTEIN KINASE C-DELTA; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, ANDROGEN; SIGNAL TRANSDUCTION; TESTOSTERONE; VASOCONSTRICTION;

EID: 84924268589     PISSN: 0194911X     EISSN: 15244563     Source Type: Journal    
DOI: 10.1161/HYPERTENSIONAHA.114.04521     Document Type: Article

References (62)

1. Fowden AL, Giussani DA, Forhead AJ. Intrauterine programming of physiological systems: causes and consequences. Physiology (Bethesda). 2006;21:29-37.
2. Fowden AL, Forhead AJ. Endocrine mechanisms of intrauterine programming. Reproduction. 2004;127:515-526.
3. Sathishkumar K, Elkins R, Yallampalli U, Balakrishnan M, Yallampalli C. Fetal programming of adult hypertension in female rat offspring exposed to androgens in utero. Early Hum Dev. 2011;87:407-414.
4. Chinnathambi V, Balakrishnan M, Yallampalli C, Sathishkumar K. Prenatal testosterone exposure leads to hypertension that is gonadal hormone-dependent in adult rat male and female offspring. Biol Reprod. 2012;206:507.e1-507.e10.
5. Chinnathambi V, Yallampalli C, Sathishkumar K. Prenatal testosterone induces sex-specific dysfunction in endothelium-dependent relaxation pathways in adult male and female rats. Biol Reprod. 2013;89:97.
6. Veiga-Lopez A, Moeller J, Patel D, Ye W, Pease A, Kinns J, Padmanabhan V. Developmental programming: impact of prenatal testosterone excess on insulin sensitivity, adiposity, and free fatty acid profile in postpubertal female sheep. Endocrinology. 2013;154:1731-1742.
7. Xu N, Chua AK, Jiang H, Liu NA, Goodarzi MO. Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes. Mol Endocrinol. 2014;28:1329-1336.
8. Ramezani Tehrani F, Noroozzadeh M, Zahediasl S, Piryaei A, Hashemi S, Azizi F. The time of prenatal androgen exposure affects development of polycystic ovary syndrome-like phenotype in adulthood in female rats. Int J Endocrinol Metab. 2014;12:e16502.
9. Yan X, Dai X, Wang J, Zhao N, Cui Y, Liu J. Prenatal androgen excess programs metabolic derangements in pubertal female rats. J Endocrinol. 2013;217:119-129.
10. Sun M, Maliqueo M, Benrick A, Johansson J, Shao R, Hou L, Jansson T, Wu X, Stener-Victorin E. Maternal androgen excess reduces placental and fetal weights, increases placental steroidogenesis, and leads to long-term health effects in their female offspring. Am J Physiol Endocrinol Metab. 2012;303:E1373-E1385.
11. Cussons AJ, Stuckey BG, Watts GF. Cardiovascular disease in the polycystic ovary syndrome: new insights and perspectives. Atherosclerosis. 2006;185:227-239.
12. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006;91:4237-4245.
13. Ojeda NB, Grigore D, Yanes LL, Iliescu R, Robertson EB, Zhang H, Alexander BT. Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring. Am J Physiol Regul Integr Comp Physiol. 2007;292:R758-R763.
14. Reckelhoff JF. Gender differences in the regulation of blood pressure. Hypertension. 2001;37:1199-1208.
15. Reckelhoff JF, Roman RJ. Androgens and hypertension: role in both males and females? Hypertension. 2011;57:681-682.
16. Huang G, Tang E, Aakil A, Anderson S, Jara H, Davda M, Stroh H, Travison TG, Bhasin S, Basaria S. Testosterone dose-response relationships with cardiovascular risk markers in androgen-deficient women: a randomized, placebo-controlled trial. J Clin Endocrinol Metab. 2014;99:E1287-E1293.
17. Ganten U, Schröder G, Witt M, Zimmermann F, Ganten D, Stock G. Sexual dimorphism of blood pressure in spontaneously hypertensive rats: effects of antiandrogen treatment. J Hypertens. 1989;7:721-726.
18. Baltatu O, Cayla C, Iliescu R, Andreev D, Bader M. Abolition of endorgan damage by antiandrogen treatment in female hypertensive transgenic rats. Hypertension. 2003;41(3 Pt 2):830-833.
19. Reckelhoff JF, Zhang H, Granger JP. Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension. 1998;31(1 Pt 2):435-439.
20. Laughlin GA, Barrett-Connor E, Kritz-Silverstein D, von Mühlen D. Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2000;85:645-651.
21. Falkner B, Sherif K, Sumner A, Kushner H. Hyperinsulinism and sex hormones in young adult African Americans. Metabolism. 1999;48:107-112.
22. Huisman HW, Schutte AE, Van Rooyen JM, Malan NT, Malan L, Schutte R, Kruger A. The influence of testosterone on blood pressure and risk factors for cardiovascular disease in a black South African population. Ethn Dis. 2006;16:693-698.
23. Hall WD, Ferrario CM, Moore MA, Hall JE, Flack JM, Cooper W, Simmons JD, Egan BM, Lackland DT, Perry M Jr, Roccella EJ. Hypertension-related morbidity and mortality in the southeastern United States. Am J Med. Sci. 1997;313:195-209.
24. Dumesic DA, Schramm RD, Abbott DH. Early origins of polycystic ovary syndrome. Reprod Fertil Dev. 2005;17:349-360.
25. Franks S. Adult polycystic ovary syndrome begins in childhood. Best Pract Res Clin Endocrinol Metab. 2002;16:263-272.
26. Nakayama K, Obara K, Tanabe Y, Saito M, Ishikawa T, Nishizawa S. Interactive role of tyrosine kinase, protein kinase C, and Rho/Rho kinase systems in the mechanotransduction of vascular smooth muscles. Biorheology. 2003;40:307-314.
27. Ohanian V, Ohanian J, Shaw L, Scarth S, Parker PJ, Heagerty AM. Identification of protein kinase C isoforms in rat mesenteric small arteries and their possible role in agonist-induced contraction. Circ Res. 1996;78:806-812.
28. Salamanca DA, Khalil RA. Protein kinase C isoforms as specific targets for modulation of vascular smooth muscle function in hypertension. Biochem Pharmacol. 2005;70:1537-1547.
29. Novokhatska T, Tishkin S, Dosenko V, Boldyriev A, Ivanova I, Strielkov I, Soloviev A. Correction of vascular hypercontractility in spontaneously hypertensive rats using shRNAs-induced delta protein kinase C gene silencing. Eur J Pharmacol. 2013;718:401-407.
30. Webster BR, Osmond JM, Paredes DA, DeLeon XA, Jackson-Weaver O, Walker BR, Kanagy NL. Phosphoinositide-dependent kinase-1 and protein kinase Cδ contribute to endothelin-1 constriction and elevated blood pressure in intermittent hypoxia. J Pharmacol Exp Ther. 2013;344:68-76.
31. Chou WH, Messing RO. Hypertensive encephalopathy and the blood-brain barrier: is deltaPKC a gatekeeper? J Clin Invest . 2008;118:17-20.
32. Palanisamy N, Viswanathan P, Ravichandran MK, Anuradha CV. Renoprotective and blood pressure-lowering effect of dietary soy protein via protein kinase C beta II inhibition in a rat model of metabolic syndrome. Can J Physiol Pharmacol. 2010;88:28-37.
33. Sasajima H, Shima H, Toyoda Y, Kimura K, Yoshikawa A, Hano T, Nishio I. Increased Ca2+ sensitivity of contractile elements via protein kinase C in alpha-toxin permeabilized SMA from young spontaneously hypertensive rats. Cardiovasc Res. 1997;36:86-91.
34. Shibata R, Morita S, Nagai K, Miyata S, Iwasaki T. Effects of H-7 (protein kinase inhibitor) and phorbol ester on aortic strips from spontaneously hypertensive rats. Eur J Pharmacol. 1990;175:261-271.
35. Bazan E, Campbell AK, Rapoport RM. Protein kinase C activity in blood vessels from normotensive and spontaneously hypertensive rats. Eur J Pharmacol. 1992;227:343-348.
36. Turla MB, Webb RC. Enhanced vascular reactivity to protein kinase C activators in genetically hypertensive rats. Hypertension. 1987;9(6 Pt 2):III150-III154.
37. Turla MB, Webb RC. Vascular responsiveness to protein kinase C activators in mineralocorticoid-hypertensive rats. J Hypertens. 1991;9:209-215.
38. Bilder GE, Kasiewski CJ, Perrone MH. Phorbol-12, 13-dibutyrate-induced vasoconstriction in vivo: characterization of response in genetic hypertension. J Pharmacol Exp Ther. 1990;252:526-530.
39. Salamanca DA, Khalil RA. Protein kinase C isoforms as specific targets for modulation of vascular smooth muscle function in hypertension. Biochem Pharmacol. 2005;70:1537-1547.
40. Orshal JM, Khalil RA. Gender, sex hormones, and vascular tone. Am J Physiol Regul Integr Comp Physiol. 2004;286:R233-R249.
41. Chinnathambi V, Balakrishnan M, Ramadoss J, Yallampalli C, Sathishkumar K. Testosterone alters maternal vascular adaptations: role of the endothelial NO system. Hypertension. 2013;61:647-654.
42. Sathishkumar K, Elkins R, Chinnathambi V, Gao H, Hankins GD, Yallampalli C. Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport. Reprod Biol Endocrinol. 2011;9:110.
43. King AJ, Olivier NB, Mohankumar PS, Lee JS, Padmanabhan V, Fink GD. Hypertension caused by prenatal testosterone excess in female sheep. Am J Physiol Endocrinol Metab. 2007;292:E1837-E1841.
44. Sir-Petermann T, Maliqueo M, Codner E, Echiburú B, Crisosto N, Pérez V, Pérez-Bravo F, Cassorla F. Early metabolic derangements in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007;92:4637-4642.
45. Kent SC, Gnatuk CL, Kunselman AR, Demers LM, Lee PA, Legro RS. Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab. 2008;93:1662-1669.
46. Buchholz RA, Dundore RL, Cumiskey WR, Harris AL, Silver PJ. Protein kinase inhibitors and blood pressure control in spontaneously hypertensive rats. Hypertension. 1991;17:91-100.
47. Bynagari-Settipalli YS, Chari R, Kilpatrick L, Kunapuli SP. Protein kinase C - possible therapeutic target to treat cardiovascular diseases. Cardiovasc Hematol Disord Drug Targets. 2010;10:292-308.
48. Snow JB, Gonzalez Bosc LV, Kanagy NL, Walker BR, Resta TC. Role for PKCβ in enhanced endothelin-1-induced pulmonary vasoconstrictor reactivity following intermittent hypoxia. Am J Physiol Lung Cell Mol Physiol. 2011;301:L745-L754.
49. Steinberg SF. Structural basis of protein kinase C isoform function. Physiol Rev. 2008;88:1341-1378.
50. Zhang H, Xiao D, Longo LD, Zhang L. Regulation of alpha1-adrenocep-tor-mediated contractions of uterine arteries by PKC: effect of pregnancy. Am J Physiol Heart Circ Physiol. 2006;291:H2282-H2289.
51. Walsh MP, Horowitz A, Clément-Chomienne O, Andrea JE, Allen BG, Morgan KG. Protein kinase C mediation of Ca(2+)-independent contractions of vascular smooth muscle. Biochem Cell Biol. 1996;74:485-502.
52. Maddali KK, Korzick DH, Tharp DL, Bowles DK. PKCdelta mediates testosterone-induced increases in coronary smooth muscle Cav1.2. J Biol Chem. 2005;280:43024-43029.
53. Korzick DH, Rishel ME, Bowles DK. Exercise and hypercholesterolemia produce disparate shifts in coronary PKC expression. Med Sci Sports Exerc. 2005;37:381-388.
54. Liu L, Liu J, Gao Y, Yu X, Dou D, Huang Y. Protein kinase Cδ contributes to phenylephrine-mediated contraction in the aortae of high fat diet-induced obese mice. Biochem Biophys Res Commun. 2014;446:1179-1183.
55. Ishida K, Matsumoto T, Taguchi K, Kamata K, Kobayashi T. Protein kinase C delta contributes to increase in EP3 agonist-induced contraction in mesenteric arteries from type 2 diabetic Goto-Kakizaki rats. Pflugers Arch. 2012;463:593-602.
56. Allahdadi KJ, Duling LC, Walker BR, Kanagy NL. Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKCdelta. Am J Physiol Heart Circ Physiol. 2008;294:H920-H927.
57. Obara K, Ukai K, Ishikawa T. Mechanism of potentiation by tea epigallocatechin of contraction in porcine coronary artery: the role of protein kinase Cδ-mediated CPI-17 phosphorylation. Eur J Pharmacol. 2011;668:414-418.
58. Khalil RA, Lajoie C, Morgan KG. In situ determination of [Ca2+]i threshold for translocation of the alpha-protein kinase C isoform. Am J Physiol. 1994;266(6 Pt 1):C1544-C1551.
59. Khalil RA, Lajoie C, Resnick MS, Morgan KG. Ca(2+)-independent isoforms of protein kinase C differentially translocate in smooth muscle. Am J Physiol. 1992;263(3 Pt 1):C714-C719.
60. Adler AJ, Scheller A, Robins DM. The stringency and magnitude of andro-gen-specific gene activation are combinatorial functions of receptor and nonreceptor binding site sequences. Mol Cell Biol. 1993;13:6326-6335.
61. Heinlein CA, Chang C. Androgen receptor (AR) coregulators: an overview. Endocr Rev. 2002;23:175-200.
62. Fan LQ, Hardy DO, Catterall JF, Zhao J, Li SX. Identification and characterization of an androgen-responsive Kap promoter enhancer located in the intron II region of human angiotensinogen gene. J Steroid Biochem Mol Biol. 2010;119:135-140.