Skip to main content
SpringerLink
Log in

Steroid Hormones and Uterine Vascular Adaptation to Pregnancy

  • Review Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Pregnancy is a physiological state that involves a significant decrease in uterine vascular tone and an increase in uterine blood flow, which is mediated in part by steroid hormones, including estrogen, progesterone, and cortisol. Previous studies have demonstrated the involvement of these hormones in the regulation of uterine artery contractility through signaling pathways specific to the endothelium and the vascular smooth muscle. Alterations in endothelial nitric oxide synthase expression and activity, nitric oxide production, and expression of enzymes involved in PGI2 production contribute to the uterine artery endothelium—specific responses. Steroid hormones also have an effect on calcium-activated potassium channel activity, PKC signaling pathway and myogenic tone, and alterations in pharmacomechanical coupling in the uterine artery smooth muscle. This review addresses current understanding of the molecular mechanisms by which steroid hormones including estrogen, progesterone, and cortisol modulate uterine artery contractility to alter uterine blood flow during pregnancy with an emphasis on the pregnant ewe model.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hall JM, Couse JF, Korach KS The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem. 2001;276:36869–36872.

    Article  CAS  PubMed  Google Scholar 

  2. Ford SP Control of uterine and ovarian blood flow throughout the estrous cycle and pregnancy of ewes, sows and cows. J Anim Sci. 55(suppl 2):32–42.

  3. Rupnow HL, Phernetton TM, Shaw CE, Modrick ML, Bird IM, Magness RR Endothelial vasodilator production by uterine and systemic arteries.VII. Estrogen and progesterone effects on eNOS. Am J Physiol Heart Circ Physiol. 2001;280: H1699–H16705.

    Article  CAS  PubMed  Google Scholar 

  4. Yi FX, Magness RR, Bird IM Simultaneous imaging of [Ca2+]i and intracellular NO production in freshly isolated uterine artery endothelial cells: effects of ovarian cycle and pregnancy. Am J Physiol Regul Integr Comp Physiol. 2005;288: R140–R148.

    Article  CAS  PubMed  Google Scholar 

  5. Magness RR, Rosenfeld CR Local and systemic estradiol-17 beta: effects on uterine and systemic vasodilation. Am J Physiol. 1989;256:E536–E542.

    CAS  PubMed  Google Scholar 

  6. Killam AP, Rosenfeld CR, Battaglia FC, Makowski EL, Meschia G. Effect of estrogens on the uterine blood flow of oophorectomized ewes. Am J Obstet Gynecol. 1973;115:1045–1052.

    Article  CAS  PubMed  Google Scholar 

  7. Magness RR, Parker CR Jr, Rosenfeld CR Systemic and uterine responses to chronic infusion of estradiol-17 beta. Am J Physiol. 1993;265:E690–E698.

    CAS  PubMed  Google Scholar 

  8. Magness RR, Phernetton TM, Zheng J. Systemic and uterine blood flow distribution during prolonged infusion of 17beta-estradiol. Am J Physiol. 1998;275:H731–H743.

    CAS  PubMed  Google Scholar 

  9. Rosenfeld CR, Cox BE, Roy T., Magness RR Nitric oxide contributes to estrogen-induced vasodilation of the ovine uterine circulation. J Clin Invest. 1996;98:2158–2166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Van Buren GA, Yang DS, 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.

    Article  PubMed  Google Scholar 

  11. Gibson TC, Phernetton TM, Wiltbank MC, Magness RR Development and use of an ovarian synchronization model to study the effects of endogenous estrogen and nitric oxide on uterine blood flow during ovarian cycles in sheep. Biol Reprod. 2004;70:1886–1894.

    Article  CAS  PubMed  Google Scholar 

  12. Byers MJ, Zangl A., Phernetton TM, Lopez G., Chen DB, Magness RR Endothelial vasodilator production by ovine uterine and systemic arteries: ovarian steroid and pregnancy control of ER-alpha and ER-beta levels. J Physiol. 2005; 565:85–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liao WX, Magness RR, Chen DB Expression of estrogen receptors-alpha and -beta in the pregnant ovine uterine artery endothelial cells in vivo and in vitro. Biol Reprod. 2005;72:530–537.

    Article  CAS  PubMed  Google Scholar 

  14. Batra S., Iosif S. Nuclear estrogen receptors in human uterine arteries. Gynecol Obstet Invest. 1987;24:250–255.

    Article  CAS  PubMed  Google Scholar 

  15. Lantta M., Karkkainen J., Lehtovirta P. Progesterone and estradiol receptors in the cytosol of the human uterine artery. Am J Obstet Gynecol. 1983;147:627–633.

    Article  CAS  PubMed  Google Scholar 

  16. Magness RR, Phernetton TM, Gibson TC, Chen DB Uterine blood flow responses to ICI 192 780 in ovariectomized oestradiol-17 beta-treated, intact follicular and pregnant sheep. J Physiol. 2005;565:71–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rosenfeld CR, Roy, T. Cox BE Mechanisms modulating estrogen-induced uterine vasodilation. Vascul Pharmacol. 2002;38:115–125.

    Article  CAS  PubMed  Google Scholar 

  18. Resnik R., Killam AP, Battaglia FC, Makowski EL, Meschia G. The stimulation of uterine blood flow by various estrogens. Endocrinology. 1974;94:1192–1196.

    Article  CAS  PubMed  Google Scholar 

  19. Rosenfeld CR, Jackson GM Induction and inhibition of uterine vasodilation by catechol estrogen in oophorectomized, nonpregnant ewes. Endocrinology. 1982;110:1333–1339.

    Article  CAS  PubMed  Google Scholar 

  20. Bird IM, Zhang L., Magness RR Possible mechanisms underlying pregnancy induced increases in uterine artery endothelial function. Am J Physiol. 2003;284:R245–R258.

    CAS  Google Scholar 

  21. Magness RR, Sullivan JA, Li Y., Phernetton TM, Bird IM Endothelial vasodilator production by uterine and systemic arteries.VI. Ovarian and pregnancy effects on eNOS and NOx. Am J Physiol Heart Circ Physiol. 2001;280:H1692–H1698.

    Article  CAS  PubMed  Google Scholar 

  22. Cale JM, Bird IM Dissociation of endothelial nitric oxide snthase phosphorylation and activity in uterine artery endothelial cells. Am J Physiol Heart Circ Physiol. 2006;290:1433–1445.

    Article  CAS  Google Scholar 

  23. Alderton WK, Cooper CE, Knowles RG Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001; 357:593–615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Boo YC, Sorescu GP, Bauer PM, et al. Endothelial NO synthase phosphorylated at SER635 produces NO without requiring intracellular calcium increase. Free Radic Biol Med. 2003;35:729–741.

    Article  CAS  PubMed  Google Scholar 

  25. Fleming I., Busse R. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol. 2003;284:R1–R12.

    Article  CAS  PubMed  Google Scholar 

  26. Takahashi S., Mendelsohn ME Synergistic activation of endothelial nitric-oxide synthase (eNOS) by HSP90 and Akt: calcium-independent eNOS activation involves formation of an HSP90-Akt-CaM-bound eNOS complex. J Biol Chem. 2003;278:30821–30827.

    Article  CAS  PubMed  Google Scholar 

  27. Yi FX, Zhang AY, Campbell W., Zou AP, Van Breemen C., Li PL Simultaneous in situ monitoring of intracellular Ca2+ and NO in endothelium of coronary arteries. Am J Physiol Heart Circ Physiol. 2002;283:H2725–H2732.

    Article  CAS  PubMed  Google Scholar 

  28. Bird IM, Sullivan JA, Di T., et al. Pregnancy-dependent changes in cell signaling underlie changes in differential control of vasodilator production in uterine artery endothelial cells. Endocrinology. 2000;141:1107–1117.

    Article  CAS  PubMed  Google Scholar 

  29. Di T., Sullivan JA, Magness RR, Zhang L., Bird IM Pregnancy-specific enhancement of agonist-stimulated ERK1/2 signaling in uterine artery endothelial cells increases Ca2+ sensitivity of endothelial nitric oxide synthase as well as cytosolic phospholipase A2. Endocrinology. 2001;142:3014–3026.

    Article  CAS  PubMed  Google Scholar 

  30. Gifford SM, Cale JM, Tsoi S., Magness RR, Bird IM Pregnancy-specific changes in uterine artery endothelial cell signaling in vivo are both programmed and retained in primary culture. Endocrinology. 2003;144:3639–3650.

    Article  CAS  PubMed  Google Scholar 

  31. Chen Z., Yuhanna IS, Galcheva-Gargova Z., Karas RH, Mendelsohn ME, Shaul PW Estrogen receptor-alpha mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen. J Clin Invest. 1999;103:401–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chen DB, Bird IM, Zheng J., Magness RR Membrane estrogen receptor-dependent extracellular signal-regulated kinase pathway mediates acute activation of endothelial nitric oxide synthase by estrogen in uterine artery endothelial cells. Endocrinology. 2004;145:113–125.

    Article  CAS  PubMed  Google Scholar 

  33. Bernier SG, Haldar S., Michel T. Bradykinin-regulated interactions of the mitogen-activated protein kinase pathway with the endothelial nitric-oxide synthase. J Biol Chem. 2000;275:30707–30715.

    Article  CAS  PubMed  Google Scholar 

  34. Hisamoto K., Ohmichi M., Kanda Y., et al. Induction of endothelial nitric-oxide synthase phosphorylation by the raloxifene analog LY117018 is differentially mediated by Akt and extracellular signal-regulated protein kinase in vascular endothelial cells. J Biol Chem. 2001;276:47642–47649.

    Article  CAS  PubMed  Google Scholar 

  35. Wyatt AW, Steinert JR, Wheeler-Jones CP, et al. Early activation of the p42/p44MAPK pathway mediates adenosine-induced nitric oxide production in human endothelial cells: a novel calcium-insensitive mechanism. FASEB J.2002;16:1584–1594.

    Article  CAS  PubMed  Google Scholar 

  36. Dimmeler S., Fleming I., Fisslthaler B., Hermann C., Busse R., Zeiher AM Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999;399: 601–605.

    Article  CAS  PubMed  Google Scholar 

  37. Michell BJ, Griffiths JE, Mitchelhill KI, et al. The Akt kinase signals directly to endothelial nitric oxide synthase. Curr Biol. 1999;9:845–848.

    Article  CAS  PubMed  Google Scholar 

  38. Tschugguel W., Dietrich W., Zhegu Z., Stonek F., Kolbus A., Huber JC Differential regulation of proteasome-dependent estrogen receptor alpha and beta turnover in cultured human uterine artery endothelial cells. J Clin Endocrinol Metab. 2003; 88:2281–2287.

    Article  CAS  PubMed  Google Scholar 

  39. Russell-Jones DL, Umpleby M. Protein anabolic action of insulin, growth hormone and insulin-like growth factor-1. Eur J Endocrinol. 1996;135:631–642.

    Article  CAS  PubMed  Google Scholar 

  40. Michel T., Feron O. Nitric oxide synthases: which, where, how, and why? J Clin Invest. 1997;100:2146–2152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chen DB, Jia S., King AG, et al. Global protein expression profiling underlines reciprocal regulation of caveolin 1 and endothelial nitric oxide synthase expression in ovariectomized sheep uterine. Biol Reprod. 2006;74:832–838.

    Article  CAS  PubMed  Google Scholar 

  42. Chambliss KL, Shaul PW Estrogen modulation of endothelial nitric oxide synthase. Endocr Rev. 2002;23:665–686.

    Article  CAS  PubMed  Google Scholar 

  43. Salhab WA, Shaul PW, Cox BE, Rosenfeld CR Regulation of types I and III NOS in ovine uterine arteries by daily and acute estrogen exposure. Am J Physiol Heart Circ Physiol. 2000; 278:H2134–H2142.

    Article  CAS  PubMed  Google Scholar 

  44. Rosenfeld CR, Cornfield DN, Roy T. Ca2+-activated K+ channels modulate basal and estradiol-induced rises in uterine blood flow in ovine pregnancy. Am J Physiol Heart Circ Physiol. 2001;281:H422–H431.

    Article  CAS  PubMed  Google Scholar 

  45. Brayden JE Potassium channels in vascular smooth muscle. Clin Exp Pharmacol Physiol. 1996;23:1069–1076.

    Article  CAS  PubMed  Google Scholar 

  46. Rosenfeld CR, White RE, Roy T., Cox BE Calcium-activated potassium channels and nitric oxide coregulate estrogen-induced vasodilation. Am J Physiol Heart Circ Physiol. 2000;279:319–328.

    Article  Google Scholar 

  47. Valverde MA, Rojas P., Amigo J., et al. Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit. Science. 1999;285:1929–1931.

    Article  CAS  PubMed  Google Scholar 

  48. Nagar D., Liu X., Rosenfeld CR Estrogen regulates beta 1-subunit expression in Ca2+-activated K+ channels in arteries from reproductive tissues. Am J Physiol Heart Circ Physiol. 2005;289:H1417–H1427.

    Article  CAS  PubMed  Google Scholar 

  49. Dick GM, Sanders KM (Xeno)estrogn sensitivity of smooth muscle BK channels conferred by the regulatory beta-1 subunit: a study of beta-1 knockout mice. J Biol Chem. 2001; 276:34594–34599.

    Article  CAS  PubMed  Google Scholar 

  50. Bell DR, Rensberger HJ, Koritnik DR, Koshy A. Estrogen pretreatment directly potentiates endothelium-dependent vasorelaxation of porcine corony arteries. Am J Physiol Heart Circ Physiol. 1990;258:H377–H383.

    Google Scholar 

  51. Forstermann U., Schmidt HHHW, Pollack JS, et al. Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem Pharmacol. 1991;42:1849–1857.

    Article  CAS  PubMed  Google Scholar 

  52. Stice SL, Ford SP, Rosazza JP, Van Orden DE Interaction of 4-hydroxylated estradiol and potential-sensitive Ca2+ channels in altering uterine blood flow during the estrous cycle and early pregnancy in gilts. Biol Reprod. 1987;36:369–375.

    Article  CAS  PubMed  Google Scholar 

  53. Farley DB, Ford SP Evidence for declining extracellular calcium uptake and protein kinase C activity in uterine arterial smooth muscle during gestation in gilts. Biol Reprod. 1992;46:315–321.

    Article  CAS  PubMed  Google Scholar 

  54. Ford SP Control of blood flow to the gravid uterus of domestic livestock species 1,2. J Anim Sci. 1995;73:1852–1860.

    Article  CAS  PubMed  Google Scholar 

  55. Kublickiene KR, Cockell AP, Nisell H., Poston L. Role of nitric oxide in the regulation of vascular tone in pressurized and perfused resistance myometrial arteries from term pregnant women. Am J Obstet Gynecol. 1997;177:1263–1269.

    Article  CAS  PubMed  Google Scholar 

  56. Kublickiene KR, Kublickas M., Lindblom B., Lunell NO, Nisell H. A comparison of myogenic and endothelial properties of myometerial and omental resistance vessels in late pregnancy. Am J Obstet Gynecol. 1997;176:560–566.

    Article  CAS  PubMed  Google Scholar 

  57. Cipolla MJ, Binder ND, Osol G. Myoendometrial versus placental uterine arteries: structural, mechanical, and functional differences in late-pregnant rabbits. Am J Obstet Gynecol. 1997; 177:215–221.

    Article  CAS  PubMed  Google Scholar 

  58. Osol G., Cipolla M. Interaction of myogenic and adrenergic mechanisms in isolated, pressurized uterine radial arteries from late-pregnant and nonpregnant rats. Am J Obstet Gynecol. 1993;168:697–705.

    Article  CAS  PubMed  Google Scholar 

  59. Veerareddy S., Cooke CL, Baker PN, Davidge ST Vascular adaptations to pregnancy in mice: effects on myogenic tone. Am J Physiol Heart Circ Physiol. 2002;283:H2226–H2233.

    Article  CAS  PubMed  Google Scholar 

  60. Xiao D., Buchholz JN, Zhang L. Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway. Am J Physiol Heart Circ Physiol. 2006;290:H2337–H2343.

    Article  CAS  PubMed  Google Scholar 

  61. Grandley RE, Conrad KP, McLaughlin MK Endothelin and nitric oxide mediate reduced myogenic reactivity of small renal arteries from pregnant rats. Am J Physiol Regul Integr Comp Physiol. 2001;280:R1–R7.

    Article  Google Scholar 

  62. Meyer MC, Brayden JE, Mclaughlin MK Characteristics of vascular smooth muscle in the maternal resistance circulation during pregnancy in the rat. Am J Obstet Gynecol. 1993;169: 1510–1516.

    Article  CAS  PubMed  Google Scholar 

  63. Meyer MC, Osol G., Mclaughlin M. Flow decreases myogenic reactivity of mesenteric arteries from pregnant rats. J Soc Gynecol Investig. 1997;4:293–297.

    Article  CAS  PubMed  Google Scholar 

  64. Davis MJ, Hill MA Signaling mechanisms underlying the vascular myogenic response. Physiol Rev. 1999;79:387–423.

    Article  CAS  PubMed  Google Scholar 

  65. Hill MA, Falcone JC, Meininger GA Evidence for protein kinase C involvement in arteriolar myogenic reactivity. Am J Physiol. 1990;259:H1586–H1594.

    CAS  PubMed  Google Scholar 

  66. Lagaud G., Gaudreault N., Moore ED, Van Breemen C., Laher I. Pressure-dependent myogenic constriction of cerebral arteries occurs independently of voltage-dependent activation. Am J Physiol Heart Circ Physiol. 2002;283:H2187–H2195.

    Article  CAS  PubMed  Google Scholar 

  67. 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.

    CAS  PubMed  Google Scholar 

  68. Osol G., Laher I., Cipolla M. Protein kinase C modulates basal myogenic tone in resistance arteries from the cerebral circulation. Circ Res. 1991;68:359–367.

    Article  CAS  PubMed  Google Scholar 

  69. Xiao D., Huang X., Longo LD, Pearce WJ, Zhang L. Regulation of baseline Ca2+ sensitivity in permeabilized uterine arteries: effect of pregnancy. Am J Physiol Heart Circ Physiol. 2006;291:H413–H420.

    Article  CAS  PubMed  Google Scholar 

  70. Xiao D., Zhang L. ERK MAP kinases regulate smooth muscle contraction in ovine uterine artery: effect of pregnancy. Am J Physiol Heart Circ Physiol. 2002;282:H292–H300.

    Article  CAS  PubMed  Google Scholar 

  71. Kanashiro CA, Alexander BT, Granger JP, Khalil RA Ca2+insensitive vascular protein kinase C during pregnancy and NOS inhibition. Hypertension. 1999;34:924–930.

    Article  CAS  PubMed  Google Scholar 

  72. Kanashiro CA, Cockrell KL, Alexander BT, Granger JP, Khalil RA Pregnancy-associated reduction in vascular protein kinase C activity rebounds during inhibition of NO synthesis. Am J Physiol. 2000;278:R295–R303.

    CAS  Google Scholar 

  73. Magness RR, Rosenfeld CR, Carr BR Protein kinase C in uterine and systemic arteries during ovarian cycle and pregnancy. Am J Physiol. 1991;260:E464–E470.

    CAS  PubMed  Google Scholar 

  74. Xiao D., Zhang L. Adaptation of uterine artery thick- and thin-filament regulatory pathway to pregnancy. Am J Physiol Heart Circ Physiol. 2005;288:H142–H148.

    Article  CAS  PubMed  Google Scholar 

  75. Xiao D., Zhang L. Direct effects of estrogen and progesterone on PKC-mediated contractions of the uterine artery. Paper presented at: the 15th World Congress of Pharmacology (IUPHAR 2006); July 2–7, 2006; Beijing, China.

  76. Yang S., Xiao D., Zhang L. Role of sex steroid hormones and ERK1/2 in pregnancy-suppressed uterine artery myogenic tone. Paper presented at: SSR 2008; May 27–31, 2008; Kona, Hawaii.

  77. Anderson SG, Hackshaw BT, Still JG, Greiss FC Jr. Uterine blood flow and its distribution after chronic estrogen and progesterone administration. Am J Obstet Gynecol. 1977;127: 138–142.

    Article  CAS  PubMed  Google Scholar 

  78. Caton D., Abrams RM, Clapp JF, Barron DH The effect of exogenous progesterone on the rate of blood flow of the uterus of ovariectomized sheep. Q Exp Physiol. 1974;59: 225–231.

    Article  CAS  Google Scholar 

  79. Greiss FC, Anderson SG Effect of ovarian hormones on the uterine vascular bed. Am J Obstet Gynecol. 1970;107:829–836.

    Article  CAS  PubMed  Google Scholar 

  80. Resnik R., Brink GW, Plumer MH The effect of progesterone on estrogen-induced uterine blood flow. Am J Obstet Gynecol. 1977;128:251–254.

    Article  CAS  PubMed  Google Scholar 

  81. Rosenfeld CR, Morriss FH Jr, Makowski EL, Meschia G., Battaglia FC Circulatory changes in the reproductive tissues of ewes during pregnancy. Gynecol Invest. 1974;5:252–268.

    Article  CAS  PubMed  Google Scholar 

  82. Meikle A., Tasende C., Sosa C., Garofalo EG The role of sex steroid receptors in sheep female reproductive physiology. Reprod Fertil Dev. 2004;16:385–394.

    Article  CAS  PubMed  Google Scholar 

  83. Buhimschi I., Yallampalli C., Chwalisz K., Garfield RE Pre-eclampsia-like conditions produced by nitric oxide inhibition: effects of L-arginine, D-arginine and steroid hormones. Hum Reprod. 1995;10:2723–2730.

    Article  CAS  PubMed  Google Scholar 

  84. Deichert U., Albrand-Thielmann C., van de Sandt M. Doppler-sonographic pelvic blood flow measurements and their prognostic value in terms of luteal phase and implantation. Hum Reprod. 1996;11:1591–1593.

    Article  CAS  PubMed  Google Scholar 

  85. Habara T., Nakatsuka M., Konishi H., Asagiri K., Noguchi S., Kudo T. Elevated blood flow resistance in uterine arteries of women with unexplained recurrent pregnancy loss. Hum Reprod. 2002;17:190–194.

    Article  CAS  PubMed  Google Scholar 

  86. Magness RR, Rosenfeld CR The role of steroid hormones in the control of uterine blood flow. In Rosenfeld CR, ed. Reproductive and Perinatal Medicine. Vol. X. Ithaca, NY: Perinatology Press; 1989:234–271.

    Google Scholar 

  87. Magness RR, Rosenfeld CR Steroid control of blood vessel function. In be]Meeting NACDA-NIH, ed. Endometrial Function and Dysfunctional Uterine Bleeding. Washington, DC: American Association for the Advancement of Science Press; 1992: 107–120.

    Google Scholar 

  88. Pecins-Thompson M., Keller-Wood M. Effects of progesterone on blood pressure, plasma volume, and responses to hypotension. Am J Physiol. 1997;272:R377–R385.

    CAS  PubMed  Google Scholar 

  89. Reynolds LP Utero-ovarian interactions during early pregnancy: role of conceptus-induced vasodilation. J Anim Sci. 1986;62(suppl 2):47–61.

    Article  PubMed  Google Scholar 

  90. Reynolds LP, Magness RR, Ford SP Uterine blood flow during early pregnancy in ewes: interaction between the conceptus and the ovary bearing the corpus luteum. J Anim Sci. 1984;58:423–429.

    Article  CAS  PubMed  Google Scholar 

  91. Roesch DM, Keller-Wood M. Progesterone rapidly reduces arterial pressure in ewes. Am J Physiol. 1997;272:H386–H391.

    CAS  PubMed  Google Scholar 

  92. Roman-Ponce H., Caton D., Thatcher WW, Lehrer R. Uterine blood flow in relation to endogenous hormones during estrous cycle and early pregnancy. Am J Physiol. 1983; 245:R843–R849.

    CAS  PubMed  Google Scholar 

  93. Wallace JM, Bourke DA, Da Silva P., Aitken RP Influence of progesterone supplementation during the first third of pregnancy on fetal and placental growth in overnourished adolescent ewes. Reproduction. 2003;126:481–487.

    Article  CAS  PubMed  Google Scholar 

  94. Magness RR, Mitchell MD, Rosenfeld CR Uteroplacental production of eicosanoids in ovine pregnancy. Prostaglandins. 1990;39:75–88.

    Article  CAS  PubMed  Google Scholar 

  95. Magness RR, Shideman CR, Habermehl DA, Sullivan JA, Bird IM Endothelial vasodilator production by uterine and systemic arteries.V. Effects of ovariectomy, the ovarian cycle, and pregnancy on prostacyclin synthase expression. Prostaglandins Other Lipid Mediat. 2000;60:103–118.

    Article  CAS  PubMed  Google Scholar 

  96. Rupnow HL, Phernetton TM, Modrick ML, Wiltbank MC, Bird IM, Magness RR Endothelial vasodilator production by uterine and systemic arteries.VIII. Estrogen and progesterone effects on cPLA2, COZ-1, and PGIS protein expression. Biol Reprod. 2002;66:468–474.

    Article  CAS  PubMed  Google Scholar 

  97. Habermehl DA, Janowiak MA, Vagnoni KE, Bird IM, Magness RR Endothelial vasodilator production by uterine and systemic arteries. IV. Cyclooxygenase isoform expression during the ovarian cycle and pregnancy in sheep. Biol Reprod. 2000;62:781–788.

    Article  CAS  PubMed  Google Scholar 

  98. Janowiak MA, Magness RR, Habermehl DA, Bird IM Pregnancy increases ovine uterine artery endothelial cyclooxygenase-1 expression. Endocrinology. 1998;139:765–771.

    Article  CAS  PubMed  Google Scholar 

  99. Jun SS, Chen Z., Pace MC, Shaul PW Estrogen upregulates cyclooxygenase-1 gene expression in ovine fetal pulmonary artery endothelium. J Clin Invest. 1998;102:176–183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kim JJ, Wang J., Bambra C., Das SK, Dey SK, Fazleabas AT Expression of cyclooxygenase-1 and -2 in the baboon endometrium during the menstrual cycle and pregnancy. Endocrinology. 1999;140:2672–2678.

    Article  CAS  PubMed  Google Scholar 

  101. Ford SP, Reynolds LP, Farley DB, Bhatnagar RK, Van Orden DE Interaction of ovarian steroids and periarterial alpha-1 adrenergic receptors in altering uterine blood flow during the estrous cycle of gilts. Am J Obstet Gynecol. 1984;150:480–484.

    Article  CAS  PubMed  Google Scholar 

  102. Annibale DJ, Rosenfeld CR, Kamm KE Alterations in vascular smooth muscle contractility during ovine pregnancy. Am J Physiol. 1989;256:H1282–H1288.

    CAS  PubMed  Google Scholar 

  103. Annibale DJ, Rosenfeld CR, Stull JT, Kamm KE Protein content and myosin light chain phosphorylation in uterine arteries during pregnancy. Am J Physiol. 1990;259:C484–C489.

    Article  CAS  PubMed  Google Scholar 

  104. D’Angelo G., Osol G. Regional variation in resistance artery diameter responses to alpha-adrenergic stimulation during pregnancy. Am J Physiol. 1993;264:H78–H85.

    PubMed  Google Scholar 

  105. D’Angelo G., Osol G. Modulation of uterine resistance artery lumen diameter by calcium and G protein activation during pregnancy. Am J Physiol. 1994;267:H952–H961.

    PubMed  Google Scholar 

  106. Klukovits A., Gaspar R., Santha P., Jancso G., Falkay G. Functional and histochemical characterization of a uterine adrenergic denervation process in pregnant rats. Biol Reprod. 2002;67:1013–1017.

    Article  CAS  PubMed  Google Scholar 

  107. Nelson SH, Steinsland OS, Johnson RL, Suresh MS, Gifford A., Ehardt JS Pregnancy-induced alterations of neurogenic constriction and dilation of human uterine artery. Am J Physiol. 1995;268:H1694–H1701.

    Article  CAS  PubMed  Google Scholar 

  108. Lotgering FK, Gilbert RD, Longo LD Maternal and fetal responses to exercise during pregnancy. Physiol Rev. 1985;65:1–36.

    Article  CAS  PubMed  Google Scholar 

  109. Keller-Wood M. Inhibition of stimulated and basal ACTH by cortisol during ovine pregnancy. Am J Physiol Regul Integr Comp Physiol. 1996;271:R130–R136.

    Article  CAS  Google Scholar 

  110. Nolten WE, Rueckert PA Elevated free cortisol index in pregnancy: possible regulatory mechanisms. Am J Obstet Gynecol. 1981;139:492–498.

    Article  CAS  PubMed  Google Scholar 

  111. Xiao D., Huang X., Bae S., Ducsay CA, Zhang L. Cortisol-mediated potentiation of uterine artery contractility: effect of pregnancy. Am J Physiol Heart Circ Physiol. 2002;283: H238–H246.

    Article  CAS  PubMed  Google Scholar 

  112. Jensen E., Wood CE, Keller-Wood M. Chronic alterations in ovine maternal corticosteroid levels influence uterine blood flow and placental and fetal growth. Am J Physiol Regul Integr Comp Physiol. 2005;288:R54–R61.

    Article  CAS  PubMed  Google Scholar 

  113. Jensen E., Wood C., Keller-Wood M. The normal increase in adrenal secretion during pregnancy contributes to maternal volume expansion and fetal homeostasis. J Soc Gynecol Investig. 2002;9:362–371.

    Article  CAS  PubMed  Google Scholar 

  114. Li F., Wood CE, Keller-Wood M. Adrenalectomy alters regulation of blood pressure and endothelial nitric oxide synthase in sheep: modulation by estradiol. Am J Physiol Regul Integr Comp Physiol. 2007;293:R257–R266.

    Article  CAS  PubMed  Google Scholar 

  115. Malek AM, Izumo S., Alper SL Modulation by pathophysiological stimuli of the shear stress-induced up-regulation of endothelial nitric oxide synthase expression in endothelial cells. Neurosurgery. 1999;45:334–344.

    Article  CAS  PubMed  Google Scholar 

  116. Yagil Y., Krakoff LR The differential effect of aldosterone and dexamethasone on pressor responses in adrenalectomized rats. Hypertension. 1988;11:174–178.

    Article  CAS  PubMed  Google Scholar 

  117. Xiao D., Huang X., Pearce WJ, Longo LD, Zhang L. Effect of cortisol on norephinephrine-mediated contractions in ovine uterine arteries. Am J Physiol Heart Circ Physiol. 2003;284:H1142–H1151.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, California, 92350, USA

    Katherine Chang BS & Lubo Zhang PhD

Authors
  1. Katherine Chang BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lubo Zhang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katherine Chang BS.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chang, K., Zhang, L. Steroid Hormones and Uterine Vascular Adaptation to Pregnancy. Reprod. Sci. 15, 336–348 (2008). https://doi.org/10.1177/1933719108317975

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719108317975

Key words

Search

Navigation