Estradiol Promotes Luteal Regression Through a Direct Effect on the Ovary and an Indirect Effect From the Celiac Ganglion via the Superior Ovarian Nerve


There is evidence suggesting that estradiol (E2) regulates the physiology of the ovary and the sympathetic neurons associated with the reproductive function. The objective of this study was to investigate the effect of E2 on the function of late pregnant rat ovaries, acting either directly on the ovarian tissue or indirectly via the superior ovarian nerve (SON) from the celiac ganglion (CG). We used in vitro ovary (OV) or ex vivo CG-SON-OV incubation systems from day 21 pregnant rats. Various concentrations of E2 were added to the incubation media of either the OV alone or the ganglion compartment of the CG-SON-OV system. In both experimental schemes, we measured the concentration of progesterone in the OV incubation media by radioimmunoassay at different times. Luteal messenger RNA (mRNA) expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) and 20α-hydroxysteroid dehydrogenase (20α-HSD) enzymes, respectively, involved in progesterone synthesis and catabolism, and of antiapoptotic B-cell lymphoma 2 (Bcl-2) and proapoptotic Bcl-2-associated X protein (Bax), were measured by reverse transcriptase–polymerase chain reaction (RT-PCR) at the end of the incubation period. Estradiol added directly to the OV incubation or to the CG of the CG-SON-OV system caused a decline in the concentration of progesterone accumulated in the incubation media. In addition, E2, when added to the OV incubation, decreased the expression of 3b-HSD and the ratio of Bcl-2/Bax. We conclude that through a direct effect on the OV, E2 favors luteal regression at the end of pregnancy in rats, in association with neural modulation from the CG via the SON.

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  1. 1.

    Casais M, Sosa ZY, Rastrilla AM, Aguado LI. Coeliac ganglion adrenergic activity modifies ovarian progesterone during pregnancy: its inter-relationship with LH. J Endocrinol. 2001;170(3):575–584.

  2. 2.

    Casais M, Delgado SM, Sosa Z, Rastrilla AM. Involvement of the coeliac ganglion in the luteotrophic effect of androstenedione in late pregnant rats. Reproduction. 2006;131(2):361–368.

  3. 3.

    Casais M, Delgado SM, Sosa Z, Rastrilla AM. Pregnancy in rats is modulated by ganglionic cholinergic action. Reproduction. 2006;131(6):1151–1158.

  4. 4.

    Casais M, Delgado SM, Sosa Z, Telleria CM, Rastrilla AM. The celiac ganglion modulates LH-induced inhibition of androstenedione release in late pregnant rat ovaries. Reprod Biol Endocrinol. 2006;4:66.

  5. 5.

    Vallcaneras SS, Casais M, Delgado SM, et al. Androgen receptors in coeliac ganglion in late pregnant rat. Steroids. 2009;74(6):526–534.

  6. 6.

    Klein CM, Burden HW. Anatomical localization of afferent and postganglionic sympathetic neurons innervating the rat ovary. Neurosci Lett. 1988;85(2):217–222.

  7. 7.

    Eranko O. Small intensely fluorescent (SIF) cells and nervous transmission in sympathetic ganglia. Annu Rev Pharmacol Toxicol. 1978;18:417–430.

  8. 8.

    Prud’homme MJ, Houdeau E, Serghini R, Tillet Y, Schemann M, Rousseau JP. Small intensely fluorescent cells of the rat paracervical ganglion synthesize adrenaline, receive afferent innervation from postganglionic cholinergic neurones, and contain muscarinic receptors. Brain Res. 1999;821(1):141–149.

  9. 9.

    Chau YP, Chien CL, Lu KS. The permeability of capillaries among the small granule-containing cells in rat superior cervical ganglia: an ultrastructural lanthanum tracer study. Histol Histopathol. 1991;6(2):261–268.

  10. 10.

    Dalsgaard CJ, Vincent SR, Hokfelt T, et al. Coexistence of cholecystokinin-and substance P-like peptides in neurons of the dorsal root ganglia of the rat. Neurosci Lett. 1982;33(2):159–163.

  11. 11.

    Cardinali DP, Vacas MI, Gejman PV, et al. The sympathetic superior cervical ganglia as “little neuroendocrine brains”. Acta Physiol Lat Am. 1983;33(3):205–221.

  12. 12.

    Stocco C, Telleria C, Gibori G. The molecular control of corpus luteum formation, function, and regression. Endocr Rev. 2007; 28(1):117–149.

  13. 13.

    Guo K, Wolf V, Dharmarajan AM, et al. Apoptosis-associated gene expression in the corpus luteum of the rat. Biol Reprod. 1998;58(3):739–746.

  14. 14.

    Gibori G, Chen YD, Khan I, Azhar S, Reaven GM. Regulation of luteal cell lipoprotein receptors, sterol contents, and steroidogenesis by estradiol in the pregnant rat. Endocrinology. 1984;114(2):609–617.

  15. 15.

    McLean MP, Puryear TK, Khan I, et al. Estradiol regulation of sterol carrier protein-2 independent of cytochrome P450 side-chain cleavage expression in the rat corpus luteum. Endocrinology. 1989;125(3):1337–1344.

  16. 16.

    Shaikh AA. Estrone and estradiol levels in the ovarian venous blood from rats during the estrous cycle and pregnancy. Biol Reprod. 1971;5(3):297–307.

  17. 17.

    Bussmann LE. Prostaglandin F-2 alpha receptors in corpora lutea of pregnant rats and relationship with induction of 20 alpha-hydroxysteroid dehydrogenase. J Reprod Fertil. 1989;85(2):331–341.

  18. 18.

    Aguado LI. Role of the central and peripheral nervous system in the ovarian function. Microsc Res Tech. 2002;59(6):462–473.

  19. 19.

    Bussmann LE, Deis RP. Studies concerning the hormonal induction of lactogenesis by prostaglandin F2 alpha in pregnant rats. J Steroid Biochem. 1979;11(4):1485–1489.

  20. 20.

    Duffy DM, Chaffin CL, Stouffer RL. Expression of estrogen receptor alpha and beta in the rhesus monkey corpus luteum during the menstrual cycle: regulation by luteinizing hormone and progesterone. Endocrinology. 2000;141(5):1711–1717.

  21. 21.

    Vaskivuo TE, Tapanainen JS. Apoptosis in the human ovary. Reprod Biomed Online. 2003;6(1):24–35.

  22. 22.

    Goodman SB, Kugu K, Chen SH, et al. Estradiol-mediated suppression of apoptosis in the rabbit corpus luteum is associated with a shift in expression of bcl-2 family members favoring cellular survival. Biol Reprod. 1998;59(4):820–827.

  23. 23.

    Depp R, Cox DW, Pion RJ, Conrad SH, Heinrichs WL. Inhibition of the pregnenolone delta 5-3 beta hydroxysteroid dehydrogenase-delta 5-4 isomerase systems of human placenta and corpus luteum of pregnancy. Gynecol Invest. 1973;4(2):106–120.

  24. 24.

    Yin XM, Oltvai ZN, Korsmeyer SJ. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature. 1994;369(6478):321–323.

  25. 25.

    Antonsson B. Bax and other pro-apoptotic Bcl-2 family “killer-proteins” and their victim the mitochondrion. Cell Tissue Res. 2001;306(3):347–361.

  26. 26.

    Gompel A, Somai S, Chaouat M, et al. Hormonal regulation of apoptosis in breast cells and tissues. Steroids. 2000;65(10–11):593–598.

  27. 27.

    Tamura H. Role of the nongravid part of the uterus in the luteolytic effects of estrogen in pregnant rats. Endocrinol Jpn. 1983;30(5):615–620.

  28. 28.

    Goyeneche AA, Telleria CM. Exogenous estradiol enhances apoptosis in regressing post-partum rat corpora lutea possibly mediated by prolactin. Reprod Biol Endocrinol. 2005;3:40.

  29. 29.

    Anesetti G, Lombide P, Chavez-Genaro R. Prepubertal estrogen exposure modifies neurotrophin receptor expression in celiac neurons and alters ovarian innervation. Auton Neurosci. 2009;145(1–2):35–43.

  30. 30.

    Campo Verde Arbocco F, Vallcaneras S, Casais M, Rastrilla AM. Influence of estradiol in the peripheral neural regulation of ovary at the end of pregnancy in the rat. Biocell. 2009;33(Suppl 1):A53–A98.

  31. 31.

    Bramley TA, Menzies GS. Subcellular fractionation of the porcine corpus luteum: sequestration of progesterone in a unique particulate fraction. J Endocrinol. 1988;117(3):341–354.

  32. 32.

    Bramley TA, Menzies GS. Particulate binding sites for steroid hormones in subcellular fractions of the ovine corpus luteum: properties and hormone specificity. Mol Cell Endocrinol. 1994;103(1–2):39–48.

  33. 33.

    Menzies GS, Bramley TA. Specific binding sites for progesterone in subcellular fractions of the porcine corpus luteum. J Endocrinol. 1994;142(1):101–110.

  34. 34.

    Telleria CM, Stocco CO, Stati AO, et al. Dual regulation of luteal progesterone production by androstenedione during spontaneous and RU486-induced luteolysis in pregnant rats. J Steroid Biochem Mol Biol. 1995;55(3–4):385–393.

  35. 35.

    Vallcaneras SS, Casais M, Anzulovich AC, et al. Androstenedione acts on the coeliac ganglion and modulates luteal function via the superior ovarian nerve in the postpartum rat. J Steroid Biochem Mol Biol. 2011;125(3-5):243–250.

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Correspondence to Marilina Casais PhD.

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Casais, M., Vallcaneras, S.S., Campo Verde Arbocco, F. et al. Estradiol Promotes Luteal Regression Through a Direct Effect on the Ovary and an Indirect Effect From the Celiac Ganglion via the Superior Ovarian Nerve. Reprod. Sci. 19, 416–422 (2012).

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  • estradiol
  • pregnancy
  • corpus luteum
  • peripheral nervous system
  • celiac ganglion