Skip to main content
SpringerLink
Log in

Gastric estrogen increases pituitary estrogen receptor α and prolactin mRNAs during the different pathological conditions of the liver

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Mammalian liver is an estrogen-responsive tissue mediated by hepatic estrogen receptors. Although Ueyama et al. (Endocrinology 143:3162–3170, 2002) have reported the presence of aromatase and active production of gastric 17β-estradiol in parietal cells, there are a few studies on gastric 17β-estradiol exploring the relationship between gastro-hepato function and the gastro-pituitary-gonadal axis. The alteration of gastric 17β-estradiol flow into the systemic circulation by portal vein ligation (PVL) or partial hepatectomy (PH), and the effect of gastric 17β-estradiol on the pituitary function was investigated. In the PVL rats, arterial 17β-estradiol increased 9.5 times that of controls on day 3, and gradually decreased near to control levels in the portal vein by 4 weeks, which was still 5 times higher than those in the arteries of the control rats. In the PH rats, arterial 17β-estradiol increased 2 times that of controls on day 3, and gradually decreased to the control levels. Regeneration and growth of the liver remnants were observed about 2 weeks after PH. In the PVL and PH animals, pituitary ERα and prolactin mRNAs levels increased, positively correlating with an increase of arterial 17β-estradiol levels. Both reduced LHβ mRNA. It is apparent that hepatic dysfunction causes changes in gastric 17β-estradiol levels in the systemic circulation; and that elevated gastric 17β-estradiol affects pituitary function(s). This data suggest that gastric 17β-estradiol has a pivotal role in the regulation of the gastro-hepato-pituitary axis.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. M. Bahnsen, C. Gluud, S.G. Johnsen, P. Bennett, S. Svenstrup, S. Micic, O. Dietrichson, L.B. Svendsen, U.A. Brodthagen, Pituitary-testicular function in patients with alcoholic cirrhosis of the liver. Eur. J. Clin. Invest. 11, 473–479 (1981)

    Article  PubMed  CAS  Google Scholar 

  2. W. Stremmel, C. Niederau, M. Berger, H.K. Kley, H.L. Krüskemper, G. Strohmeyer, Abnormalities in estrogen, androgen, and insulin metabolism in idiopathic hemochromatosis. Ann. N. Y. Acad. Sci. 526, 209–223 (1988)

    Article  PubMed  CAS  Google Scholar 

  3. E. Rubin, F. Hutterer, T. Ohshiro, J.H. Jacobson, Effect of experimental portacaval shunt on hepatic drug metabolizing enzymes. Proc. Soc. Exp. Biol. Med. 127, 444–447 (1968)

    PubMed  CAS  Google Scholar 

  4. F.W. Ossenberg, L. Pointard, J.P. Benhamou, Effect of portacaval shunt on hepatic cytochrome P-450 in rats. Rev. Eur. Etud. Clin. Biol. 17, 791–793 (1972)

    PubMed  CAS  Google Scholar 

  5. G.C. Farrell, L. Zaluzny, Portal vein ligation selectively lowers hepatic cytochrome P-450 levels in rats. Gastroenterology 85, 275–282 (1983)

    PubMed  CAS  Google Scholar 

  6. J.G. Pector, S. Verbeustel, J.P. Lambilliotte, Effect of portal arterialization on hepatic cytochrome P-450 in rats with portacaval shunt. Digestion 12, 144–151 (1975)

    Article  PubMed  CAS  Google Scholar 

  7. Y. Hirokata, S. Tong, Z.H. Siddik, M.A. Trush, E.G. Mimnaugh, T.E. Gram, Sex-dependent differences in the effects of portacaval anastomosis on hepatic monooxygenases in rats. Biochem. Pharmacol. 31, 499–502 (1982)

    Article  PubMed  CAS  Google Scholar 

  8. D.H. Van Theil, J.S. Gavaler, C.F. Cobb, C.J. McLain, An evaluation of the respective roles of portosystemic shunting and portal hypertension in rats upon the production of gonadal dysfunction in cirrhosis. Gastroenterology 85, 154–159 (1983)

    Google Scholar 

  9. G.C. Farrell, A. Koltai, L. Zaluzny, M. Murray, Effects of portal vein ligation on sex hormone metabolism in male rats: Relationship to lowered hepatic cytochrome P-450 levels. Gastroenterology 90, 299–305 (1986)

    PubMed  CAS  Google Scholar 

  10. T. Ueyama, N. Shirasawa, M. Mtasuzawa, K. Yamada, M. Shelangouski, T. Ito, Y. Tsuruo, Gastric parietal cells: potent endocrine role in secreting estrogen as a possible regulator of gastro-hepatic axis. Endocrinology 143, 3162–3170 (2002)

    Article  PubMed  CAS  Google Scholar 

  11. T. Ueyama, N. Shirasawa, T. Ito, Y. Tsuruo, Estrogen-producing steroidogenic pathways in parietal cells of the rat gastric mucosa. Life Sci. 74, 2327–2337 (2004)

    Article  PubMed  CAS  Google Scholar 

  12. A. Francavilla, P.K. Eagon, A. DiLeo, L. Polimeno, C. Panella, A.M. Aquilino, M. Ingrosso, D.H. Van Thiel, T.E. Starzl, Sex hormone-related functions in regenerating male rat liver. Gastroenterology 91, 1263–1270 (1986)

    PubMed  CAS  Google Scholar 

  13. A. Francavilla, L. Polimeno, A. DiLeo, M. Barone, P. Ove, M. Coetzee, P. Eagon, L. Makowka, G. Ambrosino, V. Mazzaferro et al., The effect of estrogen and tamoxifen on hepatocyte proliferation in vivo and in vitro. Hepatology 9, 614–620 (1989)

    Article  PubMed  CAS  Google Scholar 

  14. A. Francavilla, J.S. Gavaler, L. Makowka, M. Barone, V. Mazzaferro, G. Ambrosino, S. Iwatsuki, F.W. Guglielmi, A. DiLeo, A. Balestrazzi et al., Estradiol and testosterone levels in patients undergoing partial hepatectomy. A possible signal for hepatic regeneration. Dig. Dis. Sci. 34, 818–822 (1989)

    Article  PubMed  CAS  Google Scholar 

  15. P.J. Sheridan, D.C. Herbert, An autoradiographic and immunocytochemical study of the neonatal rat pituitary gland. Anat. Rec. 194, 507–510 (1979)

    Article  PubMed  CAS  Google Scholar 

  16. N.R. Kalla, Demonstration of direct effect of estrogen on rat spermatogenesis. Acta. Eur. Fertil. 18, 293–302 (1987)

    PubMed  CAS  Google Scholar 

  17. G.B. Cutler Jr, K.M. Barnes, M.A. Sauer, D.L. Loriaux, Estrogen receptor in rat adrenal gland. Endocrinology 102, 252–257 (1978)

    Article  PubMed  CAS  Google Scholar 

  18. C.G. Meredith, D.N. Wade, A model of portal-systemic shunting in the rat. Clin. Exp. Pharmacol. Physiol. 8, 651–652 (1981)

    Google Scholar 

  19. G.M. Higgins, R.M. Anderson, Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch. Pathol. 12, 186–202 (1931)

    Google Scholar 

  20. K.J. Livak, T.D. Schmitten, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method 25, 402–408 (2001)

    Article  CAS  Google Scholar 

  21. N. Shirasawa, Y. Mabuchi, E. Sakuma, T. Yashiro, M. Kikuchi, Y. Hashimoto, T. Tsuruo, D.C. Herbert, T. Soji, Intercellular communication within the rat anterior pituitary gland. X. Immunohisto-cytochemistry of S-100 and connexin 43 of folliculo-stellate cells in the rat anterior pituitary gland. Anat. Rec. 278A, 462–473 (2004)

    Article  CAS  Google Scholar 

  22. W.M. Van Beurden-Lamers, A.O. Brinkmann, E. Mulder, H.J. van der Molen, High-affinity binding of oestradiol-17beta by cytosols from testis interstitial tissue, pituitary, adrenal, liver and accessory sex glands of the male rat. Biochem. J. 140, 495–502 (1974)

    PubMed  Google Scholar 

  23. A.J. Eisenfeld, R. Aten, M. Weinberger, G. Haselbacher, K. Halpern, L. Krakoff, Estrogen receptor in the mammalian liver. Science 191, 862–865 (1976)

    Article  PubMed  CAS  Google Scholar 

  24. E.R. Lax, P. Baumann, H. Schriefers, Changes in the activities of microsomal enzymes involved in hepatic steroid metabolism in the rat after administration of androgenic, estrogenic, progestational, anabolic and catatoxic steroids. Biochem. Pharmacol. 33, 1235–1241 (1984)

    Article  PubMed  CAS  Google Scholar 

  25. J. Couet, J. Simard, C. Martel, C. Trudel, Y. Labrie, F. Labrie, Regulation of 3-ketosteroid reductase messenger ribonucleic acid levels and 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase activity in rat liver by sex steroids and pituitary hormones. Endocrinology 131, 3034–3044 (1992)

    Article  PubMed  CAS  Google Scholar 

  26. O. Kollmar, M. Corsten, C. Scheuer, B. Vollmar, M.K. Schilling, M.D. Menger, Portal branch ligation induces a hepatic arterial buffer response, microvascular remodeling, normoxygenation, and cell proliferation in portal blood-deprived liver tissue. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G1534–G1542 (2006)

    Article  Google Scholar 

  27. M.D. Rosenthal, E.D. Albrecht, G.J. Pepe, Estrogen modulates developmentally regulated gene expression in the fetal baboon liver. Endocrine 23, 219–228 (2004)

    Article  PubMed  CAS  Google Scholar 

  28. C. Liddle, G.C. Farrell, Role of the oestrogen receptor in liver regeneration in the male rat. J. Gastroenterol. Hepatol. 8, 524–529 (1993)

    Article  PubMed  CAS  Google Scholar 

  29. S.R. Milligan, G.S. Sarna, Effect of portacaval anastomosis and chronic underfeeding on the hypothalamic-pituitary-gonadal axis in the rat. J. Endocrinol. 88, 39–47 (1981)

    Article  PubMed  CAS  Google Scholar 

  30. E.J. Smanik, K.D. Mullen, W.G. Giroski, A.J. McCullough, The influence of portacaval anastomosis on gonadal and anterior pituitary hormones in a rat model standardized for gender, food intake, and time after surgery. Steroids 56, 237–241 (1991)

    Article  PubMed  CAS  Google Scholar 

  31. J. Knopp, J. Brtko, D. Jezová, P. Langer, Partial hepatectomy alters serum hormone levels in rats. Horm. Metab. Res. 23, 329–332 (1991)

    Article  PubMed  CAS  Google Scholar 

  32. I.A. Lüthy, R.S. Calandra, Ontogeny of the sex steroid and prolactin receptors in the male rat adrenal gland. Experientia 40, 1002–1004 (1984)

    Article  PubMed  Google Scholar 

  33. R.V. Lloyd, K. Hawkins, L. Jin, E. Kulig, K. Fields, Chromogranin A, chromogranin B and secretogranin II mRNAs in the pituitary and adrenal glands of various mammals. Regulation of chromogranin A, chromogranin B and secretogranin II mRNA levels by estrogen. Lab. Invest. 67, 394–404 (1992)

    PubMed  CAS  Google Scholar 

  34. B.G. Saruhan, N. Ozdemir, Effect of ovariectomy and of estrogen treatment on the adrenal gland and body weight in rats. Saudi Med. J. 26, 1705–1729 (2005)

    PubMed  Google Scholar 

  35. L.K. Malendowicz, H. Nikicicz, Mariola. Majchrzak, Z. Monowid, Effect of hepatectomy on secretion and metabolism of corticosterone in the rat. Endokrinologie. 77, 291–296 (1981)

    PubMed  CAS  Google Scholar 

  36. V. Tamási, A. Kiss, O. Dobozy, A. Falus, L. Vereczkey, K. Monostory, The effect of dexamethasone on P450 activities in regenerating rat liver. Biochem. Biophys. Res. Commun. 286, 239–242 (2001)

    Article  PubMed  Google Scholar 

  37. I. Tsukamoto, S. Kojo, Effects of glucocorticoid on liver regeneration after partial hepatectomy in the rat. Gut 30, 387–390 (1989)

    Article  PubMed  CAS  Google Scholar 

  38. C. Nadal, Dose-related opposite effects of hydrocortisone on hepatocyte proliferation in the rat. Liver 15, 63–69 (1995)

    PubMed  CAS  Google Scholar 

  39. P. Nagy, A. Kiss, J. Schnur, S.S. Thorgeirsson, Dexamethasone inhibits the proliferation of hepatocytes and oval cells but not bile duct cells in rat liver. Hepatology 28, 423–429 (1998)

    Article  PubMed  CAS  Google Scholar 

  40. F. Isohashi, K. Tsukanaka, M. Terada, Y. Nakanishi, H. Fukushima, Y. Sakamoto, Alteration in binding of dexamethasone to glucocorticoid receptors in regenerating rat liver after partial hepatectomy. Cancer Res. 39, 5132–5135 (1979)

    PubMed  CAS  Google Scholar 

  41. J.F. Morris, H.C. Christian, L.P. Chapman, M.J. Epton, J.C. Buckingham, H. Ozawa, M. Nishi, M. Kawata, Steroid effects on secretion from subsets of lactotrophs: role of folliculo-stellate cells and annexin 1. Arch. Physiol. Biochem. 110, 54–61 (2002)

    Article  PubMed  CAS  Google Scholar 

  42. J.A. Chowen, L.M. Frago, J. Argente, Regulation of GH secretion by sex steroids. Eur. J. Endocrinol. 151(Suppl 3), U95–U100 (2004)

    Article  PubMed  CAS  Google Scholar 

  43. C.A. Blake, S.M. Helmke, Proteomics of the anterior pituitary gland as a model for studying the physiology of heterogeneous organ. Exp. Biol. Med. (Maywood) 230, 793–799 (2005)

    CAS  Google Scholar 

  44. M. González, R. Reyes, C. Damas, R. Alonso, A.R. Bello, Oestrogen receptor alpha and beta in female rat pituitary cells: an immunochemical study. Gen. Comp. Endocrinol. 155, 857–868 (2008)

    Article  PubMed  Google Scholar 

  45. R. Counis, M. Corbani, M. Jutisz, Estradiol regulates mRNAs encoding precursors to rat lutropin (LH) and follitropin (FSH) subunits. Biochem. Biophys. Res. Commun. 114, 65–72 (1983)

    Article  PubMed  CAS  Google Scholar 

  46. M.A. Shupnik, S.D. Gharib, W.W. Chin, Estrogen suppresses rat gonadotropin gene transcription in vivo. Endocrinology 122, 1842–1846 (1988)

    Article  PubMed  CAS  Google Scholar 

  47. T. Aizawa, T. Yamada, M. Tawata, T. Shimizu, S. Furuta, K. Kiyosawa, M. Yakata, Thyroid hormone metabolism in patients with liver cirrhosis, as judges by urinary excretion of triiodothyronine. J. Am. Geriatr. Soc. 28, 485–491 (1980)

    PubMed  CAS  Google Scholar 

  48. K.L. Kelner, E.J. Peck Jr, Differential sensitivity of estrogen target tissues: implications for estrogen regulation of serum luteinizing hormone. J. Neurosci. Res. 11, 79–89 (1984)

    Article  PubMed  CAS  Google Scholar 

  49. P.M. Ingleton, G.R. Rodgers, M. Faulkner, M.A. Parsons, The pituitary in cirrhosis: ultrastructure, growth hormone, and prolactin concentrations. Exp. Mol. Pathol. 56, 119–131 (1992)

    Article  PubMed  CAS  Google Scholar 

  50. C. Castillo, V. Salazar, C. Ariznavarreta, E. Vara, J.A. Tresguerres, Effect of growth hormone and estrogen administration on hepatocyte alterations in old ovariectomized female wistar rats. Endocrine 26, 11–18 (2005)

    Article  PubMed  CAS  Google Scholar 

  51. I.M. Olazabal, J.A. Muñoz, C. Rodríguez-Navas, L. Alvarez, E. Delgado-Baeza, J.P. García-Ruiz, Prolactin’s role in the early stages of liver regeneration in rats. J. Cell. Physiol. 219, 626–633 (2009)

    Article  PubMed  CAS  Google Scholar 

  52. A.R. Buckley, C.W. Putnam, D.W. Montgomery, Russell DH, prolactin administration stimulates rat hepatic DNA synthesis. Biochem. Biophys. Res. Commun. 138, 1138–1145 (1986)

    Article  PubMed  CAS  Google Scholar 

  53. S. Kloehn, C. Otte, M. Korsanke, T. Arendt, A. Clemens, A. Glasow, S.R. Bornstein, U.R. Fölsch, H. Mönig, Expression and distribution of the prolactin receptor in normal rat liver and experimental liver cirrhosis. Horm. Metab. Res. 33, 394–401 (2001)

    Article  PubMed  CAS  Google Scholar 

  54. J. Simon-Holtorf, H. Mönig, H.J. Klomp, A. Reinecke-Lüthge, U.R. Fölsch, S. Kloehn, Expression and distribution of prolactin receptor in normal, fibrotic, and cirrhotic human liver. Exp. Clin. Endocrinol. Diabetes 114, 584–589 (2006)

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Life Science Laboratory Research Grant (grant numbers K10G05, K11G05); the Yamagata Health Support (grant number H21012); and the Yuki Plan of Yamagata University (grant number DAY0010). We acknowledged to Dr. Herbert, D.C. (University of Texas Health Science Center at San Antonio, USA) and Mr. Nathan Strange (Yamagata High School, Tokai University) for their suggestions and critically reading the manuscript.

Conflict of interests

The authors declare that there is no conflict of interest that would prejudice the impartiality of this research work.

Author information

Authors and Affiliations

  1. Department of Anatomy and Structural Science, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan

    Hiroto Kobayashi, Saori Yoshida, Ying-Jie Sun, Nobuyuki Shirasawa & Akira Naito

Authors
  1. Hiroto Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saori Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying-Jie Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nobuyuki Shirasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akira Naito
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nobuyuki Shirasawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kobayashi, H., Yoshida, S., Sun, YJ. et al. Gastric estrogen increases pituitary estrogen receptor α and prolactin mRNAs during the different pathological conditions of the liver. Endocrine 43, 170–183 (2013). https://doi.org/10.1007/s12020-012-9737-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-012-9737-5

Keywords

Search

Navigation