Skip to main content

The non-genomic Action of Sex Steroids

  • Conference paper
Hormones and the Brain

Part of the book series: Research and Perspectives in Endocrine Interactions ((RPEI))

  • 1069 Accesses

Summary

The aim of this paper is to discuss novel and rather recent evidence indicating that estradiol and testosterone have rapid actions by interacting with two different, but physiologically and chemically well-characterized proteins: 1) tubulin, a basic component of microtubules and therefore involved in cellular cytoarchitecture and cellular trafficking; and 2) glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme involved in glycolysis but also in other important, non-glycolytic functions.

Estradiol and testosterone bind to tubulin at nanomolar concentrations and exert opposite effects on microtubule polymerization in an in vitro assay that uses electron microscopy to visualize the formation of microtubules: estradiol disrupts polymerization whereas testosterone stabilizes microtubules. This finding was confirmed by spectrometric analysis and in vivo cell cultures using image visualization of tubulin. Interestingly, testosterone but not estradiol blocks the colchicine-induced depolymerization effect in both the pure tubulin assay and the cell culture model.

Previously, we reported that estradiol binds with high affinity and selectivity to GAPDH and that a single injection of estradiol (10 µg, s.c.) to ovariectomized rats significantly increased and recovered the reduced catalysis of the enzyme in the plasmalemma-microsomal fraction (P3 fraction) of the hippocampus of these rats to intact levels. Herein, we report that estradiol induces a rapid (within 30 min) translocation of the enzyme to the P3 fraction of primary hippocampus cell cultures as well in the hippocampal cell line (HT-22) that lacks functional alfa and beta estrogen receptors. Importantly, the translocation is accompanied by serine phosphorylation of the GAPDH as shown by Western blot analysis of the P3 fraction. Estradiol treatment (10 nM) of HT-22 cell cultures appears to sequester the GAPDH in membrane organelles visualized by immunocytochemistry, because they become resistant to depletion by the nonionic detergent Triton-X-100.

These results and related reports from other laboratories cited in this paper strongly support the concept that, by interacting with these two proteins and other cellular components, sex steroids are involved in rapid, non-genomic functions in a variety of cells.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Agrati P, Ma ZQ, Patrone C, Picotti, GB, Pellicciari C, Bondiolotti G, Bottone MG, Maggi A (1997) Dopaminergic phenotype induced by oestrogens in a human neuroblastoma cell line. Eur Neurosci 9: 1008–1016

    Google Scholar 

  • Aizu-Yokota E, Ichinoseki K, Sato Y (1994) Microtubule disruption induced by estradiol in estrogen receptor-positive and-negative human breast cancer cell lines. Carcinogenesis 15: 1875–1879

    PubMed  Google Scholar 

  • Aizu-Yokota E, Susaki A, Sato Y (1995) Natural estrogens induce modulation of microtubules in Chinese hamster V79 cells in culture. Cancer Res 55: 1863–1868

    PubMed  Google Scholar 

  • Blanco G, Diaz H, Carrer HF, Beauge L (1990) Differentiation of rat hippocampal neurons induced by estrogen in vitro: effects on neuritogenesis and Na, K-ATPase activity. J Neurosci Res 27:47–54

    Article  PubMed  Google Scholar 

  • Chaudoreille MM, Peyrot V,. Braguer D, Codaccioni F, Crevat A (1991) Qualitative study of the interaction mechanism of estrogenic drugs with tubulin. Biochem Pharmacol 91:685–693

    Article  Google Scholar 

  • Garcia-Segura LM, Naftolin F, Hutchison JB, Azcoitia I, Chowen JA (1999) Role of astroglia in estrogen regulation of synaptic plasticity and brain repair. J Neurobiol 40: 574–584

    Article  PubMed  Google Scholar 

  • Glaser PE, Gross RW (1995) Rapid plasmenylethanolamine-selective fusion of membrane bilayers catalyzed by an isoform of glyceraldehyde-3-phosphate dehydrogenase: discrimination between glycolytic and fusogenic roles of individual isoforms. Biochemistry 34:12193–12203

    Article  PubMed  Google Scholar 

  • Glaser PE, Han X, Gross RW (2002) Tubulin is the endogenous inhibitor of the glyceraldehyde 3-phosphate dehydrogenase isoform that catalyzes membrane fusion: implications for the coordinated regulation of glycolysis and membrane fusion. Proc Natl Acad Sci USA 99:14104–14109

    Article  PubMed  Google Scholar 

  • Harvey BJ, Alzamora R, Healy V, Renard C, Doolan CM (2002) Rapid responses to steroid hormones: from frog skin to human colon. A homage to Hans Ussing. Biochem Biophys Acta 1566: 116–128

    PubMed  Google Scholar 

  • Hyman AA, Salser S, Drechsel DN, Unwin N, Mitchison TJ (1992) Role of GTP hydrolysis in microtubule dynamics: Information from a slowly hydrolysable analogue. GMPCPP Mol Biol Cell 3:1155–1167

    Google Scholar 

  • Jaccioni RB, Cambiazo V (1995) Role of microtubule-associated proteins in the control of microtubule assembly. Physiol Rev 75: 835–64

    PubMed  Google Scholar 

  • Joe I (2003) The study of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) function targeted by estrogen and progesterone in the central nervous system and physiological implication. Thesis, Univ. Illinois, Urbana

    Google Scholar 

  • Joe I, Ramirez VD (2001) Binding of estrogen and progesterone-BSA conjugates to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the effects of the free steroids on GAPDH enzyme activity: physiological implications. Steroids 66:529–538

    Article  PubMed  Google Scholar 

  • Kipp JL, Ramirez VD (2003) Estradiol and testosterone have opposite effects on microtubule polymerization. Neuroendocrinology 77: 258–272

    Article  PubMed  Google Scholar 

  • Luquin S, Naftolin F, Garcia-Segura LM (1993) Natural fluctuation and gonadal hormone regulation of astrocyte immunoreactivity in dentate gyrus. J Neurobiol 2497: 913–924

    Article  Google Scholar 

  • McEwen BS (1999) Stress and hippocampal plasticity. Ann Rev Neurosci 22:105–22

    Article  PubMed  Google Scholar 

  • Mejillano MR, Marton JS, Himes RH (1990) Stabilization of microtubules by GTP analogues. Biochem Biophys Res Commun 166: 653–660

    Article  PubMed  Google Scholar 

  • Nogales E (2000) Structural insights into microtubule function. Annu Rev Biochem 69: 277–302

    Article  PubMed  Google Scholar 

  • Nogales E, Wolfe SG, Downing KH (1998) Structure of the αβ tubulin dimer by electron crystallography. Nature 391:199–203

    Article  PubMed  Google Scholar 

  • Puca GA, Sica V (1981) Identification of specific high affinity sites for the estradiol receptor in the erythrocyte cytoskeleton. Biochem Biophys Res Commun 103: 682–689

    Article  PubMed  Google Scholar 

  • Ramirez VD, Kipp JL (2002) A novel non-genomic action of estradiol (E) and (T): regulation of microtubule polymerization. In: Watson CS (ed) The identities of membrane receptors. Kluwer Academic Publishers, Boston, pp 147–156

    Google Scholar 

  • Ramirez VD, Zheng J (1999) Steroid receptors in brain cell membranes. In: Baulieu EE, Robel P, Schumacher M (eds) Contemporary endocrinology: neurosteroids: a new regulatory function in the nervous system. Humana Press, Totowa, NJ, pp. 269–292

    Google Scholar 

  • Ramirez VD, Kipp JL, Joe I (2001) Estradiol, in the CNS, targets several physiologically relevant membrane-associated proteins. Brain Res Rev 37: 141–152

    Article  PubMed  Google Scholar 

  • Robbins AR, Ward RD, Oliver C (1995) A mutation in glyceraldehydes 3-phosphate dehydrogenase alters endocytosis in CHO cells. J Cell Biol 130:1093–1104

    Article  PubMed  Google Scholar 

  • Sakakibara Y, Saito I, Ichinoseki K., Oda T, Kaneko M, Saito H, Kodama M, Sato Y (1991) Effects of diethylstilbestrol and its methyl ethers on aneuploidy induction and microtubule distribution in Chinese hamster V79 cells. Mutat Res 263:269–276

    Article  PubMed  Google Scholar 

  • Szego CM, Sjostrand BM, Seeler BJ, Baumer JW, Sjostrand FS (1988) Microtubule and plasmalemmal reorganization: acute response to estrogen. Am J Physiol 254, E775–85

    PubMed  Google Scholar 

  • Tisdale EJ (2002) Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase Ciota/lambda and plays a role in microtubule dynamics in the early secretory pathway. J Biol Chem 277: 3334–3341

    Article  PubMed  Google Scholar 

  • Tomkins GM, Maxwell ES (1963) Some aspects of steroid hormone action. Ann Rev Biochem 32: 677–708

    Article  PubMed  Google Scholar 

  • Toran-Allerand CD (1990) Neurite-like outgrowth from CNS explants may not always be of neuronal origin. Brain Res 513: 353–357

    Article  PubMed  Google Scholar 

  • Tranque PA, Suarez I, Olmos G, Fernandez, B, Garcia-Segura LM (1987) Estradiol-induced redistribution of glial fibrillary acidic protein immunoreactivity in the ratbrain. Brain Res 406: 348–351

    Article  PubMed  Google Scholar 

  • Valenti C, Vasas M, Cardinalli DP (1979) Effect of castration, estradiol and testosterone on tubulin levels of the medial basal hypothalamus and theadenohypophysis of the rat. Experientia 35: 120–122

    Article  PubMed  Google Scholar 

  • Wheeler WJ, Hsu TC, Tousson A, Brinkley BR (1987) Mitotic inhibition and chromosome displacement induced by estradiol in Chinese hamster cells. Cell Motil Cytoskel 7: 235–247

    Article  Google Scholar 

  • Woolley CS, McEwen BS (1993) Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 336:293–306

    Article  PubMed  Google Scholar 

  • Woolley CS, Gould E, Frankfurt M, McEwen BS (1990) Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J Neurosci 10:4035–4039

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Joe, I., Kipp, J.L., Ramirez, V.D. (2005). The non-genomic Action of Sex Steroids. In: Kordon, C., Gaillard, RC., Christen, Y. (eds) Hormones and the Brain. Research and Perspectives in Endocrine Interactions. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26940-1_4

Download citation

  • DOI: https://doi.org/10.1007/3-540-26940-1_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-21355-0

  • Online ISBN: 978-3-540-26940-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics