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Horm Metab Res 2001; 33(3): 127-130
DOI: 10.1055/s-2001-14937
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Effects of Androgens and Estrogens and Catechol and Methoxy-Estrogen Derivatives on Mitogen-Activated Protein Kinase (ERK1,2) Activity in SW-13 Human Adrenal Carcinoma Cells[1]

J. W. Brown1, 2 , C. T. Kesler1 , J. T. Neary1, 3 , L. M. Fishman1, 2
  • 1 Adrenal Research Laboratory (151), V.A. Medical Center, Miami, FL 33125, U.S.A.
  • 2 Department of Medicine, University of Miami School of Medicine, Miami, FL 33101, U.S.A.
  • 3 Department of Pathology, University of Miami School of Medicine, Miami, FL 33101, U.S.A.
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Publication History

Publication Date:
31 December 2001 (online)

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We tested the effects of 17β-estradiol as well as its catechol- and methoxy-derivatives, two androgens (DHEA and testosterone), a glucocorticoid (cortisol), a mineralocorticoid (aldosterone), and progesterone on the activity of ERK1,2, a key component of the ERK/MAPK enzyme phosphorylation cascade, in SW-13 human adrenal carcinoma cells. After a 24-hour exposure SW-13 cells incubated with 10-5 M concentrations of 17β-estradiol, its 2-hydroxy or its 2-methoxy derivative, all had elevated ERK activities (196 %, 159 %, and 275 %, respectively) relative to control cells (p < 0.01). Incubation with testosterone resulted in 162 % of control ERK activity (p < 0.01), whereas incubation with the far weaker androgen DHEA or with cortisol, aldosterone, or progesterone had no significant effects. These findings suggest sex steroid-specific influences in the induction or activation of signal transduction pathways known to play a crucial role in cellular proliferation and differentiation.

Key words:

Adrenal Carcinoma - Steroids - MAPK - ERK

1 This work was supported by the U.S. Department of Veterans Affairs.

References

  • 1 Shan J D, Porvari K, Ruokonen M, Karhu A, Launonen V, Hedberg P, Oikarinen J, Vihko P. Steroid-involved transcriptional regulation of human genes encoding prostatic acid phosphatase, prostate-specific antigen, and prostate-specific glandular kallikrein.  Endocrinology. 1997;  138 3764-3770
    CrossrefPubMedGoogle Scholar
  • 2 Myers R B, Oelschlager D, Manne U, Coan P N, Weiss H, Grizzle W E. Androgenic regulation of growth factor and growth factor receptor expression in the CWR22 model of prostatic adenocarcinoma.  Int J Cancer. 1999;  82 424-429
    CrossrefPubMedGoogle Scholar
  • 3 Bondy P K. Disorders of the adrenal cortex.  In: Williams Textbook of Endocrinology,. JD Wilson and DW Foster (eds.) . Philadelphia, PA; WB Saunders Company 1985: 816-890
    Google Scholar
  • 4 Gittes R F. Carcinoma of the prostate.  New Engl J Med. 1991;  324 236-245
    PubMedGoogle Scholar
  • 5 Stearn M E, McGarvey T. Prostate cancer, therapeutics, diagnostic and basic studies.  Lab Invest. 1992;  67 540-552
    PubMedGoogle Scholar
  • 6 Boring C C, Squires T S, Tong T. Cancer statistics.  CA Cancer J Clin. 1993;  43 7-26
    PubMedGoogle Scholar
  • 7 Craft N, Sawyers C L. Mechanistic concepts in androgen-dependence of prostate cancer.  Cancer & Metastasis Rev. 1999;  17 421-427
    PubMedGoogle Scholar
  • 8 Seger R, Krebs E G. The MAPK signaling cascade.  FASEB J. 1995;  9 726-735
    PubMedGoogle Scholar
  • 9 Neary J T. MAPK cascades in cell growth and death.  News in Physiol Sci. 1997;  12 286-293
    PubMedGoogle Scholar
  • 10 Neary J T, Kang Y, Bu Y, Yu E, Akong K, Peters C M. Mitogenic signaling by ATP P2Y purinergic receptors in astrocytes: involvement of a calcium-independent protein kinase C, extracellular signal regulated protein kinase pathway distinct from the phosphatidylinositol-specific phospholipase C, calcium pathway.  J Neurosci. 1999;  19 4211-4220
    PubMedGoogle Scholar
  • 11 Kyriakis J M, Avruch J. Sounding the Alarm: Protein kinase cascades activated by stress and inflamation.  J Biol Chem. 1996;  271 24 313-24 316
    PubMedGoogle Scholar
  • 12 Bonni A, Brunet A, West A E, Datta S R, Takasu M A, Greenberg M E. Cell survival promoted by the Ras-MAPK signalling pathway by transcription-dependent and independent mechanisms.  Science. 1999;  286 1358-1362
    CrossrefPubMedGoogle Scholar
  • 13 Bhatt R R, Ferrell J E Jr. The protein kinase p90 Rsk as an essential mediator of cytostatic factor activity.  Science. 1999;  286 1362-1365
    CrossrefPubMedGoogle Scholar
  • 14 Gross S D, Schwab M S, Lewellyn A L, Maller J L. Induction of metaphase arrest in cleaving Xenopus embryos by the protein kinase p90Rsk.  Science. 1999;  286 1365-1367
    CrossrefPubMedGoogle Scholar
  • 15 Sivaraman V S, Wang H, Nuovo G J, Malbon C C. Hyperexpression of mitogen-activated protein kinase in human breast cancer.  J Clin Invest. 1997;  99 1478-1483
    PubMedGoogle Scholar
  • 16 Brown J W, Puppala K, Neary J T, Fishman L M. Mitogen-activated protein kinase (MAPK) activity in varying types of human pheochromocytomas.  Proc Soc Expl Biol. 1998;  Abstract A7 22
    PubMedGoogle Scholar
  • 17 Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E, Auricchio F. Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells.  EMBO J. 1996;  15 1292-1300
    PubMedGoogle Scholar
  • 18 Nuedling S, Kahlert S, Loebbert K, Meyer R, Vetter H, Grohe C. Differential effects of 17beta-estradiol on mitogen-activated protein kinase pathways in rat carciomyocytes.  FEBS Lett. 1999;  454 271-276
    CrossrefPubMedGoogle Scholar
  • 19 Singh M, Setalo G J r, Guan X, Warren M, Toran-Allerand C D. Estrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants; convergence of estrogen and neurotrophin signaling pathways.  J Neurosci. 1999;  19 1179-1188
    PubMedGoogle Scholar
  • 20 Zhu X, Li H, Liu J P, Funder J W. Androgen stimulates mitogen-activated protein kinase in human breast cancer cells.  Mol Cell Endocrinol. 1999;  152 199-206
    CrossrefPubMedGoogle Scholar
  • 21 Nader S, Hickey R C, Sellin R, Samaan N A. Adrenal cortical carcinoma. A study of 77 cases.  Cancer. 1983;  51 707-711
    PubMedGoogle Scholar
  • 22 DePablos V PL, Martinez M P, Sanchez M V, Santana A C, Martinez-Martin J, Hernandez R J. An adrenal carcinoma producing androgens, estrogens, and cortisol.  Anales de Medicina Interna. 1997;  14 190-192
    PubMedGoogle Scholar
  • 23 Muthusethupathi M A, Vimala A, Jayakumar M, Rajendran S. Normotensive primary aldosteronism due to adrenocortical carcinoma.  Nephron. 1998;  79 247-248
    CrossrefPubMedGoogle Scholar
  • 24 Brown J W, Fishman L M. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas.  Brazilian J Med & Biol Res. 2000;  33 1235-1244
    PubMedGoogle Scholar
  • 25 Ehrhart-Bornstein M, Hilbers U. Neuroendocrine properties of adrenocortical cells.  Horm Metab Res. 1998;  30 436-439
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Reincke M. Mutations in adrenocortical tumors.  Horm Metab Res. 1998;  30 447-455
    PubMedGoogle Scholar

1 This work was supported by the U.S. Department of Veterans Affairs.

Dr. J. W. Brown

Adrenal Research (151)
V.A. Medical Center

1201 N.W. 16 St.
Miami, FL 33125
U.S.A.


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