Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Statistics
  • Help & Advice
University of Warwick

The Library

  • Login

Inhibition of steroid sulphatase activity in endometriotic implants by 667 COUMATE : a potential new therapy

Tools
- Tools
+ Tools

Purohit, A., Fusi, L., Brosens, Jan J., Woo, L. W. L., Potter, B. V. L. and Reed, M. J.. (2008) Inhibition of steroid sulphatase activity in endometriotic implants by 667 COUMATE : a potential new therapy. Human Reproduction, Vol.23 (No.2). pp. 290-297. ISSN 0268-1161

Full text not available from this repository.
Official URL: http://dx.doi.org/10.1093/humrep/dem308

Abstract

BACKGROUND Local biosynthesis of estrogens is thought to be important for the maintenance and growth of endometriotic implants. In addition to the formation of estrogen via the aromatase pathway, steroid sulphatase (STS), which is responsible for the hydrolysis of estrogen sulphates, may be an important source of estrogens in endometriosis. METHODS Eutopic and ectopic endometrial samples from 14 women with minimal or mild (MM) endometriosis and from 13 women with moderate to severe (MS) endometriosis were analysed for aromatase and STS activities. RESULTS Aromatase and STS activity were detected in all samples. STS enzyme activity in both eutopic and ectopic endometrium was considerably higher and less variable than aromatase activity. Moreover, STS, but not aromatase, activity in endometriotic implants correlated with the severity of the disease (mean ± SEM: 203 ± 38 nmol/4 h/g wet weight tissue in MM disease versus 423 ± 44 nmol/4 h/g wet weight tissue in MS endometriosis, P < 0.001). The STS inhibitor 667 COUMATE almost completely blocked STS activity (>99%) in both eutopic and ectopic tissues. CONCLUSIONS The high levels of STS activity detected in ectopic endometrium and the correlation with severity of disease suggest that STS inhibitors could be useful for the treatment of endometriosis.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RG Gynecology and obstetrics
Divisions: Faculty of Medicine > Warwick Medical School > Reproductive Health
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Endometriosis -- Treatment -- Research, Endometriosis -- Etiology -- Research, Sulfatases, Sulfatases -- Inhibitors, Estrogen -- Synthesis
Journal or Publication Title: Human Reproduction
Publisher: OUP
ISSN: 0268-1161
Date: February 2008
Volume: Vol.23
Number: No.2
Page Range: pp. 290-297
Identification Number: 10.1093/humrep/dem308
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: Sterix Ltd.
References: Acien P, Velasco I, Gutierrez M, Martinez-Beltran M. Aromatase expression in endometriotic tissues and its relationship to clinical and analytical findings. Fertil Steril 2007;88:32–38. Adessi GL, Proust O, Agani G, Petitjean A, Burnod J. Estrone sulfatase activity in normal and abnormal endometrium. Arch Gynecol 1984;236:13–18. Brosens J, Verhoeven H, Campo R, Gianoroli L, Gordts S, Hazkamp J, Hagglund L, Mardesic T, Varila E, Zech J et al. High endometrial aromatase P450 mRNA expression is associated with poor IVF outcome. Human Reprod 2004;19:352–356. Bulun SE, Zeitoun KM, Takayama K, Simpson ER, Sasano H. Aromatase as a therapeutic target in endometriosis. Trends Endocrinol Metab 2000; 11:22–27. Carlstrom K, Doberl A, Gershagen S, Rannevik G. Peripheral levels of dehydroepiandrosterone sulphate, dehydroepiandrosterone, androstenedione and testosterone following different doses of danazol. Acta Obstet Gynecol Scand Suppl 1984a;123:125–129. Carlstrom K, Doberl A, Pousette A, Rannevik G, Wilking N. Inhibition of steroid sulphatase by danazol. Acta Obstet Gynecol Scand Suppl 1984b;123:107–111. Carlstrom K, Bergqvist A, Ljungberg O. Metabolism of estrone sulfate in endometriosis tissue and in uterine endometrium in proliferative and secretory cyclic phase. Fertil Steril 1988;49:229–233. Duncan L, Purohit A, Howarth NM, Potter BVL, Reed MJ. Inhibition of estrone sulfatase activity by estrone-3-methylthiophosphonate—a potential therapeutic agent in breast cancer. Cancer Res 1993;53:298–303. Ezaki K, Motoyama H. Immunohistologic localization of estrone sulfatase in uterine endometrium and adenomyosis. Obstet Gynecol 2001;98:815–819. Halme J, White C, Kauma S, Estes J, Haskill S. Peritoneal macrophages from patients with endometriosis release growth factor activity in vitro. J Clin Endocrinol Metab 1998;66:1044–1049. Heilier J-F, Donnez O, Van Kerckhove V, Lison D, Donnez J. Expression of aromatase (P450/CYP19) in peritoneal and ovarian endometriotic tissues and deep endometriosis (adenomyotic) nodules of the rectovaginal septum. Fertil Steril 2006;85:1516–1518. James VHT, McNeill JM, Lai LC, Newton CJ, Ghilchik MW, Reed MJ. Aromatase activity in normal breast and tumor tissue: in vivo and in vitro studies. Steroids 1987;50:269–279. Keenan JA, Chen TT, Chadwell NL, Torry DS, Candle MR. Interferon-gamma and interleukin-6 in peritoneal fluid and macrophage-conditioned media of women with endometriosis. Am J Reprod Immunol 1994;32:180–183. Keenan JA, Chen TT, Chadwell NL, Torry DS, Candle MR. IL-1 beta, TNF-a and IL-2 in peritoneal fluid and macrophage-conditioned media of women with endometriosis. Am J Reprod Immunol 1995;34:381–385. Maitako K, Sasaki H. Gonadotropin-releasing hormone agonist inhibits estrone sulfatase expression of cystic endometriosis of the ovary. Fertil Steril 2004;82:322–326. Naitoh K, Hanjo H, Yamamoto T, Urabe M, Ogin Y, Yasumura T, Nambara T. Estrone sulfate and sufatase activity in human breast cancer and endometrial cancer. J Steroid Biochem 1989;33:1049–1064. Noble LS, Simpson ER, Johns A, Bulun SE. Aromatase expression in endometriosis. J Clin Endocrinol Metab 1996;81:174–179. Noble LS, Takayama K, Zeitoun KM, Putman JM, Johns DA, Hinshelwood MM, Agarwal VR, Zhao Y, Carr BR, Bulun SE. Prostaglandin E2 stimulates aromatase expression in endometriosis derived stromal cells. J Clin Endocrinol Metab 1997;82:600–602. Noel CT, Reed MJ, Jacobs HS, James VHT. The plasma concentration of oestrone sulphate in postmenopausal women: lack of diurnal variation, effect of ovariectomy, age and weight. J Steroid Biochem 1981;14:1101–1105. Pasqualini JR, Gelly C, Nguyen BL, Vella C. Importance of oestrogen sulphates in breast cancer. J Steroid Biochem 1989;34:155–163. Purohit A, Ghilchik MW, Duncan L, Wang DY, Singh A, Walker MM, Reed MJ. Aromatase activity and interleukin-6 production by normal and malignant breast tissues. J Clin Endocrinol Metab 1995a;80:3052–3058. Purohit A, Williams GJ, Roberts CJ, Potter BVL, Reed MJ. In vivo inhibition of oestrone sulphatase and dehydroepiandrosterone sulphatase by oestrone-3-O-sulphamate. Int J Cancer 1995b;63:106–111. Purohit A, Williams GJ, Howarth NM, Potter BVL, Reed MJ. Inactivation of steroid sulfatase by an active site-directed inhibitor estrone-3-O-sulfamate. Biochemistry 1995c;34:11508–11514. Purohit A, Wang DY, Ghilchik MW, Reed MJ. Regulation of aromatase and sulphatase in breast cancer cells. J Endocrinol 1996;150;(Suppl):S65–S71. Reed MJ, Purohit A. Breast cancer and the role of cytokines in regulating estrogen synthesis: an emerging hypothesis. Endocr Rev 1997;18:701–715. Reed MJ, Purohit A, Woo LWL, Potter BVL. The development of steroid sulphatase inhibitors. Endocr Relat Cancer 1996;3:9–23. Reed MJ, Purohit A, Woo LWL, Newman SP, Potter BVL. Steroid sulfatase: molecular biology, regulation and inhibition. Endocr Rev 2005;26:171–202. Revised American Fertility Society classification of endometriosis: 1985. Fertil Steril 1985;43:351–352. Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927;14:422–425. Santner SJ, Feil PD, Santen RJ. In situ estrogen production via estrone sulfatase pathway in breast tumors: relative importance vs the aromatase pathway. J Clin Endocrinol Metab 1984;59:29–33. Smuc T, Pucelj MR, Sinkovec J, Husen B, Thole H, Rizner TL. Expression analysis of the genes involved in estradiol and progesterone action in human ovarian endometriosis. Gynec Endocrinol 2007;23:105–111. Stanway SJ, Purohit A, Woo LWL et al. Phase I study of STX64 (667 COUMATE) in breast cancer patients: the first study of a steroid sulfatase inhibitor. Clin Cancer Res 2006;12:1585–1592. Takayama K, Zeitoun K, Gunby RT, Sasano H, Carr BR, Bulun SE. Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril 1998;69:709–713. Utsunomiya H, Ito K, Suzuki T, Kitamura T, Kaneko C, Nakata T, Niikura H, Okamura K, Yaegashi N, Sasano H. Steroid sulfatase and estrogen sulfotransferase in human endometrial carcinoma. Clin Cancer Res 2004;10:5850–5856. Velasco I, Rueda J, Acien P. Aromatase expression in endometriotic tissues and cell cultures of patients with endometriosis. Mol Hum Reprod 2006;12: 377–381. Vigano P, Parazzini F, Somigliana E, Vercellini P. Endometriosis: epidemiology and aetiological factors. Best Practice Res Clin Obset 2004;18:177–200. Waller KG, Shaw RW. Gonadotropin-releasing hormone analogues for the treatment of endometriosis: long-term follow up. Fertil Steril 1993;59:511–515. Woo LWL, Purohit A, Reed MJ, Potter BVL. Active site directed inhibition of estrone sulfatase by non-steroidal coumarin sulfamates. J Med Chem 1996;39:1349–1351. Woo LWL, Howarth NM, Purohit A, Hejaz HAM, Reed MJ, Potter BVL. Steroidal and non-steroidal sulfamates as potent inhibitors of steroid sulfatase. J Med Chem 1998;41:1068–1083. Woo LWL, Purohit A, Malini B, Reed MJ, Potter BVL. Potent active site-directed inhibitors of steroid sulfatase by tricyclic coumarin-based sulphamates. Chem Biol 2000;7:773–791. Yamamoto T, Nuguchi T, Tamura T, Kitawaki J, Okada H. Evidence for estrogen synthesis in adenomyotic tissue. Am J Obstet Gynec 1993;169:734–738. Zeitoun K, Takayama K, Sasano H, Suzuki T,Moghrabi N, Andersson S, Johns A, Meng L, Putman M, Carr B et al. Deficient 17b-hydroxysteroid dehydrogenase Type 2 expression in endometriosis: failure to metabolize 17b-estradiol. J Clin Endocrinol Metab 1998;83:4474–4480.
URI: http://wrap.warwick.ac.uk/id/eprint/45909

Request changes to a record

Actions (login required)

View Item View Item
twitter

Email us: publications@warwick.ac.uk
Contact Details
About Us