Intra-tissue steroid profiling indicates differential progesterone and testosterone metabolism in the endometrium and endometriosis lesions

Journal of Clinical Endocrinology and Metabolism

Volumn 99, Issue 11, 2014, Pages E2188-E2197

  Huhtinen, Kaisa ^a   Saloniemi Heinonen, Taija ^a   Keski Rahkonen, Pekka ^b   Desai, Reena ^c   Laajala, Daniel ^a,d   Stahle, Mia ^a   Häkkinen, Merja R ^b   Awosanya, Michael ^a   Suvitie, Pia ^a   Kujari, Harry ^a   Aittokallio, Tero ^d   Handelsman, David J ^c   Auriola, Seppo ^b   Perheentupa, Antti ^a   Poutanen, Matti ^a,e  

^a UNIVERSITY OF TURKU   (Finland)

^b UNIVERSITY OF EASTERN FINLAND   (Finland)

^c UNIVERSITY OF SYDNEY   (Australia)

^d UNIVERSITY OF HELSINKI   (Finland)

^e UNIVERSITY OF GOTHENBURG   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN RECEPTOR; AROMATASE; CHOLESTEROL MONOOXYGENASE (SIDE CHAIN CLEAVING); CYTOCHROME P450 17; CYTOCHROME P450 17A1; PROGESTERONE; STERYL SULFATASE; TESTOSTERONE; UNCLASSIFIED DRUG; 3 BETA-HYDROXYSTEROID DEHYDROGENASE TYPE II; 3BETA HYDROXY DELTA5 STEROID DEHYDROGENASE; MESSENGER RNA;

ARTICLE; CONTROLLED STUDY; ENDOMETRIOSIS; ENDOMETRIUM; FEMALE; GENE; GENE EXPRESSION; HSD3B2 GENE; HUMAN; HUMAN TISSUE; MAJOR CLINICAL STUDY; MENSTRUAL CYCLE; PRIORITY JOURNAL; PROGESTERONE BLOOD LEVEL; PROGESTERONE METABOLISM; PROLIFERATIVE PHASE; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; SECRETORY PHASE; SIGNAL TRANSDUCTION; SRD5A1 GENE; SRD5A2 GENE; SRD5A3; TESTOSTERONE BLOOD LEVEL; TESTOSTERONE METABOLISM; TISSUE LEVEL; BLOOD; GENETICS; METABOLISM; PATHOLOGY;

CHOLESTEROL SIDE-CHAIN CLEAVAGE ENZYME; ENDOMETRIOSIS; ENDOMETRIUM; FEMALE; HUMANS; MENSTRUAL CYCLE; PROGESTERONE; PROGESTERONE REDUCTASE; RNA, MESSENGER; TESTOSTERONE;

EID: 84910000143     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2014-1913     Document Type: Article

References (37)

1. Giudice L. Clinical practice. Endometriosis. N Engl J Med. 2010; 362: 2389-2398.
2. Attia GR, Zeitoun K, Edwards D, Johns A, Carr B, Bulun S. Progesterone receptor isoformAbut notBis expressed in endometriosis. J Clin Endocrinol Metab. 2000;85: 2897-2902.
3. Bulun S. Endometriosis. N Engl J Med. 2009;360: 268-279.
4. Huhtinen K, Desai R, Stahle M, et al. Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels. J Clin Endocrinol Metab. 2012;97: 4228-4235.
5. Bulun SE, Utsunomiya H, Lin Z, et al. Steroidogenic factor-1 and endometriosis. Mol Cell Endocrinol. 2009;300: 104-108.
6. Attar E, Bulun S. Aromatase and other steroidogenic genes in endometriosis: Translational aspects. Hum Reprod Update. 2006;12: 49-56.
7. Aghajanova L, Hamilton A, Kwintkiewicz J, Vo KC, Giudice LC. Steroidogenic enzyme and key decidualization marker dysregulation in endometrial stromal cells from women with versus without endometriosis. Biol Reprod. 2009;80: 105-114.
8. Gibson DA, McInnes KJ, Critchley HO, Saunders PT. Endometrial Intracrinology- generation of an estrogen-dominated microenvironment in the secretory phase of women. J Clin Endocrinol Metab. 2013;98: E1802-1806.
9. Delvoux B, D'Hooghe T, Kyama C, et al. Inhibition of type 1 17 β- hydroxysteroid dehydrogenase impairs the synthesis of 17 β-estradiol in endometriosis lesions. J Clin Endocrinol Metab. 2014;99: 276-284.
10. Colette S, Defrère S, Van Kerk O, Van Langendonckt A, Dolmans MM, Donnez J. Differential expression of steroidogenic enzymes according to endometriosis type. Fertil Steril. 2013;100: 1642-1649.
11. Harwood DT, Handelsman DJ. Development and validation of a sensitive liquid chromatography-tandem mass spectrometry assay to simultaneously measure androgens and estrogens in serum without derivatization. Clin Chim Acta. 2009;409: 78-84.
12. Keski-Rahkonen P, Huhtinen K, Poutanen M, Auriola S. Fast and sensitive liquid chromatography-mass spectrometry assay for seven androgenic and progestagenic steroids in human serum. J Steroid Biochem Mol Biol. 2011;127: 396-404.
13. Evaul K, Li R, Papari-Zareei M, Auchus RJ, Sharifi N. 3beta-hydroxysteroid dehydrogenase is a possible pharmacological target in the treatment of castration-resistant prostate cancer. Endocrinology. 2010;151: 3514-3520.
14. Thomas JL, Mason JI, Brandt S, SpencerBRJr, Norris W. Structure/function relationships responsible for the kinetic differences between human type 1 and type 2 3beta-hydroxysteroid dehydrogenase and for the catalysis of the type 1 activity. J Biol Chem. 2002; 277: 42795-42801.
15. Cloke B, Huhtinen K, Fusi L, et al. The androgen and progesterone receptors regulate distinct gene networks and cellular functions in decidualizing endometrium. Endocrinology. 2008;149: 4462-4474.
16. Marshall E, Lowrey J, MacPherson S, et al. In silico analysis identifies a novel role for androgens in the regulation of human endometrial apoptosis. J Clin Endocrinol Metab. 2011;96: E1746-1755.
17. Hiissa J, Elo LL, Huhtinen K, Perheentupa A, Poutanen M, Aittokallio T. Resampling reveals sample-level differential expression in clinical genome-wide studies. OMICS. 2009;13: 381-396.
18. Huhtinen K, Stahle M, Perheentupa A, Poutanen M. Estrogen biosynthesis and signaling in endometriosis. Mol Cell Endocrinol. 2012;358: 146-154.
19. Kim JJ, Kurita T, Bulun SE. Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev. 2013;34: 130-162.
20. Wiebe JP. Progesterone metabolites in breast cancer. Endocr Relat Cancer. 2006;13: 717-738.
21. Lovely LP, Appa Rao KB, Gui Y, Lessey BA. Characterization of androgen receptors in a well-differentiated endometrial adenocarcinoma cell line (Ishikawa). J Steroid Biochem Mol Biol. 2000;74: 235-241.
22. Apparao KB, Lovely LP, Gui Y, Lininger RA, Lessey BA. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome. Biol Reprod. 2002;66: 297-304.
23. Tuckerman E, Okon MA, Li T, Laird SM. Do androgens have a direct effect on endometrial function? An in vitro study. Fertil Steril. 2000;74: 771-779.
24. McGrath M, Lee I, Hankinson S, et al. Androgen receptor polymorphisms and endometrial cancer risk. Int J Cancer. 2006;118: 1261-1268.
25. Kajihara T, Tochigi H, Prechapanich J, et al. Androgen signaling in decidualizing human endometrial stromal cells enhances resistance to oxidative stress. Fertil Steril. 2012;97: 185-191.
26. Kajihara T, Tanaka K, Oguro T, et al. Androgens Modulate the Morphological Characteristics of Human Endometrial Stromal Cells Decidualized In Vitro. Reprod Sci. 2013.
27. Nantermet PV, Masarachia P, Gentile MA, et al. Androgenic induction of growth and differentiation in the rodent uterus involves the modulation of estrogen-regulated genetic pathways. Endocrinology. 2005;146: 564-578.
28. Selak V, Farquhar C, Prentice A, Singla A. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2007; CD000068.
29. Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Crosignani P. Endometriosis: Current therapies and new pharmacological developments. Drugs. 2009;69: 649-675.
30. Ishikawa T, Harada T, Kubota T, Aso T. Testosterone inhibits matrix metalloproteinase-1 production in human endometrial stromal cells in vitro. Reproduction. 2007;133: 1233-1239.
31. Hampton AL, Salamonsen LA. Expression of messenger ribonucleic acid encoding matrix metalloproteinases and their tissue inhibitors is related to menstruation. J Endocrinol. 1994;141: R1-R3.
32. Osteen K, Bruner-Tran K, Ong D, Eisenberg E. Paracrine mediators of endometrial matrix metalloproteinase expression: potential targets for progestin-based treatment of endometriosis. Ann N Y Acad Sci. 2002;955: 139-146; discussion 157-138, 396-406.
33. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98: 511-519.
34. Cloke B, Christian M. The role of androgens and the androgen receptor in cycling endometrium. Mol Cell Endocrinol. 2012;358: 166-175.
35. Carneiro MM, Morsch DM, Camargos AA, Reis FM, Spritzer PM. Androgen receptor and 5alpha-reductase are expressed in pelvic endometriosis. BJOG. 2008;115: 113-117.
36. Uemura M, Tamura K, Chung S, et al. Novel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer. Cancer Sci. 2008;99: 81-86.
37. Maia H Jr, Casoy J, Pimentel K, et al. Effect of oral contraceptives on vascular endothelial growth factor, Cox-2 and aromatase expression in the endometrium of uteri affected by myomas and associated pathologies. Contraception. 2008;78: 479-485.