17-Hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis

Serdar E Bulun, You Hong Cheng, MaryEllen Pavone, Ping Yin, Gonca Imir, Hiroki Utsunomiya, Stephen Thung, Qing Xue, Erica E Marsh, Hideki Tokunaga, Hiroshi Ishikawa, Takeshi Kurita, Emily J. Su

Research output: Contribution to journalReview article

47 Citations (Scopus)

Abstract

Estradiol (E2) stimulates the growth and inflammation in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Several clinical and laboratory-based observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptor (PR). In normal endometrium, progesterone acts via PR on stromal cells to induce secretion of paracrine factor(s) that in turn stimulate neighboring epithelial cells to express the enzyme 17β-hydroxysteroid dehydrogenase type 2 (HSD17B2). HSD17B2 is an extremely efficient enzyme and rapidly metabolizes the biologically potent estrogen E2 to weakly estrogenic estrone. In endometriotic tissue, progesterone is incapable of inducing epithelial HSD17B2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate HSD17B2 may be due to the very low levels of PR observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this mitogen. The molecular details of this physiological paracrine interaction between the stroma and epithelium in normal endometrium and its lack thereof in endometriosis are discussed.

Original languageEnglish (US)
Pages (from-to)44-50
Number of pages7
JournalSeminars in Reproductive Medicine
Volume28
Issue number1
DOIs
StatePublished - Feb 19 2010

Fingerprint

Endometriosis
Progesterone Receptors
Stromal Cells
Progesterone
Endometrium
Choristoma
Estrone
Enzymes
Mitogens
Estradiol
Estrogens
Epithelium
Epithelial Cells
Inflammation
17-Hydroxysteroid Dehydrogenase Deficiency
Progesterone Resistance
Growth

Keywords

  • 17β-HSD-2
  • Endometriosis
  • Endometrium
  • Epithelial-stromal
  • Estradiol
  • HSD17B2
  • Paracrine
  • Progesterone
  • Receptor
  • Resistance
  • Retinoic acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Reproductive Medicine
  • Endocrinology
  • Obstetrics and Gynecology
  • Physiology (medical)

Cite this

Bulun, Serdar E ; Cheng, You Hong ; Pavone, MaryEllen ; Yin, Ping ; Imir, Gonca ; Utsunomiya, Hiroki ; Thung, Stephen ; Xue, Qing ; Marsh, Erica E ; Tokunaga, Hideki ; Ishikawa, Hiroshi ; Kurita, Takeshi ; Su, Emily J. / 17-Hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis. In: Seminars in Reproductive Medicine. 2010 ; Vol. 28, No. 1. pp. 44-50.
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abstract = "Estradiol (E2) stimulates the growth and inflammation in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Several clinical and laboratory-based observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptor (PR). In normal endometrium, progesterone acts via PR on stromal cells to induce secretion of paracrine factor(s) that in turn stimulate neighboring epithelial cells to express the enzyme 17β-hydroxysteroid dehydrogenase type 2 (HSD17B2). HSD17B2 is an extremely efficient enzyme and rapidly metabolizes the biologically potent estrogen E2 to weakly estrogenic estrone. In endometriotic tissue, progesterone is incapable of inducing epithelial HSD17B2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate HSD17B2 may be due to the very low levels of PR observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this mitogen. The molecular details of this physiological paracrine interaction between the stroma and epithelium in normal endometrium and its lack thereof in endometriosis are discussed.",
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Bulun, SE, Cheng, YH, Pavone, M, Yin, P, Imir, G, Utsunomiya, H, Thung, S, Xue, Q, Marsh, EE, Tokunaga, H, Ishikawa, H, Kurita, T & Su, EJ 2010, '17-Hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis', Seminars in Reproductive Medicine, vol. 28, no. 1, pp. 44-50. https://doi.org/10.1055/s-0029-1242992

17-Hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis. / Bulun, Serdar E; Cheng, You Hong; Pavone, MaryEllen; Yin, Ping; Imir, Gonca; Utsunomiya, Hiroki; Thung, Stephen; Xue, Qing; Marsh, Erica E; Tokunaga, Hideki; Ishikawa, Hiroshi; Kurita, Takeshi; Su, Emily J.

In: Seminars in Reproductive Medicine, Vol. 28, No. 1, 19.02.2010, p. 44-50.

Research output: Contribution to journalReview article

TY - JOUR

T1 - 17-Hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis

AU - Bulun, Serdar E

AU - Cheng, You Hong

AU - Pavone, MaryEllen

AU - Yin, Ping

AU - Imir, Gonca

AU - Utsunomiya, Hiroki

AU - Thung, Stephen

AU - Xue, Qing

AU - Marsh, Erica E

AU - Tokunaga, Hideki

AU - Ishikawa, Hiroshi

AU - Kurita, Takeshi

AU - Su, Emily J.

PY - 2010/2/19

Y1 - 2010/2/19

N2 - Estradiol (E2) stimulates the growth and inflammation in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Several clinical and laboratory-based observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptor (PR). In normal endometrium, progesterone acts via PR on stromal cells to induce secretion of paracrine factor(s) that in turn stimulate neighboring epithelial cells to express the enzyme 17β-hydroxysteroid dehydrogenase type 2 (HSD17B2). HSD17B2 is an extremely efficient enzyme and rapidly metabolizes the biologically potent estrogen E2 to weakly estrogenic estrone. In endometriotic tissue, progesterone is incapable of inducing epithelial HSD17B2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate HSD17B2 may be due to the very low levels of PR observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this mitogen. The molecular details of this physiological paracrine interaction between the stroma and epithelium in normal endometrium and its lack thereof in endometriosis are discussed.

AB - Estradiol (E2) stimulates the growth and inflammation in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Several clinical and laboratory-based observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptor (PR). In normal endometrium, progesterone acts via PR on stromal cells to induce secretion of paracrine factor(s) that in turn stimulate neighboring epithelial cells to express the enzyme 17β-hydroxysteroid dehydrogenase type 2 (HSD17B2). HSD17B2 is an extremely efficient enzyme and rapidly metabolizes the biologically potent estrogen E2 to weakly estrogenic estrone. In endometriotic tissue, progesterone is incapable of inducing epithelial HSD17B2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate HSD17B2 may be due to the very low levels of PR observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this mitogen. The molecular details of this physiological paracrine interaction between the stroma and epithelium in normal endometrium and its lack thereof in endometriosis are discussed.

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KW - Endometriosis

KW - Endometrium

KW - Epithelial-stromal

KW - Estradiol

KW - HSD17B2

KW - Paracrine

KW - Progesterone

KW - Receptor

KW - Resistance

KW - Retinoic acid

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U2 - 10.1055/s-0029-1242992

DO - 10.1055/s-0029-1242992

M3 - Review article

C2 - 20108182

AN - SCOPUS:76649124563

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