Isoforms of 11β-hydroxysteroid dehydrogenase in human granulosa-lutein cells

Michael, Anthony E.; Evagelatou, Marianthi; Norgate, Dean P.; Clarke, Rebecca J.; Antoniw, Joseph W.; Stedman, Brian; Brennan, Alex; Welsby, Rachel; Bujalska, Iwona; Stewart, Paul M.; Cooke, Brian A.

doi:10.1016/s0303-7207(97)00118-4

Cited by 50 publications

(53 citation statements)

References 40 publications

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“…The 11bHSD enzymes control cortisol metabolism by their type 1 (that tends to generate cortisol) and type 2 (that tends to inactivate cortisol) isoforms. Numerous studies have shown clear evidence that there is a switch in 11bHSD isoforms associated with the follicularluteal transition (Michael et al 1997, Tetsuka et al 1997, Yong et al 2000, Thurston et al 2003. We have confirmed this switch in women at a protein level and localised expression to the granulosa/granulosa-lutein cells of the ovary.…”

Section: Cells (G) Of An Antral (A) Follicle (A-c) and The Granulosa-supporting

confidence: 77%

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Activin A reduces luteinisation of human luteinised granulosa cells and has opposing effects to human chorionic gonadotropin in vitro

Myers¹,

Driesche²,

McNeilly

et al. 2008

Journal of Endocrinology

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The transition of the dominant follicle into the corpus luteum is of fundamental reproductive importance. Luteinisation involves disparate changes in the gene expression of follicular granulosa cells that differentiate into the granulosa-lutein cells of the corpus luteum after the gonadotrophin surge. We have shown that activin and human chorionic gonadotropin (hCG) have opposing effects during luteolysis. Therefore, we hypothesised that activin A was an inhibitor of luteinisation that was blocked during the pre-ovulatory gonadotrophin surge. Ovarian tissue and cells were collected from women with regular cycles having hysterectomy and women undergoing oocyte retrieval for assisted conception. Genes that changes during luteinisation were investigated in primary cultures of luteinised granulosa cells exposed to activin A and hCG in vitro. hCG promotes a luteinised granulosa cell phenotype, while activin A promotes a more follicular phenotype in luteinised cells by upregulating granulosa cells markers such as FSHR, HSD11B2 and downregulating LHCGR. In addition, activin A blocked hCG upregulation of STAR, HSD3B1 and HSD11B1 and downregulation of oestrogen receptor a. Activin A antagonised hCG effects in a dose-dependent manner and could block the hCG-stimulated molecular inhibitors of activin action (inhibin a-subunit, follistatin and TGFBR3). These studies show that hCG and activin A have opposing effects on luteinised granulosa cells and some effects of activin are seen only in the presence of hCG. While hCG can inhibit activin action in granulosa cells to facilitate luteinisation, activin A can promote an unluteinised phenotype in luteinised granulosa cells. This confirms the importance of adequate activin withdrawal during luteinisation in women.

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Section: Cells (G) Of An Antral (A) Follicle (A-c) and The Granulosa-supporting

confidence: 77%

“…The HSD11B enzyme isoforms change during luteinisation (Michael et al 1997, Tetsuka et al 1997, Yong et al 2000, Thurston et al 2003. The predominant isoform in follicular granulosa cells is HSD11B2 (Fig.…”

Section: Resultsmentioning

confidence: 98%

Activin A reduces luteinisation of human luteinised granulosa cells and has opposing effects to human chorionic gonadotropin in vitro

Myers¹,

Driesche²,

McNeilly

et al. 2008

Journal of Endocrinology

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“…As human granulosa cells luteinise in culture, the increased expression of 11bHSD1 mRNA is mirrored by a progressive increase in 11bHSD1 protein expression . Consistent with this switch from 11bHSD2 to 11bHSD1 expression, luteinised human granulosa cells exhibit increased 11KSR activity (Michael et al 1997, Tetsuka et al 1997.…”

Section: Introductionmentioning

confidence: 91%

“…Previous studies have reported the expression of mRNA encoding both of the cloned 11bHSD enzymes in human, rat and bovine ovaries (Waddell et al 1996, Michael et al 1997, Tetsuka et al 1997, Ricketts et al 1998. Molecular studies indicate that the major 11bHSD isoenzyme expressed in the ovary depends on the prevalent hormonal milieu and/or functional phenotype of the cells.…”

Section: Introductionmentioning

confidence: 99%

“…In the ovaries of rats and humans, the granulosa cells lining either preantral or immature antral follicles exclusively express 11bHSD2 (Tetsuka et al 1997, Ricketts et al 1998. However, following exposure to an ovulatory concentration of luteinizing hormone, these luteinising granulosa cells cease to express 11bHSD2 and switch to the expression of 11bHSD1 (Michael et al 1997, Tetsuka et al 1997. As human granulosa cells luteinise in culture, the increased expression of 11bHSD1 mRNA is mirrored by a progressive increase in 11bHSD1 protein expression .…”

Section: Introductionmentioning

confidence: 99%

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11β-Hydroxysteroid dehydrogenase expression and activities in bovine granulosa cells and corpora lutea implicate corticosteroids in bovine ovarian physiology

Thurston

Abayasekara

Michael

2007

Journal of Endocrinology

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Cortisol-cortisone metabolism is catalysed by the bi-directional NADP(H)-dependent type 1 11b-hydroxysteroid dehydrogenase (11bHSD1) enzyme and the oxidative NAD C -dependent type 2 11bHSD (11bHSD2). This study related the expression of 11bHSD1 and 11bHSD2 enzymes (mRNA and protein) to net 11-ketosteroid reductase and 11b-dehydrogenase (11b-DH) activities in bovine follicular granulosa and luteal cells. Granulosa cells were isolated from follicles of !4, 4-8, O8 and O12 mm in diameter in either the follicular or luteal phase of the ovarian cycle. Luteal cells were obtained from corpora lutea (CL) in the early non-pregnant luteal phase. Enzyme expression was assessed by reverse transcription-PCR and western blotting, while enzyme activities were measured over 1 h in cell homogenates using radiometric conversion assays with 100 nM [ 3 H]cortisone or [ 3 H]cortisol and pyridine dinucleotide cofactors. Irrespective of follicle diameter, the expression of 11bHSD2 and NAD C -dependent oxidation of cortisol predominated in granulosa cells harvested in the follicular phase. In contrast, in granulosa cells obtained from luteal phase follicles and in bovine luteal cells, expression of 11bHSD1 exceeded that of 11bHSD2 and the major enzyme activity was NADP C -dependent cortisol oxidation. Increasing follicular diameter was associated with progressive increases in expression and activities of 11bHSD2 and 11bHSD1 in follicular and luteal phase granulosa cells respectively. In follicular phase granulosa cells from antral follicles !12 mm, 11bHSD1 migrated with a molecular mass of 34 kDa, whereas in the dominant follicle, CL and all luteal phase granulosa cells, a second protein band of 68 kDa was consistently detected. In all samples, 11bHSD2 had a molecular mass of 48 kDa, but in large antral follicles (O8 mm), there was an additional immunoreactive band at 50 kDa. We conclude that 11bHSD2 is the predominant functional 11bHSD enzyme expressed in follicular phase granulosa cells from growing bovine antral follicles. In contrast, in bovine granulosa cells from dominant or luteal phase follicles, and in bovine luteal cells from early non-pregnant CL, 11bHSD1 is the major glucocorticoid-metabolising enzyme. The increasing levels of cortisol inactivation by the combined NADP C -and NAD C -dependent 11b-DH activities suggest a need to restrict cortisol access to corticosteroid receptors in the final stages of follicle development.

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Identification of novel functional inhibitors of 17β-hydroxysteroid dehydrogenase type III (17β-HSD3)

et al. 2005

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Isoforms of 11β-hydroxysteroid dehydrogenase in human granulosa-lutein cells

Cited by 50 publications

References 40 publications

Activin A reduces luteinisation of human luteinised granulosa cells and has opposing effects to human chorionic gonadotropin in vitro

Activin A reduces luteinisation of human luteinised granulosa cells and has opposing effects to human chorionic gonadotropin in vitro

11β-Hydroxysteroid dehydrogenase expression and activities in bovine granulosa cells and corpora lutea implicate corticosteroids in bovine ovarian physiology

Identification of novel functional inhibitors of 17β-hydroxysteroid dehydrogenase type III (17β-HSD3)

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