Expression of 11beta-hydroxysteroid dehydrogenase (11betaHSD) proteins in luteinizing human granulosa-lutein cells

Thurston, L.M.; Chin, E; Jonas, Kim; Bujalska, Iwona; Stewart, Paul M.; Abayasekara, D R E; Michael, A E

doi:10.1677/joe.0.1780127

Cited by 19 publications

(16 citation statements)

References 51 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: 78%

See 1 more Smart Citation

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: 78%

“…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: 97%

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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show abstract

“…In contrast, bovine and human granulosa cells were found to express 11b-HSD1, but not 11b-HSD2 (Tetsuka et al 2003;Chandras et al 2007). Other studies showed that human granulosa cells expressed 11b-HSD2 message during the follicular phase, and upon stimulation, ceased to express 11b-HSD2 and began to express 11b-HSD1 (Thurston et al 2003a). As in our rats, both HSD enzymes were reported in the bovine corpora lutea, with 11b-HSD2 expression increasing in comparison to that of 11b-HSD1 as the corpora lutea matured (Tetsuka et al 2003).…”

Section: Discussionsupporting

confidence: 75%

“…In our present studies, IHC did not detect H6PDH in rat granulosa cells, which would further decrease the availability of NADPH. The resulting decrease in local cortisol concentrations was thought to be important in the late follicular phase (Thurston et al 2003a(Thurston et al ,2007). An endogenous inhibitor of 11b-HSD reductase activity produced by granulosalutein cells has been proposed (Thurston et al 2003b), and inappropriate production of this inhibitor has been postulated to be the cause of infertility in some women (Michael et al 1996).…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Demonstration of the Mineralocorticoid Receptor, 11β-Hydroxysteroid Dehydrogenase-1 and −2, and Hexose-6-phosphate Dehydrogenase in Rat Ovary

Gómez-Sánchez

Gomez-Sanchez

Rodriguez

et al. 2009

J Histochem Cytochem.

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An IHC survey using several monoclonal antibodies against different portions of the rat mineralocorticoid receptor (MR) molecule demonstrated significant specific MR immunoreactivity in the ovary, prompting further study of the localization of MR and of determinants of extrinsic MR ligand specificity, 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2, and hexose-6-phosphate dehydrogenase (H6PDH). MR expression (real-time RT-PCR and Western blot) did not differ significantly in whole rat ovaries at early diestrus, late diestrus, estrus, and a few hours after ovulation. MR immunostaining was most intense in corporal lutea cells, light to moderate in oocytes and granulosa cells, and least intense in theca cells. Light immunoreactivity for 11β-HSD2 occurred in most cells, with some mural granulosa cells of mature follicles staining more strongly. The distribution of immunoreactivity for 11β-HSD1 and H6PDH required to generate NADPH, the cofactor required for reductase activity of 11β-HSD1, was similar, with the most-intense staining in the cytoplasm of corporal lutea and theca cells and light or no staining in the granulosa and oocytes. MR function in the ovary is as yet unclear, but distinct patterns of distribution of 11β-HSD1 and −2 and H6PDH suggest that the ligand for MR activation in different cells of the ovary may be differentially regulated. (J Histochem Cytochem 57:633–641, 2009)

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“…The expression of steroidogenic enzyme mRNAs was also determined by RT-PCR. Additionally, western blot analysis for a steroid metabolizing enzyme, 11b-hydroxysteroid dehydrogenase (11b-HSD; Thurton et al 2003) as a marker of steroidogenic cells, was performed. The concentrations of P 4 in the conditioned medium of the preparation T SAKURAI and others .…”

Section: Isolation Culture and Characterization Of Luteal Ecsmentioning

confidence: 99%

Stimulation of tube formation mediated through the prostaglandin EP2 receptor in rat luteal endothelial cells

Sakurai¹,

Suzuki²,

Yoshie³

et al. 2011

Journal of Endocrinology

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To explore the role of prostaglandin E 2 (PGE 2 ) in angiogenesis in the developing corpus luteum, luteal microvascular endothelial-like cells (luteal ECs) were prepared from highly luteinizing ovaries of rats using the percoll density gradient method. The cells abundantly expressed the mRNAs of the endothelial markers CD31 (PECAM-1) and responded to the vascular endothelial growth factor (VEGF) to form in vitro tube structures on Matrigel. Cyclooxygenase (COX) inhibitors significantly suppressed tube formation in luteal ECs, whereas PGE 2 counteracted the COX inhibitorinduced blockage. PGE 2 -induced tube formation was blocked by a cyclic AMP-dependent protein kinase A (PKA) inhibitor, H89. The antagonist against the PGE receptor type 2 (EP2 receptor), AH6809, completely inhibited PGE 2 -induced tube formation and partly suppressed the VEGF-induced tube formation but did not attenuate PGE 2 -induced phosphorylation of both AKT kinase and extracellular signal-regulated kinase 1/2. VEGF significantly enhanced the expression of COX-2 mRNAs detected by realtime RT-PCR and PGE 2 secretion into the media measured by ELISA in luteal ECs. In turn, PGE 2 stimulated VEGF expression. In vitro co-culture of luteal ECs with steroidogenic luteal cells (SLCs) promoted tube formation. Pre-treatment of SLCs with VEGF further enhanced tube formation of ECs, and this effect was blocked by the COX-2 inhibitor. This stimulatory effect was inhibited by treatment with AH6809. These data indicate that PGE 2 exerts a direct stimulatory effect on tube formation mainly via the EP2 receptor/PKA signaling in luteal ECs. Our results suggest the possibility that the endogenous PGE 2 that is produced from luteinizing follicular cells as well as ECs may stimulate luteal angiogenesis.

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Expression of 11beta-hydroxysteroid dehydrogenase (11betaHSD) proteins in luteinizing human granulosa-lutein cells

Cited by 19 publications

References 51 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

Immunohistochemical Demonstration of the Mineralocorticoid Receptor, 11β-Hydroxysteroid Dehydrogenase-1 and −2, and Hexose-6-phosphate Dehydrogenase in Rat Ovary

Stimulation of tube formation mediated through the prostaglandin EP2 receptor in rat luteal endothelial cells

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