Ovarian 11β-hydroxysteroid dehydrogenase: potential predictor of conception by in-vitro fertilisation and embryo transfer

Michael, A.E.; Antoniw, Joseph W.; Cooke, Brian A.; Gregory, Linda; Walker, Sheila M.; Shaw, Robert W.; Edwards, C. R. W.

doi:10.1016/0140-6736(93)91710-4

Cited by 61 publications

(27 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, granulosa cell 11␤-HSD1 activity is decreased by depletion of the leukocytes in human follicular aspirates, and restored by addition of IL-4 and IFN-␥, suggesting the source of cytokines in this regulation may be leukocytes (192). The presence of 11␤-HSD2 activity (conversion of cortisol to cortisone) in cultured granulosa cells predicted pregnancy failure in women undergoing in vitro fertilization, whereas its absence was associated with successful pregnancy, although there was no association with fertilization per se (464). The underlying reason for this has not been elucidated.…”

Section: The Reproductive Systemmentioning

confidence: 95%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

709

601

View full text Add to dashboard Cite

Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

show abstract

Section: The Reproductive Systemmentioning

confidence: 95%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

709

601

View full text Add to dashboard Cite

show abstract

“…It has been shown that in-vitro characteristics such as the negative expression of 11 Beta-hydroxysteroid dehydrogenase (11β HSD) by granulosa cells (3), and the increased proliferation (4) and steroidogenic activity (2) of cumulus cells are predictors of conception in IVF.…”

Section: Introductionmentioning

confidence: 99%

Power Doppler ultrasound assessment of follicular vascularity in the early follicular phase and its relationship with outcome of in vitro fertilization

Shrestha

Costello

Sjöblom

et al. 2006

J Assist Reprod Genet

View full text Add to dashboard Cite

Objective : To determine whether ovarian perifollicular blood flow (PFBF) in the early follicular phase (EFP) was associated with treatment outcome. Design : Retrospective longitudinal cohort study. Setting : Tertiary referral centre/university hospital. Patients : Thirty-four women underwent 37 IVF cycles, which resulted in 35 embryo transfers. Interventions : Serial transvaginal scans using power Doppler ultrasound during the follicular phase. Ovarian PFBF of follicles ≥ 5 mm was subjectively assessed using a modified grading system (grades 0-4). Main outcome measures : Ovarian PFBF and pregnancy. Results : Treatment cycles were retrospectively divided into two groups: Group 1 (n = 20) had cycles with at least one small (5-10 mm) or medium (11-14 mm) size follicle(s) of high grade (2-4) PFBF on cycle day 5 or 6 or 7; and Group 2 (n = 17), had cycles that did not. Group 1 had a significantly higher proportion of high grade large follicles in the late follicular phase (35% vs. 21%) (OR 2.0; 95% CI 1.1-3.7) and higher clinical pregnancy rate (47% vs. 12%) (OR 6.3; CI 1.1-35.7) compared to Group 2. Conclusion : High grade ovarian PFBF in the EFP during IVF is associated with both high grade PFBF in the late follicular phase and a higher clinical pregnancy rate.

show abstract

“…While type 1 HSD11B (HSD11B1) is a relatively low affinity, NADP(H)-dependent bidirectional enzyme that can either inactivate cortisol or regenerate this physiological glucocorticoid from inert cortisone, HSD11B2 is a high affinity NAD C -dependent enzyme that acts exclusively as a dehydrogenase to inactivate cortisol (White et al 1997, Kotelevtsev et al 1999, Seckl & Walker 2001, Tomlinson et al 2004. Previously, the balance of cortisol-cortisone metabolism by HSD11B enzymes in human ovarian follicles has been linked to the ability of human oocytes to undergo fertilisation in vitro and to give rise to viable embryos in women undergoing assisted conception (Michael et al 1993, Keay et al 2002, Lewicka et al 2003, Thurston et al 2003a. Recently, we have reported that both cloned HSD11B isoenzymes are co-expressed in the mural granulosa cells of bovine and porcine antral follicles, and have shown that in both cows and pigs, the ability of the HSD11B enzymes to inactivate cortisol within the mural granulosa cells increases during antral follicle growth .…”

Section: Introductionmentioning

confidence: 99%

Inactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase enzymes increases during the meiotic maturation of porcine oocytes

Webb¹,

Sunak²,

Wren³

et al. 2008

Reproduction

View full text Add to dashboard Cite

Recent reports have shown that glucocorticoids can modulate oocyte maturation in both teleost fish and mammals. Within potential target cells, the actions of physiological glucocorticoids are modulated by 11b-hydroxysteroid dehydrogenase (HSD11B) isoenzymes that catalyse the interconversion of cortisol and cortisone. Hence, the objective of this study was to establish whether HSD11B enzymes mediate cortisol-cortisone metabolism in porcine oocytes and, if so, whether the rate of glucocorticoid metabolism changes during oocyte maturation. Enzyme activities were measured in cumulus-oocyte complexes (COCs) and denuded oocytes (DOs) using radiometric conversion assays. While COCs and DOs oxidised cortisol to inert cortisone, there was no detectable regeneration of cortisol from cortisone. The rate of cortisol oxidation was higher in expanded COCs than in compact COCs containing germinal vesicle (GV) stage oocytes (111G6 vs 2041G115 fmol cortisone/oocyte.24 h; P!0.001). Likewise, HSD11B activities were 17G1 fold higher in DOs from expanded COCs than in those from compact COCs (P!0.001). When GV stage oocytes were subject to a 48 h in vitro maturation protocol, the enzyme activities were significantly increased from 146G18 to 1857G276 fmol cortisone/oocyte.24 h in GV versus MII stage oocytes respectively (P!0.001). Cortisol metabolism was inhibited by established pharmacological inhibitors of HSD11B (glycyrrhetinic acid and carbenoxolone), and by porcine follicular and ovarian cyst fluid. We conclude that an HSD11B enzyme (or enzymes) functions within porcine oocytes to oxidise cortisol, and that this enzymatic inactivation of cortisol increases during oocyte maturation. Reproduction (2008) 136 725-732

show abstract

Ovarian 11β-hydroxysteroid dehydrogenase: potential predictor of conception by in-vitro fertilisation and embryo transfer

Cited by 61 publications

References 7 publications

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Power Doppler ultrasound assessment of follicular vascularity in the early follicular phase and its relationship with outcome of in vitro fertilization

Inactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase enzymes increases during the meiotic maturation of porcine oocytes

Contact Info

Product

Resources

About