Nongenomic Steroid Actions: Fact or Fantasy?

Christ, Michael; Haseroth, K.; Falkenstein, Elisabeth; Wehling, Martin

doi:10.1016/s0083-6729(08)60647-0

Cited by 54 publications

(22 citation statements)

References 192 publications

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“…Spatial homogenization of ventricular repolarization by progesterone may be explained by a direct and nongenomic action of progestagens on myocardial conduction velocities as previously reported in neuronal tissue. 18) This study highlights the need to take into account progesterone, as well as estrogen, when evaluating hormonal effects on repolarization in women. In all of the studies mentioned above, the effects of HRT on QT parameters during resting ECG were evaluated.…”

Section: Discussionmentioning

confidence: 93%

Effects of Long-Term Hormone Replacement Therapy on QT and Corrected QT Dispersion during Resting and Peak Exercise Electrocardiography in Post-Menopausal Women.

et al. 2002

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SUMMARYIt is known that the QT interval is longer in women than men. Estrogen is reported to account for the QT interval prolongation in several studies conducted with hormone replacement therapy (HRT) in postmenopausal women. Along with this, there are conflicting data as regards the effects of HRT on QT interval and dispersion. Moreover, there is no evidence about the effect of HRT on exercise QT parameters.We compared QT parameters obtained from surface electrocardiograms during resting and peak exercise before and after 6 months of HRT consisting of estrogen plus progesterone in healthy postmenopausal women. Twenty-four healthy postmenopausal women were given 0.625 mg/day conjugated estrogens and 2.5 mg/day medroxyprogesterone acetate for 6 months. Exercise stress testing using the Bruce protocol was performed before and after HRT. QT maximum, minimum, dispersion and corrected QT maximum, minimum and dispersion were calculated during resting and peak exercise.HRT resulted in a significant increase in estradiol plasma levels from 24±10 pg/mL to 117±66 pg/mL (P<0.001). There was no significant difference in resting QT parameters after HRT, whereas QT dispersion and corrected QT dispersion were significantly increased during peak exercise (20±7 versus 25±10 ms; P<0.05, 33±12 versus 41±16 ms; P<0.05, respectively). Nonetheless, the other exercise QT parameters were unchanged.The resting QT parameters are not affected by long term HRT consisting of estrogen plus progesterone, which leads to an increase in QT dispersion and corrected QT dispersion during peak exercise. (Jpn Heart J 2002; 43: 1-7)

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Section: Discussionmentioning

confidence: 93%

Effects of Long-Term Hormone Replacement Therapy on QT and Corrected QT Dispersion during Resting and Peak Exercise Electrocardiography in Post-Menopausal Women.

et al. 2002

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“…An important influence of the cell type used in the transactivation assay has been shown (50). Nongenomic effects postulated both for cortisol and aldosterone (19,51) are neither taken into account. Moreover, transrepression of genes (1,17,40) could not be evaluated by our approach.…”

Section: -Ketomentioning

confidence: 99%

Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties

et al. 2004

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Background: Glucocorticoids (GCs) are commonly used for long-term medication in immunosuppressive and anti-inflammatory therapy. However, the data describing gluco-and mineralo-corticoid (MC) properties of widely applied synthetic GCs are often based on diverse clinical observations and on a variety of in vitro tests under various conditions, which makes a quantitative comparison questionable. Method: We compared MC and GC properties of different steroids, often used in clinical practice, in the same in vitro test system (luciferase transactivation assay in CV-1 cells transfected with either hMR or hGRa expression vectors) complemented by a system to test the steroid binding affinities at the hMR (protein expression in T7-coupled rabbit reticulocyte lysate). Results and Conclusions: While the potency of a GC is increased by an 11-hydroxy group, both its potency and its selectivity are increased by the D1-dehydro-configuration and a hydrophobic residue in position 16 (16-methylene, 16a-methyl or 16b-methyl group). Almost ideal GCs in terms of missing MC effects, as defined by our in vitro assay, are therefore prednylidene, budesonide, beclomethasone and betamethasone. The MC potency of a steroid is increased by a 9a-or a 6a-fluoro substituent. A hydrophilic substituent in position 16 (like 16-hydroxylation in triamcinolone) decreases both MC and GC properties. As no substituent that leads to an isolated reduction of GC activity could be characterized in our experiments, 9a-fluorocortisol, the most frequently used steroid for MC substitution, seems to be the best choice of available steroids for this purpose.

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“…We have proposed for the first time that the member-receptor mediated rapid effects of GCs exist on mammalian neurons (Chen et al 1987). Recent evidence indicates that GCs might also act at the membrane to exert multiple rapid effects on various tissues and cells (Christ et al 1999). The rapid actions independent of the genome might be transduced by pleiotropic signaling pathway (Chen et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig

Zhou¹,

Kang²,

Xie³

et al. 2003

Journal of Endocrinology

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Glucocorticoids (GCs) are routinely believed to work solely through genomic mechanisms. Recent evidence indicates that GCs can act at the membrane to exert rapid nongenomic effects on various tissues and cells. To ascertain whether nongenomic effects of GCs exist on the allergic asthma reaction, Hartley guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received inhaled budesonide (3 mg/ml suspended in Hydroxypropyl methylcellulose vehicle) for 5 minutes before ovalbumin challenge; Other animals received saline or blank vehicle as control. We measured the changes of lung resistance and dynamic lung compliance, the pulmonary function used to evaluate allergic asthma severity. Inhaled budesonide inhibited allergic reaction within 10 minutes, which would preclude genomic-mediated responses that normally takes several hours to occur. This study infers for the first time that rapid nongenomic effect of GCs exists on allergic asthma reaction, and provides a new way to investigate nongenomic mechanism of GCs. Further study would raise the possibility of new therapeutic strategies for allergic disease including asthma.

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Nongenomic Steroid Actions: Fact or Fantasy?

Cited by 54 publications

References 192 publications

Effects of Long-Term Hormone Replacement Therapy on QT and Corrected QT Dispersion during Resting and Peak Exercise Electrocardiography in Post-Menopausal Women.

Effects of Long-Term Hormone Replacement Therapy on QT and Corrected QT Dispersion during Resting and Peak Exercise Electrocardiography in Post-Menopausal Women.

Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties

Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig

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