테스토스테론의 대사물인 androsterone의 경련억제에 대한 영향
The Effect of Androsterone as the Metabolite of Testosterone to Seizure Suppression
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Androsterone is one of the major metabolites from testosterone whose clinical importance remains unclear. This study evaluated the effects of androsterone on seizure susceptibility in mouse models of epilepsy. Methods: The efficacy of androsterone (10~200 mg/kg, i.p.) against seizures induced by various GABA receptor antagonists and glutamate receptor agonists was evaluated. Results: Androsterone protected mice against seizures induced by PTZ (pentylenetetrazol), PCX (picrotoxin), and DMCM (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) in a dose-dependent manner. Androsterone did not protect against seizures induced by kainic acid, NMDA (N-methyl-D-aspartic acid), or 4-AP (4-aminopyridine) in mice. Conclusions: These results suggest that androsterone exhibits anticonvulsant activity that occurs largely via nongenomic mechanisms. Testosterone-derived androsterone might be an endogenous protective neuroactive steroid in the brain.
Abstract
Background: Androsterone is one of the major metabolites from testosterone whose clinical importance remains unclear. This study evaluated the effects of androsterone on seizure susceptibility in mouse models of epilepsy. Methods: The efficacy of androsterone (10~200 mg/kg, i.p.) against seizures induced by various GABA receptor antagonists and glutamate receptor agonists was evaluated. Results: Androsterone protected mice against seizures induced by PTZ (pentylenetetrazol), PCX (picrotoxin), and DMCM (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) in a dose-dependent manner. Androsterone did not protect against seizures induced by kainic acid, NMDA (N-methyl-D-aspartic acid), or 4-AP (4-aminopyridine) in mice. Conclusions: These results suggest that androsterone exhibits anticonvulsant activity that occurs largely via nongenomic mechanisms. Testosterone-derived androsterone might be an endogenous protective neuroactive steroid in the brain.
참고문헌 (24)
- Smith SS, "Estrogen administration increases neuronal responses to excitatory amino acids as a long-term effect", Brain Res, 503, pp.354~357 (1989)
- Logothetis J, "The role of estrogens in catamenial exacerbation of epilepsy", Neurology, 9, pp.352~360 (1959)
- Backstrom T, "Effects of intravenous progesterone infusions on the epileptic discharge frequency in women with partial epilepsy", Acta Neurol Scand, 69, pp.240~248 (1984)
- Landgren S, "The effect of progesterone on the spontaneous interictal spike evoked by the application of penicillin to the cat’s cerebral cortex", J Neurol Sci, 36, pp.119~133 (1978)
- Backstrom T, "Epileptic seizures in women related to plasma estrogen and progesterone during the menstrual cycle", Acta Neurol Scand, 54, pp.321~347 (1976)
- Rosciszewska D, "Ovarian hormones, anticonvulsant drugs, and seizures during the menstrual cycle in women with epilepsy", J Neurol Neurosurg Psychiatry, 49, pp.47~51 (1986)
- Herzog AG, "Progesterone therapy in women with epilepsy: a 3-year follow-up", Neurology, 52, pp.1917~1918 (1999)
- Frye CA, "Androgenic neurosteroids: anti-seizure effects in an animal model of epilepsy", Psychoneuroendocrinology, 23, pp.385~399 (1998)
- Edwards HE, "Testosterone and its metabolites affect afterdischarge thresholds and the development of amygdala kindled seizures", Brain Res, 838, pp.151~157 (1999)
- Kaminski RM, "Anticonvulsant activity of androsterone and etiocholanolone", Epilepsia, 46, pp.819~827 (2005)
- Loose DS, "Estrogens and Progestins. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed", pp.1541~1572 (2006), The McGraw-Hill Companies
- Selye H, "Correlations between the chemical structure and the pharmacological actions of the steroids", Endocrinology, 30, pp.437~453 (1942)
- Majewska MD, "Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor", Science, 232, pp.1004~1007 (1986)
- Paul SM, "Neuroactive steroids", FASEB J, 6, pp.2311~2322 (1992)
- Reddy DS, "Pharmacology of catamenial epilepsy", Methods Find Exp Clin Pharmacol, 26, pp.547~561 (2004)
- Lonsdale D, "The anticonvulsant effects of progesterone and its metabolites on amygdala-kindled seizures in male rats", Brain Res, 1101, pp.110~116 (2006)
- Reddy DS, "Anticonvulsant activity of progesterone and neurosteroids in progesterone receptor knockout mice", J Pharmacol Exp Ther, 310, pp.230~239 (2004)
- Thomas J, "Castration alters susceptibility of male rats to specific seizures", Physiol Behav, 49, pp.1177~1179 (1991)
- Herzog AG, "Testosterone versus testosterone and testolactone in treating reproductive and sexual dysfunction in men with epilepsy and hypogonadism", Neurology, 50, pp.782~784 (1998)
- Reddy DS, "Testosterone modulation of seizure susceptibility is mediated by neurosteroids 3alpha-androstanediol and 17beta-estradiol", Neuroscience, 129, pp.195~207 (2004)
- Herzog AG, "Reproductive endocrine considerations and hormonal therapy for men with epilepsy", Epilepsia, 32(6), pp.S34~S37 (1991)
- Snyder PJ, "Androgens. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed", pp.1573~1586 (2006), The McGraw-Hill Companies
- Kokate TG, "Convulsant actions of the neurosteroid pregnenolone sulfate in mice", Brain Res, 831, pp.119~124 (1999)
- Gee KW, "Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action", J Pharmacol Exp Ther, 246, pp.803~812 (1988)