Disease relevance of EINECS 209-301-3

• Eubacterium lentum and phenotypically similar organisms synthesize a steroid 21-dehydroxylase which converts biliary tetrahydrodeoxycorticosterone to pregnanolone [1].
• In the present study, the effect of two synthetic neuroactive steroids, alphaxalone (5alpha-pregnane 3alpha-ol-11, 20-dione) and tetrahydrodeoxycorticosterone was studied in a rat model of generalized absence seizures induced by gamma-hydroxybutyric acid [2].
• Tetrahydroprogesterone and tetrahydrodeoxycorticosterone levels were found to be increased in a mouse model of acute liver failure, and, when THP or THDOC was injected into normal mice, sedation and Alzheimer type II astrocytic changes in the cortex, striatum, and hypothalmus were induced [3].

High impact information on EINECS 209-301-3

• In studying the levels of the mineralocorticoids, there was shown to be an increased basal level of tetrahydrodeoxycorticosterone (patients, 142-317 microgram/24 h; normal, 60-80 microgram/24 h) which was raised by ACTH stimulation [4].
• 1. The effects of the naturally occurring neurosteroid tetrahydrodeoxycorticosterone (THDOC) on GABAA receptor-mediated miniature, spontaneous and evoked IPSCs was tested using patch-clamp techniques in slices of hippocampus and cerebellum from rats at two developmental stages ( approximately 10 and approximately 20 days postnatal) [5].
• Inhibition by alpha-Tetrahydrodeoxycorticosterone (THDOC) of Pre-Sympathetic Parvocellular Neurones in the Paraventricular Nucleus of Rat Hypothalamus [6].
• In order to address this issue, gas chromatography/mass spectrometry was used to measure the neurosteroids pregnenolone, allopregnanolone, and tetrahydrodeoxycorticosterone (THDOC) in postmortem brain tissue from controls, cirrhotic patients who died without HE, a patient who died in uremic coma, and cirrhotic patients who died in hepatic coma [7].
• The neurosteroids tetrahydroprogesterone and tetrahydrodeoxycorticosterone increased [3H]GABA binding to hydra membranes with nanomolar potency (EC50, 141+/-11 and 623+/-36 nM, respectively) and high efficacy (maximal increase 79+/-6.5 and 62+/-4%, respectively), whereas the 3beta-hydroxy epimer of tetrahydroprogesterone was ineffective [8].

Biological context of EINECS 209-301-3

• Contrary to expectation, tetrahydrodeoxycorticosterone was ineffective in decreasing and if anything, enhanced the development of long-term potentiation [9].
• We characterized the interaction of 3alpha-hydroxy steroids, alphaxalone and tetrahydrodeoxycorticosterone (which are potent modulators of GABAA receptors) with GHB binding sites in rat brain cortical membranes [10].
• Oxidized ring A reduced pregnanes, tetrahydroprogesterone (THP), and tetrahydrodeoxycorticosterone (THDOC) bind to the progesterone intracellular receptor (PR), and in this way can also regulate gene expression [11].
• Our results suggest that the GABA(A) receptor delta subunit confers increased sensitivity to neurosteroid modulation and that the intrinsic gating and desensitization kinetics of alpha1beta3delta GABA(A) receptors are altered by THDOC [12].

Associations of EINECS 209-301-3 with other chemical compounds

• The neurosteroids dehydroepiandrosterone sulfate, tetrahydroprogesterone, pregnenolone sulfate, and tetrahydrodeoxycorticosterone (THDOC), products of PBR stimulation, at micromolar concentrations significantly enhanced (70%) ammonia-induced swelling [13].

Gene context of EINECS 209-301-3

• The in vitro and in vivo effects of alphaxalone, a steroid anesthetic, and two physiological steroids, tetrahydrodeoxycorticosterone (THDOC) and pregnenolone sulfate (PS), on GABAA receptor function were evaluated in long-sleep (LS) and short-sleep (SS) mice [14].

References