China
Africa
Explore chapters and articles related to this topic
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
Pregnenolone sulfate is a physiologically active sulfated derivative of pregnenolone. Endogenous pregnenolone sulfate in the hippocampus is believed to enhance memory, and age-related decline in memory function of rats correlates well with decline in hippocampal pregnenolone sulfate levels. A number of studies have shown that the physiological action of pregnenolone sulfate is reciprocal to that of allopregnanolone. Pregnenolone sulfate has convulsant properties (Kokate et al., 1999b), inhibits GABAA receptor currents (Baulieu, 1998), and enhances NMDA currents (Wu et al., 1991).
Formation and Metabolism of Steroid Conjugates: Effect of Conjugation on Excretion and Tissue Distribution
Published in Ronald Hobkirk, Steroid Biochemistry, 1979
P. I. Musey, K. Wright, J. R. K. Preedy, D. C. Collins
The formation of dehydroisoandrosterone sulfate and other steroid sulfates by the adrenal has been demonstrated using various in vitro adrenal tissue preparations.107,108,114–121 Killinger and Solomon114 incubated normal human adrenal homogenate with 7α-pregnenolone-3H and isolated dehydroisoandrosterone sulfate, 17α-hydroxypregnenolone sulfate, pregnenolone sulfate, and 5-pregn-enetriol sulfate from the incubation extract. When 7α-pregnenolone sulfate was incubated under identical conditions, no evidence for metabolism of this conjugate was obtained. This suggested that 5-pregnenetriol and its sulfate may be secretion products of the normal human adrenal gland.114
The Role of Steroid Sulfatase and Sulfotransferase Enzymes in the Metabolism of C21 and Cl9 Steroids
Published in Ronald Hobkirk, Steroid Biochemistry, 1979
Killinger and Solomon45 studied the metabolism of [3H] pregnenolone sulfate and [3H] pregnenolone by homogenates of normal human adrenal tissue. They were unable to demonstrate any steroid sulfate products after incubation with pregnenolone sulfate, but identified the following products with pregnenolone as the substrate: pregnenolone sulfate, 17α-hydroxypregnenolone sulfate, and dehydroepiandrosterone sulfate. These results indicate that, in the normal human adrenal, pregnenolone serves as a substrate for further metabolism while pregnenolone sulfate is not metabolized. Pérez-Palacios et al.43 studied the metabolism of [3H] pregnenolone sulfate by homogenates of fetal adrenals of different gestational ages. They isolated 17a-hydroxypreg-nenolone sulfate, dehydroepiandrosterone sulfate, and 16a-hydroxydehydroepiandros-terone sulfate. They interpreted this as demonstrating a direct steroid sulfate pathway because of the absence of steroid sulfatase in second trimester fetal adrenals. However, in a later study, Payne and Jaffe5 demonstrated that second trimester fetal adrenals do contain steroid sulfatase, and that it can cleave pregnenolone sulfate. The incubation media of Pérez-Palacios et al.43 contained all the necessary cofactors for steroid sulfation. In addition, because very high steroid sulfotransferase activity has been reported in fetal adrenals, their study cannot be taken as proof of the presence of a direct steroid sulfate pathway in human fetal adrenal gland. Cook et al.46 also studied pregnenolone and pregnenolone sulfate metabolism in adrenal glands of human previable fetuses. They reported very little metabolism of pregnenolone sulfate, although free pregnenolone was readily metabolized to pregnenolone sulfate, dehydroepiandrosterone sulfate, and dehydroepiandrosterone. The studies on human fetal adrenals indicate that if a direct steroid sulfate pathway exists, it is of minor significance. The major function of the fetal adrenal would appear to be the formation of steroid sulfates, which are transferred via cord blood to the placenta, where they are cleaved to free steroids and further metabolized to estrogens.
Change in gene expression levels of GABA, glutamate and neurosteroid pathways due to acoustic trauma in the cochlea
Published in Journal of Neurogenetics, 2021
Meltem Cerrah Gunes, Murat Salih Gunes, Alperen Vural, Fatma Aybuga, Arslan Bayram, Keziban Korkmaz Bayram, Mehmet Ilhan Sahin, Muhammet Ensar Dogan, Sevda Yesim Ozdemir, Yusuf Ozkul
For our investigation of the effect of AT on the genetic level Gls, Slc1a2, Slc17a8, Grin2b, Gabra1, Gad1, Slc6a1, Sult1a1 and Cyp11a1 genes were selected. Gls encodes the major enzyme that converts glutamine to glutamate, so it is responsible for the majority of glutamate synthesis (Prusiner, 1981). Slc1a2 encodes the protein required for the removal of glutamate from the synapse and termination of its excitatory effect (Shashidharan, Wittenberg, & Plaitakis, 1994). Slc17a8 encodes the protein that carries glutamate to presynaptic vesicles (Takamori, Malherbe, Broger, & Jahn, 2002). Grin2b encodes a glutamate-activated ion channel receptor located in excitatory synapses in the brain (Endele et al., 2010). Gabra1 encodes one of the GABA receptors (Garrett et al., 1988). Gad1 encodes the enzyme that catalyzes the conversion of glutamic acid to GABA, the main inhibitory neurotransmitter (Erlander & Tobin, 1991). Slc6a1 encodes the carrier that removes GABA from the synaptic cleft to presynaptic terminals (Hirunsatit et al., 2009). Cyp11a1 encodes the enzyme that catalyzes the conversion of cholesterol to pregnenolone which is the first and rate-limiting step in the synthesis of steroid hormones (John et al., 1984). Sult1a1 encodes the enzyme that converts pregnenolone to pregnenolone sulfate (PREGS) which is a neurosteroid in the brain (Wilborn et al., 1993). The genes and their pathways are shown in Table 1.
Diurnal variation of metabolites in three individual participants
Published in Chronobiology International, 2019
Fangyi Gu, Elizabeth B. Klerman, Sungduk Kim, Steve Moore, Kai Yu, Paul S. Albert, Neil E Caporaso
In contrast, steroids peak in the morning. These molecules include cortisol, pregnenolone sulfate, and bilirubin. Cortisol is a hormone that increases in response to diverse physiologic stimuli, such as stress and low blood-glucose concentration. The morning rise in cortisol serves to increase blood sugar, elevate blood pressure, suppress the immune system, and to aid in macronutrient metabolism of fat, protein, and carbohydrates (Martin PA, 2003). Our results are consistent with previous reports in humans that blood cortisol has diurnal variation and peaks in the morning (Ang et al. 2012), (Martin 2003). Pregnenolone sulfate has cognitive, memory enhancing and antidepressant effects (Reddy 2010). Bilirubin is a product of heme catabolism, which has been suggested as a potential cellular antioxidant (Sedlak et al. 2009).
GABA(A) receptor-targeted drug development -New perspectives in perioperative anesthesia
Published in Expert Opinion on Drug Discovery, 2019
Bernd Antkowiak, Gerhard Rammes
Steroids active at GABAA receptors are active as sedative-hypnotics, anticonvulsants, and anxiolytics in animal models [123,177–179] and 3α,5α-THPROG and 3α,5α-THDOC produce potent anaesthetic effects [174,180,181]. Interestingly, progesterone which was known to induce rapid anaesthesia [133] does not affect GABA-evoked currents [182]. The sulfated neuroactive steroids pregnenolone sulfate and dehydroepiandrosterone sulfate (DHEAS), which are NAMs at GABAA receptors, induce anxiogenic and proconvulsant effects [183]. However, also other mechanisms e.g via NMDA and σ1 receptors have been described [184,185].