Identification of ST2A1 as a rat brain neurosteroid sulfotransferase mRNA

Shimada, M.; Yoshinari, Kouichi; Tanabe, Emi; Shimakawa, Emi; Kobashi, Maki; Nagata, Kiyoshi; Yamazoe, Yasushi

doi:10.1016/s0006-8993(01)03061-x

Cited by 35 publications

(14 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cDNA was random-primer labeled with [␣-32 P]CTP (Amersham Biosciences). After prehybridization overnight with 15 mM sodium chloride solution containing 1.5 mM sodium citrate and 0.5% SDS, the membrane was hybridized with 32 P-labeled probe (1 ϫ 10 6 cpm/ml) in 0.5 M sodium phosphate buffer, pH 7.2, containing 7% SDS, 1% bovine serum albumin, and 1 mM EDTA overnight. After washing with 20 mM sodium phosphate buffer, pH 7.2, containing 1% SDS and 1 mM EDTA, the membrane was exposed to an imaging plate for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Protective Role of Hydroxysteroid Sulfotransferase in Lithocholic Acid-induced Liver Toxicity

Kitada

Miyata

Nakamura

et al. 2003

Journal of Biological Chemistry

Self Cite

148

149

View full text Add to dashboard Cite

Supplement of 1% lithocholic acid (LCA) in the diet for 5-9 days resulted in elevated levels of the marker for liver damage aspartate aminotransferase and alkaline phosphatase activities in both farnesoid X receptor (FXR)-null and wild-type female mice. The levels were clearly higher in wild-type mice than in FXR-null mice, despite the diminished expression of a bile salt export pump in the latter. Consistent with liver toxicity marker activities, serum and liver levels of bile acids, particularly LCA and taurolithocholic acid, were clearly higher in wild-type mice than in FXR-null mice after 1% LCA supplement. Marked increases in hepatic sulfating activity for LCA (5.5-fold) and hydroxysteroid sulfotransferase (St) 2a (5.8-fold) were detected in liver of FXR-null mice. A 7.4-fold higher 3␣-sulfated bile acid concentration was observed in bile of FXR-null mice fed an LCA diet compared with that of wild-type mice. Liver St2a content was inversely correlated with levels of alkaline phosphatase. In contrast, microsomal LCA 6␤-hydroxylation was not increased and was in fact lower in FXRnull mice compared in wild-type mice. Clear decreases in mRNA encoding sodium taurocholate cotransporting polypeptide, organic anion transporting polypeptide 1, and liver-specific organic anion transporter-1 function in bile acid import were detected in LCA-fed mice. These transporter levels are higher in FXR-null mice than wild-type mice after 1% LCA supplement. No obvious changes were detected in the Mrp2, Mrp3, and Mrp4 mRNAs. These results indicate hydroxysteroid sulfotransferase-mediated LCA sulfation as a major pathway for protection against LCA-induced liver damage. Furthermore, Northern blot analysis using FXR-null, pregnane X receptor-null, and FXR-pregnane X receptor double-null mice suggests a repressive role of these nuclear receptors on basal St2a expression.

show abstract

Section: Methodsmentioning

confidence: 99%

Protective Role of Hydroxysteroid Sulfotransferase in Lithocholic Acid-induced Liver Toxicity

Kitada

Miyata

Nakamura

et al. 2003

Journal of Biological Chemistry

Self Cite

148

149

View full text Add to dashboard Cite

show abstract

“…Enzymes responsible for synthesis of 3␣-OH-DHP from progesterone, 5␣-reductase and 3␣-OH steroid oxidoreductase, are present in the medulla (105,118,168), and ovarian hormones can regulate 3␣-OH-DHP synthesis in brain tissue (131). Importantly, differences in peripheral and CNS levels of 3␣-OH-DHP during pregnancy suggest that local regulation determines the effective concentrations of 3␣-OH-DHP in a brain region-specific manner (14,38,168,173). Preliminary data suggest that messenger RNA for both 5␣-reductase and 3␣-OH steroid oxidoreductase is increased in the RVLM of term pregnant rats (87), and treatment of near-term pregnant rats with the 5␣-reductase inhibitor Finasteride partially restores baroreflex-mediated sympathoexcitation (125).…”

Section: Neurosteroid Metabolite Of Progesterone: a Contributor To Atmentioning

confidence: 99%

Pregnancy and the endocrine regulation of the baroreceptor reflex

Brooks

Dampney

Heesch

2010

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

-The purpose of this review is to delineate the general features of endocrine regulation of the baroreceptor reflex, as well as specific contributions during pregnancy. In contrast to the programmed changes in baroreflex function that occur in situations initiated by central command (e.g., exercise or stress), the complex endocrine milieu often associated with physiological and pathophysiological states can influence the central baroreflex neuronal circuitry via multiple sites and mechanisms, thereby producing varied changes in baroreflex function. During pregnancy, baroreflex gain is markedly attenuated, and at least two hormonal mechanisms contribute, each at different brain sites: increased levels of the neurosteroid 3␣-hydroxydihydroprogesterone (3␣-OH-DHP), acting in the rostral ventrolateral medulla (RVLM), and reduced actions of insulin in the forebrain. 3␣-OH-DHP appears to potentiate baroreflex-independent GABAergic inhibition of premotor neurons in the RVLM, which decreases the range of sympathetic nerve activity that can be elicited by changes in arterial pressure. In contrast, reductions in the levels or actions of insulin in the brain blunt baroreflex efferent responses to increments or decrements in arterial pressure. Although plasma levels of angiotensin II are increased in pregnancy, this is not responsible for the reduction in baroreflex gain, although it may contribute to the increased level of sympathetic nerve activity in this condition. How these different hormonal effects are integrated within the brain, as well as possible interactions with additional potential neuromodulators that influence baroreflex function during pregnancy and other physiological and pathophysiological states, remains to be clearly delineated.3␣-hydroxy-dihydroprogesterone; angiotensin II; insulin; paraventricular nucleus of the hypothalamus NORMAL PREGNANCY is characterized by profound changes in fluid and electrolyte balance and blood pressure regulation. Blood volume and cardiac output increase by 30 -50%, but arterial pressure falls due to even greater decreases in systemic vascular resistance (120,138,189). These hemodynamic alterations are evident early in pregnancy, precede the increases in uterine blood flow, and are sustained until parturition (127,138,189). Considerable data implicate increases in relaxin and nitric oxide (NO) in the systemic vasodilation induced by pregnancy (20,127,128,177,196). In addition, peripheral vascular sensitivity to circulating vasoconstrictors including vasopressin, angiotensin II (ANG II), and norepinephrine (NE) is decreased (50,71,154).Unlike the hemodynamic changes, which likely subserve adequate fetal development, an adverse consequence of normal pregnancy is a marked impairment of the arterial baroreceptor reflex. This change was first noted by Humphreys and Joels (97,98) in an extensive series of studies in anesthetized pregnant rabbits, in which reductions in carotid sinus pressure failed to elicit normal increases in arterial pressure and peripheral vascular resistanc...

show abstract

“…Given that DHEA can be converted to DHEAS in the brain and liver in a reaction that is catalyzed by sulphotransferase (Rajkowski et al 1997;Aldred and Waring 1999;Shimada et al 2001) the antidepressive effect of DHEA can be explained by the interaction between the sigma 1 receptor agonist DHEAS (Maurice et al 1996) and noradrenaline and serotonin neurotransmission. As has already been mentioned, enhancement of noradrenaline (Delgado and Moreno 2000) and serotonin (Delgado 2000) neurotransmission is considered to have an antidepressant effect.…”

Section: Interaction Of Dhea With Sigma Receptorsmentioning

confidence: 99%