scholarly journals Retinoic Acid Stimulates 17β-Estradiol and Testosterone Synthesis in Rat Hippocampal Slice Cultures

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4260-4269 ◽  
Author(s):  
Eiji Munetsuna ◽  
Yasushi Hojo ◽  
Minoru Hattori ◽  
Hirotaka Ishii ◽  
Suguru Kawato ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
De Novo ◽  
Fold Increase ◽  
Retinoid X Receptor ◽  
Rat Hippocampus ◽  
Male Rats ◽  
Receptor Signaling ◽  
Retinoic Acids ◽  
17Β Estradiol ◽  
Testosterone Synthesis

Abstract The hippocampus is essentially involved in learning and memory processes. Its functions are affected by various neuromodulators, including 17β-estradiol, testosterone, and retinoid. Brain-synthesized steroid hormones act as autocrine and paracrine modulators. The regulatory mechanism underlying brain steroidogenesis has not been fully elucidated. Synthesis of sex steroids in the gonads is stimulated by retinoic acids. Therefore, we examined the effects of retinoic acids on estradiol and testosterone biosynthesis in the rat hippocampus. We used cultured hippocampal slices from 10- to 12-d-old male rats to investigate de novo steroidogenesis. The infant rat hippocampus possesses mRNAs for steroidogenic enzymes and retinoid receptors. Slices were used after 24 h of preculture to obtain maximal steroidogenic activity because steroidogenesis in cultured slices decreases with time. The mRNA levels for P45017α, P450 aromatase and estrogen receptor-β in the slices were increased by treatment with 9-cis-retinoic acid but not by all-trans-isomer. The magnitude of stimulation and the shape of the dose-response curve for the mRNA level for P45017α were similar to those for cellular retinoid binding protein type 2, the transcription of which is activated by retinoid X receptor signaling. 9-cis-Retinoic acid also induced a 1.7-fold increase in the protein content of P45017α and a 2-fold increase in de novo synthesis of 17β-estradiol and testosterone. These steroids may be synthesized from a steroid precursor(s), such as pregnenolone or other steroids, or from cholesterol, as so-called neurosteroids. The stimulation of estradiol and testosterone synthesis by 9-cis-retinoic acid might be caused by activation of P45017α transcription via retinoid X receptor signaling.

Modulation of the Retinoic Acid and Retinoid X Receptor Signaling Pathways in P19 Embryonal Carcinoma Cells by Calreticulin

1997 ◽  
Vol 230 (1) ◽  
pp. 50-60 ◽  
Author(s):  
Mary Shago ◽  
Grace Flock ◽  
Chung-Yee Leung Hagesteijn ◽  
Michael Woodside ◽  
Sergio Grinstein ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Signaling Pathways ◽  
Embryonal Carcinoma ◽  
Retinoid X Receptor ◽  
Carcinoma Cells ◽  
Receptor Signaling ◽  
Embryonal Carcinoma Cells ◽  
P19 Embryonal Carcinoma Cells

scholarly journals Retinoic acid receptor γ 2 gene expression is up-regulated by retinoic acid in 3T3-L1 preadipocytes

1993 ◽  
Vol 293 (3) ◽  
pp. 807-812 ◽  
Author(s):  
Y Kamei ◽  
T Kawada ◽  
R Kazuki ◽  
E Sugimoto
Keyword(s):  
Adipose Tissue ◽  
Retinoic Acid ◽  
Mrna Expression ◽  
De Novo ◽  
Retinoic Acid Receptor ◽  
Mrna Level ◽  
Fold Increase ◽  
Dependent Manner ◽  
Alpha Beta ◽  
Rat Adipose Tissue

Retinoids, especially all-trans retinoic acid (RA), have been shown to inhibit the differentiation of preadipose cells. In the present study, the expression of retinoic acid receptors (RAR alpha, beta and gamma) and retinoid X receptors (RXR alpha, beta and gamma) was examined by Northern blot analysis in rat adipose tissue and mouse 3T3-L1 adipose cells. The adipose tissue and/or 3T3-L1 cells expressed mRNAs for a number of nuclear retinoid receptors, including RAR alpha, beta and gamma, and RXR alpha, beta and gamma. RAR alpha, RAR gamma, RXR alpha and RXR beta mRNAs were abundant in adipose tissue and 3T3-L1 cells. RXR gamma mRNA was detected in adipose tissue but not in 3T3-L1 cells. Treatment of 3T3-L1 cells with 1 microM RA led to a 4-5-fold increase in the RAR gamma mRNA level, but only a trace amount of RAR beta mRNA was detected. RAR gamma mRNA expression was rapidly (within 2 h) induced by physiological concentrations of RA in a dose-dependent manner. The response of RAR gamma mRNA expression to RA was reversible; rapid disappearance of RAR gamma mRNA occurred on RA removal. In addition, the induction of RAR gamma expression did not require de novo protein synthesis, but was completely abolished by an inhibitor of RNA synthesis. Using RAR gamma 1 and gamma 2 isoform-specific probes, the patterns of RAR gamma 1 and gamma 2 mRNA expression in 3T3-L1 cells in the presence and absence of RA were examined. RAR gamma 1 mRNA was detected in 3T3-L1 cells but was not affected by RA treatment; however, RAR gamma 2 mRNA was strongly induced by RA.

scholarly journals Genetic Ablation of Nuclear Receptor Interacting Protein 1 (NRIP1) Sensitizes Acute Myeloid Leukemia Cells to Retinoic Acids

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1146-1146
Author(s):  
Raveen Stephen Stallon Illangeswaran ◽  
Sreeja Karathedath ◽  
Abhirup Bagchi ◽  
Bharathi M Rajamani ◽  
Balaji Balakrishnan ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Line ◽  
Cell Lines ◽  
Nuclear Receptor ◽  
Fold Increase ◽  
Cd11b Expression ◽  
Interacting Protein ◽  
Genetic Ablation ◽  
Retinoic Acids ◽  
Differentiation Block

Abstract The success of differentiation therapy is limited to acute promyelocytic leukemia (APL), and approaches to overcome the differentiation block in non-M3 AML have been unsuccessful. Nuclear hormone receptors (NHR) belong to ligand-inducible transcription factors that govern many cellular functions like differentiation, metabolism, and development. Retinoic Acid Receptor Alpha (RXRA) is a class of NHR that, when activated by all-trans retinoic acid (ATRA), successfully alleviates differentiation block in APL. To identify the NHRs/cofactors that could mediate or prevent differentiation in AML, we examined the differentially expressed NHRs and cofactors between ATRA sensitive (ATs) (NB4 and HL60) vs. ATRA resistant (ATr) AML cell lines (KG1a, Hel, K562, MV4-11, and OCI-AML3). Nuclear Receptor Interacting Protein 1 (NRIP1), a corepressor known to prevent transactivation of ligand-activated NHRs preferentially, was one of the top upregulated targets in the ATr cell lines (3.5 fold increase in RNA expression, figure 1a ). Immunoblot analysis also showed a significant increase in NRIP1 protein expression in the ATr than ATs cell lines (Figure 1b). Further, probing for NRIP1 expression in the publicly available TCGA and MILE AML study cohorts showed decreased NRIP1 expression in the APL cohort compared to other AML subtypes. Methylation profile from CCLE database of the NRIP1 promoter in AML cell lines showed ATs cell lines to be highly methylated compared to the ATr cell lines, suggesting the involvement of NRIP1 in mediating differentiation block in non-M3 AML (Figure 1c). To further dissect the role of NRIP1 in mediating this differentiation block, we carried out experiments in the AML cell line KG1a (having primitive blast features, high expression of NRIP1, and unresponsive to ATRA). Using CRISPR-cas9, we developed an NRIP1 knock-out (KO) cell line (Figure 1d). NRIP1 KO cell line showed a significant reduction in proliferation rate (Doubling time 26.2 vs. 36.5Hrs p<0.05). Further, cell cycle analysis revealed that NRIP1 KO leads to increased accumulation of cells in the G0 phase than in the S-phase (Figure 1e & f). We next assessed the sensitivity of the NRIP1 WT/KO cells to retinoic acids ATRA and bexarotene. Cells were treated with 1µM ATRA / bexarotene or in combination for 72 hours and evaluated for differentiation using CD11b marker by flow cytometry. NRIP1 KO alone leads to a marginal increase in basal CD11b expression compared to the WT cells (Mean CD11b expression 2.03% Vs 0.91%). ATRA treatment further increased the CD11b expression to 3.8% in KO cells compared to 1.6% in the WT cells. A similar increase in CD11b expression was observed in bexarotene-treated cells (3.7% Vs 1.24%). Combination of ATRA with bexarotene showed a 3-fold increase in CD11b expression in the KO cells compared to the WT (23.9% Vs 7.2%, Figure 1g). NRIP1 KO diminishes its repressive action on ligand-activated RARA (ATRA activated) and RXRA (Bexarotene-activated), thereby allowing synergistic differentiation induction by retinoic acids in AML cells. This study suggests a potential mechanism of differentiation inhibition mediated by corepressor NRIP1 in AML cells unresponsive to retinoic acids. Further in-depth analyses of molecular pathways governed by NRIP1 during ligand activation of NHRs are warranted to design differentiation therapies for AML. Figure 1 Figure 1. Disclosures Mathews: Christian Medical College: Patents & Royalties: US 2020/0345770 A1 - Pub.Date Nov.5, 2020; AML: Other: Co-Inventor.

The Morphology of the Rat Kidney Following Folic Acid Administration

1970 ◽  
Vol 28 ◽  
pp. 200-201
Author(s):  
Aline Byrnes ◽  
Elsa E. Ramos ◽  
Minoru Suzuki ◽  
E.D. Mayfield
Keyword(s):  
Folic Acid ◽  
De Novo ◽  
Specific Activity ◽  
Rat Kidney ◽  
Present Report ◽  
Intracellular Localization ◽  
Male Rats ◽  
Renal Hypertrophy ◽  
Electron Microscopic ◽  
Biochemical Alterations

Renal hypertrophy was induced in 100 g male rats by the injection of 250 mg folic acid (FA) dissolved in 0.3 M NaHCO3/kg body weight (i.v.). Preliminary studies of the biochemical alterations in ribonucleic acid (RNA) metabolism of the renal tissue have been reported recently (1). They are: RNA content and concentration, orotic acid-c14 incorporation into RNA and acid soluble nucleotide pool, intracellular localization of the newly synthesized RNA, and the specific activity of enzymes of the de novo pyrimidine biosynthesis pathway. The present report describes the light and electron microscopic observations in these animals. For light microscopy, kidney slices were fixed in formalin, embedded, sectioned, and stained with H & E and PAS.

scholarly journals Immunological identification and functional quantitation of retinoic acid and retinoid X receptor proteins in human skin.

1994 ◽  
Vol 269 (32) ◽  
pp. 20629-20635 ◽  
Author(s):  
G.J. Fisher ◽  
H.S. Talwar ◽  
J.H. Xiao ◽  
S.C. Datta ◽  
A.P. Reddy ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Human Skin ◽  
Retinoid X Receptor ◽  
Receptor Proteins ◽  
Immunological Identification

scholarly journals Differential 9-cis-Retinoic Acid-dependent Transcriptional Activation by Murine Retinoid X Receptor (RXR) and RXR

1996 ◽  
Vol 271 (18) ◽  
pp. 10503-10507 ◽  
Author(s):  
Paul L. Hallenbeck ◽  
Saverio Minucci ◽  
Roland Lippoldt ◽  
Marcia Phyillaier ◽  
Valerie Horn ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Transcriptional Activation ◽  
Retinoid X Receptor

scholarly journals Adrenergic control of vascular resistance varies in muscles composed of different fiber types: influence of the vascular endothelium

2011 ◽  
Vol 301 (3) ◽  
pp. R783-R790 ◽  
Author(s):  
Bradley J. Behnke ◽  
Robert B. Armstrong ◽  
Michael D. Delp
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Vascular Endothelium ◽  
Fold Increase ◽  
Male Rats ◽  
Type I ◽  
Fiber Types ◽  
Fast Twitch Muscle ◽  
Dose Responses ◽  
Fast Twitch

The influence of the sympathetic nervous system (SNS) upon vascular resistance is more profound in muscles comprised predominately of low-oxidative type IIB vs. high-oxidative type I fiber types. However, within muscles containing high-oxidative type IIA and IIX fibers, the role of the SNS on vasomotor tone is not well established. The purpose of this study was to examine the influence of sympathetic neural vasoconstrictor tone in muscles composed of different fiber types. In adult male rats, blood flow to the red and white portions of the gastrocnemius (GastRed and GastWhite, respectively) and the soleus muscle was measured pre- and postdenervation. Resistance arterioles from these muscles were removed, and dose responses to α1-phenylephrine or α2-clonidine adrenoreceptor agonists were determined with and without the vascular endothelium. Denervation resulted in a 2.7-fold increase in blood flow to the soleus and GastRed and an 8.7-fold increase in flow to the GastWhite. In isolated arterioles, α2-mediated vasoconstriction was greatest in GastWhite (∼50%) and less in GastRed (∼31%) and soleus (∼17%); differences among arterioles were abolished with the removal of the endothelium. There was greater sensitivity to α1-mediated vasoconstriction in the GastWhite and GastRed vs. the soleus, which was independent of whether the endothelium was present. These data indicate that 1) control of vascular resistance by the SNS in high-oxidative, fast-twitch muscle is intermediate to that of low-oxidative, fast-twitch and high-oxidative, slow-twitch muscles; and 2) the ability of the SNS to control blood flow to low-oxidative type IIB muscle appears to be mediated through postsynaptic α1- and α2-adrenoreceptors on the vascular smooth muscle.

Stimulation of Tetrahydrobiopterin Synthesis by 17β-Estradiol in Brain Microvascular Endothelial Cells

Pteridines ◽  
2000 ◽  
Vol 11 (4) ◽  
pp. 129-132
Author(s):  
Kazuhiro Shiota ◽  
Masakazu Ishii ◽  
Toshinori Yamamoto ◽  
Shunichi Shimizu ◽  
Yuji Kiuchi
Keyword(s):  
Endothelial Cells ◽  
De Novo ◽  
Vascular Endothelial Cells ◽  
Mrna Level ◽  
Microvascular Endothelial Cells ◽  
No Production ◽  
Brain Microvascular Endothelial Cells ◽  
Protective Effects ◽  
17Β Estradiol ◽  
Microvascular Endothelial

Abstract The purpose of this study was to examine whether 17β-estradiol stimulates the synthesis of tetrahydrobiopterin : BH4), which is one of the cofactors of nitric oxide (NO) synthase, in mouse brain microvascular endothelial cells. Addition of 17()-estradiol to endothelial cells time- and concentration-dependently increased intracellular BH4 level. 17β-Estradiol also stimulated the mRNA level of GTP-cyclohydrolase I (GTPCH), which is a rate-limiting enzyme of the de novo BH4 synthetic pathway. In addition, the 17β-estradiol-induced expression of GTPCH mRNA was strongly attenuated by treatment with an inhibitor of 17β-estradiol receptor 4-hydroxy-tamoxlfen. These results suggest that 17β-estradiol stimulates BH4 synthesis through the induction of GTPCH by tamoxifensensitive receptor in vascular endothelial cells. The 17β-estradiol-induced increase in BH4 level might be implicated in not only NO production, but also protective effects of 17β-estradiol against ischemic brain damage and atherosclerosis, since BH4 is an intracellular antioxidant.

Effects of Guanethidine and Related Compounds on Histamine Excretion

1972 ◽  
Vol 50 (6) ◽  
pp. 539-544 ◽  
Author(s):  
J. LeBlanc ◽  
J. Côté ◽  
F. Doré ◽  
S. Rousseau
Keyword(s):  
Peritoneal Fluid ◽  
Fold Increase ◽  
Female Rats ◽  
Male Rats ◽  
Daily Injection ◽  
Histamine Metabolism ◽  
Methyl Transferase ◽  
Single Intraperitoneal Injection ◽  
Urinary Histamine ◽  
Related Compounds

The basic nature of guanethidine and some of its effects suggested a possible action of this drug on histamine metabolism. A single intraperitoneal injection of guanethidine (10 mg/kg) in male rats was found to double the daily urinary excretion of free histamine; daily injection for three weeks caused a 10-fold increase. In male rats, guanethidine increased the number of mast cells in the peritoneal fluid and, in both peritoneal fluid and mesentery, caused a significant degranulation of these cells; this action was not observed in female rats. This finding may indicate that guanethidine blocks methylation of histamine by inhibiting imidazole methyl transferase since this enzyme is found in male but not in female rats. Bethanidine and reserpine had no effect on histamine excretion. Imidazole was found to be even more potent than guanethidine in causing an increase in urinary histamine. Guanethidine and imidazole neither potentiated nor mimicked the action of histamine on the isolated ileum.

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