β-catenin activation and illicit receptor expression in adrenocortical cells

2021 ◽  
Author(s):  
Julie Le Mestre ◽  
Michaël Thomas ◽  
Céline Duparc ◽  
Pierre Val ◽  
Clemence Bures ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Tumor Cells ◽  
Membrane Receptors ◽  
Receptor Expression ◽  
Zona Fasciculata ◽  
Adrenocortical Tumor ◽  
Adrenocortical Cells ◽  
Abnormal Expression ◽  
Insulinotropic Peptide ◽  
Adrenal Zona Fasciculata

Adrenal cortisol-producing tumors can express illicit membrane receptors such as luteinizing hormone (LH), glucose-dependent insulinotropic peptide (GIP) or type 4 and 7 serotonin (5-HT4/7) receptors. Abnormal expression of the LH receptor (LH-R) has been ascribed to activation of the Wnt/β-catenin signaling pathway in adrenocortical cells. In the present study, we have investigated whether β-catenin activation may also trigger illegitimate expression of GIP and 5-HT receptors. Three models of β-catenin activation in adrenocortical cells were used: an APC-mutated adrenocortical tumor, human transfected adrenocortical cells and genetically modified mouse adrenal glands. The methods employed included RT-qPCR, immunohistochemistry, and measurement of cortisol secretion by cultured tumor cells. Abnormal expression of the GIP, 5-HT7 and LH receptors was observed in the APC-mutated adrenocortical tumor tissue. In addition, GIP, 5-HT and hCG stimulated cortisol production from tumor cells in primary culture. Conversely, only the LHCGR was upregulated in human and mouse adrenocortical cells harboring activation of β-catenin. Moreover, LH-R immunoreactivity was detected in clusters of zona fasciculata cells in the β-catenin-activated mouse model. Our data indicate that activation of the β-catenin signaling pathway can promote illicit expression of functional LH receptors in adrenal zona fasciculata cells but does not favor abnormal expression of GIP and 5-HT receptors.

ACTH-induced Cl− current in bovine adrenocortical cells: correlation with cortisol secretion

2002 ◽  
Vol 282 (2) ◽  
pp. E355-E365 ◽  
Author(s):  
Sylvie Dupré-Aucouturier ◽  
Armelle Penhoat ◽  
Oger Rougier ◽  
André Bilbaut
Keyword(s):  
Carboxylic Acid ◽  
Membrane Conductance ◽  
External Solution ◽  
Membrane Depolarization ◽  
Zona Fasciculata ◽  
Cortisol Secretion ◽  
Current Clamp ◽  
Adrenocortical Cells ◽  
Induced Membrane ◽  
Adrenal Zona Fasciculata

ACTH has been shown to depolarize bovine adrenal zona fasciculata cells by inhibiting a K+ current. The effects of this hormone on such cells have been reexamined using perforated and standard patch recording methods. In current clamp experiments, ACTH (10 nM) induced a membrane depolarization to −36 ± 1 mV ( n = 56), which was mimicked by forskolin (10 μM) or by 8-(4-chlorophenylthio)-cAMP (8 mM). ACTH-induced membrane depolarizations were associated in the majority of cells with an increase in membrane conductance. In the other cells, these membrane responses could occur without change or could be correlated with a transient or with a continuous Cs+-sensitive decrease in membrane conductance. The depolarizations associated with an increase in membrane conductance were depressed by Cl− current inhibitors diphenylamine-2-carboxylic acid (DPC; 1 mM), anthracene-9-carboxylic acid (9-AC; 1 mM), DIDS (400 μM), verapamil (100 μM), and glibenclamide (20 μM). In voltage-clamped Cs+-loaded cells, ACTH activated a time-independent current that displayed an outward rectification and reversed at −21.5 mV ± 2 ( n = 6). This current, observed in the presence of internal EGTA (5 mM), was depressed in low Cl− external solution and was inhibited by DPC, 9-AC, DIDS, 5-nitro-2-(3-phenylpropylamino)benzoic acid, verapamil, and glibenclamide. ACTH-stimulated cortisol secretion was blocked by Cl− channel inhibitors DIDS (400 μM) and DPC (1 mM). The present results reveal that, in addition to inhibiting a K+current, ACTH activates in bovine zona fasciculata cells a Ca2+-insensitive, cAMP-dependent Cl− current. This Cl− current is involved in the ACTH-induced membrane depolarization, which seems to be a crucial step in stimulating steroidogenesis.

TGF‐β1/Smad2/3 signaling pathway modulates octreotide antisecretory and antiproliferative effects in pituitary somatotroph tumor cells

2021 ◽  
Author(s):  
Florencia Picech ◽  
Liliana DV. Sosa ◽  
Pablo A. Perez ◽  
Laura Cecenarro ◽  
Sergio R. Oms ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Tumor Cells ◽  
Antiproliferative Effects ◽  
Tgf Β1

scholarly journals Rho-kinase inhibitor hydroxyfasudil protects against HIV-1 Tat-induced dysfunction of tight junction and neprilysin/Aβ transfer receptor expression in mouse brain microvessels

2021 ◽  
Vol 476 (5) ◽  
pp. 2159-2170
Author(s):  
Qiangtang Chen ◽  
Yu Wu ◽  
Yachun Yu ◽  
Junxiang Wei ◽  
Wen Huang
Keyword(s):  
Tight Junction ◽  
Signaling Pathway ◽  
Mouse Brain ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Brain Microvessels ◽  
Rho Kinase Inhibitor ◽  
Hiv 1

AbstractHIV-1 transactivator protein (Tat) induces tight junction (TJ) dysfunction and amyloid-beta (Aβ) clearance dysfunction, contributing to the development and progression of HIV-1-associated neurocognitive disorder (HAND). The Rho/ROCK signaling pathway has protective effects on neurodegenerative disease. However, the underlying mechanisms of whether Rho/ROCK protects against HIV-1 Tat-caused dysfunction of TJ and neprilysin (NEP)/Aβ transfer receptor expression have not been elucidated. C57BL/6 mice were administered sterile saline (i.p., 100 μL) or Rho-kinase inhibitor hydroxyfasudil (HF) (i.p., 10 mg/kg) or HIV-1 Tat (i.v., 100 μg/kg) or HF 30 min before being exposed to HIV-1 Tat once a day for seven consecutive days. Evans Blue (EB) leakage was detected via spectrophotometer and brain slides in mouse brains. The protein and mRNA levels of zonula occludens-1 (ZO-1), occludin, NEP, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in mouse brain microvessels were, respectively, analyzed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. Exposure of the mice to HIV-1 Tat increased the amount of EB leakage, EB fluorescence intensity, blood–brain barrier (BBB) permeability, as well as the RAGE protein and mRNA levels, and decreased the protein and mRNA levels of ZO-1, occludin, NEP, and LRP1 in mouse brain microvessels. However, these effects were weakened by Rho-kinase inhibitor HF. Taken together, these results provide information that the Rho/ROCK signaling pathway is involved in HIV-1 Tat-induced dysfunction of TJ and NEP/Aβ transfer receptor expression in the C57BL/6 mouse brain. These findings shed some light on potentiality of inhibiting Rho/Rock signaling pathway in handling HAND.

scholarly journals Contributions of steroidogenic factor 1 to the transcription landscape of Y1 mouse adrenocortical tumor cells

2011 ◽  
Vol 336 (1-2) ◽  
pp. 85-91 ◽  
Author(s):  
Bernard P. Schimmer ◽  
Jennivine Tsao ◽  
Martha Cordova ◽  
Sara Mostafavi ◽  
Quaid Morris ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Adrenocortical Tumor ◽  
Steroidogenic Factor 1

scholarly journals Age-dependent Increases in Adrenal Cytochrome b5 and Serum 5-Androstenediol-3-sulfate

2016 ◽  
Vol 101 (12) ◽  
pp. 4585-4593 ◽  
Author(s):  
Juilee Rege ◽  
Shigehiro Karashima ◽  
Antonio M. Lerario ◽  
Joshua M. Smith ◽  
Richard J. Auchus ◽  
...  
Keyword(s):  
Cytochrome B5 ◽  
Serum Levels ◽  
Dehydroepiandrosterone Sulfate ◽  
Zona Fasciculata ◽  
Adrenocortical Cells ◽  
Normal Children ◽  
Age Related ◽  
Age Dependent ◽  
Lyase Activity ◽  
Liquid Chromatography Tandem Mass

Context: Adrenal production of dehydroepiandrosterone sulfate (DHEA-S) increases throughout childhood owing to expansion of the zona reticularis (ZR). ZR features cells with a steroidogenic phenotype distinct from that of the adjacent zona fasciculata, with higher expression of cytochrome b5 type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2). In addition to DHEA-S, three adrenal Δ5-steroid sulfates could provide additional tools to define adrenal maturation. Objective: This study sought to simultaneously measure serum levels of four adrenal Δ5-steroid sulfates, pregnenolone sulfate (Preg-S), 17α-hydroxypregnenolone sulfate (17OHPreg-S), DHEA-S, and 5-androstenediol-3-sulfate (Adiol-S) as a function of age and relate their production to the age-dependent adrenal localization of CYB5A. Participants and Methods: Δ5-steroid sulfates were quantified by liquid chromatography–tandem mass spectrometry in sera from 247 normal children (129 males,118 females) age 1.5–18 y and 42 adults (20 males, 22 females). Immunofluorescence localized HSD3B2 and CYB5A in normal adrenal glands from subjects age 2–35 y. Finally, HAC15 adrenocortical cells were transduced with lentiviral short hairpin RNA to suppress CYB5A expression. Results: Of the Δ5-steroid sulfates quantified, DHEA-S was most abundant. Adiol-S increased in parallel with DHEA-S. Steroid ratios (17OHPreg-S/DHEA-S) suggested increases in 17,20-lyase activity during childhood. Immunofluorescence analysis showed age-related increases in ZR CYB5A immunoreactivity. Furthermore, silencing CYB5A in HAC15 adrenocortical cells significantly reduced DHEA-S and Adiol-S production. Conclusion: Adiol-S shows a similar age-related increase to that of DHEA-S. This likely results from the childhood expansion of CYB5A-expressing ZR, which enhances 17,20-lyase activity and the production of DHEA-S and Adiol-S.

Effects of angiotensin II and ACTH on normal and tumourous human adrenocortical cells

1983 ◽  
Vol 104 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Wolfgang Belmega ◽  
Wolfgang Oelkers ◽  
Lutz Belkien ◽  
Monika Shirpai ◽  
Ulrich Fiedler ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Adrenocortical Adenoma ◽  
Response Curves ◽  
Adrenocortical Cells ◽  
Normal Cells ◽  
Fold Stimulation

Abstract. Isolated adrenocortical cells from 6 patients with a 'normal' zona fasciculata, 4 patients with a 'normal' zona glomerulosa, and tumour cells from 1 adrenocortical adenoma and 1 carcinoma were incubated with and without increasing concentrations of ACTH 1–24 (10−13 m to 10−9 m) or Asp1-Ile5-angiotensin II (10−11 m to 10−7 m). In 4/5 'normal' cases, cortisol was clearly stimulated by 10−13 m ACTH. The maximum of the dose-response curve (5-fold stimulation) was reached at 10−10 m ACTH. Angiotensin II (All) started to stimulate 'normal' cells at 10−11 m with a maximum (2-fold stimulation) at 10−9 m. Aldosterone production by 'normal' cells was less markedly stimulated by ACTH and All, although the threshold doses for both peptides were similar to those of the cortisol response curves. The cells of the adrenocortical adenoma from a patient with Cushing's syndrome produced large amounts of cortisol and small amounts of aldosterone, both steroids being clearly stimulated by ACTH and AII. The adrenocortical carcinoma cells produced small amounts of cortisol and no aldosterone. Cortisol production responded to ACTH, but not to AII. The results suggest that an activated renin-angiotensin system may stimulate the zona fasciculata, since 10−11 m All (= 10 pg AII/ml) is a normal plasma All concentration on an unrestricted diet. Clinical evidence supporting this thesis is reviewed. However, cortisol production itself will rarely be increased by All in vivo, since a downregulation of ACTH would occur.

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