scholarly journals Angiotensin II-Induced Mitogen-Activated Protein Kinase Phosphatase-1 Expression in Bovine Adrenal Glomerulosa Cells: Implications in Mineralocorticoid Biosynthesis

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5573-5581 ◽  
Author(s):  
Andrés J. Casal ◽  
Stéphane Ryser ◽  
Alessandro M. Capponi ◽  
Carine F. Wang-Buholzer
Keyword(s):  
Angiotensin Ii ◽  
Mapk Pathway ◽  
Fold Increase ◽  
Zona Glomerulosa ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Aldosterone Production ◽  
Glomerulosa Cells

Angiotensin II (AngII) stimulates aldosterone biosynthesis in the zona glomerulosa of the adrenal cortex. AngII also triggers the MAPK pathways (ERK1/2 and p38). Because ERK1/2 phosphorylation is a transient process, phosphatases could play a crucial role in the acute steroidogenic response. Here we show that the dual specificity (threonine/tyrosine) MAPK phosphatase-1 (MKP-1) is present in bovine adrenal glomerulosa cells in primary culture and that AngII markedly increases its expression in a time- and concentration-dependent manner (IC50 = 1 nm), a maximum of 548 ± 10% of controls being reached with 10 nm AngII after 3 h (n = 3, P < 0.01). This effect is completely abolished by losartan, a blocker of the AT1 receptor subtype. Moreover, this AngII-induced MKP-1 expression is reduced to 250 ± 35% of controls (n = 3, P < 0.01) in the presence of U0126, an inhibitor of ERK1/2 phosphorylation, suggesting an involvement of the ERK1/2 MAPK pathway in MKP-1 induction. Indeed, shortly after AngII-induced phosphorylation of ERK1/2 (220% of controls at 30 min), MKP-1 protein expression starts to increase. This increase is associated with a reduction in ERK1/2 phosphorylation, which returns to control values after 3 h of AngII challenge. Enhanced MKP-1 expression is essentially due to a stabilization of MKP-1 mRNA. AngII treatment leads to a 53-fold increase in phosphorylated MKP-1 levels and a doubling of MKP-1 phosphatase activity. Overexpression of MKP-1 results in decreased phosphorylation of ERK1/2 and aldosterone production in response to AngII stimulation. These results strongly suggest that MKP-1 is the specific phosphatase induced by AngII and involved in the negative feedback mechanism ensuring adequate ERK1/2-mediated aldosterone production in response to the hormone.

Endothelin-1 potentiation of angiotensin II stimulation of aldosterone production

1992 ◽  
Vol 262 (1) ◽  
pp. R85-R89 ◽  
Author(s):  
E. N. Cozza ◽  
S. Chiou ◽  
C. E. Gomez-Sanchez
Keyword(s):  
Angiotensin Ii ◽  
Zona Glomerulosa ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Aldosterone Secretion ◽  
Acth Stimulation ◽  
Endothelin 1 ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Stimulation Of

Endothelin-1 (ET-1) binds to specific receptors in cultured bovine adrenal glomerulosa cells and stimulates aldosterone secretion with a 50% effective concentration (EC50) of 300 +/- 80 pM (mean +/- SE). The relative stimulatory potency for ET-1 is significantly less than that of angiotensin II (ANG II). The incubation of calf zona glomerulosa cells in primary culture with ET-1 and ANG II resulted in a significant potentiation of ANG II effect on aldosterone secretion. The EC50 of ET-1 potentiation of ANG II-induced stimulation of aldosterone secretion was 40 +/- 5 pM (mean +/- SE, n = 4), which is lower than the EC50 for ET-1 stimulation of aldosterone secretion. Adrenocorticotropic hormone (ACTH) stimulation of aldosterone secretion, but not that of potassium, was also potentiated by ET-1, but to a lesser degree. ET-1 and ET-1-mediated potentiation of ANG II-stimulated aldosterone biosynthesis increased both the early and late pathways of aldosterone biosynthesis, but the potentiation was greater for the early pathway. Preincubation with ET-1 for at least 15 min, followed by extensive washing to remove bound ET-1, also resulted in persistent potentiation of ANG II-mediated aldosterone secretion. ET-2, sarafotoxin, and vasoactive intestinal contractor potentiation of ANG II action were very similar to that of ET-1. ET-3 and Big-ET-1 potentiated ANG II stimulation only at the highest doses tested and the proendothelin-(110-130) fragment was inactive. ET-1 potentiation of ANG II action is likely to be mediated through an ETB receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Angiotensin II-Induced Protein Kinase D Activates the ATF/CREB Family of Transcription Factors and Promotes StAR mRNA Expression

Endocrinology ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 2524-2533 ◽  
Author(s):  
Lawrence O. Olala ◽  
Vivek Choudhary ◽  
Maribeth H. Johnson ◽  
Wendy B. Bollag
Keyword(s):  
Transcription Factors ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Dominant Negative ◽  
Protein Kinase D ◽  
Dependent Manner ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Constitutively Active

Aldosterone synthesis is initiated upon the transport of cholesterol from the outer to the inner mitochondrial membrane, where the cholesterol is hydrolyzed to pregnenolone. This process is the rate-limiting step in acute aldosterone production and is mediated by the steroidogenic acute regulatory (StAR) protein. We have previously shown that angiotensin II (AngII) activation of the serine/threonine protein kinase D (PKD) promotes acute aldosterone production in bovine adrenal glomerulosa cells, but the mechanism remains unclear. Thus, the purpose of this study was to determine the downstream signaling effectors of AngII-stimulated PKD activity. Our results demonstrate that overexpression of the constitutively active serine-to-glutamate PKD mutant enhances, whereas the dominant-negative serine-to-alanine PKD mutant inhibits, AngII-induced StAR mRNA expression relative to the vector control. PKD has been shown to phosphorylate members of the activating transcription factor (ATF)/cAMP response element binding protein (CREB) family of leucine zipper transcription factors, which have been shown previously to bind the StAR proximal promoter and induce StAR mRNA expression. In primary glomerulosa cells, AngII induces ATF-2 and CREB phosphorylation in a time-dependent manner. Furthermore, overexpression of the constitutively active PKD mutant enhances the AngII-elicited phosphorylation of ATF-2 and CREB, and the dominant-negative mutant inhibits this response. Furthermore, the constitutively active PKD mutant increases the binding of phosphorylated CREB to the StAR promoter. Thus, these data provide insight into the previously reported role of PKD in AngII-induced acute aldosterone production, providing a mechanism by which PKD may be mediating steroidogenesis in primary bovine adrenal glomerulosa cells.

Inhibition of aldosterone release by hypoxia in vitro: interaction with carbon monoxide

1994 ◽  
Vol 76 (2) ◽  
pp. 689-693 ◽  
Author(s):  
H. Raff ◽  
B. Jankowski
Keyword(s):  
Carbon Monoxide ◽  
Angiotensin Ii ◽  
Zona Glomerulosa ◽  
Michaelis Constant ◽  
Aldosterone Synthase ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
In Vitro Interaction ◽  
Zona Glomerulosa Cells

We have demonstrated that the aldosteronogenic pathway of the zona glomerulosa is unusually sensitive to modest changes in PO2 (Michaelis constant for O2 approximately 95 Torr). The current study evaluated the interaction of CO (the classic ligand for P-450 enzymes) and the decreases in O2 on aldosteronogenesis in vitro. Bovine adrenocortical zona glomerulosa cells were incubated for 2 h and stimulated with either adenosine 3′,5′-cyclic monophosphate (cAMP) or angiotensin II. Ten and 20% CO led to significant decreases in cAMP- and angiotensin II-stimulated aldosteronogenesis. The combination of 20% CO and moderate decreases in PO2 (from approximately 140 to approximately 100 Torr) led to an interactive decrease in aldosterone production. The conversion of corticosterone to aldosterone catalyzed by aldosterone synthase, which is the site of O2 sensitivity, was not significantly inhibited by CO. We conclude that the aldosterone pathway is not exceptionally sensitive to CO compared with other steroidogenic pathways. This observation suggests that the unique O2-sensitive properties of the aldosterone pathway located primarily within aldosterone synthase may not reside in its CO binding site (i.e., heme).

scholarly journals Calcitonin Induces IL-6 Production via Both PKA and PKC Pathways in the Pituitary Folliculo-Stellate Cell Line

Endocrinology ◽  
2001 ◽  
Vol 142 (8) ◽  
pp. 3563-3569 ◽  
Author(s):  
Yoshimitsu Kiriyama ◽  
Hiroyuki Tsuchiya ◽  
Takeshi Murakami ◽  
Kumi Satoh ◽  
Yukiko Tokumitsu
Keyword(s):  
Cell Line ◽  
Stellate Cell ◽  
Fold Increase ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Calcitonin Receptor ◽  
Rt Pcr ◽  
Concentration Dependent Manner ◽  
Mouse Pituitary ◽  
Inhibitor Treatment

Abstract It has been demonstrated that calcitonin-binding sites are present in a variety of tissue types, including in the pituitary gland. Interleukin-6 (IL-6) is also produced in the pituitary and it regulates the secretion of various hormones. In this study, we examined the expression of the calcitonin receptor and the mechanism of IL-6 production induced by calcitonin in the pituitary folliculo-stellate cell line (TtT/GF). The mRNA of calcitonin receptor subtype C1a, but not that of C1b, was detected by RT-PCR in TtT/GF cells and in the normal mouse pituitary. Calcitonin increased cAMP accumulation and IL-6 production in a concentration-dependent manner in TtT/GF cells. As calcitonin activates the PKA and PKC pathways, we investigated the contributions of PKA and PKC to IL-6 production. IL-6 production was only slightly increased by either 8-bromo-cAMP (1 mm) or phorbol 12-myristate 13-acetate (100 nm) alone. However, IL-6 was synergistically induced in the presence of both 8-bromo-cAMP (1 mm) and phorbol 12myristate 13-acetate (100 nm). Furthermore, calcitonin-induced IL-6 production was completely suppressed by H-89 (PKA inhibitor) or GF109203X (PKC inhibitor), indicating that the activation of both PKA and PKC is necessary for calcitonin-induced IL-6 production. On the other hand, pertussis toxin (Gi/Go signaling inhibitor) treatment achieved an approximately 9-fold increase in calcitonin-induced IL-6 production. These results show that calcitonin-stimulated IL-6 production is mediated via both PKA- and PKC-signaling pathways, whereas calcitonin also suppresses IL-6 production by activating Gi/Go proteins in folliculo-stellate cells.

Mechanisms of ET-1 potentiation of angiotensin II stimulation of aldosterone production

1993 ◽  
Vol 265 (2) ◽  
pp. E179-E183 ◽  
Author(s):  
E. N. Cozza ◽  
C. E. Gomez-Sanchez
Keyword(s):  
Angiotensin Ii ◽  
Zona Glomerulosa ◽  
Ang Ii ◽  
Aldosterone Secretion ◽  
Direct Stimulation ◽  
Potentiation Effect ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Pkc Inhibitors ◽  
Stimulation Of

Endothelin-1 (ET-1) exerts the following two types of aldosterone-stimulating actions on glomerulosa cells: ET-1-mediated direct stimulation of aldosterone secretion (per se effect) and potentiation of the aldosterone secretion to angiotensin II (ANG II; potentiation effect). The role of Ca2+ and protein kinase C (PKC) systems in these two effects was investigated. Incubations of calf cultured adrenal zona glomerulosa cells in low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil reduced the aldosterone secretion to ET-1. When cells were preincubated with ET-1 in a low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil, washed, and incubated in media with normal Ca2+, ANG II showed potentiation of ANG II-stimulated aldosterone secretion. The PKC inhibitors H-7 and staurosporine did not decrease ET-1-stimulated aldosterone secretion, but they inhibited the potentiation effect of ET-1 on ANG II-mediated aldosterone secretion. Adrenocorticotropic hormone desensitization or prolonged phorbol ester stimulation of PKC resulting in desensitization also resulted in the abolition of the ET-1-mediated ANG II potentiation of aldosterone secretion. The PKC inhibitors did not affect ANG II-stimulated aldosterone secretion. We conclude that ET-1 exerts a direct stimulation of aldosterone secretion through a mechanism dependent on Ca2+ and potentiates ANG II-mediated aldosterone stimulation through a mechanism involving PKC.

Effects of Angiotensin II, Adrenocorticotropin, and Potassium on Aldosterone Production in Adrenal Zona Glomerulosa Cells from Streptozotocin-Induced Diabetic Rats*

Endocrinology ◽  
1986 ◽  
Vol 118 (1) ◽  
pp. 183-188 ◽  
Author(s):  
TOSHIKAZU KIGOSHI ◽  
NORIKO IMAIZUMI ◽  
SADAHIDE AZUKIZAWA ◽  
IKUO YAMAMOTO ◽  
KENZO UCHIDA ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Zona Glomerulosa ◽  
Diabetic Rats ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Zona Glomerulosa Cells

Effect of angiotensin II on aldosterone and its precursor steroid production in adrenal zona glomerulosa cells from heparin-treated rats

1986 ◽  
Vol 111 (2) ◽  
pp. 222-227 ◽  
Author(s):  
K. Uchida ◽  
S. Azukizawa ◽  
N. Imaizumi ◽  
T. Kigoshi ◽  
I. Yamamoto ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Corticosterone Level ◽  
Plasma Renin ◽  
Plasma Corticosterone ◽  
Zona Glomerulosa ◽  
Threshold Dose ◽  
Lower Response ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Zona Glomerulosa Cells

Abstract. To assess the nature of the heparin-induced aldosterone deficiency, we investigated the stimulatory effect of angiotensin II (All) on aldosterone and its precursor steroids in adrenal zona glomerulosa cells from heparin-treated rats compared with those in the cells from vehicle-treated rats. Heparin-treated rats had low plasma aldosterone levels, high plasma renin activity and plasma All levels, and normal plasma corticosterone level 6 weeks after the treatment (1500 IU/kg, twice daily). Basal aldosterone production, when corrected to a uniform number of cells per group, was similar in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to All; an increase by 4 orders of magnitude in the threshold dose for All and a decrease in the maximum All-stimulated level. The maximum All-stimulated levels, but not the basal levels, of pregnenolone, corticosterone and 18-OHB production were low in the cells from heparin-treated rats. ACTH caused a similar stimulatory effect on aldosterone production in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to potassium; an increase by one order of magnitude in the threshold dose for potassium and a decrease in the maximum potassium-stimulated level, presumably because of the glomerulosa hyporesponsivness to AII. These results suggest that our heparin-treated rats have selective impairment of adrenal zona glomerulosa cells,

Effect of composition of incubation medium on aldosterone and corticosterone production by isolated rat zona glomerulosa cells

1982 ◽  
Vol 94 (2) ◽  
pp. 211-224 ◽  
Author(s):  
D. J. Campbell
Keyword(s):  
Angiotensin Ii ◽  
Cyclic Amp ◽  
Incubation Medium ◽  
Zona Glomerulosa ◽  
Bicarbonate Buffer ◽  
Angiotensin Ii Antagonist ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Zona Glomerulosa Cells

The role of the composition of the incubation medium in determining the steroidogenic responsiveness of collagenase-dispersed rat zona glomerulosa cells was examined by studying the effect on production of aldosterone and corticosterone of (1) changes in the bovine serum albumin (BSA) concentration in Krebs–Ringer bicarbonate buffer (KRBGA), (2) dialysis of the BSA and (3) comparison of KRBGA with 'modified' Medium 199. Medium 199 was modified so that its electrolytic content was identical to that of KRBGA. Compared with 0·1–0·2% BSA in KRBGA, BSA concentrations of 0·5 and 4% caused inhibition of both basal and K+-stimulated, but not angiotensin II-stimulated steroidogenesis. This inhibitory property of BSA was not removed by dialysis. The BSA did, however, contain a dialysable factor which increased both basal steroidogenesis and the steroidogenic response to maximal K+ and angiotensin II stimulation. Both incubation media contained 0·2% BSA for the comparison of KRBGA with modified Medium 199. Modified Medium 199 increased both basal steroidogenesis and the aldosterone response to K+ stimulation (per cent increase above basal) by two- to threefold compared with KRBGA, with smaller increases in the response to ACTH and 5-hydroxytryptamine (5-HT) and a decrease in the response to cyclic AMP. In contrast, modified Medium 199 increased the aldosterone response to angiotensin II by sevenfold, from 60% (in KRBGA) to 420%. In KRBGA, angiotensin II inhibited K+-stimulated aldosterone production. This effect was produced by concentrations of angiotensin II below the threshold for steroidogenesis and could be reproduced with the angiotensin II antagonist [Sar1, Ileu8]-angiotensin II. Angiotensin II did not inhibit K+-stimulated aldosterone production in modified Medium 199. These data emphasize the importance of the composition of the incubation medium in determining the steroidogenic responsiveness of rat zona glomerulosa cells in vitro. Furthermore, these data indicate that the steroidogenic response to angiotensin II, compared with K+, ACTH, 5-HT and cyclic AMP, is more readily influenced by other, as yet unidentified, factors in the incubation medium, and are consistent with recent evidence that angiotensin II and K+ do not share a common mode of action on steroidogenesis by these cells.

Effects of α-human atrial natriuretic polypeptide, sodium nitroprusside and dibutyryl cyclic GMP on aldosterone production in bovine zona glomerulosa cells

1988 ◽  
Vol 119 (3) ◽  
pp. 358-366 ◽  
Author(s):  
Mitsuhiro Okamoto
Keyword(s):  
Angiotensin Ii ◽  
Sodium Nitroprusside ◽  
Cyclic Gmp ◽  
Zona Glomerulosa ◽  
Atrial Natriuretic Polypeptide ◽  
Aldosterone Production ◽  
Cast Doubt ◽  
Glomerulosa Cells ◽  
Zona Glomerulosa Cells ◽  
Atrial Natriuretic

Abstract. When bovine adrenal zona glomerulosa cells were incubated with α-human atrial natriuretic polypeptide (α-hANP), the basal aldosterone production in the cells was hardly affected, although the angiotensin II- or K+-stimulated production was completely inhibited. α-hANP was found to cause the generation of cyclic GMP in the cells. When the cells were incubated with sodium nitroprusside, the drug inhibited the angiotensin II- or K+-stimulated aldosterone production, and also generated cyclic GMP in the cells. In contrast, dibutyryl cyclic GMP was found to be a stimulator of the aldosterone response rather than an inhibitor. The results obtained in this study cast doubt on the role of cyclic GMP as an intracellular second messenger for the action of ANP on aldosterone secretion.

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