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Query: UNIPROT:P06889 (Mol)
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Fat cells were preincubated for 2 h in the presence and absence of growth hormone (GH) and Dexamethasone (Dex) before the addition of increasing concentrations of either epinephrine, theophylline or glucagon and final incubation of the cells for an additional 5 minutes. GH and Dex increased by 85%, 28% and 72%, respectively, the cAMP levels reached in the sole presence of 10(-5)M epinephrine, 10(-2)M theophylline or 5 X 10(-5)M glucagon. An adenylate cyclase particulate preparation shows that epinephrine decreases Km from 2mM to 0.6 MM and increases Vmax and the strength of interaction value (n) from 0.91 to 1.75.
Mol Cell Biochem 1976 Dec 10
PMID:Hormonal control of fat cells adenylate cyclase. 18 30

1. Pronounced hypoaldosteronism was found in five young women with low-renin hypertension and characteristic features of the mineralocorticoid hypertensive syndrome. 2. There was no overproduction of the mineralocorticoids 11-deoxycorticosterone and 18-OH-11-deoxycorticosterone. 3. Dexamethasone restored blood pressure to normal, decreased body weight, increased plasma potassium, and increased plasma renin activity and aldosterone excretion in all patients. 4. The data suggest overproduction of an unknown adrenocorticotrophic hormone-dependent mineralocorticoid maintaining hypertension in these patients.
Clin Sci Mol Med Suppl 1978 Dec
PMID:Evidence for an unidentified, adrenocorticotrophic hormone-dependent mineralocorticoid maintaining hypertension in young women with hypoaldosteronism. 28 66

In the presence of the glucocorticoid hormone dexamethasone, bovine papillomavirus-1 (BPV-1)-transformed C127 mouse fibroblasts assume a flattened morphology and reach a saturation density of only 50% of that attained without hormone. This phenotypic reversion of transformation is dependent on the continued presence of dexamethasone and occurs with concentrations as low as 1 nM. Dexamethasone also suppresses the growth of the parental C127 cells as well as that of cells transformed by polyoma middle-T. In contrast, the growth of C127 cells transformed by the oncogenes v-H-ras, v-mos, or v-fes is inhibited by low concentrations of dexamethasone (1 nM) and stimulated by higher concentrations (0.1-1 microM), possibly due to dexamethasone-induced transcription from the viral long terminal repeat promoters as is shown for v-H-ras. On the other hand, inhibition of BPV-transformed cell line growth by dexamethasone does not appear to be related to hormone effects on BPV-1 oncogene transcription. Indeed, in several cases, dexamethasone increases the steady state transcript levels of the BPV-1 oncogenes, E5 and E6-E7, while suppressing cellular proliferation. Dexamethasone also rapidly reduces the steady state levels of c-myc in the BPV-transformed cells but has less effect on c-myc expression in the ras-transformed cells. These results demonstrate that the growth-promoting actions of the papillomavirus transforming genes, but not those of several retroviral oncogenes, may be overcome by dexamethasone, which appears to act by down-regulation of c-myc expression.
Mol Endocrinol 1992 Sep
PMID:Glucocorticoid modulation of transformed cell proliferation is oncogene specific and correlates with effects on c-myc levels. 133 73

Dexamethasone administration in vitro has been shown to increase adenylyl cyclase activity in vascular smooth muscle cells (VSMC) from renal arteries and in non-vascular cell lines. To investigate whether G proteins are involved in this response, cultured VSMC from mesenteric arteries of Sprague-Dawley rats were incubated in the presence and absence of 10 nM dexamethasone for 24 and 48 h. Basal and stimulated adenylyl cyclase activities were increased by approximately 50% after treatment with dexamethasone. The changes were neither specifically associated with ligands which stimulate adenylyl cyclase catalytic unit via Gs (isoproterenol and prostaglandin E1) nor with guanylylimidodiphosphate (0.1 nM), which inhibits the catalytic unit via Gi. This suggests that dexamethasone enhances adenylyl cyclase activity through changes at the level of the catalytic unit, rather than through the G proteins which modulate its activity. No differences were seen in immunoblotting studies of the levels of Gi alpha 2, Gs alpha, Gi alpha 3 and beta subunits. Similarly, dexamethasone had no effect on the expression of mRNA for Gi alpha 2 and Gs alpha. The results indicate that glucocorticoid-induced increases of adenylyl cyclase activity are due to changes at the level of the adenylyl cyclase catalytic unit rather than alteration of the levels or turnover of Gs alpha, Gi alpha 2, Gi alpha 3 and beta subunits in the membranes of VSMC.
J Mol Endocrinol 1992 Dec
PMID:Effects of dexamethasone on G protein levels and adenylyl cyclase activity in rat vascular smooth muscle cells. 133 25

Tyrosine hydroxylase mRNA is induced in rat pheochromocytoma PC18 cells by cAMP analogs and glucocorticoids. Previous studies have shown that these increases in tyrosine hydroxylase mRNA are due at least in part to stimulation of the tyrosine hydroxylase gene. However, the involvement of post-transcriptional mechanisms in the regulation of tyrosine hydroxylase mRNA by these inducing agents has not been investigated. In the present study, using nuclear run-on assays we show that the relative transcription rate of the tyrosine hydroxylase gene is stimulated 2-5-fold within 20 min after treatment of PC18 cells with cAMP analogs or dexamethasone and that the rate of transcription remains elevated 2-3-fold for at least 24 hr in the continual presence of these inducing agents. Pulse-labeling experiments using 4-thiouridine indicate that the rate of synthesis of tyrosine hydroxylase mRNA is increased approximately 3-fold or 10-fold after treatment with either a cyclic AMP analog or dexamethasone, respectively. These increases in rates of synthesis agree well with the fold increases in tyrosine hydroxylase mRNA levels after treatment with these inducers. Treatment of the cells with cycloheximide lowers the basal relative transcription rate of the tyrosine hydroxylase gene 2-3-fold; however, the relative transcription rate of the tyrosine hydroxylase gene is still elevated in cells treated with either dexamethasone or cAMP analogs in the presence of cycloheximide, compared with the transcription rate of the gene in cells treated with cycloheximide alone. These results indicate that protein synthesis is not required for the short term regulation of the gene by these inducing agents. The apparent t1/2 for tyrosine hydroxylase mRNA has been estimated by two different procedures, approach to steady state kinetics and pulse-chase analysis. Both procedures yield an estimated apparent t1/2 of approximately 6-9 hr for tyrosine hydroxylase mRNA under basal culture conditions. Dexamethasone does not substantially alter this apparent t1/2 value; however, cAMP appears to lower this apparent t1/2 value transiently. Our results suggest that cAMP and glucocorticoid regulate tyrosine hydroxylase mRNA levels primarily by stimulating the transcription rate of the tyrosine hydroxylase gene; however, cAMP may also regulate the stability of the mRNA for a short period of time, such that it is induced more rapidly in the cells.
Mol Pharmacol 1992 Nov
PMID:Regulation of tyrosine hydroxylase gene transcription rate and tyrosine hydroxylase mRNA stability by cyclic AMP and glucocorticoid. 135 99

The control of aldosterone secretion in vivo by serotonin was studied in conscious rats. Serial blood samples were taken from indwelling arterial cannulae before and after i.p. administration of 1 ml (4 g/l) 5-hydroxytryptophan (5-HTP), the precursor of serotonin (5-HT), or saline, and analysed for 5-HTP, serotonin, 5-hydroxyindoleacetic acid, plasma renin activity (PRA), corticosterone, aldosterone, sodium and potassium concentration. The relative contribution of the hypothalamo-pituitary adrenal axis was investigated in animals pretreated with the synthetic glucocorticoid dexamethasone. 5-HTP caused a significant increase in all parameters within 45 min except for plasma sodium and potassium. Saline administration showed no significant effect. Dexamethasone pretreatment significantly impaired the corticosterone and aldosterone response to 5-HTP, although the aldosterone response was merely attenuated. No other parameter was affected by dexamethasone pretreatment. The results show that administration of 5-HTP, which increases serum serotonin levels, stimulates PRA, corticosterone and aldosterone secretion. Dexamethasone pretreatment inhibits the aldosterone response, though not completely, suggesting that the stimulatory action of 5-HTP involves the release of ACTH, which stimulates corticosterone and aldosterone secretion by the adrenal cortex. The failure of dexamethasone to block the aldosterone response completely, suggests the involvement of other mechanisms such as the renin-angiotensin system or a direct action of serotonin on the adrenal zona glomerulosa.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Serotoninergic stimulation of aldosterone secretion in vivo: role of the hypothalamo-pituitary adrenal axis. 137 72

Previous studies showed that apolipoprotein-E (apoE) mRNA is regulated in rat adrenal gland by treatments that alter adrenal gland cholesterol content and steroidogenesis. In the present study cell types expressing apoE mRNA were determined by in situ hybridizations using an [alpha-35S]UTP-labeled RNA probe. Autoradiographic grains were counted to compare apoE expression in adrenal glands from control and experimentally treated animals. In control adrenal gland, zona (z.) fasciculata and z. reticularis exhibited the highest level of apoE mRNA expression, with lower levels in z. glomerulosa and medulla. Dexamethasone (DEX) treatment selectively increased apoE mRNA 3-fold in outer z. fasciculata, but not in other adrenal zones. ApoE mRNA expression appeared to be lower in adrenal glands from 4-aminopyrazolopyrimidine-treated rats, in that differences among adrenal gland zones were abolished. DEX treatment increased adrenal gland cholesteryl ester and oil red O staining in z. fasciculata cells in which the apoE mRNA concentration was increased as well as in other cortical cells in which apoE mRNA was unchanged. Aminoglutethimide administration led to a large increase in oil red O staining throughout the cortex, including z. fasciculata, without affecting apoE mRNA expression. These data suggest that adrenal gland apoE mRNA expression is not closely coupled to cellular cholesterol concentrations. Increased apoE mRNA expression in z. fasciculata of DEX-treated animals suggests an inverse relationship between apoE mRNA concentration and the level of steroidogenesis. This result is consistent with the proposal that apoE may play a role in regulating the utilization of cholesterol for steroid production.
Mol Endocrinol 1992 Feb
PMID:Differential regulation of apolipoprotein-E messenger RNA in zona fasciculata cells of rat adrenal gland determined by in situ hybridization. 137 19

Primary cortisol receptor resistance has been reported in 6 patients and 14 asymptomatic family members. We observed an additional 6 patients (2 males and 4 females). The male patients presented with hypertension. The female patients presented with acne, hirsutism and irregular menstruations. Dexamethasone therapy (1-1.5 mg/day) was of considerable clinical benefit. All 6 patients showed insufficient suppression of cortisol after 1 mg dexamethasone. The diurnal rhythm of ACTH and cortisol was intact, albeit at an elevated level. There was a normal increase of ACTH, cortisol, and GH to insulin-induced hypoglycemia, while cortisol production was (slightly) elevated. Adrenal androgen levels were increased in all patients. Glucocorticoid receptors measured in a whole cell dexamethasone binding assay in mononuclear leukocytes showed a lowered affinity in 1, and lowered numbers of receptors in 4 patients. In 1 patient no abnormalities were found. As a "bioassay" for glucocorticoid action dexamethasone suppressibility of mitogen-stimulated incorporation of [3H]thymidine in mononuclear leukocytes was measured. In this last patient dexamethasone suppressibility of [3H]thymidine incorporation was significantly lowered. Twelve months' treatment with 200 mg RU 486 per day in meningioma patients induced a similar biochemical picture as observed in primary cortisol receptor resistance. Partial cortisol receptor resistance might be less rare than previously thought. In the 6 patients presented at least 3 different forms can be recognized. Therapy with dexamethasone was successful in female patients with acne and hirsutism, as the secondary overproduction of adrenal androgens was effectively controlled. Chronic therapy with RU 486 causes a biochemical picture similar to primary cortisol receptor resistance.
J Steroid Biochem Mol Biol 1992 Oct
PMID:Familial and iatrogenic cortisol receptor resistance. 139 Feb 87

To investigate further the molecular mechanisms of progestin regulation of human breast cancer cell growth, we studied the effect of progestins on expression of the protooncogene c-jun and other members of the jun family, jun-B and jun-D, in T-47D human breast cancer cells. The progestin medroxyprogesterone acetate (MPA) increased c-jun mRNA levels in a time- and dose-dependent fashion. Maximal effects were seen after 3 h of treatment with 10-100 nM MPA. Under these conditions, the c-jun mRNA was increased 5.4-fold above the control level. Although the c-jun mRNA level was increased by cycloheximide alone, a further 2.4-fold increase was seen when the cells were treated with MPA in the presence of cycloheximide. The p39 c-jun protein was also increased 3.8-fold by this treatment. Maximum levels of p39 c-jun protein were achieved 9 h after treatment, and this level was maintained for at least 24 h. Dexamethasone and dihydrotestosterone did not increase the p39 c-jun protein level under these conditions. However, MPA treatment of T-47D cells resulted in a 55% decrease in overall AP-1 activity, as measured by transient transfection of an AP-1-regulated chloramphenicol acetyltransferase reporter gene. These effects were all reversible by cotreatment with a 10-fold higher concentration of the antiprogestin RU 486. MPA decreased jun-B mRNA levels 50% 1 h after treatment in T-47D cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1992 Oct
PMID:Regulation of c-jun and jun-B by progestins in T-47D human breast cancer cells. 144 15

Platelet-derived growth factor (B) (PDGF(B)) from alveolar macrophages is thought to play a central role in orchestrating the fibrotic response. Because corticosteroids are widely used in the treatment of patients with lung fibrosis, we asked whether corticosteroids modulated PDGF(B) gene activation in macrophages. PDGF(B) mRNA in alveolar macrophages obtained from smokers was increased after culture in the presence of dexamethasone (P less than 0.05), interferon-gamma (IFN-gamma) (P less than 0.05), or both in combination (P less than 0.05). Dexamethasone did not alter the abundance of mRNA encoding transforming growth factor-beta (TGF-beta), but did decrease the mRNA of early growth response gene 2 (EGR2). These initial experiments required large numbers of cells and thus were performed on macrophages from smokers. The results were reproduced when PDGF(B) mRNA abundance in macrophages from healthy nonsmoking volunteers was measured by the reverse-transcriptase polymerase chain reaction (RT-PCR). There was an increase in PDGF(B) mRNA in macrophages from nonsmokers after stimulation with dexamethasone alone (P less than 0.05) or in combination with IFN-gamma (P less than 0.05). To provide adequate cell numbers for kinetic and dose-response studies, the in vitro model of phorbol ester (TPA)-induced differentiation of HL60 cells to macrophage-like cells was used. In these cells, dexamethasone caused a 20-fold increase in the abundance of PDGF(B) mRNA, which was concentration and time dependent but not associated with changes in TGF-beta or EGR2 mRNA. This study suggests that in addition to their anti-inflammatory effects, corticosteroids may also increase the abundance of PDGF(B) mRNA.
Am J Respir Cell Mol Biol 1992 Aug
PMID:Dexamethasone-induced increase in platelet-derived growth factor (B) mRNA in human alveolar macrophages and myelomonocytic HL60 macrophage-like cells. 149 7


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