scholarly journals Effects of excess corticosterone on LKB1 and AMPK signaling in rat skeletal muscle

2010 ◽  
Vol 108 (2) ◽  
pp. 298-305 ◽  
Author(s):  
G. Nathan Nakken ◽  
Daniel L. Jacobs ◽  
David M. Thomson ◽  
Natasha Fillmore ◽  
William W. Winder
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Cushing’S Syndrome ◽  
Creatine Phosphate ◽  
Cushing's Syndrome ◽  
Elevated Plasma ◽  
Ampk Signaling ◽  
Subunit Expression ◽  
Corticosterone Treatment ◽  
The Right

Cushing's syndrome is characterized by marked central obesity and insulin insensitivity, effects opposite those seen with chronic AMP-activated protein kinase (AMPK) activation. This study was designed to determine whether chronic exposure to excess glucocorticoids influences LKB1/AMPK signaling in skeletal muscle. Corticosterone pellets were implanted subcutaneously in rats (hypercorticosteronemia, Hypercort) for 2 wk. Controls were sham operated and fed ad libitum or were sham operated and food restricted (pair-weighted group, Pair) to produce body weights similar to Hypercort rats. At the end of the 2-wk treatment period, rats were anesthetized, and the right gastrocnemius-plantaris (gastroc) and soleus muscles were removed. Left muscles were removed after electrical stimulation for 5 min. No significant differences were noted between treatment groups in ATP, creatine phosphate, or LKB1 activity. The α- and β-subunit isoforms were not significantly influenced in gastroc by corticosterone treatment. Expression of the γ3-subunit decreased, and γ1- and γ2-subunit expression increased. Both α2-AMPK and α1-AMPK activities were increased in the gastroc in response to electrical stimulation, but the magnitude of the increase was less for α2 in the Hypercort rats. Despite elevated plasma insulin and elevated plasma leptin in the Hypercort rats, phosphorylation of TBC1D1 was lower in both resting and stimulated muscle compared with controls. Malonyl-CoA content was elevated in gastroc muscles of resting Hypercort rats. These changes in response to excess glucocorticoids could be responsible, in part, for the decrease in insulin sensitivity and adiposity seen in Cushing's syndrome.

scholarly journals Functioning Adrenocortical Carcinoma with Extension upto the Right Atrium Producing Cushing's Syndrome

2013 ◽  
Vol 3 ◽  
pp. 32 ◽  
Author(s):  
Santosh Kumar ◽  
Gautam R. Choudhary ◽  
Arawat Pushkarna
Keyword(s):  
Inferior Vena Cava ◽  
Cushing’S Syndrome ◽  
Adrenocortical Carcinoma ◽  
Right Atrium ◽  
Inferior Vena ◽  
Vena Cava ◽  
Cushing's Syndrome ◽  
Curative Therapy ◽  
Rare Malignancy ◽  
The Right

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Surgery is the only curative therapy available and overall 5-year survival for patients who undergo a complete resection is 32% to 48%. They are known to produce intravascular invasion and into the inferior vena cava (IVC) and in rare cases they may reach the right atrium. We report a case of functioning ACC extending into the inferior vena cava and right atrium in a female with Cushing's syndrome.

Sympathoadrenal system and activation of glycogenolysis during muscular activity

1985 ◽  
Vol 58 (4) ◽  
pp. 1122-1127 ◽  
Author(s):  
L. J. Cartier ◽  
P. D. Gollnick
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Muscular Activity ◽  
Creatine Phosphate ◽  
Stimulation Frequency ◽  
Sympathoadrenal System ◽  
Phosphate Depletion ◽  
Peak Value ◽  
Stimulation Of

Comparisons were made of the appearance of phosphorylase (PHOS) a and lactate (LA) during electrical stimulation of the gastrocnemius (GM) and soleus (SM) muscles of normal and sympathectomized (SYMPX) rats. Ten-second stimulation at 3 Hz increased PHOS a approximately fourfold in the GM of normal rats, whereafter it declined during stimulation until at 60 s it was similar to rest. The increase in PHOS a of GM from SYMPX rats after 10 s of stimulation was approximately 50% that of normal rats. Stimulation of the SM produced smaller and slower increases in PHOS a with the peak occurring after 60 s, which remained constant to 90 s. SYMPX did not alter this effect in the SM. LA production and creatine phosphate depletion in the GM were continuous throughout stimulation and uninfluenced by SYMPX. This was true for the SM with the exception of LA production being greater after SYMPX. [ATP] was unchanged by electrical stimulation. The rate and magnitude of the PHOS a appearance was a function of stimulation frequency. Reversion of PHOS to the b form after stimulation was rapid, with approximately 50% of the peak value being attained in 2.5 s, and at 5 s the values were those of rest. These data demonstrate that an intact sympathoadrenal system is not obligatory for the initiation of glycogenolysis in skeletal muscle.

scholarly journals Glucocorticoids Do Not Regulate the Expression of Proteolytic Genes in Skeletal Muscle from Cushing’s Syndrome Patients*

1997 ◽  
Vol 82 (9) ◽  
pp. 3161-3164
Author(s):  
Cécile RalliÈre ◽  
Igor Tauveron ◽  
Daniel Taillandier ◽  
Laurent Guy ◽  
Jean-Paul Boiteux ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome

scholarly journals SUN-169 A Rare Case of Adrenocortical Carcinoma Presenting as Hyperaldosteronism Combined with Cushing’s Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Emma Punni ◽  
Jonea Lim
Keyword(s):  
Adrenal Gland ◽  
Cushing’S Syndrome ◽  
Adrenocortical Carcinoma ◽  
Rare Case ◽  
Plasma Catecholamines ◽  
Cushing's Syndrome ◽  
Adrenal Crisis ◽  
Pathology Report ◽  
Dheas Level ◽  
The Right

Abstract Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Most ACC cases are hormonally functional. Commonly produced hormones are cortisol, followed by adrenal androgens. Aldosterone secretion is quite rare (< 2%) (1). Co-secretion of multiple hormones is further rare. Case Presentation: A 59 year old female presented with progressive worsening hypertension. Initial biochemical evaluation confirmed primary hyperaldosteronism. Her potassium was low at 2.9 mEq/L (N: 3.5-5.3 meq/L). Aldosterone level was elevated at 23 ng/dL (N: < or = 28 ng/mL), renin value was 0.90 ng/mL/h (N: 0.25-5.82 ng/mL/h). Aldosterone Renin Ratio was 25. CT abdomen with and without contrast showed 2 lesions within the right adrenal gland. The larger nodule was 3.7 x 2.7 x 4.9 cm with an absolute washout of 61%. A smaller nodule was 2.3x1.8 cm with an absolute washout of approximately 64%. Left adrenal gland was unremarkable. Further biochemical workup showed plasma catecholamines and metanephrines were normal. A random cortisol value was 22.8 mcg/dL (N: 3.0-16.0 mcg/dL) with a low ACTH level of 3.3 pg/mL (N: 7.2 - 63.3 pg/mL). Given suspicion for adrenal Cushing’s syndrome, we further obtained a 24 hour free urinary cortisol which was elevated at 84.1 mcg/24 h (N: 4-50 mcg/24 h). 8 am Cortisol after an overnight 1 mg Dexamethasone failed to suppress at 17.5 mcg/dL (n<1.8 mcg/dL). DHEAS level was low at 14.1 ug/dL (N: 29.4-220.5 ug/dL). The patient eventually underwent a right adrenalectomy. Post-operatively, her cortisol was suppressed at 1.9 mcg/dL (8 am ref range: 4-22 mcg/dL), and Hydrocortisone replacement dose was initiated. Surgical pathology report was consistent with adrenocortical carcinoma. The patient continues to follow-up with the endocrinology and oncology department for treatment. Conclusion: This case is particularly interesting given the co-secretion of both aldosterone and cortisol by an adrenocortical carcinoma which has been reported in only a few cases in literature. The case highlights the importance of completing a comprehensive biochemical workup pre-operatively in patients with suspicious adrenal mass. There should especially be a low threshold for initiating workup for cortisol hypersecretion as early intervention can help avoid an adrenal crisis in the post-operative period for such patients. A low DHEAS level should raise suspicion for cortisol hypersecretion in a patient with adrenal lesions. As ACTH is the primary stimulant of DHEA, the suppression of ACTH secretion in the setting of adrenal Cushing’s syndrome can contribute to a low DHEAS level. Reference 1.Else, T et al. Adrenocortical Carcinoma. Endocr Rev. 2014; 35(2):282-326.

scholarly journals Cushing's syndrome due to ectopic ACTH production by a nasal paraganglioma

2013 ◽  
Vol 2013 ◽  
Author(s):  
F Serra ◽  
S Duarte ◽  
S Abreu ◽  
C Marques ◽  
J Cassis ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Microscopic Analysis ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
List Type ◽  
Rare Tumour ◽  
Ectopic Acth ◽  
Ectopic Acth Production ◽  
The Right

Summary Ectopic secretion of ACTH is an infrequent cause of Cushing's syndrome. We report a case of ectopic ACTH syndrome caused by a nasal paraganglioma, a 68-year-old female with clinical features of Cushing's syndrome, serious hypokalaemia and a right paranasal sinus' lesion. Cranial magnetic resonance image showed a 46-mm mass on the right paranasal sinuses. Endocrinological investigation confirmed the diagnosis of ectopic ACTH production. Resection of the tumour normalised ACTH and cortisol secretion. The tumour was found to be a paraganglioma through microscopic analysis. On follow-up 3 months later, the patient showed nearly complete clinical recovery. Ectopic ACTH syndrome due to nasal paraganglioma is extremely uncommon, as only two other cases have been discussed in the literature. Learning points Ectopic Cushing's syndrome accounts for 10% of Cushing's syndrome etiologies. Most paraganglioma of the head and neck are not hormonally active. Nasal paraganglioma, especially ACTH producing, is a very rare tumour.

Renin Gene Transfer Restores Angiogenesis and VEGF Expression in Dahl S Rats

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 730-730
Author(s):  
Sandra L Amaral ◽  
Richard J Roman ◽  
Andrew S Greene
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Renin Angiotensin System ◽  
Complementation Test ◽  
Vegf Expression ◽  
Angiotensin System ◽  
Angiogenic Response ◽  
Electrical Stimulator ◽  
The Right ◽  
Stimulation Of

P204 To evaluate the importance of the renin angiotensin system (RAS) in VEGF expression and angiogenesis in skeletal muscle, we compared the angiogenic response to electrical stimulation in congenic strains of SS/Jr/Hsd rats using a complementation test design. We have previously demonstrated that both increases in VEGF expression and angiogenesis induced by electrical stimulation of skeletal muscle were absent in inbred Dahl S rats having a wildtype renin allele (S/ren ss ). In contrast, the congenic S/ren rr in which a 10 cM segment of chromosome 13 containing the normally functioning salt resistant renin allele was transferred onto the Dahl S background, exhibit the expected changes in renin. In the present study we investigate the effects of electrical stimulation on VEGF expression and angiogenesis in these rats. Congenic S/ren rr and S/ren ss rats, fed a 0.4% salt diet were surgically prepared by chronic implantation of an electrical stimulator. Another group of S/ren rr rats was treated with lisinopril, 2 days before the surgery and throughout the stimulation protocol. Rats without any drug treatment were used as control. The right tibialis anterior (TA) and extensor digitorum longus (EDL) were stimulated (10 Hz, 0.3 ms duration) for 8 hours per day for 7 days. The contralateral muscles served as controls. Western blot analysis was performed to identify VEGF protein expression in these muscles. Seven days of electrical stimulation of the skeletal muscles produced no change in vessel density of S/ren ss (Δ=5.50 ± 3.8 % and 8.14 ± 2.0 % for EDL and TA respectively). Transfer of the resistant renin allele (S/ren rr ) restored the angiogenic response (Δ=16% and 30% for EDL and TA, respectively) despite a significantly higher blood pressure (113.5 ± 2.25 mmHg and 148.67 ± 1.12 mmHg for S/ren ss and S/ren rr , respectively). Blockade of the RAS in S/ren rr restored the phenotype observed in the S/ren ss (Δ=1.46% and 1.9% to EDL and TA, respectively, p<0.05). In addition, increases in VEGF expression to electrical stimulation were observed only in S/ren rr . These results demonstrate that RAS plays an important role in the regulation of VEGF expression and angiogenesis in skeletal muscle.

Atrophy of Skeletal Muscle in Patients With Cushing's Syndrome

1970 ◽  
Vol 22 (2) ◽  
pp. 118-125 ◽  
Author(s):  
D. E. Pleasure ◽  
G. O. Walsh ◽  
W. K. Engel
Keyword(s):  
Skeletal Muscle ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome

scholarly journals Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing’s syndrome

2017 ◽  
Vol 312 (6) ◽  
pp. E495-E507 ◽  
Author(s):  
Seol-Hee Kang ◽  
Hae-Ahm Lee ◽  
Mina Kim ◽  
Eunjo Lee ◽  
Uy Dong Sohn ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Cushing’S Syndrome ◽  
Ubiquitin Ligases ◽  
Cushing's Syndrome ◽  
Skeletal Muscle Atrophy ◽  
E3 Ubiquitin Ligases ◽  
Sprague Dawley ◽  
Muscle Weight ◽  
Forkhead Box

Cushing’s syndrome is caused by overproduction of the adrenocorticotropic hormone (ACTH), which stimulates the adrenal grand to make cortisol. Skeletal muscle wasting occurs in pathophysiological response to Cushing’s syndrome. The forkhead box (FOX) protein family has been implicated as a key regulator of muscle loss under conditions such as diabetes and sepsis. However, the mechanistic role of the FOXO family in ACTH-induced muscle atrophy is not understood. We hypothesized that FOXO3a plays a role in muscle atrophy through expression of the E3 ubiquitin ligases, muscle RING finger protein-1 (MuRF-1), and atrogin-1 in Cushing’s syndrome. For establishment of a Cushing’s syndrome animal model, Sprague-Dawley rats were implanted with osmotic minipumps containing ACTH (40 ng·kg−1·day−1). ACTH infusion significantly reduced muscle weight. In ACTH-infused rats, MuRF-1, atrogin-1, and FOXO3a were upregulated and the FOXO3a promoter was targeted by the glucocorticoid receptor (GR). Transcriptional activity and expression of FOXO3a were significantly decreased by the GR antagonist RU486. Treatment with RU486 reduced MuRF-1 and atrogin-1 expression in accordance with reduced enrichment of FOXO3a and Pol II on the promoters. Knockdown of FOXO3a prevented dexamethasone-induced MuRF-1 and atrogin-1 expression. These results indicate that FOXO3a plays a role in muscle atrophy through expression of MuRF-1 and atrogin-1 in Cushing’s syndrome.

Cushing's syndrome associated with bilateral adrenal adenomas

1985 ◽  
Vol 108 (2) ◽  
pp. 245-254 ◽  
Author(s):  
Naonori Mimou ◽  
Schun-ichi Sakato ◽  
Hajime Nakabayashi ◽  
Zenzo Saito ◽  
Ryoyu Takeda ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
High Concentration ◽  
Tissue Extracts ◽  
Dynamic Studies ◽  
Adrenocortical Adenomas ◽  
Adrenocortical Tumours ◽  
Black Adenoma ◽  
Bilateral Adrenal Adenomas ◽  
The Right

Abstract. The fifth case of Cushing's syndrome with bilateral adrenocortical tumours is described. By the hormonal dynamic studies both tumours have been shown to be autonomous in the secretion of cortisol. Histopathologically, both tumours were identified as benign adrenocortical adenomas without nodules, and the right one was a so-called black adenoma. A high concentration of cortisol was obtained from both tumour tissue extracts. The differential diagnosis of Cushing's syndrome due to bilateral adrenocortical adenomas from primary adrenocortical nodular dysplasia is briefly discussed.

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