Differential effects of transforming growth factor type beta on the growth and function of adrenocortical cells in vitro.

Hotta, Mari; Baird, Andrew

doi:10.1073/pnas.83.20.7795

Cited by 96 publications

(45 citation statements)

References 40 publications

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“…Another possible mechanism for primary adrenal failure is the release of a number of factors by lipopolysaccharide-stimulated macrophages, similar as to what happens in endotoxic shock, that suppress the steroidogenic response of adrenocortical cells to ACTH, the amount of factors released regulated by lymphokines (39). Furthermore, transforming growth factor-b, another cytokine derived from monocytes, is also known to inhibit both basal and ACTH-stimulated steroidogenesis (40). A strong correlation identified between postoperative basal and peak cortisol levels and a weaker correlation between ACTH and cortisol postoperatively compared to preoperative values could support this hypothesis.…”

Section: Discussionsupporting

confidence: 60%

Assessing adrenal status in patients before and immediately after coronary artery bypass graft surgery

Debono¹,

Sheppard²,

Irving³

et al. 2011

European Journal of Endocrinology

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Objective: Patients with cortisol deficiency poorly tolerate any systemic inflammatory response syndrome (SIRS), and may die if not treated with sufficient exogenous glucocorticoids. Controversy surrounds what constitutes a 'normal' adrenal response in critical illness. This study uses conventional tests for adrenal insufficiency to investigate cortisol status in patients undergoing elective coronary artery bypass surgery, a condition frequently associated with SIRS. Design: A prospective, observational study. Methods: Thirty patients with impaired left ventricular function (ejection fraction O23% !50%) underwent basal ACTH measurement, and a short cosyntropin test (250 mg, i.v.) 1 week preoperatively, and at C4 h following induction of general anaesthesia. Preoperatively, a 30 min cortisol level post cosyntropin O550 nmol/l was taken as a normal response. Results: Prior to surgery, all patients had a normal response to cosyntropin. Postoperatively, eight patients (26.7%) did not achieve stimulated cortisol levels O550 nmol/l and the mean peak cortisol postoperatively was lower (1048 vs 730 nmol/l; P!0.001). There was a significant rise in ACTH after surgery (21 vs 184 ng/l; PZ0.007) and reduction in D-cortisol post cosyntropin (579 vs 229 nmol/l; P!0.001). There was no change in basal cortisol pre-and post-operatively (447 vs 501; PZ0.4). All patients underwent routine, uneventful postoperative recovery. Conclusion: Up to one quarter of patients with a normal cortisol status preoperatively demonstrated a raised ACTH and deficient cortisol response postoperatively. Despite these responses, all patients had uneventful outcomes. These data reinforce the need for caution when interpreting results of endocrine testing following major surgery or in the intensive care environment, and that prognostic value of these results may be of limited use.

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Section: Discussionsupporting

confidence: 60%

Assessing adrenal status in patients before and immediately after coronary artery bypass graft surgery

Debono¹,

Sheppard²,

Irving³

et al. 2011

European Journal of Endocrinology

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“…TGFh regulates adrenal development (22,23) and can inhibit adrenal steroid production (43,44). TGFh can act either as a tumor suppressor or promote cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of the Carney Complex Gene 1 (Protein Kinase A Regulatory Subunit 1A) Inhibits SMAD3 Expression and TGFβ-Stimulated Apoptosis in Adrenocortical Cells

et al. 2009

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The cyclic AMP signaling pathway can be altered at multiple levels in endocrine tumors. Its central component is the protein kinase A (PKA). Carney complex (CNC) is a hereditary multiple neoplasia syndrome resulting from inactivating mutations of the gene encoding the PKA type I A regulatory subunit (PRKAR1A). Primary pigmented nodular adrenocortical disease is the most frequent endocrine tumor of CNC. Transforming growth factor B (TGFB) regulates adrenal cortex physiology and signals through SMAD2/3. We used an interference approach to test the effects of PRKAR1A inactivation on PKA and TGFB pathways and on apoptosis in adrenocortical cells. PRKAR1A silencing stimulates PKA activity and increases transcriptional activity of a PKA reporter construct and expression of the endogenous PKA target, NR4A2, under basal conditions or after forskolin stimulation. PRKAR1A inactivation also decreased SMAD3 mRNA and protein levels via PKA, altering the cellular response to TGFB. SMAD3 expression was also inhibited by adrenocorticorticotropic hormone in the mouse adrenal gland and by forskolin in H295R cells. TGFB stimulates apoptosis in H295R cells, and this effect was counteracted by PRKAR1A inactivation. PRKAR1A silencing decreased the percentage of apoptotic cells and the cleavage of apoptosis mediators [caspase-3, poly(ADP-ribose) polymerase, and lamin A/C]. Inactivating mutations of PRKAR1A observed in adrenocortical tumors alter SMAD3, leading to resistance to TGFBinduced apoptosis. This cross-talk between the PKA and the TGFB signaling pathways reveals a new mechanism of endocrine tumorigenesis. [Cancer Res 2009;69(18):7278-84]

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“…These include basic fibroblast growth factor (FGF-2), transforming growth factor-a (TGF-a) and transforming growth factor-b1 (TGF-b1), vascular endothelial growth factor (VEGF), and interleukins (Hotta & Baird 1986, Feige et al 1991, 1998, Ilvesmaki et al 1993b, Weber et al 1997a,b, de Fraipont et al 2000, Turner et al 2003. Among these factors, FGF-2 may be a prime candidate to evaluate in adrenocortical tumors.…”

Section: Growth Factorsmentioning

confidence: 99%

Adrenocortical cancer: pathophysiology and clinical management

Libé¹,

Fratticci²,

Bertherat³

2007

Endocr Relat Cancer

237

159

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Adrenocortical cancer (ACC) is a rare tumor with a poor prognosis. By contrast, benign adrenocortical tumors are frequent, underlying the importance of a correct diagnosis of malignancy of such tumors. ACC can be diagnosed by the investigation of endocrine signs of steroid excess, symptoms due to tumor growth or an adrenal incidentaloma. Hormonal investigations demonstrate in most ACC steroid oversecretion, the dominant characteristics being a co-secretion of cortisol and androgens. Imaging by CT-scan or MRI shows a large heterogeneous tumor with a low fat content. Careful pathological investigation with the assessment of the Weiss score is important for the diagnosis of malignancy. Molecular markers can also be helpful and in the future might be important for prognosis. Tumors localized to the adrenal gland (McFarlane stages 1 and 2) have a better outcome than invasive and metastatic tumors (stages 3 and 4). Tumor removal by a specialized team is crucial for treatment and should always aim at complete removal. In patients with metastatic or progressive disease, medical treatment is started with mitotane that requires a close monitoring of its blood level. Surgery is indicated when possible for local recurrence but also in some cases of metastasis. Local treatment (radiofrequency, chemoembolization, and radiation therapy) can have some indications for metastatic disease. In patients with disease progression cytotoxic chemotherapy can be used. Despite the best care, the overall prognosis of ACC is poor with a 5-year survival rate below 30% in most series. Therefore, progress in the understanding of the pathophysiology of ACC is important. Despite the rarity of ACC, significant advances have been made in the understanding of its pathogenesis the last decade. These progresses came mainly from the study of the genetics of ACC, both at the germline level in rare familial diseases, and at the somatic level by the study of molecular alterations in sporadic tumors. These advances underline the importance of genetic alterations in ACC development and point-out to various chromosomal regions (2, 11p15, 11q, 17p13) and genes (IGF-II, p53, b-catenin, ACTH receptor). This review will summarize these advances as well as the current clinical management of ACC.

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Differential effects of transforming growth factor type beta on the growth and function of adrenocortical cells in vitro.

Cited by 96 publications

References 40 publications

Assessing adrenal status in patients before and immediately after coronary artery bypass graft surgery

Assessing adrenal status in patients before and immediately after coronary artery bypass graft surgery

Inactivation of the Carney Complex Gene 1 (Protein Kinase A Regulatory Subunit 1A) Inhibits SMAD3 Expression and TGFβ-Stimulated Apoptosis in Adrenocortical Cells

Adrenocortical cancer: pathophysiology and clinical management

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