Separate induction of the two isozymes of cytochrome P-45011β in rat adrenal zona glomerulosa cells

Müller, Jürg; Oertle, Maja

doi:10.1016/0960-0760(93)90077-a

Cited by 20 publications

(6 citation statements)

References 44 publications

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“…CYP11B1 catalyzes the last step in this pathway but also, as mentioned, the metabolic activation of MeSO 2 -DDE in the adrenal zona fasciculata (12,30,31). Since tetracosactide stimulates both CYP11A1 and CYP11B1 activity (22,24,(32)(33)(34)(35), this peptide would be expected to increase both corticosterone synthesis and irreversible MeSO 2 -[ 14 C]DDE binding in the slice culture. The observed 8fold induction of corticosterone secretion by tetracosactide was therefore expected and supports the conclusion that the cultured slices retained their functional stability throughout the experiment.…”

Section: Discussionmentioning

confidence: 91%

Irreversible binding and adrenocorticolytic activity of the DDT metabolite 3-methylsulfonyl-DDE examined in tissue-slice culture.

Lindhe

Lund²,

Bergman³

et al. 2001

Environ Health Perspect

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The persistent adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE (MeSO(2)-DDE) was originally identified in Baltic grey seals, a population suffering from adrenocortical hyperplasia. In mice, MeSO(2)-DDE induces mitochondrial degeneration and cellular necrosis in the adrenal zona fasciculata. In this study, we used precision-cut tissue slice culture to examine local CYP11B1-catalyzed irreversible binding of MeSO(2)-DDE in the murine adrenal cortex. We also examined effects on steroid hormone secretion, histology, and ultrastructure. As determined by microautoradiography, selective binding occurred in zona fasciculata of slices exposed to MeSO(2)-[(14)C]-DDE. Quantification of binding by phosphorautoradiography revealed a 3-fold reduction of binding in slices co-exposed to the CYP11B1 inhibitor metyrapone. As measured by HPLC, corticosterone and 11-deoxycorticosterone secretion to the medium increased linearly for at least 24 hr. Addition of the ACTH analog tetracosactide caused an 8-fold increase in corticosterone secretion. Addition of metyrapone reduced corticosterone secretion 4-fold. Exposure of slices to MeSO(2)-DDE (50 microM) reduced the rate of corticosterone secretion by 90% after 24 hr of incubation. As determined by electron microscopy, vacuolated mitochondria were present in zona fasciculata of slices exposed to MeSO(2)-DDE (50 microM) for 24 hr. Our findings show that all effects of MeSO(2)-DDE previously reported in vivo could be reproduced in adrenal slice culture ex vivo. This test system allows analysis of zone-specific irreversible binding and effects on steroid hormone secretion and target cell ultrastructure. We propose adrenal slice culture as a simple ex vivo test system with which to examine the adrenocorticolytic activity of xenobiotics in human and wild animal tissue.

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Section: Discussionmentioning

confidence: 91%

Irreversible binding and adrenocorticolytic activity of the DDT metabolite 3-methylsulfonyl-DDE examined in tissue-slice culture.

Lindhe

Lund²,

Bergman³

et al. 2001

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…CYP11B1 catalyzes the last step in this pathway but also, as mentioned, the metabolic activation of MeSO 2 -DDE in the adrenal zona fasciculata (12,30,31). Since tetracosactide stimulates both CYP11A1 and CYP11B1 activity (22,24,(32)(33)(34)(35), this peptide would be expected to increase both corticosterone synthesis and irreversible MeSO 2 -[ 14 C]DDE binding in the slice culture. The observed 8-fold induction of corticosterone secretion by tetracosactide was therefore expected and supports the conclusion that the cultured slices retained their functional stability throughout the experiment.…”

Section: Discussionmentioning

confidence: 99%

Irreversible Binding and Adrenocorticolytic Activity of the DDT Metabolite 3-Methylsulfonyl-DDE Examined in Tissue-Slice Culture

Lindhe¹,

Lund²,

Bergman³

et al. 2001

Environ Health Perspect

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“…The expression and activity of the steroidogenesis enzymes is regulated by the secretion of ACTH from the anterior pituitary into the bloodstream (40). Therefore, we wished to determine if the reduced expression of the steroidogenesis enzymes is a result of decreased ACTH levels in the pituitary.…”

Section: Hpa Axis Is Suppressed In Experimental Models Of Cholestasismentioning

confidence: 99%

Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat

Quinn¹,

Ueno

Pae

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitaryadrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and ␣-naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropinreleasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19-and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL-induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease.corticotropin-releasing hormone; glucocorticoids; biliary epithelium; adrenocorticotropic hormone CHOLANGIOCYTES ARE EPITHELIAL cells that line the intra-and extrahepatic bile ducts. They are constitutively mitotically dormant but possess marked proliferative capacity (2), which is apparent during experimental conditions, such as cholestasis induced by bile duct ligation (BDL) or ␣-naphthylisothiocyanate (ANIT) intoxication (1), as well as in human cholangiopathies (2). In humans, cholangiocyte proliferation occurs in extrahepatic biliary obstruction, in the course of chronic cholestatic liver diseases (e.g., primary sclerosing cholangitis, primary biliary cirrhosis, liver allograft rejection, and graft-vs.-host disease) (2), and in many forms of liver injury (e.g., in response to alcohol, toxin, or drugs) (2, 43).The hypothalamic-pituitary-adrenal (HPA) axis describes a complex set of positive-and negative-feedback influences between the hypothalamus, pituitary gland, and adrenal gland (25). These feedforward and feedback mechanisms work in a neuroendocrine manner to modulate a number of physiological processes, such as immunity (32), digestion (30), and the body's response to stress (30). In addition, the HPA axis has been shown to have an influence on human psychology (7, 53).The mechanism by which the HPA axis rem...

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Separate induction of the two isozymes of cytochrome P-45011β in rat adrenal zona glomerulosa cells

Cited by 20 publications

References 44 publications

Irreversible binding and adrenocorticolytic activity of the DDT metabolite 3-methylsulfonyl-DDE examined in tissue-slice culture.

Irreversible binding and adrenocorticolytic activity of the DDT metabolite 3-methylsulfonyl-DDE examined in tissue-slice culture.

Irreversible Binding and Adrenocorticolytic Activity of the DDT Metabolite 3-Methylsulfonyl-DDE Examined in Tissue-Slice Culture

Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat

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