Hypophysectomy does not alter the acinar zonation of gluconeogenesis or the mitochondrial redox state in rat liver

Tosh, David; Alberti, K. G. M. M.; Agius, Loranne

doi:10.1042/bj2600183

Cited by 7 publications

(3 citation statements)

References 27 publications

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“…These data demonstrate that hormonal factors influence both the total activity, and the zonation of ALAT. The effect of hypophysectomy on the zonation of ALAT was undetected in a previous study by Tosh et al [26], based on comparison of ALAT activities between periportal and perivenous cell populations isolated from hypophysectomized rats.…”

Section: Collection Of Periportal and Perivenous Cell Lysates: Alat Amentioning

confidence: 88%

Hormonal regulation of the zonated expression of cytochrome P-450 3A in rat liver

Oinonen¹,

Lindros²

1995

Biochemical Journal

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Most cytochrome P-450 enzymes are expressed characteristically in a zonated pattern in the liver. The factors responsible for this heterogenous expression are largely unknown. Here we report how growth hormone and tri-iodothyronine regulate the steroid-hydroxylating cytochrome P-450 (CYP) 3A forms, which are constitutively expressed mainly in the perivenous (downstream) liver region. By comparing cell lysates obtained from the periportal and perivenous acinar regions we observed that the elevated CYP3A expression observed after hypophysectomy was due mainly to a dramatic increase in the normally silent periportal region. This effect was particularly strong in females. Treatment with growth hormone re-established the perivenous expression pattern, a finding corroborated by immunohistochemical analysis of liver sections. Analysis of periportal and perivenous mRNA by reverse-transcriptase PCR demonstrated that in males the changes in CYP3A2 mRNA paralleled the changes at the protein level. In females, CYP3A2 mRNA was detected only after hypophysectomy, and the zonal protein changes seemed to be governed by changes in CYP3A1 mRNA levels. Treatment of hypophysectomized animals with tri-iodothyronine also suppressed the expression of CYP3A, both in males and females. However, this occurred almost exclusively in the periportal region. This was observed both at the protein level, as determined by immunoblotting and immunohistochemically, and at the CYP3A1 and 3A2 mRNA level. These results indicate that growth hormone and thyroid hormone regulate the expression of CYP3A genes zone-specifically by suppressing their transcription in the periportal (upstream) region of the liver.

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Section: Collection Of Periportal and Perivenous Cell Lysates: Alat Amentioning

confidence: 88%

Hormonal regulation of the zonated expression of cytochrome P-450 3A in rat liver

Oinonen¹,

Lindros²

1995

Biochemical Journal

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“…Moreover, the two cell populations also show differences in the relative utilization of glucose (Agius et al, 1990) and in rates of glucogenogenesis (Chen and Katz, 1988). Since hepatocytes isolated from the periportal zone have a lower D-3-hydroxybutyrate/acetoacetate ratio during culture with glucagon than perivenous hepatocytes (Tosh et al, 1989), we were interested in the study of the expression of mitochondrial HMG-CoA synthase as the main ketogenic enzyme as a way to assess possible changes in rate of ketogenesis in periportal vs. perivenous hepatocytes.…”

Section: Incmentioning

confidence: 99%

Immunolocalization of mitochondrial 3‐hydroxy‐3‐methylgutaryl CoA synthase in rat liver

Royo

Pedragosa

Ayté

et al. 1995

Journal Cellular Physiology

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We report the preparation of specific polyclonal antibodies raised against two synthetic peptides deduced from the cDNA sequence for the rat liver mitochondrial 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) synthase gene. Immunoelectron microscopy using these antibodies on hepatic cryoultrathin sections confirms the mitochondrial localization of this protein in hepatocytes. Immunofluorescence microscopy on frozen sections of adult rat liver revealed fluorescence inside all hepatocytes, with no evidence of zonation, indicating that ketogenesis may not be limited to specific regions of rat liver but is extended to all hepatocytes.

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“…Microsomes were prepared either from male adult rat liver (body weight 200-250g), freshly isolated hepatocytes or hepatocytes cultured on different substrata [4,51. Hepatocytes were isolated by the conventional collagenase perfusion technique [6] and were cultured for up to 24 hours as described previously [7] on either normal tissue culture plastic (NTCP) or NTCP coated with either collagen type IV or laminin ( 10pg/cm2). Alternatively, hepatocytes were cultured on Primaria@ dishes.…”

mentioning

confidence: 99%

Regulation of glucose-6-phosphatase by the extracellular matrix

Tosh

Burchell

Oakley

1997

Biochemical Society Transactions

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Glucose-6-phosphatase (EC 3.1.3.9) catalyses the terminal step of both gluconeogenesis and glycogenolysis. The enzyme comprises a multicomponent system found in the endoplasmic reticulum (E.R.) with the active site of the catalytic subunit directed towards the lumen of the E.R. [ 11. While there is much known about the hormonal regulation of the enzyme, there is a paucity of information on additional factors which might regulate the enzyme and its expression. The extracellular matrix (ECM) is an insoluble complex of collagens, adhesion proteins and proteoglycans. The function of the ECM was originally thought to be one of mechanical support. However, it is now well established that cell structure and function are profoundly influenced by the ECM during development and in the adult organism [2]. ECM components reconstituted in vitro have been shown to regulate the differentiated properties of hepatocytes by stimulating transcription of the albumin gene [3]. Whether the ECM regulates all or only descrete hepatic functions remains to be determined. The aim of the present investigation was to establish whether the ECM regulates the activity and expression of the microsomal gluconeogenic enzyme glucose-6phosphatase. Microsomes were prepared either from male adult rat liver (body weight 200-250g), freshly isolated hepatocytes or hepatocytes cultured on different substrata [4,51. Hepatocytes were isolated by the conventional collagenase perfusion technique [6] and were cultured for up to 24 hours as described previously [7] on either normal tissue culture plastic (NTCP) or NTCP coated with either collagen type IV or laminin ( 10pg/cm2). Alternatively, hepatocytes were cultured on Primaria@ dishes. Primaria@ is a modified tissue culture plastic that promotes attachement of cells to the substratum and has previously been used for maintaining hepatocyte gene expression in vitro [8,9].Glucose-6phosphatase activity was assayed in fully disrupted microsomes as described previously [lo].Immunoblot analysis was performed using sheep anti-rat glucose-6-phosphatase enzyme antibody [I I].Hepatocytes isolated by the collagepse perfusion technique had lower activities of glucose-6-phosphatase than in microsomes prepared from adult rat liver (Fig 1). Hepatocytes maintained in culture (irrespective of the condition) had lower activities of glucose-6-phosphatase enzyme compared with fresh liver. However, with cells cultured on either laminin or collagen, the enzyme activity (Fig 1) and expression, (Fig 2) was maintained to a level similar to that observed in freshly isolated cells. Hepatocytes cultured on Primaria@ did have higher activities of glucose-6-phosphatase compared to cells cultured on NTCP alone but lower activities compared to those cells cultured on either collagen or laminin . Fig 1 (below) The activity of glucose-6-phosphatase in microsomes prepared from adult rat liver, feshly isolated hepatocytes and hepatocytes cultured on normal tissue culture plastic, Primaria@ dishes, or laminin or collagen-coated dishes. Enzyme a...

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Hypophysectomy does not alter the acinar zonation of gluconeogenesis or the mitochondrial redox state in rat liver

Cited by 7 publications

References 27 publications

Hormonal regulation of the zonated expression of cytochrome P-450 3A in rat liver

Hormonal regulation of the zonated expression of cytochrome P-450 3A in rat liver

Immunolocalization of mitochondrial 3‐hydroxy‐3‐methylgutaryl CoA synthase in rat liver

Regulation of glucose-6-phosphatase by the extracellular matrix

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