High expression of antizyme inhibitor 2, an activator of ornithine decarboxylase in steroidogenic cells of human gonads

Mäkitie, Laura; Kanerva, Kristiina; Sankila, Anna; Andersson, Leif C.

doi:10.1007/s00418-009-0636-7

Cited by 21 publications

(22 citation statements)

References 30 publications

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“…Thus, activated mast cells were found to express important levels of AZIN2 that tend to accumulate into serotonin-containing granules [20]. It was also shown that Leydig cells accounted for the high levels of AZIN2 in testis, and that this gene was also expressed in ovarian luteinized cells [21]. This new set of AZIN2 expressing tissues have in common to possess either endocrine or paracrine functions, and therefore, to be endowed with a prominent secretory activity.…”

Section: Discussionmentioning

confidence: 95%

“…Although the presence of Azin2 mRNA in mouse spermatids suggested that AZIN2 may have a role in spermiogenesis [19], other studies showing AZIN2 immunoreactivity in mast cells [20] as well as in Leydig cells and ovarian luteinized cells [21] have related AZIN2 with the release of serotonin and steroid hormones. In addition, our studies using real-time RT-PCR detected significant Azin2 mRNA levels in several mouse tissues, including pancreas and adrenal glands, similar to those existing in brain [22].…”

Section: Introductionmentioning

confidence: 97%

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Antizyme Inhibitor 2 Hypomorphic Mice. New Patterns of Expression in Pancreas and Adrenal Glands Suggest a Role in Secretory Processes

et al. 2013

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The intracellular levels of polyamines, polycations implicated in proliferation, differentiation and cell survival, are regulated by controlling their biosynthesis, catabolism and transport. Antizymes and antizyme inhibitors are key regulatory proteins of polyamine levels by affecting ornithine decarboxylase, the rate-limiting biosynthetic enzyme, and polyamine uptake. We recently described the molecular function of a novel antizyme inhibitor (AZIN2). However, the physiological function of AZIN2 in mammals is mostly unknown. To gain insight on the tissue expression profile of AZIN2 and to find its possible physiological role, we have generated, transgenic mice with severe Azin2 hypomorphism. This mouse model expresses transgenic bacterial β-D-galactosidase as a reporter gene, under the control of the Azin2 endogenous promoter, what allows a very sensitive and specific detection of the expression of the gene in the different tissues of transgenic mice. The biochemical and histochemical analyses of β-D-galactosidase together with the quantification of Azin2 mRNA levels, corroborated that AZIN2 is mainly expressed in testis and brain, and showed for the first time that AZIN2 is also expressed in the adrenal glands and pancreas. In these tissues, AZIN2 was not expressed in all type of cells, but rather in specific type of cells. Thus, AZIN2 was mainly found in the haploid germinal cells of the testis and in different brain regions such as hippocampus and cerebellum, particularly in specific type of neurons. In the adrenal glands and pancreas, the expression was restricted to the adrenal medulla and to the Langerhans islets, respectively. Interestingly, plasma insulin levels were significantly reduced in the transgenic mice. These results support the idea that AZIN2 may have a role in the modulation of reproductory and secretory functions and that this mouse model might be an interesting tool for the progress of our understanding on the role of AZIN2 and polyamines in specific mammalian cells.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 97%

Antizyme Inhibitor 2 Hypomorphic Mice. New Patterns of Expression in Pancreas and Adrenal Glands Suggest a Role in Secretory Processes

et al. 2013

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“…In addition to neural cells, we have detected the expression of AZIN2 in Leydig cells and in mast cells (56,57) both of which are terminally differentiated cells. The expression of AZIN2 in non-proliferating neurons, however, implicates other functions.…”

Section: Discussionmentioning

confidence: 95%

“…The expression of AZIN2 in non-proliferating neurons, however, implicates other functions. In addition to neural cells, we have detected the expression of AZIN2 in Leydig cells and in mast cells (56,57) both of which are terminally differentiated cells. Most of the ODC in the brain is bound to AZ that blocks its enzymatic activity (26)(27)(28).…”

Section: Discussionmentioning

confidence: 95%

Brain Neurons Express Ornithine Decarboxylase‐Activating Antizyme Inhibitor 2 with Accumulation in Alzheimer's Disease

et al. 2010

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Polyamines are small cationic molecules that in adult brain are connected to neuronal signaling by regulating inward-rectifier K(+)-channels and different glutamate receptors. Antizyme inhibitors (AZINs) regulate the cellular uptake of polyamines and activate ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis. Elevated levels of ODC activity and polyamines are detected in various brain disorders including stroke and Alzheimer's disease (AD). We originally reported a novel brain- and testis-specific AZIN, called AZIN2, the distribution of which we have now studied in normal and diseased human brain by in situ hybridization and immunohistochemistry. We found the highest accumulation of AZIN2 in a pearl-on-the-string-like distribution along the axons in both the white and gray matter. AZIN2 was also detected in a vesicle-like distribution in the somas of selected cortical pyramidal neurons. Double-immunofluorescence staining revealed co-localization of AZIN2 and N-methyl D-aspartate-type glutamate receptors (NMDARs) in pyramidal neurons of the cortex. Moreover, we found accumulation of AZIN2 in brains affected by AD, but not by other neurodegenerative disorders (CADASIL or Lewy body disease). ODC activity is mostly linked to cell proliferation, whereas its regulation by AZIN2 in post-mitotically differentiated neurons of the brain apparently serves different purposes. The subcellular distribution of AZIN2 suggests a role in vesicular trafficking.

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“…High ODC activity is associated with rapidly proliferating normal and malignant cells. In steroidogenic cells of human gonads, Makitie et al (2009) found high expression of antizyme inhibitor 2, an activator of ODC. ISH and ICC studies identiWed high expression of antizyme inhibitor 2 not only in normal Leydig cells and Leydig cell tumors but also in ovarian luteinized cells and in hilum cells implying a possible involvement in the release of steroid hormones.…”

Section: Male Reproductive Systemmentioning

confidence: 98%

Extending the knowledge in histochemistry and cell biology

Heupel

Drenckhahn

2009

Histochem Cell Biol

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Central to modern Histochemistry and Cell Biology stands the need for visualization of cellular and molecular processes. In the past several years, a variety of techniques has been achieved bridging traditional light microscopy, fluorescence microscopy and electron microscopy with powerful software-based post-processing and computer modeling. Researchers now have various tools available to investigate problems of interest from bird's- up to worm's-eye of view, focusing on tissues, cells, proteins or finally single molecules. Applications of new approaches in combination with well-established traditional techniques of mRNA, DNA or protein analysis have led to enlightening and prudent studies which have paved the way toward a better understanding of not only physiological but also pathological processes in the field of cell biology. This review is intended to summarize articles standing for the progress made in "histo-biochemical" techniques and their manifold applications.

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High expression of antizyme inhibitor 2, an activator of ornithine decarboxylase in steroidogenic cells of human gonads

Cited by 21 publications

References 30 publications

Antizyme Inhibitor 2 Hypomorphic Mice. New Patterns of Expression in Pancreas and Adrenal Glands Suggest a Role in Secretory Processes

Antizyme Inhibitor 2 Hypomorphic Mice. New Patterns of Expression in Pancreas and Adrenal Glands Suggest a Role in Secretory Processes

Brain Neurons Express Ornithine Decarboxylase‐Activating Antizyme Inhibitor 2 with Accumulation in Alzheimer's Disease

Extending the knowledge in histochemistry and cell biology

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