Hypoxia Inducible Factor Expression and Angiogenesis – Analysis in the Pituitary Gland and Patterns of Death

Abstract

Abstract. Background The pituitary (hypophysis), a small 0.5-g endocrine gland, is located at the base of the brain, just below the hypothalamus; it is the "master gland" of the neuroendocrine system for it controls the function of other endocrine glands. The pituitary itself is regulated by the hypothalamus that is connected to the pituitary by a thin stalk, the pituitary stalk, which carries a delicate portal venous system. Microscopically, the pituitary is composed of two distinctive parts: the anterior lobe (adenohypophysis) and posterior lobe (neurohypophysis) (1). The anterior lobe is a typical endocrine gland composed of cells that contain hormone-secreting cytoplasmic granules; these, after a conventional H&E staining, characterize the adenohypophyseal cells as acidophils, basophils and chromophobes. By immunohistochemistry, however, the cells are distinguished in somatotrophs (GH cells), prolactin secreting cells (PRL cells), corticotrophs (ACTH cells), thyrotrophs (TSH cells) and gonadotrophs (FSH and LH cells).As to the posterior lobe, this being an extension of the hypothalamus, is composed largely of axons of the hypothalamic neurons, with the cell bodies of the neurons synthesizing oxytocin and antidiuretic hormone (ADH), also known as vasopressin.Recent studies suggest that hypoxia is a strong regulator of the function of both adeno-and neuro-hypophysis, presumably by regulating transcription of hormone mRNA through specific receptor activation (2, 3). Both protracted and intermittent hypoxia have been implicated in the regulation of hypophesial function (4-7). Hypoxia inducible factor 1α and 2α are principal transcription factor sensors of hypoxia (8). The α-subunits in the cytoplasm of cells dimerize with the β-subunit, enter the nuclei and exert their transcriptional activity on a large number of genes, including the key angiogenesis involved gene VEGF (9) and a variety of genes involved in glycolysis, metabolism, cell cycle and death pathways (10, 11).In the current study, we investigated the vascular density and the expression of HIF1α, HIF2α and VEGF in the adenohypophysis and neurohypophysis of patients deceased from various acute or chronic diseases, in order to assess whether death patterns involving hypoxia have an effect on the hypophyseal sensing of hypoxic conditions. Materials and MethodsPituitary glands from 97 cadavars were collected at autopsy. The study has been approved by the local Ethics and Research Committees. The procedure involved opening the sellar diaphragm and fracturing the dorsum of the sella turcica to allow the gland to 185

Hypoxia Promotes Angiogenic Effect in Extracranial Arteriovenous Malformation Endothelial Cells

“…AVM has been described as lesions enlarged through vasculogenesis, involving the formation of new vasculature or angiogenesis to form new blood vessels from the pre-existing vasculature [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. First, the effect of EC proliferation on angiogenesis was evaluated [ 14 , 15 ] and was found to be greater in AVM than in normal tissues. EC proliferation increased in AVM compared to normal tissues under hypoxic conditions, although proliferation generally decreased because of hypoxic damage ( Figure 1 and Figure 2 ).…”

“…[ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Moreover, various studies have reported that angiogenesis induced under hypoxia was effectively compared and evaluated in normal and pathophysiological situations using the CD31 expression [ 14 , 15 ].…”