The octapeptide angiotensin II (AII) is a well-known circulating hormone. Its generation in the blood involves a cascade in which the kidney enzyme renin cleaves angiotensinogen (secreted by the liver) into angiotensin I (AI). Converting enzyme then converts AI and AII. The main action of circulating AII is to increase vascular tone and promote salt and water retention. However, in addition to this system which produces the majority of circulating AII, many endocrine organs have been shown to contain renin and generate AII locally. Previous reports support the hypothesis that locally-generated AII may have paracrine effects in these organs. Nonetheless, much more work is needed to understand (1) what is the exact physiological importance of locally-generated AII; (2) which factors regulate the local production of AII; (3) what is the exact biochemical pathway leading to the local generation of AII. In the proposed study, we will address these questions in three endocrine organs where there is strong evidence for local renin- angiotensin systems (RAS), namely, the anterior pituitary gland, the adrenal cortex and the testicular Leydig cells in the rat. We have developed the appropriate techniques that enable us to (1) detect AII in tissues by immunocytochemistry, radioimmunoassay and HPLC; (2) detect renin in tissues by immunocytochemistry and enzymatic assay; (3) detect angiotensinogen in tissues by immunocytochemistry and enzymatic assay; (4) detect renin or angiotensinogen mRNA's in tissues, by in situ hybridization histochemistry. By combining the techniques, we will seek to determine which components of the RAS are present (or absent) in these tissues, where they are located and how they interact. In order to understand what regulates the local production of AII, we will determine the effect of various conditions on the concentration of AII, renin, angiotensinogen and their respective messenger RNA's in these endocrine organs. Finally, we will seek to determine whether various Leydig cell lines can be used as an experimental model to study the intracellular generation of AII.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL038774-04
Application #
3471320
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Rahemtulla, N; Deschepper, C F; Maurice, J et al. (1994) Immunocytochemical and functional characterization of an immortalized type 1 astrocytic cell line. Brain Res 642:221-7
Zahs, K R; Bigornia, V; Deschepper, C F (1993) Characterization of ""plasma proteins"" secreted by cultured rat macroglial cells. Glia 7:121-33
Mellon, S H; Deschepper, C F (1993) Neurosteroid biosynthesis: genes for adrenal steroidogenic enzymes are expressed in the brain. Brain Res 629:283-92
Hong-Brown, L Q; Deschepper, C F (1993) Regulation of the angiotensinogen gene by estrogens in rat liver and different brain regions. Proc Soc Exp Biol Med 203:467-73
Radany, E H; Brenner, M; Besnard, F et al. (1992) Directed establishment of rat brain cell lines with the phenotypic characteristics of type 1 astrocytes. Proc Natl Acad Sci U S A 89:6467-71
Bottari, S P; Obermuller, N; Bogdal, Y et al. (1992) Characterization and distribution of angiotensin II binding sites in fetal and neonatal astrocytes from different rat brain regions. Brain Res 585:372-6
Akana, S F; Scribner, K A; Bradbury, M J et al. (1992) Feedback sensitivity of the rat hypothalamo-pituitary-adrenal axis and its capacity to adjust to exogenous corticosterone. Endocrinology 131:585-94
Hong-Brown, L Q; Deschepper, C F (1992) Effects of thyroid hormones on angiotensinogen gene expression in rat liver, brain, and cultured cells. Endocrinology 130:1231-7
Deschepper, C F; Dallman, M F (1992) The stimulation of liver angiotensinogen by glucocorticoids depends on the type of steroid and its mode of administration. Endocrinology 131:2371-7
Gardner, D G; Camargo, M J; Behringer, R R et al. (1992) Atrial natriuretic peptide synthesis in atrial tumors of transgenic mice. Am J Physiol 262:E524-31

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