The studies described in this application are designed to explore the processes which generate and maintain tissue and cellular levels of retinoic acid (vitamin A acid). The identification of retinoic acid as a natural morphogen and the description of nuclear receptors for retinoic acid have greatly expanded the interest in and the research activity directed towards understanding mechanistically how retinoic acid functions in regulating gene transcription. Little information, however, is currently available regarding the origin of the retinoic acid present in tissues or cells or the factors which regulate tissue and cellular retinoic acid levels. The studies proposed in this application will provide significant new information about the cellular and tissue processes which generate and maintain tissue levels of retinoic acid. Thus, these proposed studies will provide new information regarding processes which are essentially involved in the expression of vitamin A action. This proposal is divided into four Specific Aims. The studies proposed in Specific Aim 1 are designed to investigate the plasma turnover of retinoic acid and to assess the contribution that plasma retinoic acid makes to tissue retinoic acid pools in control chow fed male rats. Specific 2 proposes studies which will explore the effects of age and sex on whole body retinoic acid synthesis rates, plasma and tissue retinoic acid levels, and the contribution which plasma retinoic acid makes to tissue retinoic acid pools. The goal of Specific Aim 3 is to gain an understanding of how different states of retinoid (vitamin A) and carotenoid nutriture influence tissue and plasma levels of retinoic acid, whole body retinoic acid synthesis rates, and the metabolic origin (plasma vs. tissue synthesis) of the retinoic acid present in tissues.
Specific Aim 4 will examine and characterize the formation of retinoic acid in isolated rat testis Sertoli cell preparations and identify factors which are responsible for regulating retinoic acid levels in these cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK043097-02
Application #
3244398
Study Section
Nutrition Study Section (NTN)
Project Start
1991-09-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Ramm, G A; Britton, R S; O'Neill, R et al. (1995) Vitamin A-poor lipocytes: a novel desmin-negative lipocyte subpopulation, which can be activated to myofibroblasts. Am J Physiol 269:G532-41
Blaner, W S; Obunike, J C; Kurlandsky, S B et al. (1994) Lipoprotein lipase hydrolysis of retinyl ester. Possible implications for retinoid uptake by cells. J Biol Chem 269:16559-65
Yu, M W; Zhang, Y J; Blaner, W S et al. (1994) Influence of vitamins A, C, and E and beta-carotene on aflatoxin B1 binding to DNA in woodchuck hepatocytes. Cancer 73:596-604
Chertow, B S; Driscoll, H K; Blaner, W S et al. (1994) Effects of vitamin A deficiency and repletion on rat glucagon secretion. Pancreas 9:475-84
van Bennekum, A M; Blaner, W S; Seifert-Bock, I et al. (1993) Retinol uptake from retinol-binding protein (RBP) by liver parenchymal cells in vitro does not specifically depend on its binding to RBP. Biochemistry 32:1727-33
Zovich, D C; Orologa, A; Okuno, M et al. (1992) Differentiation-dependent expression of retinoid-binding proteins in BFC-1 beta adipocytes. J Biol Chem 267:13884-9
Dancis, J; Levitz, M; Katz, J et al. (1992) Transfer and metabolism of retinol by the perfused human placenta. Pediatr Res 32:195-9