The goal of this application is to utilize the GH4 cell line to elucidate the cellular processes by which growth factors inhibit pituitary cell proliferation. It is proposed to investigate several aspects of TGF-alpha and TGF-beta growth-inhibitory mechanisms. First, it will be examined whether TGF-alpha or TGF-beta blocks specific states of the cell cycle. Then it will be examined whether TGF-alpha or TGF-beta inhibits cell proliferation by preventing the actions of defined growth-stimulatory factors, elevating free cytosolic calcium, or enhancing cell-substratum adhesion.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DK043107-05
Application #
2142775
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1990-07-06
Project End
1996-06-30
Budget Start
1994-07-01
Budget End
1996-06-30
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Edmunds, J S; Fairey, E R; Ramsdell, J S (1997) A rapid and sensitive high throughput reporter gene assay for estrogenic effects of environmental contaminants. Neurotoxicology 18:525-32
Xi, D; Peng, Y G; Ramsdell, J S (1997) Domoic acid is a potent neurotoxin to neonatal rats. Nat Toxins 5:74-9
Xi, D; Ramsdell, J S (1996) Glutamate receptors and calcium entry mechanisms for domoic acid in hippocampal neurons. Neuroreport 7:1115-20
Xi, D; Kurtz, D T; Ramsdell, J S (1996) Maitotoxin-elevated cytosolic free calcium in GH4C1 rat pituitary cells nimodipine-sensitive and -insensitive mechanisms. Biochem Pharmacol 51:759-69
Peng, Y G; Ramsdell, J S (1996) Brain Fos induction is a sensitive biomarker for the lowest observed neuroexcitatory effects of domoic acid. Fundam Appl Toxicol 31:162-8
Peng, Y G; Taylor, T B; Finch, R E et al. (1995) Neuroexcitatory actions of ciguatoxin on brain regions associated with thermoregulation. Neuroreport 6:305-9
Young, R C; McLaren, M; Ramsdell, J S (1995) Maitotoxin increases voltage independent chloride and sodium currents in GH4C1 rat pituitary cells. Nat Toxins 3:419-27
Finley, E L; King, J S; Ramsdell, J S (1994) Human pituitary somatotropes express transforming growth factor-alpha and its receptor. J Endocrinol 141:547-54
Finley, E L; Ramsdell, J S (1994) A transforming growth factor-alpha pathway is expressed in GH4C1 rat pituitary tumors and appears necessary for tumor formation. Endocrinology 135:416-22
Peng, Y G; Taylor, T B; Finch, R E et al. (1994) Neuroexcitatory and neurotoxic actions of the amnesic shellfish poison, domoic acid. Neuroreport 5:981-5

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