HUMAN PITUITARY ACTH/B-ENDORPHIN BIOSYNTHESIS

  • Kendall, John (PI)

Project: Research project

Project Details

Description

The specific aims of this project are to: 1) describe normal human
pituitary pro-opiomelanocortin (POMC) in biosynthesis and processing; 2)
test the hypothesis that differences in synthesis and processing of POMC
can be identified between normal and adenomatous (Cushing's Disease
pituitary tumors); 3) compare the influences of stimulators/inhibitors on
POMC, processing and release in normal and abnormal human pituitaries. Human pituitary tissue (norma, adenomatous Cushing's Disease and
adenomatous non-Cushing's Disease) will be obtained at operation, analyzed
for molecular species of ACTH/Beta-endorphin by radiommunoassay,
enzymatically and mechanically dispersed for study in tissue culture and
use in perifusion experiments. Biosynthesis and processing of POMC-derived
peptides will be examined by steady-state and pulse-chase labeling schemes
using radioactive amino acids and sugars followed by immunoprecipitation
and fractionation by gel electrophoresis under dissociating conditions.
The character and control of hormone release will be studied with advanced
perifusion techniques. Sub-human primate anterior pituitary tissue will be similarly studied to
refine our understanding of normal human physiology. Comparisons will be made between normal and adenomatous tissue of rates of
POMC production, processing of POMC-derived peptides, and effects of
stimulators/inhibitors, (CRF, neurotransmitters, glucocorticoids) on
synthesis and release in vitro. The long term goals of the project are to
understand normal human POMC biosynthesis, processing, release and
regulation and to gain knowledge of differences of these molecular events
in adenomatous pituitaries that might provide clues to the pathomechanisms
of Cushing's Disease.
StatusFinished
Effective start/end date4/1/839/30/86

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)

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