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Estrogen receptor and progesterone receptor synthesis and degradation in target cells

Thesis/Dissertation ·
OSTI ID:6602804
It was the intent of this study to determine the turnover of the estrogen receptor (ER) and progesterone receptors (PR) in rat uterine and human breast cancer cells, respectively, and to examine the effect of estrogen and progestin on PR levels. The rates of synthesis and degradation of ER were determined in rat uterine cells in vitro and in vivo. The affinity labeling antiestrogen, (/sup 3/H)tamoxifen aziridine, was used in pulse chase experiments to show that the 65,000 molecular weight ER has a half-life of 3-4h in primary cultures of rat uterine cells in vitro and in the intact rat uterus in vivo. Density shift analyses using dense (/sup 15/N, /sup 13/C, /sup 2/H) amino acid incorporation corroborate the rapid turnover of ER in rat uterine cell cultures. The regulation of PR by progestins in T47D human breast cancer cells was examined using density shift-dense amino acid incorporation. When T47D cells, which normally maintain high PR levels, are exposed to progestin (R5020), PR levels decline. Receptor half-life, which is 21h in control cells, is reduced to 6h when cells are exposed to 20 nM (/sup 3/H)R5020. In addition, PR synthesis rate declines exponentially following R5020 exposure. The reduction in receptor level is thus due to dramatic increases in PR degradation as well as marked decreases in PR synthesis.
Research Organization:
Illinois Univ., Urbana (USA)
OSTI ID:
6602804
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BIOLOGICAL HALF-LIFE
BIOSYNTHESIS
BODY
CARBON 13
CARBON ISOTOPES
CARBOXYLIC ACIDS
DEUTERIUM
ESTROGENS
EVEN-ODD NUCLEI
FEMALE GENITALS
GLANDS
HORMONES
HYDROGEN ISOTOPES
IN VITRO
IN VIVO
ISOTOPE APPLICATIONS
ISOTOPES
KETONES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MAMMARY GLANDS
MAN
MEMBRANE PROTEINS
METABOLISM
MOLECULAR WEIGHT
NITROGEN 15
NITROGEN ISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PREGNANES
PRIMATES
PROGESTERONE
PROTEINS
RATS
RECEPTORS
RODENTS
STABLE ISOTOPES
STEROID HORMONES
STEROIDS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
UTERUS
VERTEBRATES