Extensive esterification of adrenal C19-delta 5-sex steroids to long-chain fatty acids in the ZR-75-1 human breast cancer cell line

Journal Article · Mon Jun 05 00:00:00 EDT 1989 · J. Biol. Chem.; (United States)

OSTI ID:5878829

Poulin, R; Poirier, D; Merand, Y; Theriault, C; Belanger, A; Labrie, F

Estrogen-sensitive human breast cancer cells (ZR-75-1) were incubated with the 3H-labeled adrenal C19-delta 5-steroids dehydroepiandrosterone (DHEA) and its fully estrogenic derivative, androst-5-ene-3 beta,17 beta-diol (delta 5-diol) for various time intervals. When fractionated by solvent partition, Sephadex LH-20 column chromatography and silica gel TLC, the labeled cell components were largely present (40-75%) in three highly nonpolar, lipoidal fractions. Mild alkaline hydrolysis of these lipoidal derivatives yielded either free 3H-labeled DHEA or delta 5-diol. The three lipoidal fractions cochromatographed with the synthetic DHEA 3 beta-esters, delta 5-diol 3 beta (or 17 beta)-monoesters and delta 5-diol 3 beta,17 beta-diesters of long-chain fatty acids. DHEA and delta 5-diol were mainly esterified to saturated and mono-unsaturated fatty acids. For delta 5-diol, the preferred site of esterification of the fatty acids is the 3 beta-position while some esterification also takes place at the 17 beta-position. Time course studies show that ZR-75-1 cells accumulate delta 5-diol mostly (greater than 95%) as fatty acid mono- and diesters while DHEA is converted to delta 5-diol essentially as the esterified form. Furthermore, while free C19-delta 5-steroids rapidly diffuse out of the cells after removal of the precursor (3H)delta 5-diol, the fatty acid ester derivatives are progressively hydrolyzed, and DHEA and delta 5-diol thus formed are then sulfurylated prior to their release into the culture medium. The latter process however is rate-limited, since new steady-state levels of free steroids and fatty acid esters are rapidly reached and maintained for extended periods of time after removal of precursor, thus maintaining minimal concentrations of intracellular steroids.

• Research Organization: Laval Univ. Medical Centre, Quebec (Canada)
• OSTI ID: 5878829
• Journal Information: J. Biol. Chem.; (United States), Vol. 264:16
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARBOXYLIC ACIDS
BIOSYNTHESIS
MAMMARY GLANDS
NEOPLASMS
STEROIDS
ESTERIFICATION
ACETYLATION
ALKALINE HYDROLYSIS
BIOCHEMICAL REACTION KINETICS
ESTERS
LIQUID COLUMN CHROMATOGRAPHY
MAN
PRECURSOR
THIN-LAYER CHROMATOGRAPHY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
ACYLATION
ANIMAL CELLS
ANIMALS
BODY
CHEMICAL REACTIONS
CHROMATOGRAPHY
DECOMPOSITION
DISEASES
GLANDS
HYDROLYSIS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LYSIS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PRIMATES
REACTION KINETICS
SEPARATION PROCESSES
SOLVOLYSIS
SYNTHESIS
VERTEBRATES
550501* - Metabolism- Tracer Techniques
550201 - Biochemistry- Tracer Techniques