Modulation of biosynthesis and regulatory action of 24(S),25-epoxycholesterol (S-EC) in cultured cells by progesterone (PG)

Conference · Fri May 01 04:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6030058

Panini, S R; Gupta, A K; Sexton, R C; Parish, E J; Rudney, H

Treatment of IEC-6 cells with PG caused a strong inhibition of cholesterol biosynthesis at the level of desmosterol reductase. In addition, two new products were observed in PG-treated cells. The first compound was designated as cholesta-5,7,24-trien-3..beta..-ol based on its HPLC chromatographic properties. The second compound was identified as S-EC based on (1) a comparison of its chromatographic properties with those of authentic EC and (2) by its conversion to 25-hydroxycholesterol (HC) upon reduction with LiAlH/sub 4/. In spite of cellular accumulation of S-EC in the presence of PG, the activity of HMG-CoA reductase (HMGR) which is known to be sensitive to oxysterols, was elevated rather than suppressed. On the other hand, when PG-treated cells were refed fresh medium without PG, HMGR activity was suppressed. Exogenous S-EC was a potent suppressor of HMGR in untreated IEC-6 cells. Suppression of HMGR by S-EC but not by HC could be prevented by progesterone. Exogenous (/sup 3/H)S-EC was not metabolized by IEC-6 cells. These results support the hypothesis that S-EC plays a normal regulatory role in sterol biosynthesis and indicate that enhanced S-EC synthesis observed in the presence of PG may be due to interference with this regulatory action.

• Research Organization: Univ. of Cincinnati, OH
• OSTI ID: 6030058
• Report Number(s): CONF-870644-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
BIOLOGICAL FUNCTIONS
BIOSYNTHESIS
CELL CULTURES
CHOLESTEROL
CHROMATOGRAPHY
ENZYME ACTIVITY
ENZYMES
FUNCTIONS
HORMONES
HYDROXY COMPOUNDS
INHIBITION
ISOTOPE APPLICATIONS
KETONES
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PREGNANES
PROGESTERONE
SEPARATION PROCESSES
STEROID HORMONES
STEROIDS
STEROLS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS