Steroid-mediated inhibition of cAMP induced de novo synthesis of cytochrome P-450/sub 17 / in Leydig cell cultures
The present study was designed to investigate the mechanism by which testosterone (T), produced during cAMP induction of P-450/sub 17 /, modulates the rate of its de novo synthesis. Purified Leydig cells (LC) were maintained in culture for 7 days prior to the initiation of treatment. De novo synthesis was determined by TVS-methionine incorporation, immunoprecipitation with specific antibody, separation by SDS-gel electrophoresis and quantitation by laser densitometry. Treatment of LC with 0.05 mM 8-Br-cAMP (cA) results in a time-dependent increase in the rate of de novo synthesis of P-450/sub 17 / which is increased 2 fold when T production is inhibited by aminoglutethimide (AG). The addition of increasing concentrations of the androgen receptor antagonist, hydroxyflutamide (1-10 M), to cA treated LC enhances the rate of synthesis similar to that seen in cA-treated LC in which T production was inhibited by AG. The addition of increasing concentrations of T (0.05-5 M) or the androgen agonist, mibolerone (1-5 M), to cA + AG treated LC causes a dose-dependent reversal of the AG-enhanced increase in the rate of cA-induced de novo synthesis of P-450/sub 17 /. Addition of estradiol (1 M) or dexamethasone (1 M) was without effect. These data indicate that T produced during cA induction of P-450/sub 17 / negatively regulates the rate of synthesis of this cytochrome P-450 enzyme by an androgen receptor mediated mechanism.
- Research Organization:
- Univ. of Michigan Medical Center, Ann Arbor
- OSTI ID:
- 6157068
- Report Number(s):
- CONF-870644-; TRN: 87-028653
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
MIXED-FUNCTION OXIDASES
BIOSYNTHESIS
TESTOSTERONE
BIOCHEMICAL REACTION KINETICS
AMP
DOSE-RESPONSE RELATIONSHIPS
ELECTROPHORESIS
INHIBITION
METHIONINE
SULFUR 35
TRACER TECHNIQUES
AMINO ACIDS
ANDROGENS
ANDROSTANES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
HORMONES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KETONES
KINETICS
LIGHT NUCLEI
LIPOTROPIC FACTORS
NUCLEI
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
RADIOISOTOPES
REACTION KINETICS
STEROID HORMONES
STEROIDS
SULFUR ISOTOPES
SYNTHESIS
550201* - Biochemistry- Tracer Techniques