Regulation of uterine progesterone receptors by the nonsteroidal anti-androgen hydroxyflutamide

Journal Article · Mon Jul 01 00:00:00 EDT 1991 · Biology of Reproduction; (United States)

DOI:https://doi.org/10.1095/biolreprod45.1.78· OSTI ID:5045503

Chandrasekhar, Y; Armstrong, D T ^[1]

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1. Department of Physiology, University of Western Ontario, London (Canada)

The authors have recently reported that the anti-androgen hydroxyflutamide causes delayed implantation and exhibits antideciduogenic activity in the rat. The present experiments were conducted to examine whether hydroxyflutamide binds to the uterine progesterone receptors and/or alters the progesterone binding sites in the uterus. Cytosol and nuclear fractions from decidualized rat uterus were incubated with (3H)-R5020 without or with increasing concentrations of radioinert R5020, RU486, dihydrotestosterone, or hydroxyflutamide. From the log-dose inhibition curves, the relative binding affinity of both hydroxyflutamide and dihydrotestosterone was less than 0.1% and 2%, compared with R5020 (100%) for displacing (3H)-R5020 bound to uterine cytosol and nuclear fractions, respectively. Injection of estradiol-17 beta (1 microgram/rat) to ovariectomized prepubertal rats induced a 1.85-fold increase in uterine weight by 24 h. Hydroxyflutamide at 2.5 or 5.0 mg did not significantly alter the estrogen-induced increase in uterine weight. Compared to vehicle alone, estrogen induced an approximately 5-fold increase in uterine cytosolic progesterone binding sites. Hydroxyflutamide at both 2.5- and 5.0-mg doses significantly attenuated the estrogen-induced elevation in uterine progesterone binding sites. These studies demonstrate that hydroxyflutamide does not bind with high affinity to progesterone receptors, but suppresses the estrogen-induced elevation in progesterone receptor levels in the uterus.

• OSTI ID: 5045503
• Journal Information: Biology of Reproduction; (United States), Vol. 45:1; ISSN 0006-3363
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTIANDROGENS
BIOCHEMICAL REACTION KINETICS
PROGESTERONE
RECEPTORS
AFFINITY
DOSE-RESPONSE RELATIONSHIPS
ESTRADIOL
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
UTERUS
ANIMALS
BODY
DRUGS
ESTRANES
ESTROGENS
FEMALE GENITALS
HORMONE ANTAGONISTS
HORMONES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
KINETICS
MAMMALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
ORGANS
PREGNANES
PROTEINS
REACTION KINETICS
RODENTS
STEROID HORMONES
STEROIDS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques