Journal article
Androgen-uterine interactions: An assessment of androgen interaction with the testosterone- and estrogen-receptor systems and stimulation of uterine growth and progesterone-receptor synthesis
Molecular and cellular endocrinology, Vol.15(2), pp.91-108
1979
DOI: 10.1016/0303-7207(79)90010-8
PMID: 499651
Abstract
This study investigates growth and the induction of progesterone-receptor synthesis in the immature (day 20–23) rat uterus after injection of different doses of 5α-dihydrotestosterone (DHT) and testosterone (T) in long- and short-acting injection vehicles. Moderate doses of T (300 μ/day in saline for 3 days) elicit uterine growth (ca. 250% of control) that is abolished by concomitant injections of antiandrogen (1 mg flutamide/day or 8 mg DIMP/day) but is unaffected by injections of antiestrogens (60 μg CI-628 or U11,100A/day). Uterine growth evoked by 17β-estradiol (3 μg/day for 3 days) is, however, only antagonized with the antiestrogens but not antiandrogens.
Experiments employing whole uteri in vitro indicate that the specific nuclear uptake of 10
−8 M [
3H]T is markedly inhibited by the antiandrogens DIMP, flutamide and the hydroxylated flutamide metabolite (LACT) [LACT > DIMP > FLUT] while the antiestrogens CI-628 and U11,100A are ineffective. In contrast, the specific nuclear uptake of 10
−8 M [
3H]-estradiol is inhibited by only the antiestrogens and not antiandrogens.
When very high (5 or 10 mg) doses of DHT are administered in an oil-containing injection vehicle, nuclear translocation and cytoplasmic depletion of the estrogen receptor does occur and a uterotrophic response is elicited which is resistant to antagonism by antiandrogen. Likewise, the DHT-stimulated increase in progesterone-receptor content is not decreased by concomitant antiandrogen. Similar 5 or 10 mg doses of DHT, administered in a water-soluble dimethylsulfoxide vehicle, show little estrogen-receptor movement and the DHT-induced uterine growth and induction of progesterone-receptor synthesis is almost completely eliminated with antiandrogen. Regardless of the degree of uterine growth stimulation, however, the androgens are poor stimulators of uterine progesterone-receptor synthesis compared with estradiol. These results indicate that androgens may interact with both the androgen- and estrogen-receptor systems in the uterus in inducing uterine growth and that the nature of the cellular mechanism i.e., whether the androgen- and/or estrogen-receptor system is involved, is dependent critically upon the in vivo dose of androgen and the mode of hormone administration.
Details
- Title: Subtitle
- Androgen-uterine interactions: An assessment of androgen interaction with the testosterone- and estrogen-receptor systems and stimulation of uterine growth and progesterone-receptor synthesis
- Creators
- Warren N Schmidt - Department of Physiology and Biophysics, University of Illinois, U.S.ABenita S Katzenellenbogen - Department of Physiology and Biophysics, University of Illinois, U.S.A
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular endocrinology, Vol.15(2), pp.91-108
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/0303-7207(79)90010-8
- PMID
- 499651
- ISSN
- 0303-7207
- eISSN
- 1872-8057
- Language
- English
- Date published
- 1979
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984094633802771
Metrics
17 Record Views