Female Reproductive Tract

Attenuation of Estrogenic Effects by Dihydrotestosterone in the Pig Uterus Is Associated with Downregulation of the Estrogen Receptors

Abstract
Androgens are known to attenuate some effects of estradiol-17 (E) in the uterus. The objectives of the present experiment were to determine effects of 5-dihydrotestosterone (DHT) on estrogenic actions in the pig uterus and its associations with changes in expression of the estrogen receptor (ER) and ER. Postpubertal gilts (120-130 kg of BW; n = 16) were ovariectomized, and 3 to 4 weeks later, received once-a-day injections (i.m.) of one of the following treatments during four consecutive days: 1) vehicle (corn oil), 2) E (250 µg), 3) E (same dose as in 2) plus 1 mg of DHT, or 4) E (same dose as in 1) plus 10 mg of DHT. Uterine tissues were collected 24 h after the last treatment. Gilts receiving E or E plus 1 mg DHT had greater uterine wet weight, uterine horn diameter, luminal epithelium thickness, and endometrial gland diameter compared with gilts treated with vehicle or E plus 10 mg DHT. Gilts receiving E or E plus 1 mg DHT were not different in these characteristics. Relative amounts of mRNAs in the endometrium for the cell proliferation marker histone H2a and the E-inducible protein complement component C3, increased in gilts treated with E compared with gilts treated with vehicle. E-induced increases in histone H2a and C3 mRNAs were not altered by co-treatment with E plus 1 mg DHT, but were inhibited by E plus 10 mg DHT. Androgen receptor (AR) mRNA in the endometrium increased by treatment with E. Co-treatment of gilts with E and DHT did not alter the E-induced AR mRNA increase. Gilts treated with E plus 10 mg DHT had lesser amounts of immunoreactive ER in cell nuclei of the myometrium and endometrial stroma, and a tendency for a decrease in luminal epithelium compared with gilts treated with E. Amounts of immunoreactive ER in glandular epithelium were not influenced by the treatments. Relative amounts of ER and ER mRNAs decreased in the endometrium of gilts treated with E plus 10 mg DHT compared with gilts treated with E. Downregulation of the ERs, and particularly ER in the myometrium and endometrial stroma, might be a relevant mechanism in the antagonism of estrogenic effects by DHT in the pig uterus.

Key words: Androgen receptor • Estradiol receptor • Gene regulation • Steroid hormones • Uterus

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