Estrogen-induced upregulation of AR expression and enhancement of AR nuclear translocation in mouse fallopian tubes in vivo.
Female mice lacking AR display alterations in ovarian and uterine function. However, the biology of AR in the fallopian tube is not fully understood. To gain an insight into potential roles of AR in this tissue, we demonstrated that eCG treatment increased AR expression in a time-dependent manner and subsequent treatment with hCG decreased AR expression in mouse fallopian tubes. This expression pattern was positively associated with 17beta-estradiol and testosterone levels in vivo. Immunohistochemical analysis of fallopian tube epithelial cells revealed that nuclear localization of AR increased in parallel with decreased AR in the cytoplasm following eCG treatment. Moreover, we found that treatment with flutamide upregulated AR expression in immature mice in association with a decrease in serum testosterone levels, whereas the same treatment resulted in downregulation of AR expression in gonadotropin-stimulated mice with concomitant decreases in serum 17beta-estradiol concentrations, suggesting that androgen differs from estrogen in the regulation of AR expression. Furthermore, we demonstrated that DES increased both AR protein expression and nuclear location over a 48-h time course. DHT had rapid effects, with induction of AR expression and translocation at 6 h after injection, but unlike DES it had prolonged efficacy. In addition, we provided direct in vivo evidence that nuclear protein interaction between AR and p21(Cip1), a previously reported AR-regulated gene, was enhanced by gonadotropin stimulation. To our knowledge, this study provides the first demonstration to illustrate that estrogen as a principal regulator may contribute to regulate and activate AR in the fallopian tubes in vivo.
Shao
Ruijin
R
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, SE-40530 Gothenburg, Sweden. ruijin.shao@fysiologi.gu.se
Ljungström
Karin
K
Weijdegård
Birgitta
B
Egecioglu
Emil
E
Fernandez-Rodriguez
Julia
J
Zhang
Fu-Ping
FP
Thurin-Kjellberg
Ann
A
Bergh
Christina
C
Billig
Håkan
H
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005187:Fallopian Tubes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D006062:Gonadotropins / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D021381:Protein Transport / Q000187:drug effects; D011944:Receptors, Androgen / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004967:Estrogens; D006062:Gonadotropins; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D004054:Diethylstilbestrol; D005485:Flutamide