Biological implications of estrogen and androgen effects on androgen receptor and its mRNA levels in human uterine endometrium

Fujimoto, Jiro; Nishigaki, Miki; Hori, Masashi; Ichigo, Satoshi; Itoh, Takeshi; Tamaya, Teruhiko

doi:10.3109/09513599509160205

Cited by 16 publications

(15 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the normal cycle, AR is confined to the stroma, with little or no expression in the glands (21,40,41). Our observations in postmenopausal women treated with estrogen and in women with PCOS are in keeping with reports in women and nonhuman primates that estrogen stimulates AR expression in the endometrium (38,48). Increased AR expression in both stroma and glands of endometrium from women with PCO have been reported by others (49).…”

Section: Discussionsupporting

confidence: 93%

Low-Dose Mifepristone Inhibits Endometrial Proliferation and Up-Regulates Androgen Receptor

Narvekar¹,

Cameron²,

Critchley³

et al. 2004

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

Mifepristone in daily low doses has contraceptive potential by inhibiting ovulation. Follicular development is maintained, and although the endometrium is exposed to unopposed estrogen, there are no signs of hyperplasia or atypia. The mechanism of this antiestrogenic action is unknown. We have investigated the effect of daily low-dose mifepristone on proliferation markers and steroid receptors in surface epithelium, glands, and stroma of the endometrium. Endometrial biopsies were collected from 16 women before (late proliferative) and 60 and 120 d after taking 2 or 5 mg mifepristone daily for 120 d. Endometrial proliferation (H3 mitosis marker) and steroid (estrogen, progesterone, and androgen) receptor content were studied using standard immunocyotchemistry techniques. There was a significant decrease in the expression of H3 mitosis marker (P

show abstract

Section: Discussionsupporting

confidence: 93%

Low-Dose Mifepristone Inhibits Endometrial Proliferation and Up-Regulates Androgen Receptor

Narvekar¹,

Cameron²,

Critchley³

et al. 2004

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

show abstract

“…This study has confirmed previous findings [14,[19][20][21][22] that AR is induced by E 2 and has further investigated the role of AR in E 2 -induced epithelial cellular proliferation in the immature rat uterus. We propose a pathway in which, in response to E 2 , there is sequential activation of ER␣ followed by elevation of the levels of AR, increased IGF-1 secretion, and epithelial cellular proliferation.…”

Section: Discussionsupporting

confidence: 91%

“…Expression of the growth factor IGF-1 as well as the multifunctional protein thioredoxin is regulated by both estrogen and androgen in the uterus [16][17][18]. When genes are regulated by both estrogen and androgen, it is usually assumed that the ER-and AR-dependent pathways are separate, not sequential [14,[19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Involvement of Androgen Receptor in 17β-Estradiol-Induced Cell Proliferation in Rat Uterus1

Zhang

Ekman

Almkvist

et al. 2002

Biology of Reproduction

View full text Add to dashboard Cite

Although it is known that, in the uterus, estrogen receptor alpha (ERalpha) is involved in proliferation and progesterone receptor in differentiation, the role of the two other gonadal-hormone receptors expressed in the uterus, androgen receptor (AR) and estrogen receptor beta (ERbeta), remains undefined. In this study, the involvement of AR in 17beta-estradiol (E(2))-induced cellular proliferation in the immature rat uterus was investigated. AR levels were low in the untreated immature uterus, but 24 h after treatment of rats with E(2), there was an increase in the levels of AR and of two androgen-regulated genes, IGF-I and Crisp (cysteine-rich secretory protein). As expected, E(2) induced proliferation of luminal epithelial cells. These actions of E(2) were all blocked by both the antiestrogen tamoxifen and the antiandrogen flutamide. The E(2)-induced AR was found by immunohistochemistry to be localized exclusively in the stroma, mainly in the myometrium, where it colocalized with ERalpha but not with ERbeta. ERbeta, detected with two different ERbeta-specific antibodies, was expressed in both stromal and epithelial cells either alone or together with ERalpha. Treatment with E(2) caused down-regulation of ERalpha and ERbeta in the epithelium. The data suggest that, in E(2)-induced epithelial cell proliferation, ERalpha induces stromal AR and AR amplifies the ERalpha signal by induction of IGF-I. Because AR is never expressed in cells with ERbeta, it is unlikely that ERbeta signaling is involved in this pathway. These results indicate an important role for AR in proliferation of the uterus, where estrogen and androgen do not represent separate pathways but are sequential steps in one pathway.

show abstract

“…For instance, endogenous estradiol stimulates increased P 4 receptor in mouse fallopian tubes (54). Although androgens are considered the primary regulators of AR (5,20), previous studies have shown that expression of AR mRNA and protein is also regulated by estrogens in mouse (45,69) and human (17,18) uteri. The time course and steroid specificity studies show that DES treatment had a consistent stimulatory effect on AR protein expression at all time points (6, 24, and 48 h) in mouse fallopian tubes.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of AR protein has been investigated in human (2,7,17,35,60,71) and rat (23,44,61,65) ovaries and uteri, and a role for AR in the ovulatory process has been demonstrated. For example, hydroxyflutamide, a specific inhibitor of AR, suppresses ovulation rate in rats (8).…”

mentioning

confidence: 99%

Estrogen-induced upregulation of AR expression and enhancement of AR nuclear translocation in mouse fallopian tubes in vivo

Shao

Ljungström²,

Weijdegård³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

To gain an insight into potential roles of AR in this tissue, we demonstrated that eCG treatment increased AR expression in a timedependent manner and subsequent treatment with hCG decreased AR expression in mouse fallopian tubes. This expression pattern was positively associated with 17␤-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 17␤-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. androgen receptor; gonadotropins THE PHYSIOLOGICAL FUNCTIONS of androgen receptor (AR) in the male, in particular, regulating the development and function of reproduction, have been well characterized (5, 14, 25), but its regulation and biological roles in the female reproductive tissues still remains to be fully understood (15,20). The expression of AR protein has been investigated in human (2, 7, 17, 35, 60, 71) and rat (23, 44, 61, 65) ovaries and uteri, and a role for AR in the ovulatory process has been demonstrated. For example, hydroxyflutamide, a specific inhibitor of AR, suppresses ovulation rate in rats (8). Furthermore, female AR knockout mice (72) have longer estrous cycles and display reduced fertility with increased age due to lost follicle numbers (24, 58). These observations are consistent with studies in the testicular feminized mice, which have dysfunctional ARs in vivo (33). In addition, activated AR has been shown to modulate uterine growth in rats (48), and AR knockout mice lack exogenous gonadotropin-induced endometrial growth in uteri in vivo (24,58). These studies indicate a potential relationship between AR expression and normal female reproductive function.

show abstract

Biological implications of estrogen and androgen effects on androgen receptor and its mRNA levels in human uterine endometrium

Cited by 16 publications

References 22 publications

Low-Dose Mifepristone Inhibits Endometrial Proliferation and Up-Regulates Androgen Receptor

Low-Dose Mifepristone Inhibits Endometrial Proliferation and Up-Regulates Androgen Receptor

Involvement of Androgen Receptor in 17β-Estradiol-Induced Cell Proliferation in Rat Uterus1

Estrogen-induced upregulation of AR expression and enhancement of AR nuclear translocation in mouse fallopian tubes in vivo

Contact Info

Product

Resources

About