Attenuation of Estrogenic Effects by Dihydrotestosterone in the Pig Uterus Is Associated with Downregulation of the Estrogen Receptors1

Cárdenas, Horacio; Pope, W. F.

doi:10.1095/biolreprod.103.022384

Cited by 33 publications

(23 citation statements)

References 45 publications

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“…This study was designed to investigate uterotrophic effects of relaxin when administered beginning either before or after the onset of ERa expression in the neonatal porcine uterus. Recently, evidence was presented for low uterine ERb gene expression in adult porcine uterine tissues detected by quantitative PCR (Cardenas & Pope 2004). Here, immunoblot analysis failed to reveal evidence for ERb expression at the protein level in neonatal uterine tissues.…”

Section: Discussionmentioning

confidence: 79%

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

Yan

Ryan²,

Bartol³

et al. 2006

Reproduction

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While uterotrophic effects of relaxin are well documented, the mechanism through which relaxin promotes uterine growth is incompletely understood. Studies in rats suggest that relaxin-stimulated uterine edema depends on estrogen receptor (ER) activation. Here, neonatal pigs were used to investigate the interaction between relaxin and ER signaling pathways. Gilts were treated either at birth (postnatal day (PND) 0) (study 1) before the onset of endometrial ERa expression, or on PND 12 (study 2) after the onset of ERa expression. In study 1, gilts were treated with estradiol-17b or porcine relaxin for two days and uteri were collected on PND 2. In study 2, PND 12 gilts were treated with a single injection of the ER antagonist ICI 182,780 (ICI) or vehicle. Two hours later, gilts were given either estradiol-17b or porcine relaxin for two days. When administered for two days from birth (study 1), neither estradiol-17b nor relaxin affected uterine weight or protein content. However, uterine luminal epithelial height was greater in relaxin-than in vehicle-treated gilts. In contrast, in study 2, both estradiol and relaxin increased uterine weight, protein content and uterine luminal epithelial height on PND 14. These effects were inhibited by pre-treatment with ICI in both estradiol-and relaxin-treated gilts. The results indicate that uterotrophic effects of relaxin in the neonatal pig are related to age and to both the relative presence and state of activation of the ER system in developing uterine tissues between birth and PND 14.

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Section: Discussionmentioning

confidence: 79%

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

Yan

Ryan²,

Bartol³

et al. 2006

Reproduction

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“…Reducing AR levels by these various means results in the inhibition of prostate cancer cell growth and PSA expression, while the small interfering RNA knockdown of AR expression also leads to significant apoptotic cell death in androgen-sensitive and AIPC cells (39 -41). Various studies have shown that estrogens have the ability to down-regulate AR expression in different target cells (12,14,42). In particular, studies from our laboratory have shown that MCF-7 breast cancer cells treated with E 2 exhibited significantly lower levels of AR (12).…”

Section: Discussionmentioning

confidence: 88%

Fulvestrant (ICI 182,780) down-regulates androgen receptor expression and diminishes androgenic responses in LNCaP human prostate cancer cells

Bhattacharyya

Krishnan

Swami

et al. 2006

Molecular Cancer Therapeutics

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The androgen receptor (AR) plays a key role in the development and progression of prostate cancer. Targeting the AR for down-regulation would be a useful strategy for treating prostate cancer, especially hormone-refractory or androgen-independent prostate cancer. In the present study, we showed that the antiestrogen fulvestrant [ICI 182,780 (ICI)] effectively suppressed AR expression in several human prostate cancer cells, including androgenindependent cells. In LNCaP cells, ICI (10 Mmol/L) treatment decreased AR mRNA expression by 43% after 24 hours and AR protein expression by f50% after 48 hours. We further examined the mechanism of AR downregulation by ICI in LNCaP cells. ICI did not bind to the T877A-mutant AR present in the LNCaP cells nor did it promote proteasomal degradation of the AR. ICI did not affect AR mRNA or protein half-life. However, ICI decreased the activity of an AR promoter-luciferase reporter plasmid transfected into LNCaP cells, suggesting a direct repression of AR gene transcription. As a result of AR down-regulation by ICI, androgen induction of prostate-specific antigen mRNA and protein expression were substantially attenuated. Importantly, LNCaP cell proliferation was significantly inhibited by ICI treatment. Following 6 days of ICI treatment, a 70% growth inhibition was seen in androgen-stimulated LNCaP cells. These data show that the antiestrogen ICI is a potent AR downregulator that causes significant inhibition of prostate cancer cell growth. Our study suggests that AR downregulation by ICI would be an effective strategy for the treatment of all prostate cancer, especially AR-dependent androgen-independent prostate cancer. [Mol Cancer Ther 2006;5(6):1539 -49]

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“…The ovaries of eight adult Shiba goats (Capra Hircus), (cyclic; n=6 and pregnant; n=2) were excised immediately after euthanasia with an overdose of ketamine during the luteal (Day 10; n=2) and follicular (7,5,3, and 1 day before onset of estrus) phases, and pregnancy (90 and 120 days of gestation). These goats were originated from Animal Resource Science Center, the University of Tokyo (Ibaraki, Japan).…”

Section: Ovaries Sampling Fixation and Slide Preparationmentioning

confidence: 99%

“…Eight-bit images of three random areas of the different ovarian structures were used for semi-quantitative densitometric analysis of immunostaining intensity in the cytoplasm using ImageJ software (National Institutes of Health, available at http://rsb.info.nih.gov/ij/) as previously described [3]. All images were converted to binary (black and white) using the calculated threshold of the currently displayed slice and the integrated intensity was determined using the particle analysis feature of ImageJ.…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

Ovarian Expression of Inhibin-Subunits, 3.BETA.-Hydroxysteroid Dehydrogenase, and Cytochrome P450 Aromatase during the Estrous Cycle and Pregnancy of Shiba Goats (Capra hircus)

2010

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Abstract:The cellular localization of the inhibin subunits (α, β A , and β B ), steroidogenic enzymes (3β-hydroxysteroid dehydrogenase (3βHSD) and cytochrome P450 aromatase (P450arom) were evaluated in the ovaries of cyclic (n=6) and pregnant (n=2) Shiba goats (Capra Hircus). The immunointensity of inhibin α and β A subunits showed an increase in the granulosa cells (GC) of developing follicles. Inhibin β B subunit and P450arom showed high expression in GC of antral follicles. 3βHSD immunoreactivity was uniform in preantral and antral follicles. In follicular phase and late pregnancy, there was a strong expression of inhibin α subunit in GC of antral follicles. Although in mid pregnancy, antral follicles GC showed moderate immunostaining of inhibin β subunits, the immunoreactivity of inhibin β A and β B subunits was high during the follicular and luteal stages, respectively. While, immunoreactivity of GC to P450arom was moderate during all studied stages, and 3βHSD immunoreactivity was plentiful in antral follicles during the luteal phase. The immunoreactivity to inhibin α subunit and P450arom was abundant during mid pregnancy in the luteal tissues. Immunoreaction to inhibin β subunits was faint-to-moderate in cyclic and pregnancy corpora lutea. Immunoexpression of 3βHSD was maximal in late pregnancy corpora lutea. The present results suggest that, in goats, the GC of antral follicles are the main source of dimeric inhibins and that corpora lutea may partially participate in the secretion of inhibin. Changes in ovarian hormonal levels might depend on the synthesizing capacity of hormones in the follicles and corpora lutea to regulate the goat's reproductive stages.

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Attenuation of Estrogenic Effects by Dihydrotestosterone in the Pig Uterus Is Associated with Downregulation of the Estrogen Receptors1

Cited by 33 publications

References 45 publications

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

Fulvestrant (ICI 182,780) down-regulates androgen receptor expression and diminishes androgenic responses in LNCaP human prostate cancer cells

Ovarian Expression of Inhibin-Subunits, 3.BETA.-Hydroxysteroid Dehydrogenase, and Cytochrome P450 Aromatase during the Estrous Cycle and Pregnancy of Shiba Goats (Capra hircus)

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