In Vivo Treatments with Fulvestrant and Anastrozole Differentially Affect Gene Expression in the Rat Efferent Ductules1

Abstract

Estrogen plays a key role in maintaining the morphology and function of the efferent ductules. We previously demonstrated that the antiestrogen fulvestrant markedly affected gene expression in the rat efferent ductules. The mechanism of fulvestrant action to modulate gene expression may involve not only the blockade of ESR1 and ESR2 estrogen receptors, but also the activation of ESR1 and ESR2 when the receptors are tethered to AP-1 or SP1 transcription factors, or the activation of the G protein-coupled estrogen receptor 1. We therefore compared the effects of two strategies to interfere with estrogen action in the rat efferent ductules: treatment with fulvestrant or with the aromatase inhibitor anastrozole. Whereas fulvestrant markedly increased Mmp7 and Spp1, and reduced Nptx1 mRNA levels, no changes were observed with anastrozole. Fulvestrant caused changes in epithelial morphology that were not seen with anastrozole. Fulvestrant shifted MMP7 immunolocalization in the epithelial cells from the supranuclear to the apical region; this effect was less pronounced with anastrozole. In vitro studies of (35)S-methionine incorporation showed that protein release was increased, whereas tissue protein content in the efferent ductules of fulvestrant-treated rats was decreased. Although fulvestrant markedly affected gene expression, no changes were observed on AP-1 and SP1 DNA-binding activity. The blockade of ESRs seems to be the major reason explaining the differences between both treatments. At least some of the effects of fulvestrant appear to result from compensatory mechanisms activated by the dramatic changes caused by ESR1 blockade.

Seasonal variation in estrogen receptor ERα, but not ERβ, androgen receptor and aromatase, in the efferent ductules and epididymis of the big fruit-eating bat Artibeus lituratus

“…However, this receptor was more widely expressed during regression, and it was detected in most connective cells and smooth muscle cells surrounding the efferent ductules of A. lituratus. These data are in agreement with other studies that revealed interstitial components of efferent ductules as a molecular target for estrogen modulation [15,52]. A greater number of positive connective and muscle cells was also found in the regressive rete testis [38] and epididymis (present result) of A. lituratus.…”

“…A constitutive expression of ERb in the efferent ductules of rats was previously described [36]. Unaltered ERb expression in other male genital organs submitted to different experimental designs has also been found [2,3,11,15,40,42,48]. During the annual reproductive cycle of hibernating bats, there is a drastic change in testosterone, but not dihydrotestosterone (DHT), and androstenedione levels [26].…”

Novel candidate colorectal cancer biomarkers identified by methylation microarray-based scanning

“…NPTX1 and GLP1R are involved in endocrine pathways that have been linked to CRC. NPTX1 is downregulated by pharmacological inhibition of estrogen signaling, indicating that NPTX1 is a downstream effector of estrogen (Gomes, et al 2011; Yasuhara, et al 2008). Estrogen has been suggested to protect against CRC development (Hogan, et al 2009; Lin, et al 2011), and epigenetic inactivation of estrogen receptor alpha (ESR1) has been widely observed in colonic mucosae of aged individuals as well as in CRCs (Issa et al 1994).…”

Histological Changes in Reproductive Organs of Pubescent Male Mice in Response to ICI 182, 780 Treatment and Recovery of the Organs with Time

“…암컷호르몬으로 알려져 있는 에스트로겐은 암컷뿐만 아니 라 수컷 내에서도 분비된다는 사실은 이미 1930년대에 밝혀져 있었다 [24].에스트로겐이 수컷 생식계에서도 발달, 분화, 성장 에 관여하는 중요한 조절인자로 작용한다는 것이 이제 연구를 통해 널리 알려져 있으며 [4], 지금에 와서는 수컷 생식계에서 중요한 역할을 한다는 것이 많은 연구자들의 도움으로 밝혀져 있다 [5,12,16,23]. (Fig.…”