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Jan Wilde, Maria Erdmann, Michael Mertens, Gabriele Eiselt, and Martin Schmidt

Introduction Estrogen synthesis in adipose tissue is the major source of circulating estrogens in aging men and women. Besides this, the finding of elevated aromatase activity and aromatase mRNA expression in the adipose tissue of breast quadrants

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M Gohin, P Bodinier, A Fostier, J Bobe, and F Chesnel

that star was exclusively expressed by the follicular cells. Star is involved in cholesterol shuttling to the inner mitochondrial membrane and is thus necessary for androgen and estrogen synthesis. As Cyp17 ( Yang et al . 2003 ) and p450-arom are

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Camille Bois, Christelle Delalande, Hélène Bouraïma-Lelong, Philippe Durand, and Serge Carreau

Spermatogenesis, which is the fundamental mechanism allowing male gamete production, is controlled by several factors, and among them, estrogens are likely concerned. In order to enlighten the potential role of estrogen in rat spermatogenesis, seminiferous tubules (ST) from two groups of seminiferous epithelium stages (II–VIII and IX–I) were treated with either 17β-estradiol (E2) agonists or antagonists for estrogen receptors (ESRs). In this study, we show that cyclin A1 and cyclin B1 gene expression is controlled by E2 at a concentration of 10−9 M only in stages IX–I. This effect is mimicked by a treatment with the G-protein coupled estrogen receptor (GPER) agonist G1 and is abolished by treatment with the ESR antagonist ICI 182 780. Moreover, using letrozole, a drug that blocks estrogen synthesis, we demonstrate that these genes are under the control of E2 within rat ST. Thus, germ cell differentiation may be regulated by E2 which acts through ESRs and GPER, expressed in adult rat ST.

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M Watanabe, ER Simpson, N Pathirage, S Nakajin, and CD Clyne

A number of clinical studies have highlighted the importance of estrogen in bone growth and maintenance in men and postmenopausal women. In these instances, estrogen is synthesized locally within bone tissue by aromatase, encoded by the CYP19 gene. The mechanisms regulating aromatase expression in bone, however, are unclear. In this work we characterized the expression of aromatase activity and gene transcripts in the human fetal osteoblastic cell line, SV-HFO. Aromatase activity and gene transcript expression were stimulated by dexamethasone. Oncostatin M strongly stimulated aromatase expression in synergy with dexamethasone. These factors induced CYP19 transcripts that included the sequence of exon I.4 in their 5'UTR. Consistent with this, a reporter construct harboring the genomic sequence of the promoter region of exon I.4 (promoter I.4) was also activated by dexamethasone and oncostatin M. 5' deletion and mutation analysis revealed important roles for a glucocorticoid response element, an interferon gamma activating sequence and a putative binding site for Sp1. Transfection of exogenous glucocorticoid receptor, STAT3 or Sp1 increased promoter activity, indicating a potential role for these transcription factors in regulating aromatase expression in SV-HFO cells. These data suggest that the SV-HFO cell line is a valuable model with which to elucidate the mechanisms regulating local estrogen synthesis in osteoblasts.

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S Jesmin, C N Mowa, I Sakuma, N Matsuda, H Togashi, M Yoshioka, Y Hattori, and A Kitabatake

Although synthesis of estrogen by male gonads has been well documented for over half a century, it is only recently that the role of estrogen in male reproductive events has gained appreciation. We recently reported abundant expression of estrogen receptor (ER)-α and -β in different cell types of the rat penis, whose levels diminished with advancing age. The present study, which builds on data from the ER study, was designed to determine whether the penis is capable of generating its own local estrogen by examining evidence of the expression of aromatase, a microsomal enzymatic complex which irreversibly converts androgens to estrogens, using immunohistochemistry, Western blotting, in situ hybridization and real-time PCR analyses. Secondly, the effects of sex steroid hormones on penile aromatase were examined. Discrete aromatase immunoreactive cells were localized in primordial corpus cavernosum, corpus spongiosus and os penis, blood vessels and sensory corpuscle of glans penis. In situ hybridization signals corresponded with immunohistochemical findings. Western blot, enzyme immunoassay and real-time PCR analyses of rat penile samples revealed an age-dependent expression of aromatase and estrogen, with levels at week 1 almost resembling those of the ovary, but they decreased sharply by week 8, and decreased further by week 35. This expression pattern was strikingly similar to that of ER-α reported previously. Testosterone and diethylstilbesterol administered prenatally upregulate levels of aromatase mRNA and protein, and estrogen postnatally. Dihydrotestosterone upregulated aromatase mRNA and protein, but not estrogen. We conclude that estrogen acts via ER in a paracrine and/or autocrine manner to regulate penile events, particularly during development, and that estrogen synthesis is regulated by estrogen and androgens.

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M Rodríguez-Sanz, N García-Giralt, D Prieto-Alhambra, S Servitja, S Balcells, R Pecorelli, A Díez-Pérez, D Grinberg, I Tusquets, and X Nogués

, the aromatase inhibition, especially at the bone tissue level, would cause a major BMD loss ( Bouvard et al . 2014 ). However, remnant estrogen levels after aromatase inhibition may modulate the degree of bone loss. Hence, the estrogen synthesis

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Hong Zhao, Ling Zhou, Anna Junjie Shangguan, and Serdar E Bulun

endometrial cancer. Estrogen synthesis and deactivation Estrogen is synthesized in the gonads and in several extragonadal organs ( Simpson 2003 , Bulun et al. 2009 ). In premenopausal women, six enzymes encoded by five specific genes synthesize

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Denise Vizziano-Cantonnet, Daniel Baron, Sophie Mahè, Chantal Cauty, Alexis Fostier, and Yann Guiguen

Introduction The molecular mechanisms underlying early ovarian development in vertebrates still remain poorly understood ( Loffler & Koopman 2002 , Brennan & Capel 2004 , Yao 2005 ), however, modulation of both estrogen synthesis and estrogen

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Daniel Baron, Julie Cocquet, Xuhua Xia, Marc Fellous, Yann Guiguen, and Reiner A Veitia

). The expression profile of aromatase, a key gene of estrogen synthesis, was also followed by real-time RT-PCR (Fig. 3c ). In accordance with previous results, aromatase expression during natural differentiation was only detected in the female ( Guiguen

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S Kuntz, D Chardard, C-I Ko, H Dumond, M Ducatez, M Callier, S Flament, and A Chesnel

1984 ). The masculinizing temperature was shown to inhibit aromatase activity ( Chardard et al. 1995 ) and could act as a direct or indirect repressor of estrogen synthesis, since estradiol benzoate can counteract the masculinizing effect of a high