scholarly journals Aromatase expression in Xenopus oocytes: a three cell-type model for the ovarian estradiol synthesis

2011 ◽  
Vol 47 (2) ◽  
pp. 241-250 ◽  
Author(s):  
M Gohin ◽  
P Bodinier ◽  
A Fostier ◽  
J Bobe ◽  
F Chesnel
Keyword(s):  
Classical Model ◽  
Biological Significance ◽  
Type Model ◽  
Aromatase Activity ◽  
Steroid Synthesis ◽  
Aromatase Expression ◽  
Androgen Synthesis ◽  
Estrogen Synthesis ◽  
Estradiol Synthesis

In contrast to the classical model describing the synthesis of androgens and estrogens as restricted to somatic cells, a previous study demonstrated that Xenopus laevis oocytes participate in androgen synthesis. The objective of our study was to determine whether Xenopus oocytes are also involved in estrogen synthesis. More precisely, we analyzed aromatase expression by in situ hybridization and RT-QPCR and measured aromatase activity. Aromatase, the enzyme responsible for estrogen synthesis, appears to be expressed and active not only in the follicular cells but also in the vitellogenic oocytes. During late oogenesis, aromatase oocyte expression and activity decreased concomitantly with the trend observed in surrounding follicular layers. In order to investigate the role of estradiol-17β (E2), we studied its effect on oocyte meiotic resumption. It appears that, as in Rana pipiens, E2 inhibited the follicle-enclosed maturation of Xenopus oocytes, likely through inhibition of LH-induced maturation-inducing steroid synthesis. In addition, E2 exerted a slight enhancing action on denuded oocyte maturation whose biological significance remains unclear. Together, our results demonstrate that Xenopus oocyte significantly participates in ovarian E2 synthesis and this may be a common feature of vitellogenic vertebrates.

scholarly journals Aromatase expression in the human fetal osteoblastic cell line SV-HFO

2004 ◽  
Vol 32 (2) ◽  
pp. 533-545 ◽  
Author(s):  
M Watanabe ◽  
ER Simpson ◽  
N Pathirage ◽  
S Nakajin ◽  
CD Clyne
Keyword(s):  
Cell Line ◽  
Bone Growth ◽  
Genomic Sequence ◽  
Oncostatin M ◽  
Osteoblastic Cell ◽  
Aromatase Activity ◽  
Gene Transcript ◽  
Aromatase Expression ◽  
Osteoblastic Cell Line ◽  
Estrogen Synthesis

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.

Role of testosterone synthesized by skin melanocytes in preventing malignant transformation of nevi.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21066-e21066
Author(s):  
Elena Mikhaylovna Frantsiyants ◽  
Valeria Bandovkina ◽  
Yulia A. Pogorelova ◽  
Irina V. Kaplieva ◽  
Natalia D. Cheryarina ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Cutaneous Melanoma ◽  
Free Testosterone ◽  
Aromatase Activity ◽  
Genotoxic Effects ◽  
Dysplastic Nevi ◽  
Estrogen Synthesis ◽  
Steroid Binding ◽  
Pigmented Nevi

e21066 Background: Melanocytes are involved into the synthesis and metabolism of steroid hormones in the skin. Cutaneous melanoma in 75% of cases occurs in congenital or acquired pigmented nevi. There are no studies comparing local hormonogenesis in nevi and melanomas. The purpose of the study was a comparative analysis of hormone levels in tissues of dysplastic nevi and cutaneous melanoma (pТ1-2N0M0). Methods: Levels of prolactin (PRL), progesterone (P4), total and free testosterone (T and fT), estrone (E1) and estriol (E3) and sex steroid-binding globulin (SSBG) were studied by ELISA in 17 samples of рТ1-2N0M0 melanoma and in 23 samples of dysplastic nevi. Intact tissues (n = 15) obtained from non-cancer patients during surgical treatment was used as the control. Results: Levels of T in nevi, compared to intact tissues, were 1.4 times higher, fT – 8.7 times higher, while SSBG content was 1.9 times lower; E3 was 1.6 times higher, PRL – 1.4 times lower, and levels of E1 in nevi were similar to the values in intact tissues. рТ1-2N0M0 melanomas, compared to intact tissues, demonstrated local androgen imbalance: T levels were decreased by 1.8 times, while fT exceeded the norm by 1.8 times, and SSBG – by 6 times. E1 content increased by 1.6 times, E3 decreased by 2.8 times. The E1/E3 ratio in nevi was reduced by 1.6 times, while in melanoma it was increased by 4.4 times. The T/E1 ratio in nevi was increased by 1.4 times, and in melanoma it was decreased by 2.8 times. Levels of PRL and P4 in melanomas, nevi and in intact tissues did not differ significantly. Conclusions: Melanoma was characterized by hyperestrogenia due to increased levels of E1 and low E3 concentrations which caused malignant transformation of melanocytes. Most likely, in melanoma spent SVT estrone synthesis, as evidenced by increase in the E1 / E3 and decrease T / E1.Apparently, fT in melanoma is used for estrogen synthesis, as indicated by the E1/E3 increase and decrease in the T/E1 ratio. Increased E1 synthesis can contribute to the realization of estrogen genotoxic effects. These mechanisms are absent in tissues of nevi. Hyperandrogenism in nevi probably prevents malignant transformation due to low aromatase activity.

scholarly journals Effect of β-agonist on the dexamethasone-induced expression of aromatase by the human monocyte cells

2017 ◽  
Vol 6 (2) ◽  
pp. 82-88 ◽  
Author(s):  
Masatada Watanabe ◽  
Shuji Ohno ◽  
Hiroshi Wachi
Keyword(s):  
Atopic Dermatitis ◽  
Human Skin ◽  
Human Monocyte ◽  
Skin Thickness ◽  
Aromatase Activity ◽  
Gene Transcript ◽  
Aromatase Expression ◽  
Estrogen Synthesis ◽  
Peripheral Monocyte

Emerging evidence suggests that sex steroids are important for human skin health. In particular, estrogen improves skin thickness, elasticity and moisture of older women. The major source of circulating estrogen is the ovary; however, local estrogen synthesis and secretion have important roles in, for example, bone metabolism and breast cancer development. We hypothesized that infiltrated peripheral monocytes are one of the sources of estrogen in skin tissues. We also hypothesized that, during atopic dermatitis under stress, a decline in the hypothalamus–pituitary–adrenal axis (HPA) and facilitation of the (hypothalamus)–sympathetic–adrenomedullary system (SAM) attenuates estrogen secretion from monocytes. Based on this hypothesis, we tested aromatase expression in the human peripheral monocyte-derived cell line THP-1 in response to the synthetic glucocorticoid dexamethasone (Dex), the synthetic β-agonist isoproterenol (Iso) and the β-antagonist propranolol (Pro). Dex mimics glucocorticoid secreted during excitation of the HPA, and Iso mimics catecholamine secreted during excitation of the SAM. We found that aromatase activity and the CYP19A1 gene transcript were both upregulated in THP-1 cells in the presence of Dex. Addition of Iso induced their downregulation and further addition of Pro rescued aromatase expression. These results may suggest that attenuation of estrogen secretion from peripheral monocytes could be a part of the pathology of stress-caused deterioration of atopic dermatitis. Further examination using an in vitro human skin model including THP-1 cells might be a valuable tool for investigating the therapeutic efficacy and mechanism of estrogen treatment for skin health.

scholarly journals Modulation of in Situ Estrogen Synthesis by Proline-, Glutamic Acid-, and Leucine-Rich Protein-1: Potential Estrogen Receptor Autocrine Signaling Loop in Breast Cancer Cells

2008 ◽  
Vol 22 (3) ◽  
pp. 649-664 ◽  
Author(s):  
Rajib Rajhans ◽  
Hareesh B. Nair ◽  
Sujit S. Nair ◽  
Valerie Cortez ◽  
Kijima Ikuko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Glutamic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Breast Tumors ◽  
Aromatase Activity ◽  
Aromatase Expression ◽  
Estrogen Synthesis

Abstract In situ estrogen synthesis is implicated in tumor cell proliferation through autocrine or paracrine mechanisms especially in postmenopausal women. Several recent studies demonstrated activity of aromatase, an enzyme that plays a critical role in estrogen synthesis in breast tumors. Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1/MNAR) is an estrogen receptor (ER) coregulator, and its expression is deregulated in breast tumors. In this study, we examined whether PELP1 promotes tumor growth by promoting local estrogen synthesis using breast cancer cells (MCF7) that stably overexpress PELP1. Immunohistochemistry revealed increased aromatase expression in MCF7-PELP1-induced xenograft tumors. Real-time PCR analysis showed enhanced activation of the aromatase promoter in MCF7-PELP1 clones compared with MCF7 cells. Using a tritiated-water release assay, we demonstrated that MCF7-PELP1 clones exhibit increased aromatase activity compared with control MCF-7 cells. PELP1 deregulation uniquely up-regulated aromatase expression via activation of aromatase promoter I.3/II, and growth factor signaling enhanced PELP1 activation of aromatase. PELP1-mediated induction of aromatase requires functional Src and phosphatidylinositol-3-kinase pathways. Mechanistic studies revealed that PELP1 interactions with ER-related receptor-α and proline-rich nuclear receptor coregulatory protein 2 lead to activation of aromatase. Immunohistochemistry analysis of breast tumor array showed increased expression of aromatase in ductal carcinoma in situ and node-positive tumors compared with no or weak expression in normal breast tissue. Fifty-four percent (n = 79) of PELP1-overexpressing tumors also overexpressed aromatase compared with 36% (n = 47) in PELP1 low-expressing tumors. Our results suggest that PELP1 regulation of aromatase represents a novel mechanism for in situ estrogen synthesis leading to tumor proliferation by autocrine loop and open a new avenue for ablating local aromatase activity in breast tumors.

Submicroscopical observations on the differentiation of chick gonads

Development ◽  
1966 ◽  
Vol 16 (1) ◽  
pp. 41-47
Author(s):  
Roberto Narbaitz ◽  
Ruben Adler
Keyword(s):  
Morphological Changes ◽  
Morphological Differentiation ◽  
Sex Identification ◽  
The Other ◽  
Gonadal Differentiation ◽  
Steroid Production ◽  
Steroid Synthesis ◽  
Estrogen Synthesis ◽  
Exact Moment

The role of hormones in gonadal differentiation has not been fully elucidated. One of the main problems consists in determining the exact moment in which steroid synthesis begins. If, as has been claimed, sex hormones act as organizers and are responsible for the morphological changes which characterize gonadal differentiation, then they should appear before these changes take place. Although the morphological differentiation of chick gonads is evident only after the eighth day of incubation small differences in epithelium height permit sex identification on the seventh day. Biological (Wolff, 1946), biochemical (Gallien & Le Foulgoc, 1961) and histochemical (Scheib, 1959; Narbaitz & Sabatini, 1963; Narbaitz & Kolodny, 1964; Chieffi, Manelli, Botte & Mastrolia, 1964) evidence suggests that estrogen synthesis takes place in embryonic ovaries after the eighth day. On the other hand, steroid production by embryonic testes has not been proven.

scholarly journals Melatonin as an Oncostatic Molecule Based on Its Anti-Aromatase Role in Breast Cancer

2021 ◽  
Vol 22 (1) ◽  
pp. 438
Author(s):  
Yunho Jin ◽  
Yoo Jin Choi ◽  
Kyu Heo ◽  
Seong Joon Park
Keyword(s):  
Breast Cancer ◽  
Developmental Stages ◽  
Therapeutic Option ◽  
Chemotherapeutic Agents ◽  
Common Type ◽  
Aromatase Activity ◽  
Estrogen Synthesis ◽  
Radiation Induced ◽  
Estrogen Biosynthesis

Breast cancer is the most common type of cancer. In the developmental stages of breast cancer, estrogens are strongly involved. As estrogen synthesis is regulated by the enzyme aromatase, targeting the activity of this enzyme represents a therapeutic option. The pineal hormone melatonin may exert a suppressive role on aromatase activity, leading to reduced estrogen biosynthesis. A melatonin-mediated decrease in the expression of aromatase promoters and associated genes would provide suitable evidence of this molecule’s efficacy as an aromatase inhibitor. Furthermore, melatonin intensifies radiation-induced anti-aromatase effects and counteracts the unwanted disadvantages of chemotherapeutic agents. In this manner, this review summarizes the inhibitory role of melatonin in aromatase action, suggesting its role as a possible oncostatic molecule in breast cancer.

scholarly journals Cellular Sources of Sex Steroids in Teleost Gonads

1982 ◽  
Vol 39 (1) ◽  
pp. 56-64 ◽  
Author(s):  
Y. Nagahama ◽  
H. Kagawa ◽  
G. Young
Keyword(s):  
Steroid Synthesis ◽  
Androgen Synthesis ◽  
Amago Salmon ◽  
Salvelinus Leucomaenis ◽  
Thecal Cells ◽  
Cellular Source ◽  
Estradiol 17Β ◽  
White Spotted Char

Histochemical and ultrastructural data on the cellular source of gonadal steroids are reviewed, together with some recent observations on in vitro steroidogenesis by the ovarian follicles of the amago salmon, Oncorhynchus rhodurus. The interstitial cells of the testis appear to be homologous with mammalian Leydig cells and are considered to be the major site of androgen synthesis. Studies on lobule boundary cells suggest that in some species they may be involved in phagocytosis and transport of metabolites while in others they may be steroidogenic. The granulosa cells and the special thecal cells are the major sites of steroid synthesis in the teleost ovary. Studies on the amago salmon using isolated thecal and granulosa layers indicate that both follicle layers are necessary for estradiol-17β production in vitro in response to salmon gonadotropin. The role of the thecal layer during the major part of vitellogenesis is postulated to be the production of estrogen precursors which are converted to estradiol-17β in the granulosa layer. Histochemical and ultrastructural evidence from a number of species for steroid biosynthesis by postovulatory follicles is supported by our recent radioimmunoassay data from white-spotted char, Salvelinus leucomaenis, and the amago salmon showing that young postovulatory follicles can secrete progesterone; the physiological significance of this observation remains to be explained.Key words: teleosts, gonad, steroidogenesis, in vitro, morphology

scholarly journals Aromatase activity induction in human adipose fibroblasts by retinoic acids via retinoic acid receptor α

2013 ◽  
Vol 51 (2) ◽  
pp. 247-260 ◽  
Author(s):  
Jan Wilde ◽  
Maria Erdmann ◽  
Michael Mertens ◽  
Gabriele Eiselt ◽  
Martin Schmidt
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Retinoic Acid ◽  
Reporter Gene ◽  
Site Directed Mutagenesis ◽  
Luciferase Reporter ◽  
Aromatase Activity ◽  
Aromatase Expression ◽  
Estrogen Synthesis ◽  
Activity Induction

Estrogen synthesis in adipose tissue is associated with the development of breast cancer. Tumors are preferentially found in breast quadrants with strongest expression of the cytochrome P450 aromatase (encoded by the geneCYP19A1). Several promoters regulated by various hormonal factors drive aromatase expression in human breast adipose fibroblasts (BAFs). As adipose tissue is a major source of retinoids, in this study, we investigated their role in the regulation of aromatase expression. The retinoids all-trans-retinoic acid (at-RA) and 9-cis-RA induce aromatase activity in human BAFs. In BAFs, at-RA induces aromatase gene expression via promoter I.4. In 3T3-L1 cells, both retinoids specifically drive luciferase reporter gene expression under the control of aromatase promoter I.4, whereas other promoters active in human adipose tissue are insensitive. Activation by retinoids depends on a 467 bp fragment (−256/+211) of promoter I.4 containing four putative retinoic acid response elements (RAREs). Site-directed mutagenesis revealed that only RARE2 (+91/+105) mediates the retinoid-dependent induction of reporter gene activity. In 3T3-L1 preadipocytes and human BAFs, RA receptor α (RARα (RARA)) expression is predominant, whereas RARβ (RARB) or RARγ (RARG) expression is low. Electrophoretic mobility shift assays with nuclear extracts obtained from human BAFs and 3T3-L1 cells identified a specific RARE2-binding complex. Retinoids enhanced complex formation, whereas pre-incubation with anti-RARα antibodies prohibited the binding of RARα to RARE2. Chromatin immunoprecipitation showed RA-dependent binding of RARα to the RARE2-containing promoter regionin vivo. Furthermore, we provide evidence that RARE2 is also necessary for the basal activation of promoter I.4 in these cells. Taken together, these findings indicate a novel retinoid-dependent mechanism of aromatase activity induction in adipose tissue.

Role of Prolactin in the Polycystic Ovary Syndrome

1980 ◽  
Vol 25 (4) ◽  
pp. S89-S93 ◽  
Author(s):  
Emilio del Pozo ◽  
Paolo Falaschi
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Control Mechanisms ◽  
Plasma Prolactin ◽  
Adrenal Androgen ◽  
Ovary Syndrome ◽  
Steroid Synthesis ◽  
Androgen Synthesis ◽  
Lh Secretion

Studies with a dopamine agonist (Bromocriptine) and an antagonist (Haloperidol) suggest that elevated sex steroid synthesis such as may be found in the polycystic ovary syndrome (PCO) influence the pituitary lactotrope response to endogenous control mechanisms. A distinction between PCO with occasional elevation of plasma prolactin (PRL) and the galactorrhoea-amenorrhoea syndrome (GA) associated with hyperprolactinaemia can be established on the basis of differences in circulating levels of sex steroids and in the pattern of response to lactotrope cell stimulation. Thus, adrenal androgen synthesis can be strengthened in GA whereas in PCO both pathways, adrenal and ovarian, may be overstimulated. Also blunted PRL response to TRH or dopaminergic blockade is often seen in GA. The use of bromocriptine in patients with PCO and elevated PRL plasma levels has been shown to restore ovulation. The possible implications of dopaminergic mechanisms in the control of LH secretion independent of PRL release are discussed.

Problematic Political Consumerism

2018 ◽  
pp. 698-720
Author(s):  
Michele Micheletti ◽  
Didem Oral
Keyword(s):  
South African ◽  
Moral Dilemmas ◽  
Ideal Type ◽  
Type Model ◽  
Political Consumerism ◽  
Research Challenges ◽  
Moral Claims

Typically, political consumerism is portrayed in straightforward, unproblematic ways. This chapter discusses how and why political consumerism—and particularly boycotts—can be confusing and problematic. Theoretically it focuses on moral dilemmas within political consumerism and the key role of overriding moral claims in the motivations for and actions of political consumer causes. An ideal type model, constructed for analyzing unproblematic and problematic political consumerism, is applied to cases of more unproblematic political consumerism (e.g., the Nestlé, Nike, and South African boycotts) and more problematic political consumerism (e.g., the Disney boycott and the movement against Israeli settlements in the occupied Palestine territories). The chapter also addresses why other forms of political consumerism (buycotts and discursive actions) seem less vulnerable to moral dilemmas as well as the research challenges in studying more problematic cases of political consumerism.

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