Extra-gonadal sites of estrogen biosynthesis and function

Barakat, Radwa; Oakley, Oliver R.; Kim, Heehyen; Jin, Juyoun; Ko, Che Myong

doi:10.5483/bmbrep.2016.49.9.141

Cited by 152 publications

(120 citation statements)

References 126 publications

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“…However, the older rats were fatter than the young rats, making it difficult to separate the effects of chronological age from increased adiposity. It is generally believed that an increased fat mass might help to maintain local tissue production of estrogens due to aromatization of androgens [20]. Though evidence for this has yet to be demonstrated in human subcutaneous adipose tissue, elevated local estrogen production could in theory preserve or change ER in adipose tissue with aging.…”

Section: Discussionmentioning

confidence: 99%

Age- and menopause-related differences in subcutaneous adipose tissue estrogen receptor mRNA expression

Park¹,

Erickson²,

Bessesen

et al. 2017

Steroids

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Objectives Changes in estrogen receptor (ER) expression likely underlie differential metabolic effects of estrogen in pre-and postmenopausal women. The aim of the current study was to determine whether ER gene expression in abdominal and femoral subcutaneous adipose tissue (SAT) was associated with age, menopause, or regional adiposity. Methods We studied pre-and post-menopausal (n=23 and 22, respectively; age 35–65 y) normal weight (mean±SD; BMI 23.7±2.5 kg/m2) women with similar total fat mass. Abdominal and femoral SAT ERα (ESR1) and ERβ (ESR2) mRNA expression was determined by qPCR. Results Total fat mass did not differ between pre-and postmenopausal women (22.7±5.3 vs. 21.7±5.3 kg). Compared to premenopausal women, ESR1 and the ratio of ESR1 to ESR2 were lower (p≤0.05) in postmenopausal abdominal and femoral SAT. ESR1 and ESR1:ESR2 were inversely associated with age in abdominal SAT (r=−0.380 and r=−0.463, respectively; p<0.05) and femoral SAT (r=−0.353 and r=−0.472, respectively; p<0.05). ESR2 was not related to age or menopause. The inverse association between ESR1 and age persisted after adjusting for trunk fat mass, estradiol, or leptin. Conclusion Among healthy pre-and postmenopausal women, increased age was associated with a decreased balance of ERα to ERβ in abdominal and femoral subcutaneous adipose tissue.

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Section: Discussionmentioning

confidence: 99%

Age- and menopause-related differences in subcutaneous adipose tissue estrogen receptor mRNA expression

Park¹,

Erickson²,

Bessesen

et al. 2017

Steroids

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“…Males also produce local estrogen by aromatization in cells of the reproductive tract, including Sertoli cells, Leydig cells, and mature spermatocytes. Overall, estrogens are normally produced by the ovaries and in smaller amounts by other tissues such as the liver, pancreas, adrenal glands, adipose tissue, and breast (Barakat, Oakley, Kim, Jin, & Ko, 2016). In specific physiological conditions, such as pregnancy, estrogen is also synthesized by the placenta.…”

Section: Estrogen Biosynthesismentioning

confidence: 99%

Estrogen receptor signaling mechanisms

Fuentes

Silveyra

2019

Advances in Protein Chemistry and Structural Biology

652

461

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The primary female sex hormones, estrogens, are responsible for the control of functions of the female reproductive system, as well as the development of secondary sexual characteristics that appear during puberty and sexual maturity. Estrogens exert their actions by binding to specific receptors, the estrogen receptors (ERs), which in turn activate transcriptional processes and/or signaling events that result in the control of gene expression. These actions can be mediated by direct binding of estrogen receptor complexes to specific sequences in gene promoters (genomic effects), or by mechanisms that do not involve direct binding to DNA (non-genomic effects). Whether acting via direct nuclear effects, indirect non-nuclear actions, or a combination of both, the effects of estrogens on gene expression are controlled by highly regulated complex mechanisms. In this chapter, we summarize the knowledge gained in the past 60 years since the discovery of the estrogen receptors on the mechanisms governing estrogen-mediated gene expression. We provide an overview of estrogen biosynthesis, and we describe the main mechanisms by which the female sex hormone controls gene transcription in different tissues and cell types. Specifically, we address the molecular events governing regulation of gene expression via the nuclear estrogen receptors (ERα, and ERβ) and the membrane estrogen receptor (GPER1). We also describe mechanisms of cross-talk between signaling cascades activated by both nuclear and membrane estrogen receptors. Finally, we discuss natural compounds that are able to target specific estrogen receptors and their implications for human health and medical therapeutics.

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“…Estrogens are derived from the androgenic precursors androstenedione and testosterone by means of aromatization. 61,65 While concentrations of extragonadal estrogens are low compared with gonadal estrogens, the local concentration of estrogens within the tissue can be high enough to exert local impact, such as in adipose tissues, where locally synthesized estrogens inhibit adipose tissue hypertrophy. 61 Localized aromatization has been well documented within adipose tissue; indeed, the first extragonadal site of estrogen synthesis discovered was in adipose tissues, 62 where local aromatization can maintain high levels of estrogens within fatty tissue in postmenopausal women.…”

Section: The Role Of Estrogens In the Microenvironment And Their Inflmentioning

confidence: 99%

The role of estrogens in the adipose tissue milieu

Bracht

Vieira‐Potter

Santos

et al. 2019

Annals of the New York Academy of Sciences

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One of the leading causes for the development of adverse metabolic effects, including type 2 diabetes, dyslipidemia, and cardiovascular diseases, is the accumulation of excess body weight, often measured by body mass index (BMI). Although BMI, calculated using weight and height, is the standard measure used to determine body adiposity in clinical and public health guidelines, an inherent limitation is that BMI does not distinguish where in the body adiposity is deposited. Central obesity, characterized by greater accumulation of adiposity in the abdominal region, has been associated with a higher risk of mortality, independent of BMI. Importantly, one of the determinants of body fat distribution is sex hormones. Both estrogens and androgens appear to directly and indirectly influence body fat distribution. Our review will focus specifically on the role of estrogens and their influence in determining body fat distribution and overall health of adipose tissues, and the role of epigenetic mechanisms in regulating the production and function of estrogens.

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Extra-gonadal sites of estrogen biosynthesis and function

Cited by 152 publications

References 126 publications

Age- and menopause-related differences in subcutaneous adipose tissue estrogen receptor mRNA expression

Age- and menopause-related differences in subcutaneous adipose tissue estrogen receptor mRNA expression

Estrogen receptor signaling mechanisms

The role of estrogens in the adipose tissue milieu

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