Adipose Tissue Sex Steroids in Postmenopausal Women with and without Menopausal Hormone Therapy.

Context: The decrease in serum estrogens after menopause is associated with a shift from a gynoid to an android adipose tissue (AT) distribution. Menopausal hormone therapy (HT) mitigates this change and accompanying metabolic dysfunction, but its effects on AT sex steroid metabolism have not been characterized.

Objective: We studied effects of HT on subcutaneous and visceral AT estrogen and androgen concentrations and metabolism in postmenopausal women.

Adipose tissue estrogen production and metabolism in premenopausal women.

Objective: Although the ovaries produce the majority of estrogens in women before menopause, estrogen is also synthesized in peripheral tissues such as adipose tissue (AT). The typical female AT distribution, concentrated in subcutaneous and femoro-gluteal regions, is estrogen-mediated, but the significance of estrogen synthesis in AT of premenopausal women is poorly understood.

Design And Methods: Serum and subcutaneous and visceral AT homogenates from 28 premenopausal women undergoing non-malignant surgery were analyzed for estrone, estradiol, and serum estrone sulfate (ES) concentrations with liquid chromatography-tandem mass spectrometry.

Increased body fat mass and androgen metabolism - A twin study in healthy young women.

Objective: Obesity may alter serum steroid concentrations and metabolism. We investigated this in healthy young women with increased body fat and their leaner co-twin sisters.

Design: Age and genetic background both strongly influence serum steroid levels and body composition.

Estrogen biosynthesis in breast adipose tissue during menstrual cycle in women with and without breast cancer.

Circulating estrogens fluctuate during the menstrual cycle but it is not known whether this fluctuation is related to local hormone levels in adipose tissue. We analyzed estrogen concentrations and gene expression of estrogen-regulating enzymes in breast subcutaneous adipose tissue in premenopausal women with (n = 11) and without (n = 17) estrogen receptor-positive breast cancer. Estrone (E) was the predominant estrogen in premenopausal breast adipose tissue, and E and mRNA expression of CYP19A1 in adipose tissue correlated positively with BMI.

Estrogen Metabolism in Abdominal Subcutaneous and Visceral Adipose Tissue in Postmenopausal Women.

Context: In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots.

Objective: We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women.

Metabolism of sex steroids is influenced by acquired adiposity-A study of young adult male monozygotic twin pairs.

Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs.

Steroid sulfatase activity in subcutaneous and visceral adipose tissue: a comparison between pre- and postmenopausal women.

Objective: Adipose tissue is an important extragonadal site for steroid hormone biosynthesis. After menopause, estrogens are synthesized exclusively in peripheral tissues from circulating steroid precursors, of which the most abundant is dehydroepiandrosterone sulfate (DHEAS). Our aim was to study activity of steroid sulfatase, an enzyme hydrolyzing DHEAS, and expression of steroid-converting enzyme genes in subcutaneous and visceral adipose tissue derived from pre- and postmenopausal women.

Quantitative determination of estrone by liquid chromatography-tandem mass spectrometry in subcutaneous adipose tissue from the breast in postmenopausal women.

Estrone is the most abundant estrogen after the menopause. We developed a liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for determination of estrone in adipose tissue. Subcutaneous adipose tissue from the breast was collected during elective surgery in postmenopausal women undergoing mastectomy for treatment of breast cancer (n=13) or reduction mammoplasty (controls, n=11).

Novel structural features increase the antioxidant effect of estrogen analogues on low density lipoprotein.

Many known estrogens, both natural and synthetic, may act as antioxidants. We designed and synthesized 22 novel estrogen analogues with different ring junctions or substitutions, such as fluorine. We studied the antioxidant capacity in vitro of 35 synthetic estrogen analogues in aqueous lipoprotein solution by monitoring the formation of conjugated dienes.

Steroid biosynthesis in adipose tissue.

Tissue-specific expression of steroidogenic enzymes allows the modulation of active steroid levels in a local manner. Thus, the measurement of local steroid concentrations, rather than the circulating levels, has been recognized as a more accurate indicator of the steroid action within a specific tissue. Adipose tissue, one of the largest endocrine tissues in the human body, has been established as an important site for steroid storage and metabolism.

Breast adipose tissue estrogen metabolism in postmenopausal women with or without breast cancer.

Context: It has been shown that breast tumor actively produces and metabolizes steroid hormones. However, little is known about the possible mechanisms through which the nonmalignant adipose tissue contributes to steroid hormone metabolism.

Objective: We compared the metabolic pathways producing active estradiol in breast sc adipose tissue of postmenopausal women with or without breast cancer.

17β-Estradiol and estradiol fatty acyl esters and estrogen-converting enzyme expression in adipose tissue in obese men and women.

Context: Obesity is associated with increased circulating 17β-estradiol (E₂), but less is known about E₂ concentrations in adipose tissue. In addition to E₂, adipose tissue synthesizes E₂ fatty acyl esters (E₂-FAE).

Objective: The aim was to compare estrogen concentrations and expression of estrogen-converting enzymes in adipose tissue between severely obese men and women.

Fatty acyl esterification and deesterification of 17β-estradiol in human breast subcutaneous adipose tissue.

Context: Adipose tissue has an important role in peripheral estrogen synthesis. One of the metabolic pathways of estradiol (E(2)) is its conversion to lipophilic fatty acyl esters.

Objective: The aim was to study the metabolism of E(2) fatty acyl esters in adipose tissue and, specifically, the role of hormone-sensitive lipase (HSL) in steroid ester hydrolysis.

Are there endogenous estrone fatty acyl esters in human plasma or ovarian follicular fluid?

Background: Estrone and its sulfated esters are the most abundant estrogens in blood in men and in women after the menopause. However, previous studies on the esterification of estrone with fatty acids have yielded conflicting results, some studies reporting high nanomolar concentrations of estrone fatty acyl esters in plasma.

Methods: We developed an estrone radioimmunoassay (RIA) method to determine endogenous concentrations of estrone and after saponification, applied it to male and female plasma.

Quantitative determination of dehydroepiandrosterone fatty acyl esters in human female adipose tissue and serum using mass spectrometric methods.

Dehydroepiandrosterone-fatty acyl esters (DHEA-FAE) are naturally occurring water-insoluble metabolites of DHEA, which are transported in plasma exclusively by lipoproteins. To find out whether DHEA, like estradiol, might be stored in adipose tissue in FAE form, we set up a mass spectrometric method to quantify DHEA-FAE and free DHEA in human adipose tissue and serum. The method consists of chromatographic purification steps and final determination of hydrolyzed DHEA-FAE and free DHEA, which was carried out by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Fatty acid esters of steroids: synthesis and metabolism in lipoproteins and adipose tissue.

At the end of the last century ideas concerning the physiological role of the steroid fatty acid ester family were emerging. Estrogens, fatty acylated at C-17 hydroxyl group and incorporated in lipoproteins were proposed to provide antioxidative protection to these particles. A large number of studies involving non-estrogenic adrenal steroids, and their fatty acylated forms, demonstrated their lipoprotein-mediated transport into cells and subsequent intracellular activation, suggesting a novel transport mechanism for lipophilic steroid derivatives.

Dehydroepiandrosterone fatty acyl esters in high density lipoprotein: interaction with human vascular endothelial cells and vascular responses ex vivo.

Dehydroepiandrosterone (DHEA) fatty acyl esters once incorporated in high density lipoprotein (HDL) induce a stronger vasodilatory response in rat mesenteric arteries ex vivo compared to native HDL. We studied the role of HDL receptor, scavenger receptor class B, type 1 (SR-B1), as well as estrogen and androgen receptors in the vasodilatory response of HDL-associated DHEA fatty acyl esters. Using cultured human vascular endothelial cells (HUVEC), we investigated the possible internalization and cellular response of HDL-associated DHEA esters.

Estradiol fatty acid esters in adipose tissue and serum of pregnant and pre- and postmenopausal women.

Context: The 17beta-estradiol fatty acid esters are hormone derivatives with long-lasting estrogenic effect. They are transported in serum lipoproteins and thought to be sequestered in adipose tissue.

Objective: Our objective was to determine the 17beta-estradiol fatty acid ester concentrations in serum and adipose tissue in women of various hormonal states.

Postmenopausal estrogen therapy and serum estradiol fatty acid esters in women with and without previous intrahepatic cholestasis of pregnancy.

Background: Fatty acid esters of 17beta-estradiol (E2) are estrogen metabolites associated with lipoproteins in blood.

Aim: To study the effects of estrogen therapy on concentrations of serum E2 fatty acid esters in postmenopausal women with a history of an estrogen-related liver disorder, intrahepatic cholestasis of pregnancy (ICP), and in healthy women in a double-blind, crossover fashion.

Method: ICP (n = 10) and control women (n = 10) received increasing doses of E2 valerate orally 2-4 mg/day, or transdermal E2 50-100 microg/day for 6 weeks.

Quantitative determination of estradiol fatty acid esters in lipoprotein fractions in human blood.

According to experimental studies, 17 beta-estradiol associates with lipoproteins in blood in the form of fatty acid esters. However, concentrations of endogenous estradiol esters in human lipoprotein fractions have not been previously reported. We investigated the distribution of estradiol fatty acid esters between plasma lipoproteins in 10 healthy women during late pregnancy.

Differential effects of oral and transdermal estradiol treatment on circulating estradiol fatty acid ester concentrations in postmenopausal women.

Estradiol fatty acid esters are potent lipophilic estrogens with antioxidant properties, transported by lipoproteins in blood. We investigated effects of oral and transdermal estradiol replacement therapy on concentrations of estradiol fatty acid esters in serum in postmenopausal women in a double-blind, randomized fashion. The first group (n = 9) received oral (2 mg/d); the second (n = 10), transdermal estradiol (patch delivering 50 microg/d); and the third group (n = 7), placebo treatment for 12 wk.

Lipoprotein-associated estrogens.

The discovery of a family of hormonal steroids esterified with fatty acid has raised questions concerning their physiologic role. Because of their water-insolubility these compounds are present in the circulation only as components of lipoprotein particles. Current evidence supports the hypothesis that estrogen esterification is catalyzed by lecithin:cholesterol acyltransfearse associated with HDL.