Steroid hormone
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PROVIDER: S-EPMC2884628 | biostudies-literature | 2009 Nov
REPOSITORIES: biostudies-literature
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Project description:Biologically active steroids are transported in the blood by albumin, sex hormone-binding globulin (SHBG), and corticosteroid-binding globulin (CBG). These plasma proteins also regulate the non-protein-bound or 'free' fractions of circulating steroid hormones that are considered to be biologically active; as such, they can be viewed as the 'primary gatekeepers of steroid action'. Albumin binds steroids with limited specificity and low affinity, but its high concentration in blood buffers major fluctuations in steroid concentrations and their free fractions. By contrast, SHBG and CBG play much more dynamic roles in controlling steroid access to target tissues and cells. They bind steroids with high (~nM) affinity and specificity, with SHBG binding androgens and estrogens and CBG binding glucocorticoids and progesterone. Both are glycoproteins that are structurally unrelated, and they function in different ways that extend beyond their transportation or buffering functions in the blood. Plasma SHBG and CBG production by the liver varies during development and different physiological or pathophysiological conditions, and abnormalities in the plasma levels of SHBG and CBG or their abilities to bind steroids are associated with a variety of pathologies. Understanding how the unique structures of SHBG and CBG determine their specialized functions, how changes in their plasma levels are controlled, and how they function outside the blood circulation provides insight into how they control the freedom of steroids to act in health and disease.
| S-EPMC5064763 | biostudies-literature
Project description:The nine human NR3 nuclear receptors translate steroid hormone signals in transcriptomic responses and operate multiple highly important processes ranging from development over reproductive tissue function to inflammatory and metabolic homeostasis. Although several NR3 ligands such as glucocorticoids are invaluable drugs, this family is only partially explored, for example, in autoimmune diseases and neurodegeneration, but may hold therapeutic potential in new areas. Here we report a chemogenomics (CG) library to reveal elusive effects of NR3 receptor modulation in phenotypic settings. 34 highly annotated and chemically diverse ligands covering all NR3 receptors were selected considering complementary modes of action and activity, selectivity and lack of toxicity. Endoplasmic reticulum stress resolving effects of N3 CG subsets in proof-of-concept application validate suitability of the set to connect phenotypic outcomes with targets and to explore NR3 receptors from a translational perspective.
| S-EPMC11790914 | biostudies-literature
Project description:Steroid hormones are a large family of cholesterol derivatives regulating development and physiology in both the animal and plant kingdoms, but little is known concerning mechanisms of their secretion from steroidogenic tissues. Here, we present evidence that in Drosophila, endocrine release of the steroid hormone ecdysone is mediated through a regulated vesicular trafficking mechanism. Inhibition of calcium signaling in the steroidogenic prothoracic gland results in the accumulation of unreleased ecdysone, and the knockdown of calcium-mediated vesicle exocytosis components in the gland caused developmental defects due to deficiency of ecdysone. Accumulation of synaptotagmin-labeled vesicles in the gland is observed when calcium signaling is disrupted, and these vesicles contain an ABC transporter that functions as an ecdysone pump to fill vesicles. We propose that trafficking of steroid hormones out of endocrine cells is not always through a simple diffusion mechanism as presently thought, but instead can involve a regulated vesicle-mediated release process.
| S-EPMC4636736 | biostudies-literature
Project description:SIRT1 protects against several complex metabolic and ageing-related diseases (MARDs), and is therefore considered a polypill target to improve healthy ageing. Although dietary sirtuin-activating compounds (dSTACs) including resveratrol are promising drug candidates, their clinical application has been frustrated by an imprecise understanding of how their signals are transduced into increased healthspan. Recent work indicates that SIRT1 and orthologous sirtuins coactivate the oestrogen receptor/ER and the worm steroid receptor DAF-12. Here they are further shown to ligand-independently transduce dSTACs signals through these receptors. While some dSTACs elicit ER subtype-selectivity in the presence of hormone, most synergize with 17β-oestradiol and dafachronic acid respectively to increase ER and DAF-12 coactivation by the sirtuins. These data suggest that dSTACs functionally mimic gonadal steroid hormones, enabling sirtuins to transduce the cognate signals through a conserved endocrine pathway. Interestingly, resveratrol non-monotonically modulates sirtuin signalling, suggesting that it may induce hormesis, i.e. "less is more". Together, the findings suggest that dSTACs may be informational molecules that use exploitative mimicry to modulate sirtuin signalling through steroid receptors. Hence dSTACs' intrinsic oestrogenicity may underlie their proven ability to impart the health benefits of oestradiol, and also provides a mechanistic insight into how they extend healthspan or protect against MARDs.
| S-EPMC7093472 | biostudies-literature
Project description:Steroid hormones are derived from cholesterol and can be classified into sex hormones (estrogens, androgens, progesterone) that are primarily synthesized in the gonads and adrenal hormones (glucocorticoids and mineralocorticoids) that are primarily synthesized in the adrenal gland. Although, it has long been known that steroid hormones have potent effects on the immune system, recent studies have led to renewed interest in their role in regulating anti-tumor immunity. Extra-glandular cells, such as epithelial cells and immune cells, have been shown to synthesize glucocorticoids and thereby modulate immune responses in the tumor microenvironment. Additionally, new insight into the role of androgens on immune cell responses have shed light on mechanisms underpinning the observed sex bias in cancer survival outcomes. Here, we review the role of steroid hormones, specifically glucocorticoids and androgens, in regulating anti-tumor immunity and discuss how their modulation could pave the way for designing novel therapeutic strategies to improve anti-tumor immune responses.
| S-EPMC9622373 | biostudies-literature
Project description:Essentials Endogenous hormone levels' influence on hemostatic factor levels is not fully characterized. We tested for associations of endogenous hormone with hemostatic factor levels in postmenopause. Estrone levels were inversely associated with the natural anticoagulant, protein S antigen. Dehydroepiandrosterone sulfate levels were inversely associated with thrombin generation.SummaryBackground Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 μg mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.
| S-EPMC5280337 | biostudies-literature
Project description:The multidrug resistance-associated protein 1 (MRP1/ABCC1) is a member of the ABC active transporter family that can transport several steroid hormone conjugates, including 17beta-estradiol glucuronide, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate. The present study investigated the role that MRP1 plays in maintaining proper hormone levels in the serum and testes. Serum and testicular steroid hormone levels were examined in both wild-type mice and Mrp1 null mice. Serum testosterone levels were reduced 5-fold in mice lacking Mrp1, while testicular androstenedione, testosterone, estradiol, and dehydroepiandrosterone (DHEA) were significantly reduced by 1.7- to 4.5-fold in Mrp1 knockout mice. Investigating the mechanisms responsible for the reduction in steroid hormones in Mrp1-/- mice revealed no differences in the expression or activity of enzymes that inactivate steroids, the sulfotransferases or glucuronosyltransferases. However, steroid biosynthetic enzyme levels in the testes were altered. Cyp17 protein levels were increased by 1.6-fold, while Cyp17 activity using progesterone as a substrate was also increased by 1.4- to 2.0-fold in mice lacking Mrp1. Additionally, the ratio of 17beta-hydroxysteroid dehydrogenase to 3beta-hydroxysteroid dehydrogenase, and steroidogenic factor 1 to 3beta-hydroxysteroid dehydrogenase were significantly increased in the testes of Mrp1-/- mice. These results indicate that Mrp1-/- mice have lowered steroid hormones levels, and suggests that upregulation of steroid biosynthetic enzymes may be an attempt to maintain proper steroid hormone homeostasis.
| S-EPMC2862834 | biostudies-literature
Project description:The mechanisms by which GnIH regulates the steroid synthesis pathway in duck granulosa cells remain poorly understood. In this study, we measured steroid hormone secretion by ELISA and reproduction-associated gene expression by quantitative real-time Polymerase Chain Reaction (qPCR) in duck granulosa cells treated with different concentrations of GnIH (0, 0.1, 1, 10, and 100 ng/mL) for 24 h. The genome-wide expression profiles of GnIH-treated cells (0 and 10 ng/mL) were evaluated by high-throughput RNA sequencing. Compared with untreated cells, the secretion of the steroid hormones E2, E1, P4, and T was downregulated, with that of E1 and P4 reaching statistical significance (P<0.05); in contrast, the secretion of ACV and INH was significantly upregulated (P<0.05) after treatment with 10 and 100 ng/mL GnIH. The expression of encoding steroidogenic proteins and enzymes genes (STAR, CYP11A1, CYP17A1, CYP19A1, and 3-β-HSD) and encoding gonadotropin receptors genes (FSHR, LHR) were significantly declined (P<0.05) in the 10 and 100 ng/mL GnIH treatments. Transcriptome sequencing identified 348 differentially expressed genes (DEGs), including 253 upregulated and 95 downregulated genes. The DEGs were mainly involved in cell growth and death, immune response, and steroid biosynthesis pathways. We identified four novel DEGs (MROH5, LOC113840576, SDR42E1, and LOC113841457) with key roles in the regulation of steroid hormone biosynthesis. Our study revealed changes in gonadal steroid hormone secretion and steroid biosynthesis pathway-related gene expression in duck granulosa cells under the inhibitory effect of GnIH. These data contribute to our understanding of the molecular and genetic mechanisms underlying reproduction in ducks.
| S-EPMC8291778 | biostudies-literature
Project description:Correct spatial and temporal induction of numerous cell type-specific genes during development requires regulated removal of the repressive histone H3 lysine 27 trimethylation (H3K27me3) modification. Here we show that the H3K27me3 demethylase dUTX is required for hormone-mediated transcriptional regulation of apoptosis and autophagy genes during ecdysone-regulated programmed cell death of Drosophila salivary glands. We demonstrate that dUTX binds to the nuclear hormone receptor complex Ecdysone Receptor/Ultraspiracle, and is recruited to the promoters of key apoptosis and autophagy genes. Salivary gland cell death is delayed in dUTX mutants, with reduced caspase activity and autophagy that coincides with decreased apoptosis and autophagy gene transcripts. We further show that salivary gland degradation requires dUTX catalytic activity. Our findings provide evidence for an unanticipated role for UTX demethylase activity in regulating hormone-dependent cell death and demonstrate how a single transcriptional regulator can modulate a specific complex functional outcome during animal development.
| S-EPMC3973156 | biostudies-literature
Project description:BackgroundNeighborhood walkability (NW) has been linked to increased physical activity, which in turn is associated with lower concentrations of sex hormones and higher concentration of SHBG in women. However, no study has directly examined the association of NW with female sex hormone levels.ObjectiveWe conducted a cross-sectional study to evaluate the association between NW and circulating levels of sex hormones and SHBG in pre- and post-menopausal women.MethodsWe included 797 premenopausal and 618 postmenopausal women from the New York University Women's Health Study (NYUWHS) who were healthy controls in previous nested case-control studies in which sex hormones (androstenedione, testosterone, DHEAS, estradiol and estrone) and SHBG had been measured in serum at enrollment. Baseline residential addresses were geo-coded and the Built Environment and Health Neighborhood Walkability Index (BEH-NWI) was calculated. Generalized Estimating Equations were used to assess the association between BEH-NWI and sex hormone and SHBG concentrations adjusting for individual- and neighborhood-level factors.ResultsIn premenopausal women, a one standard deviation (SD) increment in BEH-NWI was associated with a 3.5% (95% CI 0.9%-6.1%) lower DHEAS concentration. In postmenopausal women, a one SD increment in BEH-NWI was related to an 8.5% (95% CI 5.4%-11.5%) lower level of DHEAS, a 3.7% (95% CI 0.5%-6.8%) lower level of testosterone, a 1.8% (95% CI 0.5%-3.0%) lower level of estrone, and a 4.2% (95% CI 2.7%-5.7%) higher level of SHBG. However, the associations with respect to DHEAS and estrone became apparent only after adjusting for neighborhood-level variables. Sensitivity analyses using fixed effects meta-analysis and inverse probability weighting accounting for potential selection bias yielded similar results.ConclusionOur findings suggest that NW is associated with lower concentrations of androgens and estrone, and increased SHBG, in postmenopausal women, and lower levels of DHEAS in premenopausal women.
| S-EPMC10039647 | biostudies-literature