Dataset Information

Sex Steroid Hormones Regulate Leptin Transcript Accumulation and Protein Secretion in 3T3-L1 Cells.

ABSTRACT: Leptin is an adipokine produced by fat cells that regulates food consumption and metabolic activity. Sexual dimorphism in leptin and fat stores have been observed in humans and rodents with females having more leptin and greater levels of subcutaneous fat than males. One potential mechanism leading to this dimorphism is steroid hormone regulated synthesis of transcripts encoding leptin. Identification of direct regulatory mechanisms is difficult in animals or primary adipocytes due to these intertwined dimorphisms. We used well-characterized 3T3-L1 murine adipocytes to demonstrate that dihydrotestosterone (DHT) reduced Leptin (Lep) transcript abundance and cytosolic and secreted leptin protein. The magnitude of this effect was greatest on secreted leptin, which was decreased by DHT to 30% of the control. In contrast, 17?-estradiol significantly increased the abundance of transcripts encoding leptin and increased secreted leptin to 230% of the control. Treatment with estrogen and androgen receptor antagonists had opposite effects on Lep transcript abundance to steroid treatments, indicating that these transcriptional effects are mediated through the canonical steroid hormone signaling pathways. These results indicate that short-term treatments with steroid hormones are sufficient to alter both Lep transcript accumulation and leptin protein secretion, and may play a role in the sexual dimorphism of this adipokine.

SUBMITTER: Jenks MZ

PROVIDER: S-EPMC5558017 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Sex Steroid Hormones Regulate Leptin Transcript Accumulation and Protein Secretion in 3T3-L1 Cells.

Jenks Mónica Z MZ Fairfield Heather E HE Johnson Erik C EC Morrison Ron F RF Muday Gloria K GK

Scientific reports 20170815 1

Leptin is an adipokine produced by fat cells that regulates food consumption and metabolic activity. Sexual dimorphism in leptin and fat stores have been observed in humans and rodents with females having more leptin and greater levels of subcutaneous fat than males. One potential mechanism leading to this dimorphism is steroid hormone regulated synthesis of transcripts encoding leptin. Identification of direct regulatory mechanisms is difficult in animals or primary adipocytes due to these inte ...[more]

PMID: 28811502

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Project description:ObjectiveSex steroid hormones may play a role in insulin resistance and glucose dysregulation. However, evidence regarding associations between early-pregnancy sex steroid hormones and hyperglycemia during pregnancy is limited. The primary objective of this study was to assess the relationships between first trimester sex steroid hormones and the subsequent development of hyperglycemia during pregnancy; with secondary evaluation of sex steroid hormones levels in mid-late pregnancy, concurrent with and subsequent to diagnosis of gestational diabetes.MethodsRetrospective analysis of a prospective pregnancy cohort study was conducted. Medically low-risk participants with no known major endocrine disorders were recruited in the first trimester of pregnancy (n=319). Sex steroid hormones in each trimester, including total testosterone, free testosterone, estrone, estradiol, and estriol, were assessed using high-performance liquid chromatography and tandem mass spectrometry. Glucose levels of the 1-hour oral glucose tolerance test and gestational diabetes diagnosis were abstracted from medical records. Multivariable linear regression models were fitted to assess the associations of individual first trimester sex steroids and glucose levels.ResultsIn adjusted models, first trimester total testosterone (β=5.24, 95% CI: 0.01, 10.46, p=0.05) and free testosterone (β=5.98, 95% CI: 0.97, 10.98, p=0.02) were positively associated with subsequent glucose concentrations and gestational diabetes diagnosis (total testosterone: OR=3.63, 95% CI: 1.50, 8.78; free testosterone: OR=3.69; 95% CI: 1.56, 8.73). First trimester estrone was also positively associated with gestational diabetes (OR=3.66, 95% CI: 1.56, 8.55). In mid-late pregnancy, pregnant people with gestational diabetes had lower total testosterone levels (β=-0.19, 95% CI: -0.36, -0.02) after adjustment for first trimester total testosterone.ConclusionEarly-pregnancy sex steroid hormones, including total testosterone, free testosterone, and estrone, were positively associated with glucose levels and gestational diabetes in mid-late pregnancy. These hormones may serve as early predictors of gestational diabetes in combination with other risk factors.

Project description:AbstractIn patients with coronavirus disease 2019 (COVID-19), men are more severely affected than women. Multiple studies suggest that androgens might play a role in this difference in disease severity. Our objective was to assess the association between sex hormone levels and mortality in patients with severe COVID-19.We selected patients from the Amsterdam University Medical Centers COVID-19 Biobank, in which patients admitted to hospital in March and April 2020, with reverse transcription-polymerase chain reaction proven severe acute respiratory syndrome-coronavirus-2 infection, were prospectively included. Specifically, we included postmenopausal women (>55 years) and age-matched men, with a mortality of 50% in each group. Residual plasma samples were used to measure testosterone, estradiol, sex hormone binding globulin (SHBG), and albumin. We investigated the association of the levels of these hormones with mortality in men and women.We included 16 women and 24 men in March and April 2020 of whom 7 (44%) and 13 (54%), respectively, died. Median age was 69 years (interquartile range [IQR] 64-75). In men, both total and free testosterone was significantly lower in deceased patients (median testosterone 0.8 nmol/L [IQR 0.4-1.9] in deceased patients vs 3.2 nmol/L [IQR 2.1-7.5] in survivors; P < .001, and median free testosterone 33.2 pmol/L [IQR 15.3-52.2] in deceased patients vs 90.3 pmol/L [IQR 49.1-209.7] in survivors; P = .002). SHBG levels were significantly lower in both men and women who died (18.5 nmol/L [IQR 11.3-24.3] in deceased patients vs 34.0 nmol/L [IQR 25.0-48.0] in survivors; P < .001). No difference in estradiol levels was found between deceased and surviving patients.Low SHBG levels were associated with mortality rate in patients with COVID-19, and low total and free testosterone levels were associated with mortality in men. The role of testosterone and SHBG and potential of hormone replacement therapy needs further exploration in COVID-19.

Dataset Information

Sex Steroid Hormones Regulate Leptin Transcript Accumulation and Protein Secretion in 3T3-L1 Cells.

Publications

Sex Steroid Hormones Regulate Leptin Transcript Accumulation and Protein Secretion in 3T3-L1 Cells.

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