Steroids最新文献

To elucidate the effect of cyclooxygenase-2 (COX-2) inhibition on corticosterone release, mice were divided into a group receiving NS398, a selective COX-2 inhibitor at a dose of 3 mg/kg for seven days, and a group receiving NS398 for fourteen days. After this time, the mice were sacrificed, and blood serum was collected. An ELISA protocol was used to analyze serum corticosterone levels. Short-term COX-2 inhibition increased corticosterone levels, while long-term inhibition lowered them. The exact schedule of experiments was repeated after the lipopolysaccharide (LPS) Escherichia coli challenge in mice to check the influence of stress stimuli on the tested parameters. In this case, we observed increases in corticosterone levels, significant in a seven-day pattern. These results indicate that corticosterone levels are regulated through a COX-2-dependent mechanism in mice.

Steroid myopathy is a non-inflammatory toxic myopathy that primarily affects the proximal muscles of the lower limbs. Due to its non-specific symptoms, it is often overshadowed by patients’ underlying conditions. Prolonged or high-dosage use of glucocorticoids leads to a gradual decline in muscle mass. There are no tools available to identify the course of steroid myopathy before the patient displays substantial clinical symptoms. In this study, we investigated individuals with nephrotic syndrome receiving prednisone who underwent muscle ultrasound to obtain cross-sectional and longitudinal pictures of three major proximal muscles in the lower limbs: the vastus lateralis, tibialis anterior, and medial gastrocnemius muscles. Our findings revealed that grip strength was impaired in the prednisolone group, creatine kinase levels were reduced within the normal range; echo intensity of the vastus lateralis and medial gastrocnemius muscles was enhanced, the pennation angle was reduced, and the tibialis anterior muscle exhibited increased echo intensity and decreased thickness. The total dose of prednisone and the total duration of treatment impacted the degree of muscle damage. Our findings indicate that muscle ultrasound effectively monitors muscle structure changes in steroid myopathy. Combining clinical symptoms, serum creatine kinase levels, and grip strength improves the accuracy of muscle injury evaluation.

Multiple epidemiologic studies have revealed that gender is considered one of the important factors in the frequency and severity of certain infectious diseases, in which estrogens may play a vital role. There is growing evidence that estrogens as female sex hormone can modulate multiple biological functions outside of the reproductive system, such as in brain and cardiovascular system. However, it is largely unknown about the roles and mechanisms of estrogens/estrogen receptors in immune health and infection disease. Thence, by reading a lot of literature, we summarized the regulatory mechanisms of estrogens/estrogen receptors in immune cells and their roles in certain infectious diseases with gender differences. Therefore, estrogens may have therapeutic potentials to prevent and treat these infectious diseases, which needs further clinical investigation.

A variety of progestogens are widely used by women for contraception and menopausal hormone therapy. The progestogens undergo extensive metabolism by oral and parenteral routes of administration to form many metabolites. Although a small number of metabolites have been shown to be biologically active, most have not been tested for biologic activity. The present review shows that we know most about progesterone metabolism, followed by the metabolism of levonorgestrel and norethindrone. Very few studies have been carried out on metabolism of most of the progestogens. The clinical significance of this deficiency is that those progestogen metabolites that bind to the progesterone receptors may also bind to other steroid receptors and be responsible for some of the well-documented side effects of administered progestogens. We also discuss how obesity and genetic polymorphisms alter progestogen metabolism, and how development of oral progestogen formulations that are targeted to the colon, where the concentration of steroid-metabolizing enzymes is much lower than in the proximal gut, may have a beneficial effect on progestogen metabolism.

Objective

This study aimed to evaluate the effects of dehydroepiandrosterone (DHEA) and DHEA combined with a high-fat diet (HFD) treatment of reproductive and endocrine metabolism in rats and then identify an ideal model of polycystic ovary syndrome (PCOS).

Methods

Three-week-old female Sprague–Dawley rats were injected subcutaneously with DHEA or oil, fed with or without a HFD, for 21 days, during which body weight, feed intake, and estrous cycle monitoring were carried out. Fasting blood glucose was measured, and serum fasting insulin, testosterone, dihydrotestosterone (DHT), estradiol, progesterone, luteinizing hormone (LH), anti-Müllerian hormone (AMH), and follicle-stimulating hormone (FSH) were estimated by ELISA. Serum total cholesterol (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by colorimetric assay. Whereas, histologic changes in rat ovaries were evaluated by H&E staining. Ovarian steroid hormone synthases and their protein levels (StAR, 3β-HSD2, 17β-HSD1, CYP11A1, CYP17A1, and CYP19A1) were examined by Western blotting.

Results

Both DHEA and DHEA + HFD-treated rats lost a regular estrous cycle; had polycystic ovarian changes, significantly higher serum fasting insulin and testosterone levels; and increased ovarian StAR, 3β-HSD2, and CYP11A1 protein levels. Additionally, rats in the DHEA + HFD-treated group were obese; had elevated fasting blood glucose, TG, DHT, AMH levels and LH:FSH ratios; increased ovarian 17β-HSD1 protein levels.

Conclusion

DHEA combined with HFD treatment is more effective at inducing PCOS than DHEA alone. The reproductive and endocrine metabolic aspects of this method are more consistent with the clinical characteristics of PCOS patients.

Background

Depo-medroxyprogesterone acetate (DMPA) functions as a contraceptive method by inhibiting the secretion of gonadotropins, which prevents follicular maturation and ovulation, as well as thinning of the endometrium leading to unscheduled vaginal bleeding and subsequent discontinuation of DMPA. Our study aimed to evaluate the efficacy and safety of clomiphene citrate (CC) in stopping bleeding among DMPA users.

Materials and Methods

We randomly assigned 200 DMPA users using a computer-generated random numbers table in a 1:1 ratio to one of two groups; the study group, which received CC at a dose of 50 mg twice daily for five days (n = 100), and the control group, which received a placebo for five days (n = 100). Our primary outcome measure was the onset and duration of bleeding cessation. Secondary outcomes included endometrial thickness, recurrence of vaginal bleeding, and any reported side effects associated with CC use.

Results

Clomiphene citrate significantly resulted in early cessation of vaginal bleeding in 83 % of the patients, which continued for three months of follow-up. In addition, the recurrence of vaginal bleeding was significantly reduced in the CC group compared to the control group (11 % vs. 67 %; p < 0.001). Endometrial thickness was significantly greater in the CC group than in the control group (p < 0.001). Breast tenderness was more frequently reported in the study group, with no difference in dyspareunia between the two groups.

Conclusions

Clomiphene citrate is effective in controlling bleeding among DMPA users. Further studies are encouraged to confirm our findings.

There are considerable sex differences regarding the risk of cardiovascular disease (CVD), including arterial hypertension, coronary artery disease (CAD) and stroke, as well as chronic renal disease. Women are largely protected from these conditions prior to menopause, and the risk increases following cessation of endogenous estrogen production or after surgical menopause. Cardiovascular diseases in women generally begin to occur at a later age than in men (on average with a delay of 10 years). Cessation of estrogen production also impacts metabolism, increasing the risk of developing obesity and diabetes. In middle-aged individuals, hypertension develops earlier and faster in women than in men, and smoking increases cardiovascular risk to a greater degree in women than it does in men. It is not only estrogen that affects female cardiovascular health and plays a protective role until menopause: other sex hormones such as progesterone and androgen hormones generate a complex balance that differentiates heart and blood vessel function in women compared to men. Estrogens improve vasodilation of epicardial coronary arteries and the coronary microvasculature by augmenting the release of vasodilating factors such as nitric oxide and prostacyclin, which are mechanisms of coronary vasodilatation that are more pronounced in women compared to men. Estrogens are also powerful inhibitors of inflammation, which in part explains their protective effects on CVD and chronic renal disease. Emerging evidence suggests that sex chromosomes also play a significant role in shaping cardiovascular risk. The cardiovascular protection conferred by endogenous estrogens may be extended by hormone therapy, especially using bioidentical hormones and starting treatment early after menopause.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers that results in death in worldwide. The Hedgehog (HH) signalling pathway regulates the initiation and progression of CRC. Inhibiting the HH pathway has been presented as a potential treatment strategy in recent years. Cynanbungeigenin C (CBC) is a new type of C₂₁ steroid that has been previously reported for the treatment of medulloblastoma. However, its further investigation was limited by its poor water solubility. In this study, six new CBC derivatives were synthesized through the structural modification of CBC, and four of them showed better water solubility than CBC. Moreover, their antiproliferative activities on CRC were evaluated. It was found that CBC-1 presented the best inhibitory effect on three types of CRC cell lines, and this effect was superior to that of CBC. Mechanistically, CBC-1 inhibited the proliferation of CRC cells through regulation of mRNA and proteins of the HH pathway according to qRT–PCR and Western blotting analysis. Furthermore, Cellular Thermal Shift Assay results indicated that CBC-1 regulated this signalling pathway by targeting glioma‑associated oncogene (GLI 1).In addition, cell apoptosis was induced increasingly by transfection with GLI 1 siRNA or treatment with CBC-1 to downregulate GLI 1. Last, the in vivo results demonstrated that CBC-1 significantly reduced tumour size and downregulated GLI 1 in CRC. Therefore, this study suggests that CBC-1, a new GLI 1 inhibitor derived from natural products, may be developed as a potential antitumour candidate for CRC treatment.

Objectives

To investigate the associations between sex hormones and gout.

Methods

A total of 448,836 individuals free of gout at baseline were included from the UK Biobank. Cox regression models were used to estimate hazard ratios (HRs) for gout. Besides, we investigated the causal relationship between bioavailable testosterone (BAT) and gout using mendelian randomization (MR).

Results

There were differential effects in different testosterone active states in gout. One-unit higher log-transformed total testosterone (TT) was associated with a 52 % [95 % CI, 0.39–0.58] lower risk of gout in males. In contrast, free testosterone (FT) and BAT were associated with a 74 % [95 % CI, 1.38–2.20] and a 78 % [95 % CI, 1.41–2.25] higher risk of gout in males respectively. For MR, the weighted median [OR, 1.70; 95 % CI, 1.14–2.56;] and inverse variance-weighted [OR, 1.25; 95 % CI, 0.96–1.62; P = 0.09] method revealed significant and approximately significant positive effect of genetic liability to BAT levels on the risk of gout respectively.

Conclusions

Sex hormones were potentially associated with gout. Notably, we were the first to explore different testosterone states on gout and found that FT and BAT may increase the risk of gout in males, which is opposite to TT. And the former are active states of androgens, may be more accurately reflect the association between androgens and gout.

The use of steroids in livestock animals is a source of concern for consumers because of the risks associated with the presence of their residues in foodstuffs of animal origin. Technological advances such as mass spectrometry have made it possible to play a fundamental role in controlling such practices, firstly for the discovery of marker metabolites but also for the monitoring of these compounds under the regulatory framework. Current control strategies rely on the monitoring of either the parent drug or its metabolites in various matrices of interest. As some of these steroids also have an endogenous status specific strategies have to be applied for control purposes. This review aims to provide a comprehensive and up-to-date knowledge of analytical strategies, whether targeted or non-targeted, and whether they focus on markers of exposure or effect in the specific context of chemical food safety regarding the use of anabolic steroids in livestock. The role of new approaches in data acquisition (e.g. ion mobility), processing and analysis, (e.g. molecular networking), is also discussed.