Assessment of Estradiol, Progesterone and Lipid Profile among Breast Cancer Patients in Ethiopia: Hospital-based Comparative Cross-Sectional Study

Background Breast cancer is the most often diagnosed type of cancer and the leading cause of death worldwide. Estrogen, also known as estradiol, influences progesterone metabolism and modifies lipid metabolism. Thus, steroid hormone and lipid profile levels for breast cancer patients must be evaluated. However, this has yet to be explored and used for therapy in Ethiopia. As a result, the present study at Tikur Anbessa Specialized Hospital attempted to assess serum estrogen, progesterone, and lipid profile levels in breast cancer patients and healthy controls. Methods A hospital-based comparative cross-sectional study was conducted on a total of 80 participants (40 newly diagnosed breast cancer patients and 40 healthy control females). A convenient sampling method was used to recruit the study participants. Steroid hormones and lipid profile were determined using immunoassays and an enzymatic colorimetric technique, respectively. SPSS version 20.0 was used for statistical analysis, and p-values of 0.05 were considered statistically significant. Results When compared to healthy controls, the mean serum progesterone, TC, and HDL-C levels in breast cancer patients were considerably lower, while estradiol, TG, and LDL-C levels were insignificantly higher. Conclusions Breast cancer may be to blame for changes in progesterone, estradiol, and lipid profile levels, which can lead to secondary problems.

Progesterone Metabolism by Human and Rat Hepatic and Intestinal Tissue

Following oral administration, the bioavailability of progesterone is low and highly variable. As a result, no clinically relevant, natural progesterone oral formulation is available. After oral delivery, first-pass metabolism initially occurs in the intestines; however, very little information on progesterone metabolism in this organ currently exists. The aim of this study is to investigate the contributions of liver and intestine to progesterone clearance. In the presence of NADPH, a rapid clearance of progesterone was observed in human and rat liver samples (t1/2 2.7 and 2.72 min, respectively). The rate of progesterone depletion in intestine was statistically similar between rat and human (t1/2 197.6 min in rat and 157.2 min in human). However, in the absence of NADPH, progesterone was depleted at a significantly lower rate in rat intestine compared to human. The roles of aldo keto reductases (AKR), xanthine oxidase (XAO) and aldehyde oxidase (AOX) in progesterone metabolism were also investigated. The rate of progesterone depletion was found to be significantly reduced by AKR1C, 1D1 and 1B1 in human liver and by AKR1B1 in human intestine. The inhibition of AOX also caused a significant reduction in progesterone degradation in human liver, whereas no change was observed in the presence of an XAO inhibitor. Understanding the kinetics of intestinal as well as liver metabolism is important for the future development of progesterone oral formulations. This novel information can inform decisions on the development of targeted formulations and help predict dosage regimens.

Multi-omic characterization of the thermal stress phenome in the stony coral Montipora capitata

We used network methods to analyze transcriptomic and polar metabolomic data generated from the stress resistant stony coral Montipora capitata. Corals were exposed to ambient or thermal stress conditions over a five-week period that coincided with a mass spawning event of this species. Gene co-expression networks showed that the early thermal stress response involves downregulation of growth and DNA replication, whereas signaling and the immune response are strongly upregulated. Later stages are dominated by suppression of metabolite transport and biomineralization and enhanced expression of transcriptional regulators. Integration of gene-metabolite data demonstrates that the major outcome of the thermal treatment is activation of animal redox stress pathways with detoxification of reactive oxygen species being dominant. Differential regulation of the highly conserved cytochrome P450 gene family was of particular interest with downregulation of CYP1A1, involved in progesterone metabolism, potentially explaining the attenuated mass spawning observed during the sampling period.

Inhibition of 5α-reductase alters pregnane metabolism in the late pregnant mare

In the latter half of gestation in the mare, progesterone concentrations decline to near undetectable levels while other 5α-reduced pregnanes are elevated. Of these, 5α-dihydroprogesterone and allopregnanolone have been reported to have important roles in either pregnancy maintenance or fetal quiescence. During this time, the placenta is necessary for pregnane metabolism, with the enzyme 5α-reductase being required for the conversion of progesterone to 5α-dihydroprogesterone. The objectives of this study were to assess the effects of a 5α-reductase inhibitor, dutasteride on pregnane metabolism (pregnenolone, progesterone, 5α-dihydroprogesterone, 20α-hydroxy-5α-pregnan-3-one, 5α-pregnane-3β,20α-diol and allopregnanolone), to determine circulating dutasteride concentrations and to assess effects of dutasteride treatment on gestational parameters. Pregnant mares (n = 5) received dutasteride (0.01 mg/kg/day, IM) and control mares (n = 4) received vehicle alone from 300 to 320 days of gestation or until parturition. Concentrations of dutasteride, pregnenolone, progesterone, 5α-dihydroprogesterone, 20α-hydroxy-5α-pregnan-3-one, 5α-pregnane-3β,20α-diol, and allopregnanolone were evaluated via liquid chromatography–tandem mass spectrometry. Samples were analyzed as both days post treatment and as days prepartum. No significant treatment effects were detected in pregnenolone, 5α-dihydroprogesterone, 20α-hydroxy-5α-pregnan-3-one, 5α-pregnane-3β,20α-diol or allopregnanolone for either analysis; however, progesterone concentrations were increased (P < 0.05) sixfold in dutasteride-treated mares compared to control mares. Dutasteride concentrations increased in the treated mares, with a significant correlation (P < 0.05) between dutasteride concentrations and pregnenolone or progesterone concentrations. Gestational length and neonatal outcomes were not significantly altered in dutasteride-treated mares. Although 5α-reduced metabolites were unchanged, these data suggest an accumulation of precursor progesterone with inhibition of 5α-reductase, indicating the ability of dutasteride to alter progesterone metabolism.