Steroids are a class of medicines with important physiological and pharmacological effects. In pharmaceutical industry, steroidal intermediates are mainly prepared through Mycobacteria transformation, and then modified chemically or enzymatically into advanced steroidal compounds. Compared with the "diosgenin-dienolone" route, Mycobacteria transformation has the advantages of abundant raw materials, cost-effective, short reaction route, high yield and environmental friendliness. Based on genomics and metabolomics, the key enzymes in the phytosterol degradation pathway of Mycobacteria and their catalytic mechanisms are further revealed, which makes it possible for Mycobacteria to be used as chassis cells. This review summarizes the progress in the discovery of steroid-converting enzymes from different species, the modification of Mycobacteria genes and the overexpression of heterologous genes, and the optimization and modification of Mycobacteria as chassis cells.
Mycobacterium/metabolism* ; Steroids/metabolism* ; Phytosterols/metabolism* ; Genomics

Mycobacterium neoaurum has the ability to produce steroidal intermediates known as 22-hydroxy-23, 24-bisnorchol-4-en-3-one (BA) upon the knockout of the genes for either the hydroxyacyl-CoA dehydrogenase (Hsd4A) or acyl-CoA thiolase (FadA5). In a previous study, we discovered a novel metabolite in the fermentation products when the fadA5 gene was deleted. This research aims to elucidate the metabolic pathway of this metabolite through structural identification, homologous sequence analysis of the fadA5 gene, phylogenetic tree analysis of M. neoaurum HGMS2, and gene knockout. Our findings revealed that the metabolite is a C23 metabolic intermediate, named 24-norchol-4-ene-3, 22-dione (designated as 3-OPD). It is formed when a thioesterase (TE) catalyzes the formation of a β-ketonic acid by removing CoA from the side chain of 3, 22-dioxo-25, 26-bisnorchol-4-ene-24-oyl CoA (22-O-BNC-CoA), followed by spontaneously undergoing decarboxylation. These results have the potential to contribute to the development of novel steroid intermediates.
Mycobacterium/metabolism* ; Phylogeny ; Steroids/metabolism* ; Metabolic Networks and Pathways ; Sterols/metabolism*

OBJECTIVETo study the chemical constituents of Monascus purpureus metabolite.

METHODThe compounds were isolated by column chromatography methods, and their structures were determined by spectroscopic methods.

RESULTEight compounds were isolated from the petroleum ether fraction of ethanolic extract and elucidated as stigmast-4-en-3-one (1), 3-oxo-24-methylenecycloarane (2), stigmasterol (3), 7beta-hydroxystigmasterol (4), 3beta-hydroxystigmast-5-en-7-one (5), 3beta-hydroxystigmast-5,22-dien-7-one (6), 5alpha, 8alpha-epidioxyergosta-6,22-dien-3beta-ol (7), sitosterol (8).

CONCLUSIONAll of the compounds were isolated from this genu for the first time except compound 3 and 7.

Drugs, Chinese Herbal ; chemistry ; isolation & purification ; metabolism ; Monascus ; chemistry ; metabolism ; Steroids ; chemistry ; isolation & purification ; metabolism

We reported clinical and physical responses to 7 weeks of anabolic-androgenic steroid (AAS) self-administration in a male recreational bodybuilder. He was self-administrating a total of 3,250 mg of testosterone when his previous and current clinical and physical trials records were revisited. Body shape, performance, and biochemistry results were clustered into three phases labeled PRE (before the self-use), POST I (immediately at the cessation of the 7-week administration), and POST II (12 weeks after the cessation). Elevated testosterone and estradiol levels were observed in the POST I phase, while hepatic and renal functions remained altered in the POST II phase. Body mass and body fat percentages increased throughout the three phases. When adjusted according to body mass, drops in aerobic and anaerobic power and capacity (2.1% to 12.9%) were observed across the phases. This case report shows that overall performance decreased when a bodybuilding practitioner self-administered AAS.
Adipose Tissue ; Biochemistry ; Doping in Sports ; Estradiol ; Humans ; Lipid Metabolism ; Male ; Resistance Training ; Steroids* ; Testosterone

To examine the electrophysiological properties of luteal cells and the relationship between membrane potential and luteal steroidogenic capacity, the membrane potential of luteal cells and the luteal steroidogenesis were measured under different ionic conditions following treatment with various drugs and gonadotropins. The membrane potential of luteal cells did not vary throughout the estrous cycle and was -55 +/- 1 mV. The membrane potential was highly dependent upon the external K+ concentration and was depolarized by the deprivation of external Ca2+, however) there seemed to be a lower K+ permeability in luteal membranes as the presence of 10-9 M valinomycin, a K+ ionophore Caused hyperpolarization from -55 to -91 mV. Luteal progestin production was increased in a high K+ solution but not m a Ca2+-free solution indicating that Ca2+ may be essential for steroid synthesis and/or secretion by luteal cells. Gonadotropins and ouabain induced a depolarization of the membrane potential and stimulated luteal steroidogenesis; however; prostaglandin F2alpha stimulated only steroidogenesis without any changes in membrane potential. These results suggest that the relationship between steroidogenesis and the changes in membrane potential by drugs and gonadotropins is still obscure and remains to be eluridated. The relationship between membrane potential and steroidogenesis in the luteal cell may be dependent upon the availability of intracelluar Ca2+.
Animal ; Corpus Luteum/*metabolism ; Estrus/metabolism ; Female ; Ions ; Luteal Cells/*metabolism ; Membrane Potentials ; Rats ; Rats, Inbred Strains ; Steroids/*biosynthesis ; Support, Non-U.S. Gov't

OBJECTIVETo explore the role of metabolism of fatty substance and osteoclast activity during the process of steroid-induced necrosis of femoral head through mice model inducing and model index measurement.

METHODSForty SD male mice were divided into 2 groups randomly, the control group and the experiment group. After the gluteal injection of colibacillus endotoxin,the experiment group was given gluteal injection of prednisolone acetate 35.5 mg/kg per week, and 2 ml of normal saline to the control group. The mice were killed 12 weeks later and tested the content of Trap-5b, TC and TG of the blood serum. Vitodynamics, bone density were measured and sections of HE staining, Ca2+ and TRACP staining was made then statistic analysis was performanced.

RESULTSThe content of TC, TG and Trap-5b increased apparently (P < 0.01). Large amount of osteoclasts were found in local medullary cavity. There was severe bone loss and decrease of vitodynamics in subchondral bone (P < 0.01) in experiment group.

CONCLUSIONMetabolic disorder of fatty substance is the key pathogenesis of steroid-induced avascular necrosis of femoral head. Decrease of vitodynamics in subchondral bone due to hyperactivity and increase of osteoclast lead to collapse of femoral head directly.

Animals ; Bone Density ; Disease Models, Animal ; Fatty Acids ; metabolism ; Femur Head Necrosis ; metabolism ; physiopathology ; Humans ; Male ; Osteoclasts ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Steroids ; pharmacology

Chronic obstructive pulmonary disease (COPD) is characterized by a not entirely reversible limitation in the airflow. An airflow limitation is progressive and associated with an abnormal inflammatory response of the lung to gases and harmful particles. In COPD, the weight loss is commonly observed and there is a negative impact on the respiratory as well as skeletal muscle function. The pathophysiological mechanisms that result in weight loss in COPD are not fully understood. However, the mechanisms of weight loss in COPD may be the result of an increased energy expenditure unbalanced by an adequate dietary intake. The commonly occurring weight loss and muscle wasting in COPD patients adversely affect the respiratory and peripheral muscle function, the exercise capacity, the health status, and even the survival rates. Therefore, it is very valuable to include management strategies that the increase energy balance in order to increase the weight and fat free mass. A Better understanding of the molecular and cellular pathological mechanisms of COPD can improve the many new directions for both the basic and clinical investigations. The Nutritional supply is an important components of a multidisciplinary pulmonary rehabilitation program. Future studies combining an exercise program, the role of anabolic steroids, nutritional individualization, a more targeted nutritional therapy, and the development of new drugs including anti-cytokines is needed for the effective management of COPD.
Energy Metabolism ; Gases ; Humans ; Lung ; Muscle, Skeletal ; Pulmonary Disease, Chronic Obstructive* ; Rehabilitation ; Steroids ; Survival Rate ; Weight Loss

OBJECTIVE: To identify 1) whether the endogenous steroid hormone metabolism in patients with pelvic organ prolapse was different from that of normal women, 2) the relationship between endogenous steroid hormone metabolites and the stage of the pelvic organ prolapse. METHODS: Twenty postmenopausal women who were clinically diagnosed as having pelvic organ prolapse and 20 volunteer postmenopausal women not having pelvic organ prolapse were included in the study. We compared the urinary profiles of endogenous steroids between the two groups and investigated the relationship between urinary profiles of the endogenous steroids and the degree of pelvic organ prolapse. Urinary profiles of the endogenous steroids were assayed by gas chromatography-mass spectrometry. RESULTS: The ages of the patients and control group were 64.6 +/- 6.5 and 63.5 +/- 3.9 years, and the Body Mass Index (BMI) was 23.96 +/- 3.14 and 24.11 +/- 2.73 kg/m2 in patients and in normal subjects, respectively. The number of patients in each stage were 4 in stage I, 4 in stage II, 6 in stage III and 6 in stage IV. 5-androstene-3beta, 16beta, 17beta-triol (5-AT), 11beta-hydroxy androstenedione (An) and 17beta-estradiol were significantly increased in patients with pelvic organ prolapse over that of the control group (0.76 +/- 0.67 vs 0.06 +/- 0.03 micro mole/g creatinine; p=0.002, 1.16 +/- 0.83 vs 0.65 +/- 0.23 micro mole/g creatinine; p=0.04, 15.08 +/- 9.81 vs 8.53 +/- 6.19 micro mole/g creatinine; p=0.04). However, tetrahydrocortisone (THE) was significantly increased in the control group over that in patients having pelvic organ prolapse (9.80 +/- 6.21 vs 5.22 +/- 4.89 micro mole/g creatinine; p=0.04). The androgen metabolites, 5-AT and THE significantly correlated with the POP-Q stage (R=0.418; p=0.027, R=0.46; p=0.016). Among the estrogen metabolites, 17beta-estradiol was correlated to the POP-Q stage but not mathematically significantly (R=0.38; p=0.05) and the 17beta-estradiol/estrone ratio weakly correlated to pelvic organ prolapse stage (R=0.14; p=0.49), by showing a low correlation coefficiency. CONCLUSION: The urinary concentrations of 17beta-estradiol, 5-AT and 11beta-hydroxy An increased in patients with pelvic organ prolapse over that of the control group and 5-AT, THE and 17beta-estradiol showed a relationship to the progression of pelvic organ prolapse in Korean women. The metabolites of endogenous steroid hormones could be contributing factors in the pathogenesis of pelvic organ prolapse.
Androstenedione ; Body Mass Index ; Creatinine ; Estrogens ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Metabolism* ; Pelvic Organ Prolapse* ; Steroids ; Tetrahydrocortisone ; Volunteers

The aim of this study was to evaluate the effects of low concentrations of DEHP and MEHP on steroidogenesis in a murine Leydig tumor cell line (MLTC-1) in vitro. The result of flow cytometry analysis revealed that the proportion of apoptotic cells was significantly increased after the exposure to DEHP. All three genes (P450scc, P450c17, and 3βHSD) under study showed an increased expression following exposure to DEHP or MEHP, although some insignificant inhibitory effects appeared in the 10 μmol/L treatment group as compared with the controls. It was also found that compared with the controls. It was also found that DEHP or MEHP stimulated INSL3 mRNA and protein especially in the 0.001 μmol/L treatment group. Testosterone secretions were stimulated after the exposure to DEHP or MEHP. Alternations of steroidogenic enzymes and INSL3 in MLTC-1 cells might be involved in the biphasic effects of DEHP/MEHP on androgen production.
Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Diethylhexyl Phthalate ; analogs & derivatives ; toxicity ; Leydig Cell Tumor ; metabolism ; pathology ; Mice ; Steroids ; biosynthesis

Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines, especially Vernonia amygdalina, a famous nature medicine for the treatment of tonsillitis, diabetes, pneumonia. The current study was designed to combine molecular networking (MN) with diagnostic ions for rapid identification of Δ^7,9(11) stigmastane-type saponins which were the α-glucosidase inhibitory active substances in V. amygdalina. First, the α-glucosidase inhibitory activities of five Δ^7,9(11) stigmastane-type steroid saponins that were previously isolated were screened, which indicated that the Δ^7,9(11) stigmastane-type steroid saponin was one of the active constituents responsible for ameliorating diabetes. Furthermore, a strategy was proposed to identify stigmastane-type steroid saponins and verify the plausibility of derived fragmentation pathways by applying MN, MolNetEnhancer and unsupervised substructure annotation (MS2LDA). Based on this strategy, other seven Δ^7,9(11) stigmastane-type steroid saponins were identified from this plant. Our research provide scientific evidence for the antidiabetic potential of the steroid saponin-rich extract of V. amygdalina leaf.
alpha-Glucosidases/metabolism* ; Vernonia/chemistry* ; Plant Extracts/chemistry* ; Plant Leaves/chemistry* ; Saponins/chemistry* ; Steroids/chemistry* ; Diabetes Mellitus