Steroid biosynthesis

About: Steroid biosynthesis is a research topic. Over the lifetime, 1721 publications have been published within this topic receiving 58977 citations.

R 75251, a new inhibitor of steroid biosynthesis.

Abstract: R 75251, a new imidazole derivative, inhibited the conversion of androgens to estrogens, of progestins to androstenedione and testosterone, and of 11-deoxycorticosterone to corticosterone in human placenta microsomes, subcellular fraction of rat testis, bovine adrenocortical mitochondria, in cultured rat granulosa, testicular and adrenal cells, respectively. In vitro, no effect on cholesterol synthesis and cholesterol side-chain cleavage was found at concentrations up to 10 microM. In rat granulosa cells, no effect on progesterone production was detected. In vitro, no effect on steroid radioligand binding was observed. In male volunteers, a single dose of 300 mg of R 75251 significantly lowered plasma testosterone and estradiol for 24 hours and increased plasma concentration of 17 alpha-hydroxyprogesterone and progesterone. As compared with ketoconazole high dose (600 mg b.i.d), R 75251 (300 mg b.i.d) was at least as efficacious as inhibitor of testosterone synthesis when studied during ACTH stimulation. In contrast to ketoconazole, R 75251 did not significantly affect circulating adrenal androgen levels in male volunteers. Precursors of gluco- and mineralocorticoids such as 11-deoxycortisol and 11-deoxycorticosterone accumulated more than after ketoconazole administration. The data show that the cytochrome P450-dependent aromatase, 17-hydroxylase/17,20-lyase, and 11-hydroxylase are the target enzymes for R 75251.

Mutation in the human gene for 3β-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss

Abstract: A 5-year-old XY pseudohermaphrodite was found to have a defect of steroid biosynthesis consistent with a partial deficiency of the enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). Circulating concentrations of delta 5 steroids and delta 5 urinary steroid metabolites were elevated and remained elevated after orchidectomy. There was no evidence of salt loss, plasma renin being within normal limits, and no detectable glucocorticoid abnormality. The coding sequences of the genes for 3 beta-HSD types I and II were amplified by PCR and screened for mutations by denaturing gradient gel electrophoresis (DGGE) and manual and automatic DNA sequencing. A mutation in the gene for 3 beta-HSD type II was observed at codon 173 (CTA-->CGA), leading in the affected patient to a homozygous substitution in which the leucine at residue 173 was altered to an arginine (L173R). The propositus's 2-year-old XX sister was also homozygous for L173R and showed the biochemical characteristics of partial 3 beta-HSD deficiency without clinical symptoms or signs. The mutation segregated as an autosomal recessive. Three related heterozygous adult females showed evidence of a small over-production of delta 5 steroids and steroid metabolites and a variable reduction in ovarian function. Concentrations of delta 5 steroids and steroid metabolites in the heterozygous father of the propositus were within the normal range. These data are discussed in relation to the endocrine causes of pseudohermaphroditism and hirsutism. Evidence for tight linkage between the genes for 3 beta-HSD types I and II was obtained using a microsatellite polymorphism in the third intron of the gene for 3 beta-HSD type II and synonymous and non-synonymous mutations and polymorphisms in the gene for 3 beta-HSD type I. The latter polymorphisms were located 88 bp apart at the 3' end of the type I coding sequence and could be physically resolved as haplotypes using DGGE. The application of DGGE to the analysis of mutations in members of a multigene family is discussed.

Transcriptional insights into key genes and pathways controlling muscle lipid metabolism in broiler chickens

Abstract: Intramuscular fat (IMF) is one of the most important factors positively associated with meat quality. Triglycerides (TGs), as the main component of IMF, play an essential role in muscle lipid metabolism. This transcriptome analysis of pectoralis muscle tissue aimed to identify functional genes and biological pathways likely contributing to the extreme differences in the TG content of broiler chickens. The study included Jingxing-Huang broilers that were significantly different in TG content (5.81 mg/g and 2.26 mg/g, p < 0.01) and deposition of cholesterol also showed the same trend. This RNA sequencing analysis was performed on pectoralis muscle samples from the higher TG content group (HTG) and the lower TG content group (LTG) chickens. A total of 1200 differentially expressed genes (DEGs) were identified between two groups, of which 59 DEGs were related to TG and steroid metabolism. The HTG chickens overexpressed numerous genes related to adipogenesis and lipogenesis in pectoralis muscle tissue, including the key genes ADIPOQ, CD36, FABP4, FABP5, LPL, SCD, PLIN1, CIDEC and PPARG, as well as genes related to steroid biosynthesis (DHCR24, LSS, MSMO1, NSDHL and CH25H). Additionally, key pathways related to lipid storage and metabolism (the steroid biosynthesis and peroxisome proliferator activated receptor (PPAR) signaling pathway) may be the key pathways regulating differential lipid deposition between HTG group and LTG group. This study showed that increased TG deposition accompanying an increase in steroid synthesis in pectoralis muscle tissue. Our findings of changes in gene expression of steroid biosynthesis and PPAR signaling pathway in HTG and LTG chickens provide insight into genetic mechanisms involved in different lipid deposition patterns in pectoralis muscle tissue.