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Steroid biosynthesis

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


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Journal ArticleDOI
TL;DR: Kinetic analyses of vinblastine and daunomycin accumulation in both the wild-type and the mutant cell lines during ACTH-stimulated steroidogenesis show that in the mutant cells both drugs accumulated to higher levels than in Y1 cells, suggesting that the remaining mdr1b allele in the Mutant cells is relatively inactive as an exporter of steroids.

64 citations

Journal ArticleDOI
TL;DR: A significant increase in 17alpha-OH-pregnenolone and dehydroepiandrostenedione concentrations confirms an inhibitory effect of trilostane on the 3beta-HSD, and seems to influence additional enzymes of the hormone cascade, like the 11 beta-hydroxylase and possibly the 11beta-hydroxysteroid dehydrogenase.

64 citations

Journal ArticleDOI
TL;DR: Leptin may play a minor, but direct regulatory role on unstimulated human ovarian steroidogenesis by interfering with either the translational or post-translational steps of the baseline CYP17 and/or aromatase synthesis and or the activation of the enzymes.
Abstract: Absence of leptin secretion compromises reproductive function and fertility in the ob/ob mouse which, when given leptin, shows a rise in serum LH levels and becomes fertile. Recently, the long and active isoform of the leptin receptor was detected in the ovary, indicating that leptin may also show direct gonad-related activity. To examine this, we studied the effect of graded doses of human leptin on estradiol (E2) and progesterone (P4) concentrations in the culture media of human granulosa-lutein cells obtained from follicular fluid of women undergoing in vitro fertilization. We also evaluated the mRNA expression of steroidogenic acute regulatory protein (StAR), aromatase, and cytochrome P450 17alpha (CYP17) in these cells at baseline and after exposure to leptin. Estradiol levels were significantly decreased in the media 24 hours after incubation of the cells with increasing hLeptin concentrations (10(-11) - 10(-7) mol/l). The maximal 30% decrease in E2 production was caused by the 10(-9) mol/l hLeptin concentration; however, P4 levels in the media were not influenced by leptin. Exposure of granulosa-lutein cells to 10(-9) mol/l hLeptin did not produce any measurable changes on StAR, aromatase, or CYP17 mRNA expression. When hLeptin (10(-9) mol/l) was co-incubated with increasing concentrations of hCG (1.25 - 10 mlU/ml), IGF-II (15-60 ng/ml) or 1-6 desaminated IGF-II (deslGF-II; 15-60 ng/ml), it did not modify the elevation of E2 concentrations caused by each of the different stimuli. We conclude that leptin suppresses E2 secretion by human granulosa-lutein cells but does not impair the stimulatory effects of hCG and IGFs on these cells. Leptin may play a minor, but direct regulatory role on unstimulated human ovarian steroidogenesis by interfering with either the translational or post-translational steps of the baseline CYP17 and/or aromatase synthesis and/or the activation of the enzymes.

64 citations

Journal ArticleDOI
TL;DR: This study was designed to seek evidence, from endocrine and genetic studies, for impaired steroid biosynthesis in patients with acne.
Abstract: OBJECTIVE Previous endocrine studies of women with acne have produced diverse results. This study was designed to seek evidence, from endocrine and genetic studies, for impaired steroid biosynthesis in patients with acne. DESIGN Adrenal stimulation tests with synthetic adrenocorticotrophic hormone (ACTH) were performed. MEASUREMENTS Steroid hormones were measured basally and 30 minutes after ACTH. The results were correlated with analysis of the steroid 21-hydroxylase gene (CYP21). PATIENTS Fifty-one consecutive female patients (mean age 27.1 years) referred with acne. RESULTS The median plasma 17-hydroxyprogesterone (17-OHP) before and 30 minutes after ACTH were 2.5 nmol/l (range 1.1-8.2) and 7.3 (2.1-17.8) nmol/l which were significantly above normal female controls (n = 11, mean age 25.6 years) at 1.5 (0.9-4.2) and 4.6 (2.6-8.4) nmol/l. Eighteen of 51 acne patients showed an abnormal 17-OHP response. The 21-hydroxylase gene (CYP21) was examined for major deletions and for three common point mutations in 31 of the patients (14 with exaggerated 17-OHP response). One patient had a deletion of CYP21 on one allele consistent with carrier status for the classical congenital adrenal hyperplasia (CAH). Five patients, one of whom had a normal 17-OHP response to Synacthen, were heterozygous for the val 281 leu mutation in exon 7 of the CYP21 and were therefore carriers for a mutation associated with late-onset CAH. One patient with a raised 17-OHP response was homozygous for the splice site mutation in intron 2 and one patient with a normal 17-OHP response was heterozygous for the mutation. None of the patients had the ile 172 asn mutation. Eight of the 31 acne patients who had CYP21 gene analysis were carriers for mutations in the 21-hydroxylase gene but only six would have been detected by an abnormal response of 17-OHP on stimulation. CONCLUSION Although alterations of the CYP21 gene were more common in acne than in controls there is a poor correlation between these events and raised steroids and acne. Factors other than mild impairment of CYP21 contribute to the variability of the clinical phenotype in hyperandrogenic states including acne.

64 citations

Journal ArticleDOI
H. C. Freeman1, G. B. Sangalang1
TL;DR: Anin vitro study on the effects of the contaminants polychlorinated biphenyl (Aroclor 1254) (PCB), methyl mercury (MeHg), arsenic (As), cadmium (Cd), and selenium (Se) on the biosynthesis of steroid hormones in the gray seal indicated altered steroid biosyntheses.
Abstract: An in vitro study on the effects of the contaminants polychlorinated biphenyl (Aroclor 1254) (PCB), methyl mercury (MeHg), arsenic (As), cadmium (Cd), and selenium (Se) on the biosynthesis of steroid hormones in the gray seal (Halichoerus grypus) indicated altered steroid biosynthesis. Biotransformed delta4-androstene-3, 17-dione (delta 4A), dehydroepiandrosterone, 11-ketotestosterone (11-KT), and testosterone (T) were detected in all seal testicular incubates. Yields of 11-KT were greatly increased in the presence of Aroclor 1254. All contaminants except As and Se stimulated the in vitro biosyntheses of T, with the greatest increase in production of T being in the Cd-treated tissue. Cortisol (F), corticosterone (B), aldosterone (ALDO) but no cortisone (E), were biosynthesized by the seal adrenal tissue. Corticosterone (B) was the principal transformation product in all incubations with less B produced by the treated adrenals than by the control. The lowest yeild of B was achieved by the Se-treated adrenal. The yeild of ALDO was also lower in all contaminant treated incubations, with Se and Cd giving the greatest inhibition. More F was biosynthesized by all the treated adrenals than by the control. The greatest increase of production of F(6-fold) from progesterone was by the As-treated adrenal.

63 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202315
202221
2021117
2020109
201975
201860