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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: Spectrophotometric studies with ketoconazole, clotrimazole and miconazole show strong type-II interactions with several cytochromes P-450, particularly with the 11 beta-hydroxylase of adrenal mitochondria and 17 alpha/20 lyase of testis microsomes, and consequently inhibition of steroidogenesis will occur at these sites.
Abstract: 1. Spectrophotometric studies with ketoconazole, clotrimazole and miconazole show strong type-II interactions with several cytochromes P-450, particularly (Ks107M−1; pH 7.4; 25.C) with the 11β-hydroxylase of adrenal mitochondria, with the 17α/20 lyase of testis microsomes and with some forms of cytochromes P-450 of liver.2. A tight binding of the azoles also occurs to the reduced cytochromes, giving rise to an impeded CO binding to the haem iron.3. The binding of the azoles to 11β-hydroxylase and 17α/20 lyase is much tighter than the binding of endogenous substrates, and consequently inhibition of steroidogenesis will occur at these sites. The metabolism of xenobiotic substrates by the cytochromes P-450 of liver will also be severely impeded.4. In contrast, the allylamines naftifine and SF 86–327 are type-I substrates for a small portion of cytochromes P-450 of liver microsomes only and there is no spectral evidence for binding to the cytochromes P-450 involved in steroid biosynthesis.

82 citations

Journal ArticleDOI
TL;DR: The present study has attempted to define both the cytochromes present in the beef adrenal cortex, as well as their distribution among the cell fractions, and indicates the likelihood that cy tochrome cl is the unknown cytochrome mentioned by Huszák.

82 citations

Journal ArticleDOI
TL;DR: It is suggested that cyclins and CDKs are functionally involved in the rhythmic proliferation of normal human endometrial tissue, and the action of these agents may be related to theendometrial levels of sex steroids and Ki67.
Abstract: Cell cycle regulatory molecules were analysed in normal human endometrial tissue using antibodies against cyclins D1, E, A, and B1 and cyclin-dependent kinases (CDKs) cdk4, cdk2, and cdc2. The expression of these regulatory molecules in gland cells and stromal cells was compared with the expression of oestrogen receptors (ER), progesterone receptors (PR), and Ki67 (a growth-related molecule). In general, a substantially higher percentage of the gland cells stained positive for cyclins and CDKs during the proliferative phase of the menstrual cycle. Cyclin E, cdk2 and/or cdk4 were especially apparent in the cytoplasm of most of the gland cells as well as in the stromal cells. In contrast, most of the regulatory molecules were undetectable in the gland cells by the end of the secretory phase of the cycle, but they did not decline in the stromal cells. The data also revealed that ER, PR, and Ki67 in both gland cells and stromal cells follow the same basic pattern of expression as the cyclins and CDKs. These results suggest that cyclins and CDKs are functionally involved in the rhythmic proliferation of normal human endometrial tissue, and the action of these agents may be related to the endometrial levels of sex steroids and Ki67.

81 citations

Journal ArticleDOI
TL;DR: Given the drawbacks of 17α-hydroxylase inhibition, there is considerable interest in developing new CYP17A1 inhibitors that more specifically inhibit lyase activity and are therefore less likely to require glucocorticoid coadministration.
Abstract: A significant proportion of castration-resistant prostate cancers (CRPC) remain driven by ligand activation of the androgen receptor. Although the testes are the primary source of testosterone, testosterone can also be produced from peripheral conversion of adrenal sex hormone precursors dehydroepiandrosterone (DHEA) and androstenedione (AD) in the prostate and other tissues. CYP17A1 catalyzes two essential reactions in the production of DHEA and androstenedione: the hydroxylation (hydroxylase activity) and the subsequent cleavage of the C17-20 side-chain (lyase activity). Potent and selective inhibition of CYP17A1 by abiraterone depletes residual non-gonadal androgens and is an effective treatment for CRPC. Elucidation of the mechanisms that underlie resistance to abiraterone will inform on the development of novel therapeutic strategies post abiraterone. Preclinical evidence that androgen biosynthesis in prostate cancer cells does not necessarily follow a single dominant pathway and residual androgens or alternative ligands (including administered glucocorticoids) can reactivate androgen receptor signaling supports co-targeting of more than one enzyme involved in steroidogenesis and combining a CYP17A1 inhibitor with an anti-androgen. Furthermore, given the drawbacks of 17α-hydroxylase inhibition, there is considerable interest in developing new CYP17A1 inhibitors that more specifically inhibit lyase activity and are therefore less likely to require glucocorticoid co-administration.

81 citations

Journal ArticleDOI
TL;DR: Future investigations will be important to understand the relative role of the individual regulators in the physiological control of adrenal sensitivity to AII, and how activation of various intracellular messenger systems results in changes in activity of the enzymes of the aldosterone biosynthetic pathway.

80 citations


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