Steroid biosynthesis

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

Allylamine Derivatives—a New Class of Active Substances in Antifungal Chemotherapy

Abstract: Fungal infections (mycoses) are found throughout the world. Only a few structural classes of compounds currently satisfy the demands of modern chemotherapy in their treatment; hence, the quest for new types of active substances is of major scientific and therapeutic importance. The first representative of a new class of substances–the allylamine derivatives–namely naftifine ((E)-N-methyl-N-(1-naphthylmethyl)-3-phenylallylamine) was discovered by accident and has recently become commercially available as a topical antimycotic. The exploration of structure-activity relationships on the basis of naftifine and new synthetic strategies led to the discovery of the currently most active compound of this type, terbinafine, the first pharmaceutical agent to contain a (E)-1, 3-enyne structural element. Terbinafine exhibits considerably higher activity than the original “lead” structure naftifine both in vitro and in vivo; it is also up to one order of magnitude more effective than standard preparations in various chemotherapeutic animal tests after topical or oral administration. According to clinical experience gained so far, terbinafine is well tolerated and shows promising activity against various types of mycoses. Allylamines act as potent, selective inhibitors of fungal squalene epoxidase via a novel mechanism, which, unlike in the case of other inhibitors of steroid biosynthesis, does not depend on cytochrome P450.

Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors.

Abstract: A recognition site for benzodiazepines structurally different from that linked to various γ-aminobutyric acid A (GABAA) receptor subtypes is located on the outer mitochondrial membranes of steroidogenic cells. This protein has been signified to be important in the regulation of steroid biosynthesis. Because of its location it is designated herein as the mitochondrial benzodiazepine receptor (MBR). A putative endogenous ligand for MBR is the peptide diazepam binding inhibitor (DBI), previously shown to displace drugs from MBR and to be expressed and stored in steroidogenic cells rich in MBR. The two model systems used to study steroidogenic regulation by DBI were the Y-l adrenocortical and MA-10 Leydig cell lines previously shown to be applicable in studies of mitochondrial steroidogenesis. Both cell lines contain DBI as well as DBI processing products, including the DBI fragments that on reverse phase HPLC coelute with the naturally occurring triakontatetraneuropeptide [TTN; DBI-(17–50)] and octadecaneuro...

Regulation of adrenocorticosteroid receptor mRNA expression in the central nervous system.

Abstract: 1. The adrenocorticosteroid receptors are hormone-activated transcription factors that have the potential to influence gene expression in a wide variety of CNS neurons. This review summarizes the present state of knowledge regarding the localization and regulation of glucocorticoid (or type II corticosteroid) receptor and mineralocorticoid (or type I corticosteroid) receptor mRNAs in brain, from the perspective of their potential influence on a wide variety of hormone-responsive genes. 2. Corticosteroid receptors are widely but not uniformly localized in the CNS and exhibit very complex regulation by glucocorticoids, gonadal steroids, neurotransmitter systems, and endogenous circadian drive. Both receptor species are present during development, implying an ability for these transcription factors to interact with neuronal differentiation, growth, and viability, and both receptors appear to regulate with age, suggesting relationships between adrenocorticosteroid receptor populations and brain aging. Regulation of adrenocorticosteroid receptor mRNA expression at the level of polyadenylation and splicing indicates that GR and MR biosynthesis is a dynamic process susceptible to numerous classes of information. 3. Further study of GR and MR biosynthesis at the gene, mRNA, and protein level is required to determine the true meaning of the regulatory complexities seen in defined neuronal circuits.