Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to clarify the transcriptional regulation of the human type 1 angiotensin II receptor (AT1) gene and its pathophysiological roles in steroidogenesis by adrenal tumors. A cDNA encoding type 1 angiotensin II receptor (AT1) was isolated from a human liver cDNA library encoding a protein of 359 amino acids with seven transmembrane segments. It is very likely that human has only one type of AT1 receptor, in contrast with rodents. A genomic clone containing 217 bp of exon 1 and 2558 bp of the 5'-flanking region of human AT1 receptor gene was isolated. Its proximal promoter region contained putative TATA and GC boxes, CRE and AP1 sites. Aldosterone-producing adenoma (APA) contained significantly higher levels of mRNA for AT1 and ACTH receptors than normal tissues adjacent to APA. There were no mutations within the cytoplasmic third loops of AT1 and ACTH receptors in APAs examined. APA showed increased expression of the mRNA for P450c11 and decreased expression of the mRNA for P450c17. These results suggest that renin-independent overproduction and clinically observed ACTH-dependent production of aldosterone in APAs may results from the enhanced transcription of P450c11 and ACTH receptor genes. The mechanism of the discordantly increased expression of AT1 receptor in APA remains to be clarified.
Steroids 1995 Jan
PMID:Type 1 angiotensin II receptors of adrenal tumors. 779 12

The mineralocorticoid and glucocorticoid receptors (MR and GR, respectively) are closely related members of the nuclear receptor superfamily. Despite marked functional similarities and a high degree of sequence conservation between MR and GR, the mineralocorticoid and glucocorticoid hormones elicit markedly different physiological effects, even in cells expressing both receptors. Hormone specificity is, in part, determined by the actions of 11 beta-hydroxysteroid dehydrogenase. However, other mechanisms must obtain in cells that express both receptors and respond differentially to the two classes of hormone. Indeed, MR and GR, while functionally redundant in some contexts, in others display distinct transcriptional specificities. In particular, in the presence of members of the AP1 family of regulatory factors, cJun and cFos, a composite response element, plfG, is GR-specific. Transcription from a plfG-linked gene is stimulated by GR in the presence of cJun and repressed by GR in the presence of cJun and cFos. MR neither stimulates nor represses transcription in the same contexts, thus indicating that receptor transcriptional specificities can be distinguished by differential interactions with nonreceptor factors at a composite response element. The implications of these findings for mineralocorticoid and glucocorticoid hormone specificity in various tissues are discussed.
Steroids 1994 Feb
PMID:A mechanistic basis for distinct mineralocorticoid and glucocorticoid receptor transcriptional specificities. 819 46

The first step in the synthesis of all steroids is the cleavage of cholesterol side chain, catalyzed by an electron transport system located in mitochondria consisting of ferredoxin reductase, ferredoxin, and cytochrome P450scc. These proteins are present in adrenal, gonad, placenta, and some parts of the brain. In addition, ferredoxin and ferredoxin reductase are also found in the kidney and liver. Whereas ferredoxin reductase levels remain constant in the cell, ferredoxin and P450scc levels are stimulated by trophic hormones using cAMP as an intracellular messenger. The ferredoxin promoter is relatively simple, consisting of a TATA box and two Sp1-binding sites. This simple module is enough to direct cAMP-dependent transcription in a steroidogenic cell-specific fashion. The regulatory region for the P450scc gene is more complex, containing many protein binding sites for different regulation purposes. Its TATA box directs cAMP-dependent transcription in a cell-type-specific manner. A transcription factor, steroidogenic factor 1 (SF1), activates P450scc gene expression. The tissue-specific expression of the P450scc gene is probably accomplished through the interaction of SF1 with other protein factors located further upstream of the control region. SF1 may also be involved in the cAMP response. An upstream region binding to cAMP-Responsive Element Binding Protein CREB and AP1 can respond to cAMP for gene activation. These analyses of regulatory elements provide the structural architecture for transcriptional regulation of the ferredoxin and the CYP11A11 gene.
Steroids 1997 Jan
PMID:Transcriptional regulation of the CYP11A1 and ferredoxin genes. 902 12