摘要:

AbstractThe regulation of steroid 17α-hydroxylase in human and bovine adrenocortical cells in culture is reviewed. It is shown that (i) the long-term growth and cloning of normal human fetal adrenocortical cells in culture is feasible; (ii) the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) is an effective mitogen in both clonal cultures and non-clonal early cultures of human adrenocortical cells, and shows a selective action in promoting adrenocortical cell growth and inhibiting fibroblast growth; (iii) the key steroidogenic enzymes, 17α-hydroxylase and 3β-hydroxysteroid dehydrogenase (3β-HSD), are under dual regulation by the cyclic AMP and protein kinase C second messenger systems; (iv) for 17α-hydroxylase, this dual regulation is mediated by changes in 17α-hydroxylase mRNA levels; (v) bovine adrenocortical cells can be transfected with SV40 T antigen, producing lines with elevated differentiated functions, including stabilized high expression of 17α-hydroxylase; (vi) human adrenocortical cells can also be transfected with SV40 large T antigen, giving rise to functional cell lines which may be useful in future studies of 17α-hydroxylase regulation.

ISSN:0743-5800    

DOI:10.1080/07435808909039095

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

The 17-deoxy steroids (17-DOS) of the zona fasciculata (ZF) are deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-deoxycorticosterone (18-OHDOC) and under special conditions, 18-hydroxycorticosterone (18-OHB). In general, studies have been performed to examine the regulation of DOC rather than all the steroids of this pathway. The circadian rhythm of DOC parallels cortisol (1,2). DOC is stimulated by ACTH and completely suppressed by short-term treatment with dexamethasone (2,3,4,5). The renin-angiotensin system (RAS) has some effect on DOC secretion but the results must be interpreted with caution because of early methodology (2,4,6). Short-term infusions with angiotensin II (7) and III (8) had little effect on plasma DOC levels. In a signle study the zona glomerculosa (ZG) stimulation by sodium restriction, and angiotensin II infusion caused slight increases in plasma DOC in a patient with isolated ACTH deficiency but not in normal sub

ISSN:0743-5800    

DOI:10.1080/07435808909039096

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Mineralocorticoid hormones increase sodium reabsorption and promote potassium and hydrogen secretion in a variety of high resistance (“tight'') epithelia, such as the distal part of the colon or of the nephron. Clearly the kidney plays a major role in controlling the sodium homeostasis of the extracellular space. The distal part of the mammalian nephron, more specifically the cortical collecting tubule (CCT) (or its counterpart, the amphibian urinary bladder) has been recognized as the major site of hormonal control

ISSN:0743-5800    

DOI:10.1080/07435808909039097

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

The circulating levels of glucocorticoid hormones are commonly several orders of magnitude higher than those of the mineralocorticoid aldosterone. Paradoxically, cytosol Type I receptors from a variety of tissues, or recombinant-derived human kidney mineralocorticoid receptors, have essentially indistinguishable affinity for aldosterone, corticosterone and cortisol. In vivo, however, though injected corticosterone and aldosterone are equivalently taken up and retained by rat hippocampus or heart, binding of corticosterone is very much lower in classical mineralocorticoid target tissues (kidney, parotid, colon). The genesis of this aldosterone-selectivity in vivo appears to be the expression, in physiologic mineralocorticoid target tissues, of the microsomal enzyme 11βhydroxysteroid dehydrogenase (11βOHSD). Whereas cortisol and corticosterone have affinity for Type I receptors equivalent to

ISSN:0743-5800    

DOI:10.1080/07435808909039098

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractSteroid 21-hydroxylase deficiency is the most frequent cause of congenital adrenal hyperplasia, an inherited inability to synthesize cortisol. Mutations causing this disorder have been characterized by hybridization analysis of patient DNA samples using cDNA and oligonucleotide probes, and by cloning and sequencing of mutant 21-hydroxylase (CYP21B) genes. About 20% of mutant alleles carry a 30 kilobasepair deletion that includes the 3’end of the CYP21A pseudogene, the C4B complement gene, and the 5’end of CYP21B, leaving behind a single CYP21A-like gene that is not functional. Non-deletional mutations include a nonsense mutation at codon 318 that is associated with severe disease and missense mutations at codons 172 (isoleucine to asparagine) and 281 (valine to leucine) that are respectively associated with intermediate and mild deficiency states. All of these alleles have apparently resulted from gene conversion events that have transferred deleterious mutations from the CYP21A pseudogene to CYP21B. Thus, recombinations between CYP21A and CYP21B probably account for the majority of 21-hydroxylase deficiency alleles.

ISSN:0743-5800    

DOI:10.1080/07435808909039099

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractNonclassic steroid 21-hydroxylase deficiency is a frequent, relatively mild disorder of cortisol biosynthesis characterized by variable signs of postnatal androgen excess. It is inherited as an allelic variant of the CYP21B gene encoding the 21-hydroxylase enzyme. CYP21B is located in the HLA histocompatibility complex, and a nonclassic allele is often associated with characteristic HLA antigens: B14;DR1.A CYP21B gene from a HLA-B14;DR1 homozygous patient with nonclassic 21-hydroxylase deficiency was cloned and analyzed. Five deviations from the normal sequence of CYP21B were found, but only one appeared likely to affect the functional integrity of the protein: codon 281,GTG, encoding valine, was changed toTTG, leucine. An oligonucleotide probe was constructed corresponding to the mutant sequence surrounding codon 281 and hybridized with DNA samples digested with restriction endonuclease Taq I. Samples from 8 nonclassic 21-hydroxylase deficiency patients carrying HLA-B14;DR1 contained a hybridizing fragment 3700 base-pairs long, indicating presence of the val-281 mutation in the CYP21B gene. In contrast, unaffected individuals and one patient who lacked HLA-B14;DR1 showed no evidence of the val-281 mutation in CYP21B.We conclude that the codon 281 mutation is a consistent molecular genetic marker for nonclassic 21-hydroxylase deficiency associated with HLA-B14;DR1.

ISSN:0743-5800    

DOI:10.1080/07435808909039100

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

A multicentric study of prenatal treatment of congenital adrenal hyperplasia (CAH) resulting from 21-hydroxylase deficiency in 43 pregnancies at risk for CAH is presented. The mothers were given dexamethasone per os, 0.5 mg either 12-hourly or 8-hourly. From the analysis of the results obtained in the present study and review of the literature, it would appear that the first condition for successful prevention of female virilization in utero (a total of 6 cases) is to start treatment as early as possible, no later than the 7th week. The dose of dexamethasone should be related to maternal size: 20μg/kg/day (in 2 or 3 fractioned) doses would seem to be both efficient and safe. Adrenal suppression of both maternal and fetal adrenal function should be controlled by appropriate hormonal determinations. Finally, the advantages of early prenatal diagnosis or no prenatal diagnosis are discussed.

ISSN:0743-5800    

DOI:10.1080/07435808909039101

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

ISSN:0743-5800    

DOI:10.1080/07435808909039084

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor