摘要:

Adrenocortical growth is discussed with respect to its relation to body weight, elevated ACTH (provoked by sustained stress, adrenal enzyme deficiency, and adrenal enucleation), and unilateral adrenalectomy. It seems likely that these three conditions under which adrenal growth occurs are each controlled and mediated by different agents. Least is known about the growth of adrenals with the growth of the organism; however, because treatment with growth hormone is known to stimulate adrenal mitogenesis, and because adrenals grow in proportion to body growth by increasing cell number, it is proposed that this growth may be mediated by growth hormone (via somatomedin). ACTH causes primarily adrenocortical cellular hypertrophy which is subsequently followed by hyperplasia. It has been shown that the application of a sustained stressor, induction of adrenal enzyme deficiency and adrenal enucleation all result in persistant elevation in circulating ACTH levels and adrenal growth. It appears that the stimulus to ACTH secretion is a virtual or real decrease in corticosteroid feedback signal, and that ACTH secretion is regulated by corticosteroid levels. An additional humoral factor may be triggered by adrenal enucleation, and the possibility that a fragment of the N-terminal peptide of the ACTH precursor molecule plays this role is entertained. Finally, the evidence that the proliferative adrenal growth after unilateral adrenalectomy is mediated by afferent and crossed efferent neural pathways, and is regulated by aldosterone, pineal peptides and exposure to constant light is discussed.

ISSN:0743-5800    

DOI:10.1080/07435808409036499

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

ISSN:0743-5800    

DOI:10.1080/07435808409036500

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

The regulation of the proliferation of adrenocortical cells in culture is reviewed. The hormones and growth factors affecting adrenocortical proliferation in culture and their physiological relevance are discussed. The following general conclusions are made:(i) ACTH is growth-stimulatory in vivo, but directly replication-inhibitory both in culture and in vivo, and is therefore an indirect mitogen.(ii) Insulin, IGFs, some pituitary and brain growth factors, and other unknown factors in serum, stimulate growth in culture, but their role in control of adrenocortical size in vivo is unknown.(iii) Pure, known pituitary hormones, other than ACTH, have no effect on adrenocortical proliferation in culture.(iv) Angiotensin is mitogenic in culture and perhaps also in vivo under some circumstances.

ISSN:0743-5800    

DOI:10.1080/07435808409036501

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

The mechanism and properties of the adrenal cortex enzyme system which catalyzes the side chain cleavage of cholesterol to form pregnenolone are summarized. Cytochrome P-450scc, an integral inner mitochondrial membrane protein, interacts with its electron donor adrenodoxin via an aqueous-exposed (matrix side) site, and with its substrate cholesterol via an active site in communication with the hydrophobic phospholipid milieu. In a purified, phospholipid vesicle-reconstituted system, membrane-dissolved cholesterol interacts rapidly with and can be readily metabolized by the membrane-associated cytochrome, and thus represents a readily accessible cholesterol pool. Evidence for a rapidly metabolizable mitochondrial substrate pool (presumably that in the inner mitochondrial membrane) and the regulation by ACTH of cholesterol movement from other site(s) (presumably the outer mitochondrial membrane) into the reactive pool is reviewed; additional evidence is provided which supports the idea that the outer mitochondrial membrane/intermembrane space provides the rate-limiting block to cholesterol utilization. Possible mechanisms by which ACTH might regulate intramitochondrial cholesterol movement are discussed. ACTH has been found to regulate intramitochondrial aqueous volumes (both the matrix and the intermembrane space) in a cycloheximide-inhibitable manner, and it is proposed that these volume changes reflect an altered relationship of outer and inner membranes which may promote movement of cholesterol.

ISSN:0743-5800    

DOI:10.1080/07435808409036502

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

ISSN:0743-5800    

DOI:10.1080/07435808409036503

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

Recombinant plasmids specific for bovine adrenocortical cytochromes P-450sccand P-45011βhave been identified and characterized. Using these cDNA inserts as probes, it is found that tissue specificity of gene expression for these two proteins is as expected. Cytochrome P-450 mRNA is found in adrenocortical and corpus luteum RNA while cytochrome P-45011βmRNA is found only in adrenocortical RNA. Neither mRNA was detected in heart, liver or kidney RNA. Cytochrome P-450sccmRNA is found to be 1.9 kb in length while cytochrome P-45011βmRNA is found to be 4 kb in length. Treatment of bovine adrenocortical cells with ACTH or other modulators results in increased levels of cytochrome P-450sccand cytochrome P-45011βmRNAs. Cytochrome P-450sccis found to be encoded by a limited number or even a single gene.

ISSN:0743-5800    

DOI:10.1080/07435808409036504

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

Congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency is HLA-linked. The haplotype HLA-(A3); Bw47; DR7 is strongly associated with 21-OH deficiency and always carries a null allele at the complement C4A (Rodgers) locus. It seemed likely that this haplotype carries a deletion encompassing both the C4A and 21-OH loci. We hypothesized that the HLA-linked defect involved a structural gene for the adrenal microsomal cytochrome P-450 specific for steroid 21-hydroxylation. We isolated a plasmid with a 520 bp bovine adrenal cDNA insert encoding the middle third of the P-450 peptide. When human DNA was digested with Taq I restriction endonuclease and hybridized with the cDNA probe, DNA from 13 unrelated normal individuals yielded two hybridizing bands of equal intensity at 3.7 and 3.2 kb. The upper band was not present in DNA from a patient homozygous for Bw47. DNA from six unrelated patients heterozygous for Bw47 yielded, in five, diminished relative intensity of the upper band consistent with a heterozygous deletion, and complete disappearance of the upper band in one. Thus 21-OH deficiency sometimes results from the deletion of a gene and sometimes, presumably, from smaller mutations. This gene is probably located very near the C4A gene encoding the 4th component of complement.

ISSN:0743-5800    

DOI:10.1080/07435808409036505

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

The detection and characterization of the physiologically relevant receptors for corticotropin (ACTH) in rat adrenocortical cells is described. By the use of a radioligand with full biological potency and high specific radioactivity (1800 + 75 Ci/mmol), a single class of receptors with an apparent Kdof 1.41 + 0.21 nM was detected and the number of sites was estimated to be 3840 + 1045 per cell. The binding curve was superimposable on the concentration-response curve for cAMP but dissociated from that for steroidogenesis. These data are best explained by the receptor - reserve model in which occupancy of a small fraction of the receptors is sufficient for inducing maximal steroidogenesis.

ISSN:0743-5800    

DOI:10.1080/07435808409036506

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

Forskolin reduced the plating efficiency of Y1 adrenocortical tumor cells in a concentration-dependent manner—more than 5-orders of magnitude at 10 uM forskolin and at least 6-orders of magnitude at 50 uM forskolin. This effect was related to the diterpene's ability to increase adenylate cyclase activity and adenosine 3′,5′-monophosphate (cAMP) levels in Y1 cells. Stable, forskolin-resistant mutants were isolated following growth of Y1 cells for 3 to 4 weeks in the presence of 10 uM forskolin. These mutants were stable, were present in the population at a ratio of approximately 15 mutants per million cells and appeared to result from a defect in cAMP accumulation rather than cAMP action. The forskolin-resistant phenotype was associated with a reduced ability of forskolin to stimulate adenylate cyclase activity in intact cells and in cell homogenates. The adenylate cyclase system of forskolin-resistant mutants was responsive to NaF, but was virtually insensitive to corticotropin (ACTH). As determined by a modified fluctuation analysis, the forskolin-resistant phenotype arose by spontaneous mutation at a frequency consistent with a mutational event at a single genetic locus (2 mutants per million cells per generation). These results indicate that the mutation which rendered Y1 cells insensitive to ACTH likely was the same as that which led to forskolin-resistance. Furthermore, the mutation seemed to behave dominantly. Although the gene product altered by the mutation is unknown, it does not appear to be the catalytic subunit of the enzyme.

ISSN:0743-5800    

DOI:10.1080/07435808409036507

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

ACTH has both short-term (acute) and long-term (chronic) effects to regulate steroid hormone biosynthesis in the adrenal cortex. The acute action of ACTH involves the mobilization of cholesterol and its binding to cytochrome P-450scc. The long-term action of ACTH involves the regulation of synthesis of the various enzymes involved in steroidogenesis. Evidence is presented that cholesterol may have a role to play in this regulatory process as it does in the short-term action of ACTH, consistent with the concept that substrates of specific forms of cytochrome P-450 are frequently able to regulate the synthesis of these specific forms.

ISSN:0743-5800    

DOI:10.1080/07435808409036508

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor