Disease relevance of Adrenal Cortex

• Idiopathic Addison's disease is characterised by a progressive failure in the synthesis of all classes of steroid hormones and by an immune response against the steroid-producing cells of the adrenal cortex; the nature of the adrenal autoantigens is not known [1].
• Because of the impaired cortisol secretion, adrenocorticotropic hormone levels rise due to impairment of a negative feedback system, which results in hyperplasia of the adrenal cortex [2].
• Congenital adrenal hyperplasia is a family of inborn errors of steroidogenesis, each characterized by a specific enzyme deficiency that impairs cortisol production by the adrenal cortex, and can lead to sexual ambiguity in both genetic males and females [3].
• These data indicate that LPL is expressed in human adrenal cortex and regulated in NCI-H295 adrenocortical carcinoma cells by activators of the protein kinase A and protein kinase C second messenger pathways in a manner comparable to P450scc, which catalyzes the first step in adrenal steroidogenesis [4].
• In the adrenal cortex, increased expression of seladin-1/DHCR24, which appears to be modulated by ACTH, has been recently reported in cortisol-secreting adenomas, compared with the adjacent atrophic tissue [5].

High impact information on Adrenal Cortex

• Familial glucocorticoid deficiency (FGD), or hereditary unresponsiveness to adrenocorticotropin (ACTH; OMIM 202200), is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex, which stimulates glucocorticoid production [6].
• Here, we provide evidence for this hypothesis by the cloning and characterization of a serine protease that is upregulated during growth of the adrenal cortex [7].
• Acth in turn activates Acth receptors in the adrenal cortex to increase synthesis and release of glucocorticoids [8].
• Hyperandrogenemia is the hallmark of the polycystic ovary syndrome, yet the relative contributions of the adrenal cortex and ovary to the overproduction of androgen remain unclear [9].
• At the onset, all patients with autoimmune AD (100%) had detectable adrenal cortex and/or steroid 21-hydroxylase autoantibodies [10].
• The expression of neuron-specific proteins in the zona glomerulosa and/or aldosterone-producing adenomas of the human adrenal has been reported; those include synaptophysin, neuronal cell adhesion molecule (NCAM), serotonin-receptor 4 (5-HT4), metabotropic glutamate receptor 3 (GRM3 / mGluR3) among other glutamate receptors, Purkinje cell protein 4 (PCP4), metallothionein 3 (MT3), activating transcription factor 3 (ATF3), and voltage-dependent calcium channels, indicating the possible common regulatory processes between neurons and aldosterone-producing cells [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21].

Chemical compound and disease context of Adrenal Cortex

• We studied six human adrenal carcinomas and normal adrenal cortex from three subjects for beta-adrenergic agonist-sensitive adenylate cyclase and beta-adrenergic binding sites [22].
• The increase in adrenal weight with EGF administration was due to hypertrophy of definitive zone cells of the adrenal cortex, whereas the reduction in adrenal weight after beta-methasone treatment was due to a decrease in the size of definitive and fetal zone cells of the adrenal cortex [23].
• In the present study, we have investigated quantitatively and qualitatively the expression of the 5-HT4 receptor in both normal adrenal cortex and tissues removed from six patients (P1-P6) with cisapride-responsive AIMAH and Cushing's syndrome [19].
• Acute studies showed that this effect is largely independent of methaqualone-induced hypothermia but can be blocked by pretreatment with dexamethasone, thus demonstrating that the adrenal cortex is not being directly stimulated [24].
• However, there was no lack of androgens in the patient in this report, because the testicular ablation was compensated by nodular hyperplasia of the adrenal cortex maintaining a normal plasma testosterone [25].

Biological context of Adrenal Cortex

• However, no increase in fetal plasma ACTH has been observed before the corticosteroid surge in sheep or humans, although differential responsiveness of the fetal adrenal cortex to ACTH at various gestational ages and a possible role of extra-adrenal inhibitory factors have been proposed [26].
• Indirect evidence, based on effects of P450c21 deficiency and maternal estriol concentrations, indicate that the fetal adrenal cortex produces cortisol and DHEA-S early in gestation (6-12 weeks) [27].
• The parallel stimulation of membrane guanylate cyclase and corticosterone production in isolated fasciculata cells of rat adrenal cortex has supported the hypothesis of a mediatory role for cyclic guanosine monophosphate (cyclic GMP) in signal transduction [28].
• Gene expression, localization, and characterization of endothelin A and B receptors in the human adrenal cortex [29].
• Cells with nuclear p21 and p53 appeared in the adrenal cortex together with DNA damage detected by in situ end-labeling [30].

Anatomical context of Adrenal Cortex

• Both exposure to cold and administration of aminophylline result in rapid increases in cyclic adenosine monophosphate (cyclic AMP) in the adrenal medulla and adrenal cortex [31].
• Adrenocorticotropin (ACTH) secretion from the anterior pituitary gland influences glucocorticoid secretion from the adrenal cortex and in turn is controlled mainly by corticotropin-releasing factor (CRF) release from the hypothalamus [32].
• The final three steps of aldosterone synthesis, 11 beta- and 18-hydroxylation and 18-oxidation, are mediated by a cytochrome P450 in the zona glomerulosa of the adrenal cortex termed CYP11B2 [33].
• Delivery of cholesterol to inner mitochondrial membranes is rate-limiting for steroidogenesis in the zona fasciculata of adrenal cortex [34].
• Although this functional steroidogenic pathway can be incorporated into this nonsteroidogenic cell type, it is found to be nonresponsive to cAMP, a potent activator of steroid hormone biosynthesis in adrenal cortex, testis, and ovary [35].

Associations of Adrenal Cortex with chemical compounds

• Those findings were among the first indications of the function and physiological role of the human fetal adrenal cortex and led Diczfalusy and co-workers to propose the concept of the feto-placental unit, in which DHEA-S produced by the fetal adrenal cortex is used by the placenta for estrogen synthesis [27].
• Guanosine triphosphate cyclohydrolase, the enzyme that is apparently rate-limiting in biopterin biosynthesis, is increased in adrenal cortex and medulla of rats treated with insulin or reserpine [36].
• The first gene so far tested, which encodes the alpha chain of Gi2, showed mutations that replaced arginine-179 with either cysteine or histidine in 3 of 11 tumors of the adrenal cortex and 3 of 10 endocrine tumors of the ovary [37].
• High-flux mitochondrial cholesterol trafficking, a specialized function of the adrenal cortex [38].
• Regulation of angiotensin II receptors in the rat adrenal cortex by dietary electrolytes [39].

Gene context of Adrenal Cortex

• Accordingly, we wished to investigate whether the genes of ET-1 and of its receptors A and B are expressed in the normal human adrenal cortex [29].
• We found that PF-4 (10 microg/mL) inhibited the FGF2-induced proliferation of adrenal cortex capillary endothelial (ACE) cells [40].
• The highest levels of VPF/VEGF transcripts were found in epithelial cells of lung alveoli, renal glomeruli and adrenal cortex, and in cardiac myocytes [41].
• We have found that a dual-specificity phosphatase is essential for conveying ACTH/cAMP-stimulated transcription of several steroidogenic genes in the human adrenal cortex [42].
• Induction of interferon-gamma inducing factor in the adrenal cortex [43].

Analytical, diagnostic and therapeutic context of Adrenal Cortex

• In situ hybridization revealed a heterogenous proDyn mRNA distribution limited almost exclusively to the adrenal cortex; the inner cortical layers contained the highest amounts [44].
• Synthetic ACTH stimulation of the adrenal cortex during heart-lung bypass produced a positive response (i.e., a rise in plasma cortisol greater than 7.5 mug/100 ml) in all six patients studied while the six mitral valvotomy patients had no response to synthetic ACTH administration during operation (P less than 0.01) [45].
• Cytochrome P450 aldosterone synthase expression in the adrenal cortex was stimulated by nephrectomy alone and by nephrectomy combined with low salt intake (P < .05), with consequent increases in PA concentrations [46].
• HL was localized by immunohistochemistry to the liver and to the adrenal cortex [47].
• We show by Northern blot analysis, immunoblots, and immunohistochemistry that TRP4 transcripts and TRP4 protein are present in the adrenal cortex but absent in the medulla [48].

References