Adrenal cortex, cells

An example of a hormone that exerts its effects through a surface receptor-second messenger system is ACTH.36 ACTH is a polypeptide that binds to a surface receptor on adrenal cortex cells. The surface receptor then stimulates the adenylate cyclase enzyme to increase production of cAMP, which acts as a second messenger (the hormone was the first messenger), and increases the activity of other enzymes within the cell to synthesize adrenal steroids such as cortisol. For a more detailed description of surface receptor-second messenger systems, see Chapter 4. 

Figure 16.5 The renin-angiotensin system controlling aldosterone secretion by the adrenal cortex cells.

Ishihara, S. L., and Morohashi, K. (2005). A boundary for histone acetylation allows distinct expression patterns of the Ad4BP/SF-l and GCNF loci in adrenal cortex cells. Biochem Biophys Res Commun 329, 554-562. 

Adrenal cortex cells have many low-density lipoprotein receptors on their surface. This enables them to take up cholesterol rapidly, from which the adrenal steroid hormones are synthesized (Fig.. 1). The adrenal glands are also capable of synthesizing cortisol from acetate, though this appears to be of minor importance. 

In short, all these data suggest that disruption of interactions between CPT I and cytoskeletal component(s) may de-inhibit CPT I and, therefore, increase enzyme activity. This is in line with the current notion that the dynamics and intracellular distribution of mitochondria in living cells may result from specific interactions of mitochondria with components of the cytoskeleton. In the case of rat-brain mitochondria, accruing evidence indicates that specific interactions occur between mitochondrial-outer-membrane proteins and cytoskeletal proteins. A well described example being the interaction between porin, microtubule-associated protein 2, and the neurofilamental proteins NF-H and NF-M. The existence of direct contact sites between intermediate filaments and the mitochondrial outer membrane has been reported not only in neurons, but also in smooth muscle myocytes and adrenal cortex cells. As far as we know, although rat-liver mitochondria have been shown to interact with microtubules, direct evidence for their interaction with intermediate filaments is still lacking. 

Fig. 11. A. Typical aspect of a cluster of interchromatin granules in normal rat liver nucleus. Glutaraldehyde>Epon, EDTA method chr, bleached chromatin ->, perichromatin granules fibrils ig interchromatin granules. X42,300. B. Cluster of interchromatin granules in the nucleus of an adrenal cortex cell from normal rat. Glutaraldehyde-Epon, EDTA method. The granules are irregularly shaped and have a striking tendency to form chainlike aggregates. small rods may be found,...

In the periphery, dopamine receptor levels are generally lower than those observed in brain, particularly in comparison to striatal dopamine receptor levels. Due to these low levels, knowledge of receptor distribution in the periphery is not yet comprehensive. Nevertheless, Dl-like receptors have been reported in the parathyroid gland and in the tubular cells of the kidney. D2-like dopamine receptors have also been observed in the kidney. In addition, dopamine D2 and D4 receptors have been found in the adrenal cortex, where they modulate aldosterone secretion. The... 

Glucocorticoids are secreted by the cells of the zona fasciculata in the adrenal cortex. Hydrocortisone is the most important, and regulates intermediary metabo-... 

The adrenals of rabbits given a single dermal dose of 100 mg/kg of endosulfan exhibited microscopic changes, including swollen cells with foamy cytoplasm and eccentric nuclei (Gupta and Chandra 1975). Also, release of lipids from the adrenal cortex was observed in rats that died following daily application... 

Angiotensin II binds to specific adrenal cortex glomerulosa cell receptors. The hormone-receptor interaction does not activate adenylyl cyclase, and cAMP does not appear to mediate the action of this hormone. The actions of angiotensin II, which are to stimulate the conversion of cholesterol to pregnenolone and of corticosterone to 18-hydroxycorticosterone and aldosterone, may involve changes in the concentration of intracellular calcium and of phospholipid metabolites by mechanisms similar to those described in Chapter 43. 

Steroidogenic agents—including ACTH and cAMP in the adrenal cortex angiotensin 11, K", serotonin, ACTH, and cAMP in the zona glomerulosa of the adrenal LH in the ovary and LH and cAMP in the Ley dig cells of the testes—have been associated with increased amounts of phosphatidic acid, phosphatidylinositol, and polyphosphoinositides (see Chapter 14) in the respective target tissues. Several other examples could be cited. 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

Steroid hormones are produced by the adrenal cortex, testes, ovaries, and placenta. Synthesized from cholesterol, these hormones are lipid soluble therefore, they cross cell membranes readily and bind to receptors found intracellularly. However, because their lipid solubility renders them insoluble in blood, these hormones are transported in the blood bound to proteins. Furthermore, steroid hormones are not typically preformed and stored for future use within the endocrine gland. Because they are lipid soluble, they could diffuse out of the cells and physiological regulation of their release would not be possible. Finally, steroid hormones are absorbed easily by the gastrointestinal tract and therefore may be administered orally. 

In the presence of renin, an enzyme produced by specialized cells in the kidney, angiotensinogen is split to form angiotensin I. This prohormone is then acted upon by angiotensin-converting enzyme (ACE) as the blood passes through the lungs to form Ag II. Angiotensin II acts directly on the adrenal cortex to promote aldosterone secretion. 

Sodium reabsorption is also influenced by ANP. The original decrease in plasma volume leads to a decrease in atrial filling and a decrease in the release of ANP from the myocardium. Atrial natriuretic peptide, which acts on vascular smooth muscle, granular cells of the kidney, and the adrenal cortex, normally causes the following ... 

Cholesterol, mostly esterified, is utilized in the buildup of cell biomembranes. Besides, cholesterol is a precursor to biologically important steroid compounds bile acids (in liver), steroid hormones (in adrenal cortex, male and female sexual glands, and placenta), and vitamin D3, or cholecalciferol (in skin). 

Steroid hormones are produced by only two tissue types, the adrenal cortex and the gonads. A summary of the steroid hormones is given in Table 4.2. Steroid hormones are synthesized from cholesterol (Figure 4.2). This sterol lipid may itself be synthesized within the steroidogenic cell or it may be delivered to the cell by circulating lipoprotein complexes such as low density lipoprotein (LDL) or high density lipoprotein (HDL). 

Angiotensin II has two effects first, as a vasoconstrictor acting via receptors on vascular smooth muscle cells, and second, it stimulates the adrenal cortex gland to produce aldosterone (a mineralocorticoid steroid hormone, see Chapter 4). Aldosterone promotes the reabsorption of sodium from the renal tubule into the bloodstream and the resulting increase in osmolality (osmotic potential) of the blood causes water reabsorption in the nephrons. The outcome is an increase in blood volume and, therefore, pressure which inhibits (by negative feedback) further renin secretion from the JGA. 

Other Systemic Effects. Mild nonspecific endocrine lesions were observed after inhalation exposure to 1,2-dibromoethane. After subchronic exposure to 75 ppm, rats had adrenal lesions consisting of swelling and/or cytoplasmic vacuolization of cells in the zona fasciculata of the cortex and thyroid lesions consisting of slight decreases in follicular size. Degenerative changes in the adrenal cortex occurred at elevated incidence in female Fischer 344 rats after chronic exposure to 40 ppm... 

This process is important for proliferating cells, in which cholesterol is reqnired for formation of new membranes, and for some endocrine cells (in the testis, ovary and adrenal cortex) for the synthesis of steroid hormones. 

The hormone cortisol is lip, 17a, 21-trihydroxy-4-pregnene-3,20 dione. It is the major glucocorticoid synthesised and secreted by the human adrenal cortex. Cortisol enters the cell then binds to its receptor. The cortisol-receptor complex enters the nucleus and binds to DNA. 

In relatively recent years, it has become clear that under-nntrition of mother leads to low birth weight of the baby and this can increase the risk of development of degenerative disease in later life, e.g. hypertension, obesity, type 2 diabetes. One hypothesis is that the foetus adapts meta-bolically to deficiencies by increasing the number of cells in organs that perform specific functions that can overcome the deficiency, e.g. an increase in the number of liver cells that carry out gluconeogenesis, an increase in cells in the adrenal cortex to produce more of the chronic stress hormone, cortisol. These changes are carried over into adnlthood which can lead to an inadequate response of the liver to insulin so that insulin resistance develops. So far, however, it is unclear whether deficiencies in specific nntrients or undemutrition per se are responsible for snch changes (Chapter 15). 

Angiotensin-II-receptor antagonists These block the binding of this messenger to its receptors on the two target tissues, i.e. smooth muscle in the arterioles and the aldosterone-secreting cells in the adrenal cortex. 

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