Adrenocortical cells

Figure 5. Y1 adrenocortical cells in culture. Y1 mouse adrenocortical tumor cells (a) in the absence and (b) in the presence of 1 mM 8-bromocyclic AMP overnight. (Photos courtesy of Margaret Wong and Dr. Bernard Schimmer.)...

Chen YF, Shin SJ, Lin SR. Etsl was significantly activated by ERKl/2 in mutant K-ras stably transfected human adrenocortical cells. DNA Cell Biol 2005 24 126-32. 

The observation that mitotane (Lysodren) could produce adrenocortical necrosis in animals led to its use in the palliation of inoperable adrenocortical adenocarcinomas. A reduction in both tumor size and adrenocortical hormone secretion can be achieved in about half of the patients taking the drug. Because normal adrenocortical cells also are affected, endogenous glucocorticoid production should be monitored and replacement therapy administered when appropriate. 

Y Hathout, G Maume, BF Maume. High performance hquid chromatographic study of phosphohpid metabolism in cultured adrenocortical cells. J Chromatogr B 652 1-8, 1994. 

Prolonged stimulation by corticotropin leads to adrenocortical cell hyperplasia and an increase in the size and weight of the adrenal glands massive enlargement can be demonstrated by computerized tomography as well as clinical examination (16). 

Even a single dose of corticotropin can cause inhibition of thyrotrophic hormone secretion (19), although the effect is brief. Conversely, thyroid hormones increase the sensitivity of adrenocortical cells in vitro to corticotropin (20) and hyperthyroidism increases sensitivity to corticotropin (21,22). 

Simonian MH. ACTH and thyroid hormone regulation of 3 beta-hydroxysteroid dehydrogenase activity in human fetal adrenocortical cells. J Steroid Biochem 1986 25(6) 1001-6. 

Varga I, Racz K, Kiss R, Futo L, Toth M, Sergev O, Glaz E. Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells. Steroids 1993 58(2) 64-8. 

Y1 Mouse adrenocortical tumor Adrenocortical cell Methyl sulfone metabolites of DDT and PCBs Inhibition of corticosterone synthesis by competitive inhibition of cytochrome P450... 

Figure 18.3. Endocrine-immune inter-relationship in depression. In depression, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated with a down-regulation of its negative feedback controls. Corticotrophin releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocortico-trophic hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.

ACTH stimulates the synthesis of steroids by the cells of the adrenal cortex. The steroidogenic action of ACTH is mediated primarily by the intracellular messenger cyclic AMP acting via cyclic AMP-dependent protein kinase. The evidence for this is that (i) ACTH stimulates cyclic AMP production in intact adrenocortical cells and in plasma membrane preparations (ii) cyclic AMP analogues added to adrenocortical cells stimulate steroidogenesis to the same extent as ACTH and (iii) mutant adrenocortical cells with defective cyclic AMP-dependent protein kinase lack stimulation of steroidogenesis by ACTH [2],... 

The short-term action of ACTH on the adrenocortical cell is the stimulation of the conversion of cholesterol to glucocorticoid, mineralocorticoid or androgen-precursor steroids (Fig. 2). The conversion of cholesterol to the end-product steroids involves two mitochondrial cytochrome P-450 enzymes, cytochrome P-450scc (cho-... 

The relative levels of the enzymes expressed by the individual adrenocortical cell determine the series of hydroxylation steps that occurs and the ultimate steroid that is produced. Thus, the rate of production of a given adrenocortical steroid is determined by the product of... 

ACTH is directly anti-mitogenic for adrenocortical cells, but indirectly stimulates the hypertrophy and hyperplasia of the adrenal cortex (reviewed in Ref. 29). Although the mechanism of the indirect stimulation of proliferation of adrenocortical cells by ACTH is not known it appears to be mediated by cyclic AMP [29], A plausible model for this indirect growth stimulation is that ACTH stimulates the growth... 

ACTH has several other effects on adrenocortical cell metabolism. It increases the synthesis of adrenocortical cell phospholipids this may also have a long-term supportive role for increased steroidogenic capacity. It increases the rate of glycolysis in the adrenocortical cell this may have a supportive role in the supply of pyruvate for the mitochondrial steroid hydroxylases [32],... 

Fig. 8. Known and potential interactions of the ACTH/adenylate cyclase/cyclic AMP-dependent protein kinase system in the adrenocortical cell with other hormones and intracellular messengers. Epinephrine activates adenylate cyclase in the adrenocortical cell [33]. Adrenocortical cells have receptors for several hormones which may activate G, including angiotensin II [34], acetylcholine [35], and endogenous opioid peptides [36]. Angiotensin II, acetylcholine and vasopressin [37-39] have all been demonstrated to activate the breakdown of PIP2 in adrenocortical cells and to stimulate steroidogenesis 5-hydroxytrypt-amine is also a known steroidogenic agent [40]. Probable receptor subtypes involved are indicated (/3 M (muscarinic) 5-HT, and V,). This is not a comprehensive diagramming of all stimuli or all possible interactions. Modified from Ref. 7.

However, it is clear that the calcium/calmodulin pathway can be activated by ACTH [54]. ACTH, like other steroidogenic hormones, increases the influx of calcium into the adrenocortical cell, probably by an action on voltage-sensitive calcium channels [41]. Because stimuli which act only to increase cyclic AMP, such as forskolin, do not enhance calcium influx, it is probable that to some extent the ACTH receptor is coupled to a calcium channel, with intermediacy of a G-protein, or may act by some other mechanism (for example, inactivation of a potassium channel [55]). 

Protein kinase C is present in the adrenocortical cell, and phorbol esters, which are potent activators of protein kinase C, stimulate adrenocortical steroidogenesis [62] and cell growth [63]. 

VLCFA accumulation has an adverse effect on membrane structure and function. For example, in cultured adrenocortical cells, the addition of C26 0 to the media results in increased microviscosity of the cell membrane and decreased secretion of cortisol after ACTH stimulation. Although similar studies have not been carried out in nerve cells, the effect of VLCFA on neural cell membranes may also result in the neurological manifestations of patients with X-ALD. 

Whitcomb RW, LinehanWM, Knazek RA. Effects of long-chain, saturated fatty acids on membrane microviscosity and adrenocorticotropin responsiveness of human adrenocortical cells in vitro. J Clin Invest 81 185-188,1988. 

Schioth et al. (1996) described the pharmacological distinction of the ACTH receptor from other melanocortin receptors in the mouse adrenocortical cell line Yl. Melanocortin receptors do not have a binding epitope for ACTH beyond the sequence of alpha-MSH (Schioth et al. 1997). 

Addison s disease results from reduction in glucocorticoid secretion, which maybe caused by infection or autoimmune disease. In the latter, proliferation of immunocytes against specific antibodies occurs because of a deficiency of immune suppresser cells in the adrenocortical cells. This causes chronic reduction in the levels of aldosterone and cortisol. Reduced aldosterone secretion decreases renal sodium and water reabsorption, leading to hypovolaemia and... 

ACTH is a 39-amino acids polypeptide hormone cleaved from a precursor peptide called pro-opiomelanocortin, which is released from corticotrope cells of the anterior pituitary gland. ACTH acts through the stimulation of cell surface ACTH receptors, which are primarily located on the adrenocortical cells, ft... 

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