Glomerulosa cells

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. 

I Kojima, H Shibata, E Ogata. (1986). Pertussis toxin blocks angiotensin II-induced calcium influx but not inositol trisphosphate production in adrenal glomerulosa cell. FEBS Lett 204 347-351. 

Angiotensin II stimulates aldosterone synthesis and secretion from the glomerulosa cells of the adrenal cortex. The aldosterone secretion induced by angiotensin II in humans is not accompanied by an increase in glucocorticoid plasma levels. Chronic administration of angiotensin II will maintain elevated aldosterone secretion for several days to weeks unless hypokalemia ensues. 

Balia, T. Hunyadi, L. Baukal, A.J. Catt, K.J. Structures and metabolism of inositol tetrakisphosphates and inositol pentakisphosphate in bovine adrenal glomerulosa cells. J. Biol. Chem., 264, 9386-9390 (1989)... 

Possibly relevant to the natriuretic activity of SK F 38393 is emerging evidence that dopamine may be a physiological regulator of aldosterone synthesis (28). Dopamine receptors in a particulate fraction of calf adrenal glomerulosa cells have been shown to bind 3H-2-amino-1,2,3,4-tetrahydro-6,7-dihydroxynaptha-lene (3H-ADTN) in a specific (displaceable by 10 pM dopamine) saturable manner (29) (Kj, 0.29 mM maximal binding capacity,... 

The 5-HT7 receptors also are expressed in the periphery, where their best characterized function is to mediate relaxation of vascular smooth muscle (397). In particular, 5-HT7 receptors are expressed throughout the gut (398) and stomach (399), as well as in vasculature (400,401). 5-HT7 receptors are also expressed in adrenal glomerulosa cells (402,403) and corneal epithelial cells (404). In the adrenal gland, 5-HT7 receptors stimulate the release of aldosterone from adrenal glomerulosa cells (402,403) by increasing cAMP levels. 

Lenglet S, Delarue C, Lefebvre H, Vaudry H, Contesse V. Rat glomerulosa cells express functional 5-HT7 receptors. Endocr Res 2000 26 597-602. 

Lenglet S, Louiset E, Delarue C, Vaudry H, Contesse V. Involvement of T-type calcium channels in the mechanism of action of 5-HT in rat glomerulosa cells a novel signaling pathway for the 5-HT7 receptor. Endocr Res 2002 28 651-655. 

Yet, experiments on changes in intracellular Ca2+ levels in adrenal glomerulosa cells exposed to ACTH or Ang II strongly suggest that hormone receptors may also stimulate Ca2+ channels, and that regulation may be directly by a G protein (Gs ). Glomerulosa cells respond to both hormones by secreting aldosterone. However,... 

Thus, the possibility exists that Ca2+ channels are under dual control by stimulatory and inhibitory G proteins, as well as dual control by protein kinases. However, other explanations may apply. There may be more than one type of ACTH receptors on glomerulosa cells, one activating Gs, the other affecting Ca2+ channels activity by means independent of a G protein, such as activation of phospholipase A2 activity and/or formation of cGMP. Future research in this area should clarify this question. 

An increase in the extracellular K+ concentration from 2 to 8 mM (the limits of the physiological range) leads to a 4-5-fold increase in the rate of aldosterone secretion by the adrenal glomerulosa cell [24,25]. This increase in [K+] leads to a depolarization of the plasma membrane of the cell. This depolarization causes the opening of two types of voltage-dependent Ca2+ channel in this membrane, and thus to a 4-fold increase in the rate of Ca2+ influx. The total cell calcium and the [Ca2+]j both... 

The integrated cellular response of the adrenal glomerulosa cell is determined by the activities of three different protein kinases cAMP-dependent protein kinase, CaM-dependent protein kinases, and C-kinase. A sustained response can be produced by the combined activation either of the cAMP- and CaM-dependent kinases, or of the CaM-dependent kinases and C-kinase. Activation of each type of... 

Fig. 9. The interaction of ACTH with the cyclic AMP and calcium intracellular messenger systems in the regulation of steroidogenesis in the adrenocortical zona glomerulosa cell comparison with angiotensin II and potassium. ACTH activates both adenylate cyclase and calcium influx, here shown as involving two receptor subtypes (R, and R2) although such receptor subtypes have not been identified. The A-kinase and calmodulin systems produce individual responses of characteristic amplitudes and time-courses, which combine to give the observed response of the intact cell. The sequence of events for ACTH is compared to those for the other two major stimuli of steroidogenesis in the zona glomerulosa cell, angiotensin II and potassium. From Ref. 41.

Calcium, via calmodulin, also activates cyclic AMP phosphodiesterases which inactivate cyclic AMP by metabolism to AMP. Inhibition of phosphodiesterase yields a small increase in ACTH-stimulated steroidogenesis [2], This is relatively slight in the adrenocortical zona fasciculata-reticularis cell, which has a low phosphodiesterase level the zona glomerulosa cell has a higher activity [60,61], which may result from higher level of activation of the calcium/calmodulin intracellular messenger system in the zona glomerulosa. 

In the adrenal the All-regulated calcium uptake pathway has been extensively characterized. All-induced calcium influx into glomerulosa cells is dependent on the concentration of extracellular potassium within the range 2 to 8 mM and with a threshold value of 2 mM [47], Because glomerulosa cells are exquisitely sensitive... 

This shift in the substrate specificity of phospholipase C may persist for some time after the removal of agonist and may contribute to the phenomenon of cellular memory in the adrenal. When glomerulosa cells are sequentially exposed to All (20 minutes)-, no agonist (10 minutes), and again All, the character of the response elicited by the second addition of All differs dramatically from that elicited by the first the cell seems to remember its prior exposure to All [29], Although this second addition of All induces a smaller calcium transient, the rate of aldosterone secretion increases more rapidly and reaches a higher plateau value than is seen in response to the first exposure to the hormone. This result suggests either that the second addition of All elicits a smaller increase in 1,4,5-IP3 as a result of an altered... 

Drolet P, Bilodeau L, Chorvatova A, Laflamme L, Gallo-Payet N, Payet MD (1997) Inhibition of the T-type Ca2+ current by the dopamine Dl receptor in rat adrenal glomerulosa cells requirement of the combined action of the G betagamma protein subunit and cyclic adenosine 3, 5 - monophosphate. Mol Endocrinol 11 503-514. 

The release of IP3 from lipids of the plasma membrane is illustrated here by a study involving adrenal glomerulosa cells. Angiotensin was added to the cells at 0 seconds (Figure 10.43). Samples of cells were collected at the indicated times and immediately mixed with acid to halt further metabolism the soluble metabolites were then analyzed- Ihc data illustrate an increase in free intracellular IPS immediately after addition of the hormone. 

FIGURE 10.5 Results of a study on rat zona glomerulosa cells. The effect of angiotensin n was measured as the amount of aldosterone released into the medium by the cells. (Redrawn with permission from Braley et al, 1989.)... 

The release of Ca from the endoplasmic reticulum and into the cytoplasm is illustrated in another study of adrenal glomerulosa cells. The cells were incubated... 

FIGURE 10.43 Adrenal glomerulosa cells were incubated in a medium of salts and other nutrients. Inositol was added to the medium. The inositol was radioactive to allow the researcher to determine if metabolism resulted in its incorporation into phospholipids or its modification by phosphorylation. Incubation of [ H]inositol with the cells resulted in its incorporation as phosphatidylpH]inositol diphosphate pH is called tritium). (Redrawn with permission from Balia et al, 1988.)... 

Balia, T., Baukal, A. J., Guillemette, G., and Catt, K. J. (1988). Multiple pathways of inositol polyphosphate metabolism in angiotensin-stimidated adrenal glomerulosa cells. /. Biol. Chem. 263,4083-4091. 

Connor, J. A., Cornwall, M. C., and Williams, G. H. (1987). Spatially resolved qrtosolic calcium response to angiotensin II and potassium in rat glomerulosa cells measured by digital imaging techniques. /. Biol. Chem. 262,2919-2927. 

Lang, U., and Vallotton, M. B. (1987). Angiotensin II but not potassium induces subcellular redistribution of protein kinase C in bovine adrenal glomerulosa cells. /. Biol. Chem. 262, 8047-8050. 

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