Neuropeptide Y modulates the sensitivity of the rat adrenal cortex to stimulation by ACTH

Abstract Neuropeptide Y (NPY) has been identified in nerves supplying the adrenal cortex of several mammalian species, although its function in this tissue is unknown. The present studies, employing adrenocortical cells prepared by collagenase digestion, have shown that NPY, in the absence of other stimulants, has no effect on steroid secretion by the rat adrenal over a range of peptide concentrations (10−11 to 10 −6 mol/l). However, in the presence of physiological concentrations of ACTH, which are submaximal for the stimulation of aldosterone secretion, NPY (10−6 mol/l) significantly enhanced the secretion rate of aldosterone by rat zona glomerulosa cells in response to ACTH. This effect was specific to the rat zona glomerulosa as NPY had no effect on the response to ACTH in rat zona fasciculata cells. The effect of NPY appears to be biphasic, however, as NPY significantly attenuated the steroidogenic response to supramaximal ACTH concentrations: in rat zona glomerulosa cells the aldosterone response to 10 −8 mol ACTH/l was significantly inhibited by NPY. The effect of NPY on the ACTH response appeared to be mediated by changes in the cAMP response. NPY had no effect on the steroidogenic response to potassium ions (K+), but enhanced the response to angiotensin II. NPY (10 −6 mol/l) significantly stimulated inositol 1,4,5-trisphosphate (InsP3) production although this concentration of peptide had no effect on steroid secretion. The effects of NPY on InsP3 production were additive with those of angiotensin II. These results suggest that the role of NPY in the adrenal cortex may be to regulate the sensitivity of the zona glomerulosa to peptide stimulation. Journal of Endocrinology (1995) 145, 283–289

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The properties of adrenal zona glomerulosa cells after purification by gravitational sedimentation

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1974.0025 ◽

1974 ◽

Vol 185 (1081) ◽

pp. 375-407 ◽

Cited By ~ 39

Keyword(s):

Angiotensin Ii ◽

Cyclic Amp ◽

Microscopic Examination ◽

Zona Glomerulosa ◽

Maximal Response ◽

Zona Fasciculata ◽

Gravitational Sedimentation ◽

Rat Adrenals ◽

Glomerulosa Cells ◽

Zona Glomerulosa Cells

The densities of latex spheres and biological cells can be reliably determined from their sedimentation rate in an albumin gradient under unit gravitational force. The densities of zona glomerulosa and fasciculata cells of rat adrenals were found to be 1.072 ± 0.004 and 1.040 ± 0.001 respectively. Purified zona glomerulosa cells of rat adrenals can be prepared by gravitational sedimentation of dispersed cells from capsule strippings of the gland, which originally contain 3 to10% zona fasciculata contamination. Electron and phase microscopic examination of the sedimented glomerulosa cells and their steroidogenic response to ACTH and cyclic AMP indicate that they are reasonably free of contamination from zona fasciculata cells. Electron microscopic examination of the purified glomerulosa cells indicates that most of them are reasonably normal in structure. Their basal production of corticosterone is decreased after sedimentation. However, their maximal response of corticosterone output to serotonin and potassium and their response to all potassium concentrations is not significantly altered, indicating normal function for the cells producing steroids. Their maximal responses to ACTH, valine angiotensin II and cyclic AMP are decreased, but, at the doses used, steroidogenesis by the zona fasciculata contamination in the unfractionated preparation would be stimulated by these substances. Purified zona glomerulosa cells have about the same maximal response of corticosterone output (about twofold) to potassium, valine and isoleucine angiotensin II, serotonin and ACTH. The maximal response of the purified zona glomerulosa cells to cyclic AMP is similar to that elicited by valine and isoleucine angiotensin II, potassium, serotonin or ACTH. This indicates that if these stimuli act by increasing cyclic AMP output, then the maximal response of corticosterone output (about twofold) is defined by the limited response of the biosynthetic pathways to cyclic AMP.

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Long-term effects of ACTH combined with angiotensin II on steroidogenesis and adrenal zona glomerulosa morphology in the rat

Acta Endocrinologica ◽

10.1530/acta.0.1140047 ◽

1987 ◽

Vol 114 (1) ◽

pp. 47-54 ◽

Cited By ~ 5

Author(s):

Anne M. Riondel ◽

Piera Rebuffat ◽

Giuseppina Mazzochi ◽

Gastone G. Nussdorfer ◽

Rolf C. Gaillard ◽

...

Keyword(s):

Angiotensin Ii ◽

Morphological Changes ◽

Zona Glomerulosa ◽

Zona Fasciculata ◽

Homogeneous Population ◽

Long Term Treatment ◽

Acth Treatment ◽

Glomerulosa Cells ◽

Zona Glomerulosa Cells

Abstract. To test the hypothesis that the trophic action of angiotensin II on the adrenal zona glomerulosa may allow a sustained stimulation of aldosterone by ACTH by preventing the morphological changes of the zona glomerulosa cells into zona fasciculata-like elements we investigated the effects in rats of a 6-day treatment with ACTH (100 μg/kg/day) alone or combined with angiotensin II (300 ng/kg/day) on corticosterone and aldosterone production and adrenal morphology. The responsiveness of both steroids to an acute ACTH dose was also studied on the last day of long-term treatment. Morphologic data showed that prolonged ACTH treatment stimulated the growth of zona glomerulosa cells, though it transformed the tubulo-lamellar cristae of mitochondria into a homogeneous population of vesicles. Angiotensin II furthered the trophic effects of ACTH but prevented the mitochondrial transformation. Despite its ability to conserve the well differentiated aspect of the zona glomerulosa cells, the administration of angiotensin II was unable to prevent the fall in the secretion of aldosterone caused by chronic ACTH treatment and its subsequent unresponsiveness to ACTH stimulation.

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Effects of sodium depletion on the response of rat adrenal zona glomerulosa cells to stimulation by neuropeptides: actions of vasoactive intestinal peptide, enkephalin, substance P, neuropeptide Y and corticotrophin-releasing hormone

Journal of Endocrinology ◽

10.1677/joe.0.1460209 ◽

1995 ◽

Vol 146 (2) ◽

pp. 209-214 ◽

Cited By ~ 12

Author(s):

J P Hinson ◽

S Kapas

Keyword(s):

Angiotensin Ii ◽

Substance P ◽

Neuropeptide Y ◽

Vasoactive Intestinal Peptide ◽

Zona Glomerulosa ◽

Angiotensin Ii Receptors ◽

Sodium Depletion ◽

Aldosterone Secretion ◽

Glomerulosa Cells ◽

Zona Glomerulosa Cells

Abstract There are several neuropeptides, present in nerves supplying the rat adrenal zona glomerulosa, which have been shown to stimulate aldosterone secretion in the intact perfused rat adrenal preparation. The purpose of the present study was twofold: first, to determine whether these peptides acted directly on adrenocortical cells by examining their effects on collagenase-dispersed rat zona glomerulosa cells, and second, to investigate the likely physiological significance of these actions, by determining whether the responses of zona glomerulosa cells to neuropeptides were changed by prior sodium depletion. Of the peptides tested, neuropeptide Y (NPY) and substance P had only a minor effect on aldosterone secretion, which was not substantially affected by sodium depletion. Corticotrophin-releasing hormone (CRH) had a significant stimulatory effect on aldosterone secretion, but neither the threshold concentration for significant stimulation nor the maximal response to stimulation were altered by prior sodium depletion. Vasoactive intestinal peptide (VIP), on the other hand, had little effect on aldosterone secretion by cells from normal animals, but was a potent stimulus to aldosterone secretion in cells obtained from sodium-depleted animals. The response to the Met-enkephalin analogue, [d-Ala2-Met2]-enkephalinamide (DALA), was also significantly enhanced by prior sodium depletion. Experiments using the angiotensin II receptor blocker, saralasin, were carried out to determine whether the enhanced actions of DALA and VIP seen in sodium depletion may be a result of activation of angiotensin II receptors, known to be increased in sodium depletion. Saralasin did not affect the response to either peptide. These data suggest that all the peptides tested may be able to stimulate aldosterone secretion. However, the data obtained with substance P, NPY and CRH do not support a major role for these peptides in the regulation of aldosterone secretion either under control conditions, or in sodium depletion. The finding that the responses to VIP and DALA were altered by sodium depletion suggests that the actions of VIP and opioid peptides may have physiological significance in the regulation of aldosterone secretion in response to sodium depletion. Furthermore, the observation that saralasin does not inhibit the responses to these peptides strongly suggests that they are not acting through angiotensin II receptors, and may indicate altered VIP- and opioid-receptor regulation in sodium depletion. Journal of Endocrinology (1995) 146, 209–214

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LACK OF EFFECT OF ANGIOTENSIN ON LEVELS OF CYCLIC AMP IN ISOLATED ADRENAL ZONA GLOMERULOSA CELLS FROM THE RAT

Journal of Endocrinology ◽

10.1677/joe.0.0910145 ◽

1981 ◽

Vol 91 (1) ◽

pp. 145-154 ◽

Cited By ~ 25

Author(s):

J. B. G. BELL ◽

J. F. TAIT ◽

S. A. S. TAIT ◽

G. D. BARNES ◽

B. L. BROWN

Keyword(s):

Angiotensin Ii ◽

Bovine Serum Albumin ◽

Cyclic Amp ◽

Phosphodiesterase Inhibitor ◽

Zona Glomerulosa ◽

Zona Fasciculata ◽

Angiotensin Iii ◽

Independent Mechanism ◽

Glomerulosa Cells ◽

Zona Glomerulosa Cells

The effects of pure [Asp1, Val5]- and [Asn1, Val5]-angiotensin II and also [des-Asp1, Ile5]-angiotensin II (angiotensin III) on cyclic AMP and steroid outputs by dispersed rat capsular cells, comprising 95% zona glomerulosa and 5% zona fasciculata cells, have been studied. The results showed that [Asp1, Val5]- and [Asn1, Val5]-angiotensin II, at doses between 2·5 × 10−1 1 and 2 × 10−4 mol/l, which produced typical increases in steroidogenesis, failed to increase output of cyclic AMP. This lack of effect was observed whether the nucleotide was measured by radioimmunoassay or by adrenal binding protein and under the same conditions in which 8·4 mm-K+ consistently increased the output of cyclic AMP. Instead the results showed a small but significant decrease in cyclic AMP output with angiotensin II. Similar results were obtained with incubations for 60 rather than 120 min and with medium containing a concentration of 5 or 40 g bovine serum albumin/l. Although the levels of cyclic AMP were generally higher in the presence of the phosphodiesterase inhibitor, 3-isobutyl-l-methylxanthine, the same decrease relative to basal outputs was observed with angiotensin II which increased steroidogenesis. Angiotensin III also failed to increase output of cyclic AMP at doses (2·5×10−9 to 2·5×10−6 mol/l) which produced increases in steroid output equivalent to those obtained with angiotensin II. These results indicate that angiotensin II and III can act through a cyclic AMP- independent mechanism.

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The mechanism of the effect of K + on the steroidogenesis of rat zona glomerulosa cells of the adrenal cortex: role of cyclic AMP

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1986.0007 ◽

1986 ◽

Vol 227 (1246) ◽

pp. 21-42 ◽

Cited By ~ 17

Keyword(s):

Cyclic Amp ◽

Adrenal Cortex ◽

Zona Glomerulosa ◽

Free Concentration ◽

Mean Values ◽

Glomerulosa Cells ◽

Zona Glomerulosa Cells ◽

Stimulation Of

The effects of various concentrations of extracellular K + (3.6 - 13 mM) on the steroid (corticosterone and aldosterone) and cyclic AMP outputs of capsular cells (95% zona glomerulosa) of the rat adrenal cortex were studied at different concentrations of extracellular Ca 2+ . Small amounts of EGTA (50 μM) were added to reduce the free Ca 2+ concentrations effectively to zero at the lowest possible total Ca 2+ concentration. At a total extracellular concentration of 2.5 mM Ca 2+ , in 27 experiments the mean values of the steroid and cAMP outputs showed a maximum at 8.4 mM K + . The increase in steroid and cAMP outputs at 5.9, 8.4 and 13 mM K + compared with that at 3.6 mM were highly significant ( p < 0.01). The overall correlation of either corticosterone or aldosterone with cAMP outputs was also highly significant and was even better from 3.6 to 8.4 mM K + . Lowering the effective free concentration of Ca 2+ to zero decreased the steroid and cAMP outputs significantly at all K + concentrations, and no output was then significantly higher than at 3.6 mM. With the pooled data on outputs at all total Ca 2+ (2.5, 0.5, 0.25, 0.10, 0.05 and 0.0 mM) and K + (3.6, 5.9, 8.4 and 13 mM) concentrations, the correlation of either steroid with cAMP outputs was highly significant (but again optimally from 3.6 to 8.4 mM K + ). Nifedipine (10 -6 to 10 -4 M) was added to the incubations with the aim of specifically inhibiting Ca 2+ influx at total extracellular Ca 2+ concentrations of 2.5, 1.25 and 0.25 mM and with the usual K + concentrations. The cAMP outputs were reduced at all K + concentrations above 3.6 mM K + . The effect was highly significant at 10 -4 M nifedipine and a total Ca 2+ of 1.25 mM, which with the incubation conditions used, corresponds to the free Ca 2+ concentrations in vivo . These results indicate that cAMP plays a significant role in the stimulation of steroid output by K + particularly between 3.6 and 8.4 mM K + . In this range of K + concentrations the stimulation of cAMP seems to be controlled by increases in Ca 2+ influx. The correlation of steroid and cAMP output at the higher K + concentrations (between 8.4 and 13 mM K) and at the various total Ca 2+ concentrations is less significant. Also, with all concentrations of added nifedipine there is an ‘anomalous’ increase in steroid output at 13 mM K + and at total Ca 2+ concentrations of 2.5 and 1.25 mM. However, at the same K + concentrations and at 0.25 mM Ca 2+ , nifedipine decreases steroid outputs. Our previous data, obtained after addition of maximally effective amounts of cAMP, indicated that there were also non-cAMP mechanisms involved in the stimulation of steroidogenesis by K + in z. g. cells. The present data confirm this conclusion, particularly at K + concentrations above 8.4 mM. They also indicate that at these higher K + concentrations, by non-cAMP mechanisms increasing intracellular Ca 2+ concentrations probably inhibit steroidogenesis. We conclude, however, that in the physiological range of K + concentrations, the role of cAMP in zona glomerulosa cells is at least comparable in importance to that of non-cAMP mechanisms.

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Long-term trophic action of α-melanocyte-stimulating hormone on the zona glomerulosa of the rat adrenal cortex

Acta Endocrinologica ◽

10.1530/acta.0.1120404 ◽

1986 ◽

Vol 112 (3) ◽

pp. 404-408 ◽

Cited By ~ 17

Author(s):

Claudia Robba ◽

Piera Rebuffat ◽

Giuseppina Mazzocchi ◽

Gastone G. Nussdorfer

Keyword(s):

Plasma Level ◽

Adrenal Cortex ◽

Zona Glomerulosa ◽

Zona Fasciculata ◽

Short Term ◽

Melanocyte Stimulating Hormone ◽

Glomerulosa Cells ◽

Zona Glomerulosa Cells ◽

Stimulating Hormone

Abstract. The effects of α-melanocyte-stimulating hormone (α-MSH) on the rat adrenal cortex were investigated by coupled morphometric and radioimmunological techniques. Short-term α-MSH administration provoked a significant increase in the aldosterone plasma level along with a notable lipid droplet depletion in zona glomerulosa cells. Long-term α-MSH treatment induced a notable hypertrophy of zona glomerulosa cells and a further rise in the blood concentration of aldosterone. α-MSH did not affect zona fasciculata morphology and corticosterone plasma level. The possibility is discussed that α-MSH may be specifically involved in the control of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

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