Changes in the glomerulosa cell phenotype during adrenal regeneration in rats

1999 ◽  
Vol 276 (5) ◽  
pp. R1374-R1382 ◽  
Author(s):  
W. C. Engeland ◽  
B. K. Levay-Young

In situ hybridization was used to examine cellular differentiation during rat adrenal regeneration, defining zona glomerulosa [cytochrome P-450 aldosterone synthase ( P-450aldo) mRNA positive], zona fasciculata [cytochrome P-450 11β-hydroxylase ( P-45011β) mRNA positive], or zona intermedia [negative for both but 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA positive]. After unilateral adrenal enucleation with contralateral adrenalectomy (ULE/ULA), the expression of all mRNA was reduced at 2 days. From 5 to 10 days, P-45011β and 3β-HSD mRNA increased while P-450aldo remained low; at 20 days, all mRNA were increased. From 2 to 10 days, cells adjacent to the capsule showed intermedia cell differentiation; by 20 days, the subcapsular glomerulosa cells reappeared. This suggests that after enucleation the glomerulosa dedifferentiates to zona intermedia. The experiment was repeated in rats where the postenucleation ACTH rise was prevented. Rats underwent ULE with sham ULA (ULE/SULA) or ULE/SULA with ACTH treatment. Adrenals from ULE/SULA rats expressed increased P-450aldo mRNA at 10 days and reduced P-45011β mRNA and adrenal weight at 30 days. ACTH treatment reversed the pattern toward that seen in ULE/ULA. These findings show that the enucleation-induced dedifferentitation of the glomerulosa cell may result in part from elevated plasma ACTH and that prevention of dedifferentiation may result in impaired regeneration.

1987 ◽  
Vol 114 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Anne M. Riondel ◽  
Piera Rebuffat ◽  
Giuseppina Mazzochi ◽  
Gastone G. Nussdorfer ◽  
Rolf C. Gaillard ◽  
...  

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.


Endocrinology ◽  
1998 ◽  
Vol 139 (10) ◽  
pp. 4397-4403 ◽  
Author(s):  
Cheryl Wotus ◽  
Brett K. Levay-Young ◽  
Lisa M. Rogers ◽  
Celso E. Gomez-Sanchez ◽  
William C. Engeland

Abstract The adult rat adrenal cortex is comprised of three concentric steroidogenic zones that are morphologically and functionally distinguishable: the zona glomerulosa, zona intermedia, and the zona fasciculata/reticularis. Expression of the zone-specific steroidogenic enzymes, cytochrome P450 aldosterone synthase (P450aldo), and P450 11β hydroxylase (P45011β), produced by the zona glomerulosa and zona fasciculata/reticularis, respectively, can be used to define the adrenal cortical cell phenotype of these two zones. In this study, immunohistochemistry and in situ hybridization were used to determine the ontogeny of expression of P450aldo and P45011β to monitor the pattern of development of the rat adrenal cortex. RIA was used to measure adrenal content of aldosterone and corticosterone, the resulting products of the two enzymatic pathways. Double immunofluorescent staining for both enzymes at gestational day 16 (E16) showed P45011β protein expressed in cells distributed throughout most of the adrenal intermixed with a separate, but smaller, population of cells expressing P450aldo protein. Whereas expression of P45011β protein retained a similar pattern of distribution from E16 to adulthood (ignoring distribution of SA-1 positive, presumptive medullary cells), P450aldo protein changed its pattern of distribution by E19, becoming localized in a discontinuous ring of cells adjacent to the capsule. By postnatal day 1, P450aldo protein distribution was similar to that observed in adult glands; P450aldo-positive cells formed a continuous zone underlying the capsule. In situ hybridization showed that the pattern of P45011β messenger RNA expression paralleled protein expression at all times, whereas P450aldo messenger RNA paralleled protein at E19 and after, but was undetectable before E19. However, adrenal aldosterone and corticosterone, as measured by RIA, were detected by E16, supporting the functional capacity of both phenotypes for all ages studied. These data suggest that the development of the adrenal zona glomerulosa occurs in two distinct phases; initial expression of the glomerulosa phenotype in scattered cells of the inner cortex before E17, followed by a change in distribution to the outer cortex between E17 and E19. It is hypothesized that this change in distribution occurs via cell differentiation, rather than cell migration, and that a possible regulator of these events is the fetal renin-angiotensin system.


2001 ◽  
Vol 280 (2) ◽  
pp. C265-C272 ◽  
Author(s):  
Andrew D. Schrier ◽  
Hongge Wang ◽  
Edmund M. Talley ◽  
Edward Perez-Reyes ◽  
Paula Q. Barrett

The low voltage-activated (T-type) Ca2+ channel has been implicated in the regulation of aldosterone secretion from the adrenal zona glomerulosa by extracellular K+ levels, angiotensin II, and ACTH. However, the identity of the specific subtype mediating this regulation has not been determined. We utilized in situ hybridization to examine the distribution of three newly cloned members of the T-type Ca2+ channel family, α1G, α1H, and α1I, in the rat and bovine adrenal gland. Substantial expression of only the mRNA transcript for the α1H-subunit was detected in the zona glomerulosa of both rat and bovine. A much weaker expression signal was detected for the α1H transcript in the zona fasciculata of bovine. Whole cell recordings of isolated bovine adrenal zona glomerulosa cells showed the native low voltage-activated current to be inhibited by NiCl2 with an IC50 of 6.4 ± 0.2 μM. Because the α1H subtype exhibits similar NiCl2 sensitivity, we propose that the α1Hsubtype is the predominant T-type Ca2+ channel present in the adrenal zona glomerulosa.


1974 ◽  
Vol 185 (1081) ◽  
pp. 375-407 ◽  

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.


1986 ◽  
Vol 109 (3) ◽  
pp. 351-NP ◽  
Author(s):  
F. W. Chu ◽  
P. J. Hyatt

ABSTRACT Percoll density gradient centrifugation is a simple, inexpensive and convenient method to eliminate contaminating zona fasciculata (ZF) cells from unpurified rat adrenal capsular glomerulosa (ZG) cell preparations (with less than 0·1% ZF cells in the final cell preparation). Basal steroid (aldosterone and corticosterone) output by the purified (PG) cells was unchanged. These purified cells, although free from ZF contamination, were more highly responsive than expected to ACTH (3 nmol/l). When PG cells were further separated by Sephadex column filtration, the filtered PG cells exhibited the steroidogenic response of ZG cells purified by unit gravity sedimentation and Sephadex column filtration, i.e. reduced basal steroid output and an ACTH response reduced to that stimulated by K+ (8·4 mmol/l). Although the cells retained in the column resembled the filtered PG cells ultrastructurally, they showed unchanged basal steroid output and a high ACTH response with increased latepathway activity (the conversion of corticosterone to aldosterone). By combining Percoll density gradient centrifugation and Sephadex column filtration we have a method for the isolation and study of both the high-and low-response rat ZG cells which are free from ZF contamination. J. Endocr. (1986) 109, 351–358


1996 ◽  
Vol 271 (3) ◽  
pp. F709-F716 ◽  
Author(s):  
D. Z. Wang ◽  
Q. Song ◽  
L. M. Chen ◽  
L. Chao ◽  
J. Chao

The tissue kallikrein-kinin system has been implicated in regulating blood pressure and electrolyte homeostasis. To understand the function of this system, we identified the expression and cellular localization of its components including tissue kallikrein, kallistatin, kininogen, and bradykinin B1 and B2 receptors in human adrenal gland. Reverse transcription-polymerase chain reaction followed by Southern blot analysis showed that these five components of this system were all expressed in human adrenal gland. In situ hybridization histochemistry with respective digoxigenin-labeled antisense riboprobes revealed localization of kallikrein transcript throughout the adrenal cortex and medulla except the zona glomerulosa, whereas kallistatin mRNA was only localized in the zona fasciculata. Low-molecular-weight kininogen and B2 receptor mRNAs were colocalized in the zona glomerulosa and zona fasciculata and also in the zona reticularis and chromaffin cells but to a lesser degree. The B1 receptor mRNA was stained in the zona fasciculata and medulla. These results show the expression and differential colocalization of the components of the tissue kallikrein-kinin system and reveal the potential action sites of this system in the adrenal gland.


2019 ◽  
Vol 104 (11) ◽  
pp. 5642-5650 ◽  
Author(s):  
Keisuke Nonaka ◽  
Junko Aida ◽  
Kaiyo Takubo ◽  
Yuto Yamazaki ◽  
Shoichiro Takakuma ◽  
...  

Abstract Context Adrenocortical zonation is associated with a markedly complex developmental process, and the pathogenesis and/or etiology of many disorders of adrenocortical zonal development have remained unknown. Cells from the three adrenocortical zones are morphologically and functionally differentiated, and the mature stage of cell development or senescence has been recently reported to be correlated with telomere length. However, the telomere length of each adrenocortical zonal cell has not yet been studied in human adrenal glands. Objective We aimed to study the telomere lengths of adrenocortical parenchymal cells from three different zones of the adrenal glands present during childhood, adolescence, and adulthood. Methods Adrenal glands of 30 autopsied subjects, aged between 0 and 68 years, were retrieved from pathology files. The normalized telomere to centromere ratio (NTCR), an index of telomere length, was determined in the parenchymal cells of the zona glomerulosa, zona fasciculata, and zona reticularis (ZR), using quantitative fluorescence in situ hybridization. Results NTCR of ZR cells was the longest, followed in decreasing order by that of zona glomerulosa and zona fasciculata cells in subjects aged 20 to 68 years, but no substantial differences in NTCR were detected among these three zones in the group <20 years of age. NTCR of ZR increased with age in subjects aged 20 to 68 years, whereas no important age-dependent changes in NTCR were detected in the group <20 years of age. Conclusion The telomere lengths for three zones in adrenal cortex were correlated with their differentiation in adulthood but not in childhood and adolescence.


1954 ◽  
Vol 10 (3) ◽  
pp. 266-NP ◽  
Author(s):  
I. CHESTER JONES ◽  
A. WRIGHT

SUMMARY The adrenal of male and female rats with persistent diabetes insipidus showed a prominent zona fasciculata and zona reticularis. The zona glomerulosa was narrow or absent. The results from this and the preceding three papers are here reviewed together. It is concluded that control of salt-electrolyte metabolism cannot be ascribed to the zona glomerulosa. It is probable that the zona fasciculata is reponsible for most of the adrenocortical secretions. The zona glomerulosa is a vegetative back-water of cells, which is able to produce minimal amounts of adrenocortical secretions without stimulation by pituitary hormones, but is only of significance when the latter are absent. Rising amounts of circulating adrenocorticotrophic hormone (ACTH) can transform the zona glomerulosa into actively secreting cells of the zona fasciculata type. After cessation of such activity the zona glomerulosa re-forms, as the amount of ACTH will maintain only a certain volume of zona fasciculata (and zona reticularis) against the rigid limiting inner circumference formed by the medulla; some of the cells derived from the chief area of cell division in the outer part of the zona fasciculata do not mature to cells of the zona fasciculata type, but form zona glomerulosa cells. It is thought that cell migration occurs from the cells of the outer region of the zona fasciculata to the zona reticularis and that this is, normally, a slow process.


1982 ◽  
Vol 101 (3) ◽  
pp. 436-441 ◽  
Author(s):  
Karl-Eric Karlmar

Abstract. The individual steps in the formation of aldosterone and cortisol from cholesterol were assayed in different subcellular preparations from the inner and outer zones of bovine adrenal cortex. In zona glomerulosa the 11β-, 18- and 21-hydroxylase activities were relatively high, whereas the 17α-hydroxylase activity was relatively low. Cholesterol side-chain cleavage and 3β-hydroxysteroid-Δ5-oxidoreductase activity were similar in zona glomerulosa and zona fasciculata-reticularis. The differences were however only quantitative. In no case one specific fraction was totally devoid of enzyme activity. The total content of mitochondrial cytochrome P-450 was relatively high in zona fasciculata-reticularis whereas the content of microsomal cytochrome P-450 was similar in the two fractions. In view of the relatively small differences observed, it seems likely that other factors than distribution of the above enzymes are of major importance for the specific production of gluco- and mineralocorticoids in the two layers.


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