Studies on Cytogenesis in Adult Rat Adrenal Cortex: Circadian and Zonal Variations and Their Modulation by Adrenocorticotropic Hormone

Miyamoto, Hirokuni; Mitani, Fumiko; Mukai, Kuniaki; Suematsu, Makoto; Ishimura, Yuzuru

doi:10.1093/oxfordjournals.jbchem.a022564

Cited by 30 publications

(30 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the abundant ACTHR expression was reported in the zona glomerulosa, it is likely that the mitogenic effect of ACTH is a direct action on the cells via ACTHR. It has been demonstrated that there exists a zone containing stem cells between the zona glomerulosa and zona fasciculata in adult rats, especially in Sprague-Dawley rats, which is called the zona intermedia or undifferentiated cell zone (Mitani et al 2003, Vinson 2003, and that cell proliferation in this zone is associated with the circadian rhythm of plasma ACTH levels (Miyamoto et al 1999). Our results are partially compatible with these reports, although the cell proliferation observed in our study is mainly in the zona glomerulosa, but is not confined to the specific zone.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of cyclin-dependent kinase inhibitors, p27Kip1 and p57Kip2, by corticotropin in rat adrenal cortex

Kobayashi¹,

Kambe²,

Imai³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

An important role for the cyclin-dependent kinase inhibitors (CDKIs), p27Kip1 and p57Kip2, in the proliferation and differentiation of adrenal cells has been suggested by their knockout mice, which display adrenal hyperplasia. Adrenal development and function are primarily regulated by ACTH. In the present study, we investigated the effects of ACTH on the expression of p27Kip1, p57Kip2 and proliferating cell nuclear antigen (PCNA) in rat adrenals. Male Wistar rats were treated with dexamethasone (Dex) to inhibit endogenous ACTH secretion. ACTH was then administered to the rats, and the adrenals were examined by Western blot and immunohistochemical analyses. Dex treatment induced shrinkage of adrenals where no PCNA-expressing cells were detected, but most of the cells expressed p27Kip1. Subsequent ACTH treatment resulted in the marked suppression of p27Kip1 expression, specifically in adrenocortical cells at 12 h after the stimulus. At 48 h, the p27Kip1 suppression still continued in the cortex, while the PCNA-expressing cells appeared mainly around the zona glomerulosa and increased at 72 h. At this time, the p27Kip1-expressing cells also appeared in the same zone. In contrast to p27Kip1, the expression of p57Kip2 was not detected in the Dex-treated adrenal. However, its expression was markedly induced by ACTH in the zona glomerulosa at 48 and 72 h. The results demonstrate that the primary site for mitogenic action of ACTH in rat adrenocortex is the zona glomerulosa, and that ACTH modulates proliferation of adrenocortical cells by regulating p27Kip1 and p57Kip2 expression in a time-and site-specific manner.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential expression of cyclin-dependent kinase inhibitors, p27Kip1 and p57Kip2, by corticotropin in rat adrenal cortex

Kobayashi¹,

Kambe²,

Imai³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…This observation supports previous work supporting a role for ACTH in the maintenance of adrenal cortical mass under nonstress conditions. For example, circadian increases in fasciculata cell proliferation that are preceded by increases in plasma ACTH can be blocked by dexamethasone (34), and adrenal atrophy produced by chronic dexamethasone treatment can be prevented (28,40) or reversed (29) by ACTH replacement. In contrast to its suppressive effect in the outer fasciculata, dexamethasone treatment unmasked a proliferative response to unilateral adrenalectomy in glomerulosa cells.…”

Section: Discussionmentioning

confidence: 99%

Zone-specific cell proliferation during compensatory adrenal growth in rats

Engeland¹,

Ennen²,

Elayaperumal³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Compensatory adrenal growth after unilateral adrenalectomy (ULA) leads to adrenocortical hyperplasia. Because zonal growth contributions are not clear, we characterized the phenotype of cortical cells that proliferate using immunofluorescence histochemistry and zone-specific cell counting. Rats underwent ULA, sham adrenalectomy (sham), or no surgery and were killed at 2 or 5 days. Adrenals were weighed and sections immunostained for Ki67 (proliferation), cytochrome P-450 aldosterone synthase (P450aldo, glomerulosa), and cytochrome P-450 11␤-hydroxylase (P45011␤, fasciculata). Unbiased stereology was used to count proliferating glomerulosa and fasciculata cells. Adrenal weight increased after ULA compared with sham and no surgery at both time points, and there was no difference between sham and no surgery. However, either ULA or sham increased Ki67-positive cells in the outer fasciculata at both time points compared with no surgery. Outer fasciculata-restricted proliferation is thus associated with adrenal weight gain in ULA but not sham. Experiment repetition using proliferating cell nuclear antigen and bromodeoxyuridine showed similar results. After ULA, adrenal DNA, RNA, and protein increased at both time points, whereas after sham, only adrenal DNA increased at 2 days. Compensatory growth thus results from hyperplasia and hypertrophy, whereas sham induces only a transient adrenal hyperplasia. Dexamethasone pretreatment prevented the increase in adrenal weight after ULA and blocked Ki67 labeling in the outer fasciculata but not zona glomerulosa in all groups. These results clearly show that the outer fasciculata is the primary adrenal zone responsible for compensatory growth, responding to steroid-suppressible stress signals that alone are ineffective in increasing adrenal mass. adrenal cortex; stress; zona fasciculata; zona glomerulosa; adrenal weight COMPENSATORY ADRENAL GROWTH after unilateral adrenalectomy is a well established model of adrenal growth in rodents. The increase in adrenal weight results from cell proliferation, as reflected by increases in adrenal DNA content (11,36). Although increases in weight are restricted to the adrenal cortex and not the medulla (10, 43), it is unclear which cortical zones are responsible for the growth response. Using [ 3 H]thymidine incorporation as an index of proliferation, Reiter and Pizzarello (38) reported increased in vivo labeling in the capsule, glomerulosa, and outer fasciculata after unilateral adrenalectomy in rats, with the largest response in the fasciculata. The finding of proliferation in the capsule and zona glomerulosa in rats after unilateral adrenalectomy is consistent with studies showing increased incorporation of [ 3 H]thymidine in vitro in adrenal capsule-glomerulosa tissue (2). After unilateral adrenalectomy in mice, labeling for proliferating cell nuclear antigen (PCNA) was increased in cells adjacent to the capsule, suggesting that glomerulosa cells were responsible for the growth response in this species (4). However, other studies have su...

show abstract

“…Although it is absolutely clear that CYP11B2 (aldosterone synthase) is located only in zona glomerulosa cells (Mitani et al 1994, Halder et al 1998, Peters et al 2007 and thus the glomerulosa is undeniably the source of secreted aldosterone, the other steroidogenic enzymes required for aldosterone synthesis are sparse at best in comparison (Vinson 2004), and in any case even in glomerulosa cells, only the outermost contain either CYP11B2 or even StAR (and then only following induction by nephrectomy or high potassium) (Peters et al 1998(Peters et al , 2006. The rest of the glomerulosa is enigmatic, though because of its lack of significant steroidogenic function it has been postulated to be a stem cell population for both glomerulosa and fasciculata cells (Mitani et al 1996, Miyamoto et al 1999, 2001). Here, proof has been elusive, since mitoses can occur throughout the gland (Wright 1971, Horiba et al 1987, McNicol & Duffy 1987, Clark et al 1992, Basile & Holzwarth 1993, Holzwarth 1995, Zieleniewski et al 1995, McEwan et al 1996, Ennen et al 2005, including in the immediate subcapsular region and in the capsule itself (McNeill et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Eph receptors and zonation in the rat adrenal cortex

Brennan¹,

Chittka²,

Barker³

et al. 2008

Journal of Endocrinology

View full text Add to dashboard Cite

Although the zonation of the adrenal cortex has a clear functional role, the mechanisms that maintain it remain largely conjectural. The concept that an outer proliferative layer gives rise to cells that migrate inwards, adopting sequentially the zona glomerulosa, fasciculata and reticularis phenotypes, has yet to be explained mechanistically. In other tissues, Eph receptor (EphR)/ephrin signalling provides a mechanism for cellular orientation and migration patterns. Real-time PCR and other methods were used to determine the possible role of Eph/ephrin systems in the rat adrenal. mRNA coding for several members of the EphR family was detected, but out of these, EphA2 provided the closest parallel to zonal organisation. In situ hybridisation showed that EphA2 mRNA and EphA protein were predominantly located in the zona glomerulosa. Its transcription closely reflected expected changes in the glomerulosa phenotype, thus it was increased after a low-sodium diet, but decreased by pretreatment with the angiotensin-converting enzyme inhibitor, captopril. It was also decreased by ACTH treatment, but unaffected by betamethasone. mRNA coding for ephrin A1, the major ligand for the EphA receptors, was also detected in the rat adrenal, though changes evoked by the various pretreatments did not clearly reflect the expected changes in zonal function. Because the maintenance of cellular zonation requires clear positional signals within the adrenal cortex, these data support a role for Eph forward and reverse signalling in the maintenance of adrenocortical zonation.

show abstract

Studies on Cytogenesis in Adult Rat Adrenal Cortex: Circadian and Zonal Variations and Their Modulation by Adrenocorticotropic Hormone

Cited by 30 publications

References 30 publications

Differential expression of cyclin-dependent kinase inhibitors, p27Kip1 and p57Kip2, by corticotropin in rat adrenal cortex

Differential expression of cyclin-dependent kinase inhibitors, p27Kip1 and p57Kip2, by corticotropin in rat adrenal cortex

Zone-specific cell proliferation during compensatory adrenal growth in rats

Eph receptors and zonation in the rat adrenal cortex

Contact Info

Product

Resources

About