Effect of Dexamethasone on Cell Population Kinetics in the Adrenal Cortex of the Prepubertal Male Rat

Wright, N. A.; Appleton, David R.; Morley, A. R.

doi:10.1677/joe.0.0620527

Cited by 32 publications

(13 citation statements)

References 18 publications

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“…In contrast to its suppressive effect in the outer fasciculata, dexamethasone treatment unmasked a proliferative response to unilateral adrenalectomy in glomerulosa cells. This observation differs from previous results showing that dexamethasone treatment decreases glomerulosa cell proliferation in rats (34,45). There are two possible explanations for this apparent inconsistency.…”

Section: Discussioncontrasting

confidence: 99%

“…Representative sections immunostained for P450aldo (red), P45011␤ (green), and Ki67 (blue) from adrenals collected at 2 days after rats were treated with saline (A) or dexamethasone (B), followed by ULA. Horizontal bar ϭ 100 m. tical cells to a single injection of dexamethasone; suppression of proliferation in the zona glomerulosa occurs during the initial 12-24 h (34, 45), followed by an increase in proliferation occurring from 48 to 72 h (45). In the present study, with assessment of proliferation at 48 h, the suppressive effect of dexamethasone on glomerulosa cells may have been missed.…”

Section: Discussionmentioning

confidence: 55%

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Zone-specific cell proliferation during compensatory adrenal growth in rats

Engeland¹,

Ennen²,

Elayaperumal³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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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...

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 55%

Zone-specific cell proliferation during compensatory adrenal growth in rats

Engeland¹,

Ennen²,

Elayaperumal³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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“…Our studies support both of the first two possibilities, but not the last. In other tissues, glucocorticoids have been shown to lengthen the cell cycle by increasing the duration of the G, phase, whereas the length of the S phase is unaffected [16,17,21,22,44], We have previously de monstrated that the mitotic index in the EGL and the labeling index in the proliferative zone of the EGL are depressed after HCA treatment [8,9], Taken together, these ob servations indicate that the cell cycle in the EGL may be lengthened relative to the length of the S phase accounting for a decreased rate of cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Cerebellar Granule Cell Genesis in the Hydrocortisone-Treated Rat

Bohn

Lauder

1980

Dev Neurosci

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The development of the cerebellar cortex was studied by quantitative light microscopic methods in rats treated with hydrocortisone on postnatal days 7–18. This treatment resulted in a decreased number of cells in the external granular layer (EGL) and an early disappearance of the EGL. In the adult cerebellum of these neonatally treated animals, the total number of granule cells in lobule VIII was decreased by 41% and that of molecular layer microneurons by 28%. Autoradiographic determinations of the ''birthdays'' (time of origin) of cerebellar microneurons showed that the peaks of cell formation in the internal granular and molecular layers occurred at earlier ages than in controls. In the granule cell population, this observation was the result of both decreased cell proliferation during the treatment and premature cessation of division in granule cell precursors in the EGL. The morphological effects of ''late'' hydrocortisone treatment on the cerebellum observed in this study are compared with those of ''early'' hydrocortisone treatment on days 1–4 and those of thyroid hormone from previous studies. It is suggested that endogenous levels of both thyroid and glucocorticoid hormones during the neonatal period may influence the rate of neurogenesis in the postnatal rat cerebellum.

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“…In all three zones of the cortex, ACTHR expression has been demonstrated in humans and rodents, although the expression level in each zone appears to vary among species (Xia & Wikberg 1996, Reincke et al 1998, Muller et al 2001. ACTH stimulates the synthesis and secretion of glucocorticoids, mineralocorticoids and adrenal androgen via ACTHR (Rosenfeld et al 1975, Kater et al 1989; it also induces the proliferation of adrenocortical cells (Wright et al 1974, Imai et al 1990). In clinical and animal studies, it has been established that circulating ACTH levels are positively correlated with the size of the adrenals, and that chronic hypersecretion of ACTH induces bilateral diffuse hyperplasia of adrenals (Bland et al 2003).…”

Section: Introductionmentioning

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

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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.

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Effect of Dexamethasone on Cell Population Kinetics in the Adrenal Cortex of the Prepubertal Male Rat

Cited by 32 publications

References 18 publications

Zone-specific cell proliferation during compensatory adrenal growth in rats

Zone-specific cell proliferation during compensatory adrenal growth in rats

Cerebellar Granule Cell Genesis in the Hydrocortisone-Treated Rat

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

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