Zonal Differentiation in the Rat Adrenal Cortex

Whitworth, E; Vinson, Gavin P.

doi:10.3109/07435800009048625

Cited by 7 publications

(4 citation statements)

References 5 publications

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“…Patterns of expression of the DKK3 gene suggest that it could be a morphogen in the adrenal cortex. Previous studies of differences in gene expression among the zones have yielded information on receptors, signal transduction mechanisms, and steroid biosynthetic enzymes, but have so far not yielded clues as to the underlying mechanisms of zonal differentiation (Wolkersdorfer & Bornstein 1998, Mitani et al 1999, Rainey 1999, Whitworth & Vinson 2000, Alesci & Bornstein 2001. In the present experiments we found that the DKK3 gene was expressed in the ZG at a higher level than in the ZF and ZR.…”

Section: Discussionsupporting

confidence: 68%

“…At various times in the past they have been thought of as entirely separate cell types, sustained by proliferation within each zone, but currently it is generally thought that the three zones of the cortex represent forms of differentiation of a single cell type (Wolkersdorfer & Bornstein 1998, Mitani et al 1999, Rainey 1999, Whitworth & Vinson 2000, Alesci & Bornstein 2001. However, questions of the nature of stem cells within the adrenal cortex, if they exist, have not yet been resolved (Hornsby 2001).…”

Section: Introductionmentioning

confidence: 99%

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Zonal expression of dickkopf-3 and components of the Wnt signalling pathways in the human adrenal cortex

Suwa¹,

Chen²,

Hawks³

et al. 2003

Journal of Endocrinology

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The mechanisms underlying the differentation of the adrenal cortex into zones are unclear. Microarray studies on RNA from microdissected zona reticularis (ZR) and zona fasciculata/zona glomerulosa (ZF/ZG) derived from adult human adrenal glands showed that a gene of the dickkopf family (DKK), DKK3, is differentially expressed in the zones. The Dickkopf proteins are morphogens involved in Wnt signalling. Northern blotting showed higher DKK3 transcript levels in ZF/ZG than ZR samples. In situ hybridization on adult human adrenal gland sections showed that DKK3 expression was much higher in the ZG than in the ZF or ZR. DKK3 expression was also higher in the medulla. We screened for expression of other members of the DKK family and the related Wingless-type mouse mammary tumor virus integration site gene family (WNT), frizzled (FZD), and dishevelled (DVL) gene families. Among dickkopf family members, only DKK3 was expressed at a detectable level in both human and mouse adrenocortical RNA samples. Consistent with previously published data on the effects of Wnt4 gene disruption in the mouse, we found only WNT4 expression within the WNT family in both human and mouse RNA. Northern blotting showed that WNT4 was expressed at a higher level in ZF/ZG cells than in ZR. The higher level of DKK3 and WNT4 expression in ZF/ZG cells was confirmed by real-time PCR. In the frizzled and dishevelled families we found FZD1, FZD2 and DVL3 transcripts in human adrenocortical RNA, and FZD2 and DVL3 in mouse adrenocortical RNA. These data show that a variety of genes of the Wnt signalling pathways are expressed in the adrenal cortex. The zonal distribution of DKK3 expression suggests that it could be involved in zonal differentiation or growth.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Zonal expression of dickkopf-3 and components of the Wnt signalling pathways in the human adrenal cortex

Suwa¹,

Chen²,

Hawks³

et al. 2003

Journal of Endocrinology

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“…Both of these are much more abundant in the inner zones (of the mouse and rat adrenal, respectively) Raza and Vinson, 2000) than in the glomerulosa, again consistent with the view that there is relatively little P450 activity in the glomerulosa and that it is probably only a poor de novo source of steroid. Roskelley and Auersperg, 1990;Halder et al, 1998;Mitani et al, 1999 CYP11B1 Ϫ ϩϩϩ Mitani et al, 1999;Ho and Vinson, 1993a;Halder et al, 1998CYP11B2 ϩ Ϫ Mitani et al, 1999Peters et al, 1998;Halder et al, 1998 CYP21 No Yamaguchi et al, 1990;Oda et al, 1991;Husain et al, 1987;Mulrow, 1992b;Shier et al, 1989;Vinson and Ho, 1998b Signalling MAPK: Vinson et al, 2000;Vinson, 2000 c-fos Lehoux et al, 1998;Raza et al, 1998;Vinson et al, 1998c-jun Lehoux et al, 1998Raza et al, 1998;Vinson et al, 1998 Halder et al, 1998;Whitworth and Vinson, 2000;Raza et al, 1998 Distinctions between the steroidogenic activities of fasciculata and reticularis in the rat are less clear. As in other species, including the human, the range of steroid products is essentially the same, although the response to ACTH stimulation is less, and it may be for this reason that overall steroid output appears significantly lower.…”

Section: Functional Zonation In the Rat Adrenal Cortexmentioning

confidence: 99%

Adrenocortical zonation and ACTH

Vinson¹

2003

Microscopy Res & Technique

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The clear morphological distinction between the cells of the different adrenocortical zones has attracted speculation and experiment to interpret their functions and the ways in which they are regulated. Considerable data have been produced in recent years that has benefited a fuller understanding of the processes of steroidogenesis and of cell proliferation at the molecular level. This now enables the reexamination of earlier concepts. It is evident that there is considerable species variation, and this article, dealing mainly with the rat, reaches conclusions that do not necessarily apply to other mammals. In the rat adrenal, however, the evidence suggests that the greatest differences between the functions of the zones are between the glomerulosa and the fasciculata. Here the sometimes all-or-nothing demarcation in their complement of components associated with steroidogenesis or with cell proliferation suggests a stark division of labor. In this model the fasciculata is the main engine of steroid hormone output and the glomerulosa is the site of cell proliferation, recruitment, and differentiation. Regulating these functions are angiotensin II and other paracrine components that modulate and maintain the glomerulosa, and ACTH, that maintains the fasciculata, and recruits new fasciculata cells by transformation of proliferating glomerulosa cells. Grafted onto this mostly vegetative function of the glomerulosa is CYP11B2, limited to just a fraction of the outer glomerulosa in rats on a normal laboratory diet and generating aldosterone (and 18-hydroxycorticosterone) from precursors whose origin is not, from the evidence summarized here, very clear, but may include the fasciculata, directly or indirectly. The biosynthesis of aldosterone in the rat certainly requires reinterpretation.

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“…The zona reticularis participates in androgen production, except in rodents (8 -11). In addition, the adrenal medulla secretes catecholamines into the bloodstream (8,10).…”

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confidence: 99%

The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats

et al. 2016

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Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.

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Zonal Differentiation in the Rat Adrenal Cortex

Cited by 7 publications

References 5 publications

Zonal expression of dickkopf-3 and components of the Wnt signalling pathways in the human adrenal cortex

Zonal expression of dickkopf-3 and components of the Wnt signalling pathways in the human adrenal cortex

Adrenocortical zonation and ACTH

The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats

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