Zonal expression of dickkopf-3 and components of the Wnt signalling pathways in the human adrenal cortex.
The mechanisms underlying the differentiation 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.
Suwa
T
T
Department of Physiology and Sam and Ann Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas 78245, USA.
Chen
M
M
Hawks
C L
CL
Hornsby
P J
PJ
D048868:Adaptor Proteins, Signal Transducing; D000302:Adrenal Cortex / Q000196:embryology* / Q000378:metabolism; D000328:Adult; D015152:Blotting, Northern / Q000379:methods; D018925:Chemokines; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D005260:Female; D051157:Frizzled Receptors; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009024:Morphogenesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D015383:Zona Fasciculata / Q000378:metabolism; D015384:Zona Glomerulosa / Q000378:metabolism; D015385:Zona Reticularis / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; C000606584:DVL3 protein, human; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; C000606585:Dvl3 protein, mouse; C489740:FZD1 protein, human; C489742:FZD2 protein, human; D051157:Frizzled Receptors; C489739:Fzd1 protein, mouse; C489743:Fzd2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C000606588:dsh protein, Drosophila; C432152:frizzled protein 4, Drosophila