New Insights in the Functional Zonation of the Canine Adrenal Cortex

K. Sanders, J. A. Mol, H. S. Kooistra, A. Slob, S. Galac

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Samenvatting

Background: Current understanding of adrenal steroidogenesis is that the production of aldosterone or cortisol depends on the expression of aldosterone synthase (CYP11B2) and 11β-hydroxylase cytochrome P450 (CYP11B1), respectively. However, this has never been studied in dogs, and in some species, a single CYP11B catalyzes both cortisol and aldosterone formation. Analysis of the canine genome provides data of a single CYP11B gene which is called CYP11B2, and a large sequence gap exists near the so-called CYP11B2 gene. Objectives: To investigate the zonal expression of steroidogenic enzymes in the canine adrenal cortex and to determine whether dogs have 1 or multiple CYP11B genes. Animals: Normal adrenal glands from 10 healthy dogs. Methods: Zona fasciculata (zF) and zona glomerulosa (zG) tissue was isolated by laser microdissection. The mRNA expression of steroidogenic enzymes and their major regulators was studied with RT-qPCR. Southern blot was performed to determine whether the sequence gap contains a CYP11B gene copy. Immunohistochemistry (IHC) was performed for 17α-hydroxylase/17,20-lyase (CYP17). Results: Equal expression (P = .62) of the so-called CYP11B2 gene was found in the zG and zF. Southern blot revealed a single gene. CYP17 expression (P = .05) was significantly higher in the zF compared with the zG, which was confirmed with IHC. Conclusions and Clinical Importance: We conclude that there is only 1 CYP11B gene in canine adrenals. The zone-specific production of aldosterone and cortisol is probably due to zone-specific CYP17 expression, which makes it an attractive target for selective inhibition of cortisol synthesis without affecting mineralocorticoid production in the zG.
Originele taal-2Nederlands
Pagina's (van-tot)741-750
Aantal pagina's10
TijdschriftJournal of Veterinary Internal Medicine
Volume30
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - 1 mei 2016
Extern gepubliceerdJa

Trefwoorden

  • CYP11B1
  • CYP11B2
  • CYP17
  • Steroidogenesis

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