Redefining the initiation and maintenance of zebrafish interrenal steroidogenesis by characterizing the key enzyme Cyp11a2

Parajes, S., Griffin, A., Taylor, A.E., Rose, I.T., Miguel-Escalada, I., Hadzhiev, Y., Arlt, W., Shackleton, C., Muller, F., and Krone, N.
Endocrinology   154(8): 2702-11 (Journal)
Registered Authors
Griffin, Aliesha, Hadzhiev, Yavor, Müller, Ferenc
MeSH Terms
  • Animals
  • Cholesterol Side-Chain Cleavage Enzyme/classification
  • Cholesterol Side-Chain Cleavage Enzyme/genetics*
  • Cholesterol Side-Chain Cleavage Enzyme/metabolism
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Gastrulation/drug effects
  • Gastrulation/genetics
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Gene Knockdown Techniques
  • Interrenal Gland/embryology
  • Interrenal Gland/growth & development
  • Interrenal Gland/metabolism*
  • Isoenzymes/genetics
  • Isoenzymes/metabolism
  • Larva/genetics
  • Larva/growth & development
  • Phenotype
  • Phylogeny
  • Pregnenolone/metabolism
  • Pregnenolone/pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steroids/biosynthesis*
  • Time Factors
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
23671259 Full text @ Endocrinology

Zebrafish are emerging as a model to study steroid hormone action and associated disease. However, steroidogenesis in zebrafish is not well characterized. Mammalian P450 side-chain cleavage enzyme (CYP11A1) catalyzes the first step of steroidogenesis, the conversion of cholesterol to pregnenolone. Previous studies describe an essential role for zebrafish Cyp11a1 during early development. Cyp11a1 has been suggested to be the functional equivalent of mammalian CYP11A1 in the zebrafish interrenal gland (equivalent to the mammalian adrenal), gonad and brain. However, reported cyp11a1 expression is inconsistent in zebrafish larvae, after active cortisol synthesis commences. Recently, a duplicated cyp11a gene, cyp11a2, has been described, which shares an 85% identity with cyp11a1. We aimed to elucidate the specific role of the two cyp11a paralogs. cyp11a1 was expressed from 0–48 hours post-fertilization (hpf), whilst cyp11a2 expression started after development of the interrenal primordium (32 hpf), and was the only paralog in larvae. cyp11a2 is expressed in adult steroidogenic tissues, such as the interrenal, gonads, and brain. In contrast, cyp11a1 was mainly restricted to the gonads. Anti-sense morpholino knockdown studies confirmed abnormal gastrulation in cyp11a1 morphants. cyp11a2 morphants showed impaired steroidogenesis and a phenotype indicative of metabolic abnormalities. The phenotype was rescued by pregnenolone replacement in cyp11a2 morphants. Thus, we conclude that cyp11a1 is required for early development, whereas cyp11a2 is essential for initiation and maintenance of zebrafish interrenal steroidogenesis. Importantly, this study highlights the need for a comprehensive characterization of steroidogenesis in zebrafish prior its implementation as a model organism in translational research of adrenal disease.

Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes