High levels of plasma cortisol and impaired hypoosmoregulation in a mutant medaka deficient in P450c17I

• Plasma cortisol in P450c17I-deficient (scl) medaka is at a high physiological level.
• After seawater transfer, scl is more dehydrated than wild type medaka.
• Intestinal GRs and Na/K/2Cl cotransporter are not induced in scl after the transfer.
• scl may provide a model to study the roles of glucocorticoids and sex steroids.

scl is a spontaneous medaka mutant deficient in P450c17I, which is required for production of sex steroids, but not of cortisol, the major role of which is osmoregulation in teleost fish. The scl mutant provides a new model to study the functions of these hormones. We first found that fish homozygous for this mutation have plasma cortisol constitutively at a high physiological level (1000 nM). Since we previously showed that this level reversed the seawater-type differentiation of the medaka gastrointestinal tract, hypoosmoregulation of the scl mutant was analyzed. Muscle water contents in freshwater were normal in scl homozygotes, but the contents were lower than those of the wild type (WT) after seawater transfer. There were no differences in gill mRNA levels of corticosteroid receptors or ion transporters between scl homozygotes and WT. In the intestine, expression of glucocorticoid receptors and Na+/K+/2Cl− cotransporter were induced in WT during seawater acclimation, but not in scl homozygotes. The high plasma cortisol may prevent hypoosmoregulation by inhibition of increased intestinal water absorption, essentially by the Na+/K+/2Cl− cotransporter, in seawater.