High corticosterone and sex reversal in common carp (Cyprinus carpio L.) with adrenal hyperplasia caused by P450c17a2 deficiency

The aim of this study was to investigate the inheritance of adrenal hyperplasia, caused by 17α-hydroxylase deficiency, and its association with female to male sex reversal in common carp. Inbred strains used in this experiment were E4 (XX, female, normal), E5 (XX, male, adrenal hyperplasia) and E7 (XX, male, adrenal hyperplasia). F1 females (E4E5: XX, normal) were crossed to E5 and E7 males to produce backcross progeny (BC5 and BC7), or reproduced by gynogenesis to produce doubled haploid progeny (DH). Fish (age 6 months) were subjected to a net confinement stressor and sacrificed to collect blood plasma for analysis of cortisol and corticosterone, and to determine sex. Values for plasma corticosterone showed a clear segregation pattern, consistent with a single recessive gene model. There was a highly significant difference between high and low corticosterone responders in BC and DH progeny groups. Mean corticosterone values for high corticosterone responders in the three groups BC5, BC7 and DH were, respectively: 1706, 1760 and 1366 ng/ml. For low corticosterone responders values were 1.5, 1.1 and 0.6 ng/ml. High corticosterone responders had on average low levels of cortisol: 21.3, 24 and 17.3 ng/ml for BC5, BC7 and DH. Low corticosterone responders had normal levels (66.7, 105.1 and 65.2 ng/ml for BC5, BC7 and DH, respectively). Sex ratios were significantly different between high and low corticosterone responders. High corticosterone responders were predominantly male, while low corticosterone responders were female or intersex. High corticosterone responders had well developed testis and were fertile indicating that in the gonads, 17α-hydroxylase is not impaired. The observed effect on sex shows that 17α-hydroxylase deficiency most likely augments sex reversal in common carp, either directly through high levels of plasma corticosterone, or through paracrine effects of elevated ACTH production.