Expression of isotocin is male-specifically upregulated by gonadal androgen in the medaka brain

Abstract

Oxytocin, a mammalian neuropeptide primarily synthesized in the supraoptic and paraventricular nuclei of the hypothalamus, mediates a variety of physiological and behavioral processes ranging from parturition and lactation to affiliation and prosociality. Multiple studies in rodents have shown that the expression of the oxytocin gene (Oxt) is stimulated by estrogen, while androgen has no apparent effect. However, this finding is not consistent across all studies, and no study has examined sex steroid regulation of Oxt or its orthologs in other animals. Here, we show that in the teleost fish, medaka (Oryzias latipes), the expression of the isotocin gene (it), the teleost ortholog of Oxt, in the parvocellular preoptic nuclei (homologous to the mammalian supraoptic nucleus) is male-specifically upregulated by gonadal androgen, whereas it expression in the magnocellular/gigantocellular preoptic nuclei (homologous to the mammalian paraventricular nucleus) is independent of sex steroids in both sexes. None of the it-expressing neurons appear to co-express androgen receptors, suggesting that the effect of androgen on it expression is indirect. We found that the expression of a kisspeptin gene, kiss2, in the male brain is dependent on gonadal androgen, raising the possibility that the androgen-dependent expression of it may be mediated by kiss2 neurons. Our data also shows that the isotocin peptide synthesized in response to androgen is axonally transported to the posterior pituitary to act peripherally. Given that levels of it expression are higher in females than in males, androgen may serve to compensate for the female-biased it expression to ensure a role for isotocin that is equally important for both sexes. These results are unexpectedly quite different from those reported in rodents, indicating that the regulatory role of sex steroids in Oxt/it expression has diverged during evolution, possibly with accompanying changes in the role of oxytocin/isotocin.

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