Abstract

The preoptic area (POA) is one of the most evolutionarily conserved regions of the vertebrate brain and contains subsets of neuropeptide-expressing neurons. Here we found in the teleost medaka that two neuropeptides belonging to the secretin family, pituitary adenylate cyclase-activating polypeptide (Pacap) and vasoactive intestinal peptide (Vip), exhibit opposite patterns of sexually dimorphic expression in the same population of POA neurons that project to the anterior pituitary: Pacap is male-biased, whereas Vip is female-biased. Estrogen secreted by the ovary in adulthood was found to attenuate Pacap expression and, conversely, stimulate Vip expression in the female POA, thereby establishing and maintaining their opposite sexual dimorphism. Pituitary organ culture experiments demonstrated that both Pacap and Vip can markedly alter the expression of various anterior pituitary hormones. Collectively, these findings show that males and females use alternative preoptic neuropeptides to regulate anterior pituitary hormones as a result of their different estrogen milieu.

Highlights

  • The preoptic area (POA) is one of the most evolutionarily conserved regions of the vertebrate brain and contains subsets of neuropeptide-expressing neurons

  • We found that in medaka two neuropeptides belonging to the secretin family, pituitary adenylate cyclaseactivating polypeptide (Pacap) and vasoactive intestinal peptide (Vip), have opposite patterns of sex-biased expression in the same population of POA neurons, whereby Pacap is male-biased and Vip is female-biased

  • Given that Pacap and Vip share common receptors, our finding indicates that males and females use different neuropeptides for equivalent signaling functions

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Summary

Vipr2b

Pomc merge+DAPI pretectum; NRL, NDTL, PGm and NGp in the hypothalamus; and is, CC and RI in the brain stem (Supplementary Fig. 5c, d). Expression of the luteinizing hormone (Lh) β subunit (lhb) gene in both male and female pituitaries was increased by Pacap supplementation (p = 0.0045 and 0.0452, respectively), whereas Vip had no significant effect (main effect of sex, p = 0.0743; main effect of treatment, p < 0.0001; interaction between sex and treatment, p = 0.6211) (Fig. 8). Neither Pacap nor Vip had no significant effects on pomc expression in female pituitaries (main effect of sex, p < 0.0001; main effect of treatment, p = 0.1068; interaction between sex and treatment, p = 0.0239) Both Pacap and Vip have sex-independent stimulatory effects on the expression of sl and prl and femalespecific inhibitory effects on fshb. Independent stimulatory effects on lhb and male-specific inhibitory effects on pomc

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