Androgen-dependent sexual dimorphism in pituitary tryptophan hydroxylase expression: relevance to sex differences in pituitary hormones

Serotonin is a biogenic monoamine conserved across phyla that is implicated in diverse physiological and behavioural functions. On examining the expression of the rate-limiting enzymes in serotonin synthesis, tryptophan hydroxylases (TPHs), in the teleost medaka (Oryzias latipes ), we found that males have much higher levels oftph1 expression as compared with females. This robust sexual dimorphism was found to probably result from the direct stimulation oftph1 transcription by androgen/androgen receptor binding to canonical bipartite androgen-responsive elements in its proximal promoter region. Our results further revealed thattph1 expression occurs exclusively in pro-opiomelanocortin (pomc )-expressing cells and that the resulting serotonin and its derivative melatonin inhibit the expression of the pituitary hormone genes,fshb ,sl andtshb . This suggests that serotonin and/or melatonin synthesized inpomc -expressing cells act in a paracrine manner to suppress pituitary hormone levels. Consistent with these findings and the male-biased expression oftph1 , the expression levels offshb ,sl andtshb were all higher in females than in males. Taken together, the male bias intph1 expression and consequent serotonin/melatonin production presumably contribute to sex differences in the expression of pituitary hormones and ultimately in the physiological functions mediated by them.