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

Abstract

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 of tph1 expression as compared with females. This robust sexual dimorphism was found to probably result from the direct stimulation of tph1 transcription by androgen/androgen receptor binding to canonical bipartite androgen-responsive elements in its proximal promoter region. Our results further revealed that tph1 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 and tshb . This suggests that serotonin and/or melatonin synthesized in pomc -expressing cells act in a paracrine manner to suppress pituitary hormone levels. Consistent with these findings and the male-biased expression of tph1 , the expression levels of fshb , sl and tshb were all higher in females than in males. Taken together, the male bias in tph1 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.

3D Atlas of the Pituitary Gland of the Model Fish Medaka (Oryzias latipes)

“…For instance, we show for the first time that tshba -expressing cell volumes are the largest in adult females, and pomca -expressing cell volumes are the largest in adult males. Our qPCR data on tshba and pomca levels agree with a previous study in medaka ( 60 ) and further support the sexual dimorphism. In that study, androgens were shown to stimulate transcription of tph1 , which encodes an enzyme required for serotonin synthesis, in pomc -expressing cells.…”

3D atlas of the pituitary gland of the model fish medaka

“…We also observed sexual dimorphism of fshb and lhb mRNA levels in adults, in agreement with a previous medaka study (56). This suggests a difference in gonadotrope cell activity as we did not observe a difference in population size, also supported by the absence of significant differences in Lh or Fsh cell numbers in previous studies (9,63).…”

“…For instance, we show for the first time that tshba-and pomca-expressing cell populations are more numerous in adult females and males, respectively. Our qPCR data on tshba and pomca levels agree with previous studies in medaka (56) and further support the sexual dimorphism. In the previous medaka study, androgens were suggested to be involved in tshb suppression in adult males via activation of tph1 transcription expressed in pomc-expressing cells.…”

A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis

“…Previous postmortem analysis of brain tissues reported that TPH2 mRNA expression is abundant in the dorsal raphe nucleus, median raphe nucleus, and raphe nuclei-containing regions such as pons and medullar, not the pituitary gland [35,36]. Although TPH1 is mainly expressed in peripheral tissues, some papers have already reported the existence of TPH1 in the brain, especially in the pituitary gland [37][38][39]. Our results showed that the pituitary gland expressed TPH1 as well as TPH2, and the expression levels were higher Previous postmortem analysis of brain tissues reported that TPH2 mRNA expression is abundant in the dorsal raphe nucleus, median raphe nucleus, and raphe nuclei-containing regions such as pons and medullar, not the pituitary gland [35,36].…”