Androgen-dependent sexual dimorphism in pituitary tryptophan hydroxylase expression: relevance to sex differences in pituitary hormones
Androgen-dependent sexual dimorphism in pituitary tryptophan hydroxylase expression: relevance to sex differences in pituitary hormones
复制标题
DOI：
10.1098/rspb.2020.0713
复制
发表时间：
2020-06-10
影响因子：
4.7
通讯作者：
Okubo, Kataaki
中科院分区：
文献类型：
--
作者：
Kawabata-Sakata, Yukika;Nishiike, Yuji;Okubo, Kataaki
5-羟色胺是一种跨门保守的生物源性单胺，涉及多种生理和行为功能。在研究5-羟色胺合成的限速酶色氨酸羟化酶（TPHs）的表达，在硬骨鱼青（Oryzias latipes），我们发现，男性有更高的水平oftph 1的表达相比，女性。这种强大的性二态性被认为可能是由于雄激素/雄激素受体结合到其近端启动子区的典型二分雄激素反应元件直接刺激tph 1转录。我们的研究结果进一步揭示了attph 1的表达只发生在表达阿黑皮素原（pomc）的细胞中，由此产生的5-羟色胺及其衍生物褪黑激素抑制垂体激素基因fshb、slandtshb的表达。这表明，5-羟色胺和/或褪黑激素的合成inpomc表达细胞的行为，在旁分泌的方式，以抑制垂体激素水平。与这些发现和tph 1的男性偏好表达相一致，shb、slan和tshb在女性中的表达水平均高于男性。两者合计，男性偏见intph 1的表达和随之而来的5-羟色胺/褪黑激素的生产大概有助于性别差异的垂体激素的表达，并最终在生理功能介导的。
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 oftph1expression as compared with females. This robust sexual dimorphism was found to probably result from the direct stimulation oftph1transcription by androgen/androgen receptor binding to canonical bipartite androgen-responsive elements in its proximal promoter region. Our results further revealed thattph1expression 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,slandtshb. 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,slandtshbwere all higher in females than in males. Taken together, the male bias intph1expression 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.