Gonadotrope and thyrotrope development in the human and mouse anterior pituitary gland.

Abstract Genes and orthologous intrinsic and extrinsic factors critical for embryonic pituitary gonadotrope and thyrotrope cell differentiation have been identified mainly in rodents, but data on the human are very limited. In human fetal pituitaries examined between 14 and 19 weeks of gestation using immunofluorescent confocal microscopy, we found that most fetal gonadotropes expressed α-GSU, LHβ, and FSHβ gonadotropin subunits while almost no cells expressed α-GSU and LHβ  alone. Gonadotropes expressing α-GSU and FSHβ only were detected in both male and female pituitaries, increasing in proportion to total gonadotropes in both males and females from 14 (approximately 4.5%) to 19 weeks (approximately 16.5%) with a peak in males of 45.5% compared with females of 16.5% at 17 weeks of gestation. When FSHβ or LHβ genes were expressed, gonadotropes were non-dividing. This profile of human fetal gonadotrope development differs from the current mouse model. Furthermore, while expression of α-GSU appears to be the lead protein in gonadotropes, in thyrotropes which ultimately express α-GSU with TSHβ, we observed that most if not all thyrotropes were TSHβ-positive but α-GSU-negative until around 19 weeks in human, and e15 in mouse, fetal pituitaries. Furthermore, the TSHβ-only thyrotropes were dividing, and TSHβ rather than α-GSU was the lead protein in thyrotrope development. Thus, while biologically active dimeric FSH and LH can be produced by the human fetal pituitary by 14 weeks, dimeric biologically active TSH will only be produced from around 17 weeks of gestation. The mechanism(s) responsible for the different molecular regulation of α-GSU gene expression in gonadotropes and thyrotropes in the developing human fetal pituitary now requires investigation.