Gonadotrope and thyrotrope development in the human and mouse anterior pituitary gland.
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 alpha-GSU, LHbeta, and FSHbeta gonadotropin subunits while almost no cells expressed alpha-GSU and LHbeta alone. Gonadotropes expressing alpha-GSU and FSHbeta 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 FSHbeta or LHbeta genes were expressed, gonadotropes were non-dividing. This profile of human fetal gonadotrope development differs from the current mouse model. Furthermore, while expression of alpha-GSU appears to be the lead protein in gonadotropes, in thyrotropes which ultimately express alpha-GSU with TSHbeta, we observed that most if not all thyrotropes were TSHbeta-positive but alpha-GSU-negative until around 19 weeks in human, and e15 in mouse, fetal pituitaries. Furthermore, the TSHbeta-only thyrotropes were dividing, and TSHbeta rather than alpha-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 alpha-GSU gene expression in gonadotropes and thyrotropes in the developing human fetal pituitary now requires investigation.
Pope
Caroline
C
Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
McNeilly
Judy R
JR
Coutts
Shiona
S
Millar
Mike
M
Anderson
Richard A
RA
McNeilly
Alan S
AS
D000818:Animals; D002454:Cell Differentiation; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000378:metabolism; D005865:Gestational Age; D015292:Glycoprotein Hormones, alpha Subunit / Q000378:metabolism; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D037101:Luteinizing Hormone, beta Subunit / Q000378:metabolism; D051379:Mice; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D013045:Species Specificity; D013972:Thyrotropin / Q000378:metabolism*
D037201:Follicle Stimulating Hormone, beta Subunit; D015292:Glycoprotein Hormones, alpha Subunit; D006062:Gonadotropins; D037101:Luteinizing Hormone, beta Subunit; D013972:Thyrotropin