Pituitary estrogen receptor alpha and dopamine subtype 2 receptor gene expression in transgenic mice with overproduction of heterologous growth hormones.
Pituitary somatotrophs are suppressed in mice transgenic for human (h) or bovine (b) growth hormone (GH) genes fused with metallothionein (MT) or phosphoenolpyruvate carboxykinase (PEPCK) promoters. Previous morphologic studies revealed that lactotrophs are inhibited in hGH transgenic lines probably due to prolactin-like effects of hGH whereas in female bGH transgenics, the lactotrophs are stimulated. In the present study, estrogen receptor (ERalpha) mRNA was studied by autoradiographic in situ hybridization (ISH), ERalpha protein by immunocytochemistry, and dopamine subtype 2 receptor (D2R) mRNA by ISH. In MT/ and PEPCK/hGH transgenic mice, silver grains signaling ERalpha mRNA were significantly decreased compared to controls; the reduction was stronger in males (8.6 and 37%) than in females (4.6 and 11%). The decrease in the number of ERalpha-immunoreactive nuclei followed the same pattern (13.3 and 6% in males vs 3.2 and 5.2% in females). In MT/hGH mice the D2R mRNA signal was significantly increased in males (6 and 15.4%) and females (16%). In MT/bGH transgenics, ERalpha mRNA and ERalpha-immunoreactive nuclei were significantly increased (25 and 6%) only in males; D2R mRNA was more decreased in females (23%) than in males (15%). In conclusion, the opposite changes in ERalpha and D2R gene expressions are correlated with lactotroph inhibition in hGH transgenic mice and their stimulation in bGH transgenic mice. The changes in ERalpha expression were stronger in males, whereas those of D2R were more pronounced in females.
Vidal
S
S
Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Ontario, Canada.
Stefaneanu
L
L
Kovacs
K
K
Yamada
S
S
Bartke
A
A
D000818:Animals; D047628:Estrogen Receptor alpha; D005260:Female; D005786:Gene Expression Regulation; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D011960:Receptors, Estrogen; D019382:Human Growth Hormone