Pituitary estrogen receptor a 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 b ovine (b) growth hormone (GH) genes fused with metallothionein (MT) or phos phoenolpyruvate carboxykinase (PEPCK) promoters. Previous morphologic studi es revealed that lactotrophs are inhibited in hGH transgenic lines probably due to prolactin-like effects of hGH whereas in female bGH transgenics, th e lactotrophs are stimulated. In the present study, estrogen receptor (ER a lpha) mRNA was studied by autoradiographic in situ hybridization (ISH), ER alpha protein by immunocytochemistry, and dopamine subtype 2 receptor (D2R) mRNA by ISH. In MT/ and PEPCK/hGH transgenic mice, silver grains signaling ER alpha mRNA were significantly decreased compared to controls; the reduc tion was stronger in males (8.6 and 37%) than in females (4.6 and 11%). The decrease in the number of ER alpha-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, ER alpha mRNA and ER alpha-immunoreac tive nuclei were significantly increased (25 and 6%) only in males; D2R mRN A was more decreased in females (23%) than in males (15%). In conclusion, t he opposite changes in ER alpha and D2R gene expressions are correlated wit h lactotroph inhibition in hGH transgenic mice and their stimulation in bGH transgenic mice. The changes in ER alpha expression were stronger in males , whereas those of D2R were more pronounced in females.