Glucocorticoid-inducible glutamine synthetase in GH cells of chick embryos, Gallus domesticus: Ontogeny of glutamine synthetase, GH, and Pit-1 protein in the pituitary gland

It has been known that glutamine synthetase (GS, L-glutamate ammonia ligase) is an enzyme that catalyzes ATP-dependent condensation of glutamate and ammonia to form glutamine, and that GS and growth hormone (GH) are proteins that are induced by glucocorticoid-treatment during the development of animals. To understand the relationship between these glucocorticoid-inducible proteins, we studied pituitary GS and GH cells during the development of chick embryos, Gallus domesticus. GS cells were immunohistochemically identified in epithelia of Rathke's pouch as early as embryonic day 4 (E4) following corticosterone-treatment. The population of GS cells and GS activity gradually increased by E14, and then rose sharply after E 1 6. Pituitary GS activity was precociously induced by corticosterone-treatment starting around E7. GH cells were first demonstrable in the pituitary gland on E11, and then increased until hatching. Corticosterone-treatment also caused premature induction of GH in the pituitary cells after E8, but not before. Dual-fluorescence immunohistochemistry showed a large population of GS cells in the cephalic lobe that was identical to the ACTH cells, and in the caudal lobe of the gland they were the same as the GH cells. Ontogeny of pituitary Pit1 protein, an important transcription factor of GH, was also studied by immunohistochemistry. Pit-1 positive cells appeared at E6 and increased in number by E 12 of development. The population of Pit-1 cells was, however, not affected by corticosterone-treatment. These result demonstrate that glucocorticoid receptors are present in pituitary GS cells even before day 8 when GH cells start to differentiate, and that a large population of GS cells may have some physiological roles in the gland. This is the first report showing that pituitary GS is a glucocorticoid-inducible marker protein to regulate pituitary functions.