Multistep differentiation of GH-producing cells from their immature cells.
In order to study GH cell differentiation, we used the clonal cell lines called MtT/E and MtT/S cells, which were derived from a rat mammotrophic pituitary tumor. Although MtT/E cells are non-hormone-producing ones, Pit-1 protein is present in their nuclei, which suggests that MtT/E cells are progenitor cells of the Pit-1 cell lineage and have the potential to differentiate into hormone-producing cells. On the other hand, MtT/S cells produce GH; however, the responsiveness to GH-releasing hormone (GHRH) is weak and only a small number of secretory granules are present in their cytoplasm, which suggests that MtT/S cells are premature GH cells. In order to differentiate into GH cells from MtT/E cells as a progenitor cell, we examined several differentiation factors and found that retinoic acid (RA) induced the differentiation of MtT/E cells into GH-producing cells. RA-induced GH cells partially matured with the glucocorticoid treatment; however, the responsiveness to GHRH on GH secretion was incomplete. In order to elucidate the mechanism underlying full differentiation of GH cells, we used MtT/S cells. We treated MtT/S cells with glucocorticoid and found that they differentiated into mature GH cells with many secretory granules in their cytoplasm and they responded well to GHRH. These results suggested that MtT/E and MtT/S cells are progenitor or premature GH cells, and show different responses to differentiation factors. Our data also suggested that GH cells differentiate from their progenitor cells through multistep processes.
Mogi
C
C
Department of Regulation Biology, Faculty of Science, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama 338-8570, Japan.
Goda
H
H
Mogi
K
K
Takaki
A
A
Yokoyama
K
K
Tomida
M
M
Inoue
K
K
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D003345:Corticosterone / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D013006:Growth Hormone / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D015850:Interleukin-6 / Q000378:metabolism; D008854:Microscopy, Electron; D009414:Nerve Growth Factors / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010903:Pituitary Gland, Anterior / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D013268:Stimulation, Chemical; D014212:Tretinoin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D015850:Interleukin-6; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016222:Fibroblast Growth Factor 2; D014660:Vasoactive Intestinal Peptide; D014212:Tretinoin; D013006:Growth Hormone; D003345:Corticosterone