Luteinizing hormone-releasing hormone and neuropeptide Y influence deoxyribonucleic acid replication in three anterior pituitary cell types. Evidence for mediation by growth factors released from gonadotrophs.
Treatment of anterior pituitary reaggregate cell cultures from 14-day-old female rats with physiological doses of the gonadotropin-releasing hormone LHRH or neuropeptide Y (NPY) for 40 h dose-dependently increased [3H]thymidine ([3H]T) incorporation into DNA of cells expressing PRL immunoreactivity (PRL-ir) and of those expressing ACTH-ir, whereas these peptides decreased the number of [3H]T-labeled cells expressing GH-ir. The effects of NPY were of the same magnitude as those of LHRH. The effects of LHRH were not seen in a gonadotroph-deprived cell population obtained by sequential velocity and buoyant density gradient sedimentation. When the latter cell population was coaggregated with purified gonadotrophs from 14-day-old rats, LHRH did enhance [3H]T labeling of lactotrophs and decreased that of somatotrophs. Gonadotroph-conditioned medium obtained by continuous perifusion of gonadotroph-rich reaggregates contained four different high molecular weight substances mimicking the effects of LHRH and NPY on [3H]T incorporation in the respective pituitary cell types. These substances were partially purified and separated from each other by concentration on a Bond-elut C18-reversed phase cartridge, ultrafiltration, and C18-reversed phase HPLC. One factor stimulated [3H]T labeling of lactotrophs, another that of corticotrophs, and two others inhibited [3H]T labeling of somatotrophs. The present data suggest that the development of PRL-, GH-, and ACTH-containing cells in the pituitary is modulated by LHRH and/or NPY and that the action of LHRH and probably also of NPY is mediated by specific paracrine growth factors released from gonadotrophs.
Tilemans
D
D
Laboratory of Cell Pharmacology, University of Leuven, School of Medicine, Belgium.
Andries
M
M
Denef
C
C
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient / Q000379:methods; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008940:Mitotic Index; D009478:Neuropeptide Y / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D006133:Growth Substances; D009478:Neuropeptide Y; D014316:Tritium; D007987:Gonadotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D004247:DNA; D013936:Thymidine