Peripheral benzodiazepine stimulates secretion of growth hormone and mitochondrial proliferation in pituitary tumour GH3 cells.
High affinity receptors for peripheral benzodiazepines (PBD) are present within the pituitary gland. Whether these receptors influence cell growth, mitochondrial morphology and secretion of growth hormone was examined in pituitary tumour GH3 cells. Cells were incubated in medium with either 10% calf serum, or serum free medium, or serum free medium plus 10 nM of selective PBD ligands (PK11195 or Ro5-4864) or a central benzodiazepine ligand (clonazepam). Peripheral or central ligands had no effect on cell growth. Quantitative electron micrography, however, revealed that cells treated with PBDs had a 2.5-fold increase in the total mitochondrial area within cells, a 1.6-fold increase in the number of mitochondria, and a 2.0 to 2.7-fold increase on the number of dividing mitochondria compared to serum free controls. The activity of DNA polymerase gamma, which replicates mitochondrial DNA, was increased approximately 3 times the initial value after 6 h exposure to PBDs. The number of nucleolar organizer regions (NORs), which relate to the ultimate synthesis of cellular protein, showed a 1.4-fold increase in PBDs treated cells. Secretion of growth hormone was stimulated (240% of serum free control) by exposure to PBDs for 12 h. The central benzodiazepine ligand, clonazepam, had little effect on mitochondrial morphology or secretion of growth hormone. These findings suggest that PBD receptors may be involved in mitochondrial proliferation and may affect the secretion of pituitary hormones.
Black
K L
KL
Brain Research Institute, Jonsson Cancer Center, Los Angeles, CA.
Shiraishi
T
T
Ikezak
K
K
Tabuchi
K
K
Becker
D P
DP
D000236:Adenoma / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004258:DNA Polymerase III / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D010911:Pituitary Neoplasms / Q000473:pathology / Q000503:physiopathology*; D011388:Prolactin / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D004272:DNA, Mitochondrial; D001569:Benzodiazepines; D011388:Prolactin; D013006:Growth Hormone; D004258:DNA Polymerase III