Pyridoxal phosphate inhibits pituitary cell proliferation and hormone secretion.

Abstract

Pyridoxal phosphate (PLP), a bioactive form of pyridoxine, dose-dependently (10-1000 microm) inhibited cell proliferation in rat pituitary MMQ and GH3 cells and in mouse AtT-20 cells. After 4 d, MMQ cell numbers were reduced by up to 81%, GH3 cell numbers were reduced by up to 64% (P < 0.05), and AtT-20 cell numbers were reduced by up to 90%. Cell proliferation rates recovered and dose-dependently reverted to control levels after PLP withdrawal. After 4 d, PLP (400 and 1000 microm) decreased [3H]thymidine incorporation by up to 71% (P < 0.05). PLP (400-1000 microm) reduced GH3 cell GH and prolactin secretion and AtT-20 cell ACTH secretion (adjusted for cell number) by approximately 70% after 2 d. The 100 microm PLP also inhibited prolactin secretion (65%, P < 0.05) in primary rat pituitary cells treated for 2 d. PLP decreased the percentage of AtT-20 and GH3 cells in S phase and increased those in G0-G1 phase. Furthermore, PLP induced AtT-20 and GH3 cell apoptosis (28 vs. 6, P < 0.05; 26 vs. 3, P < 0.05, respectively) and dose-dependently reduced content of the antiapoptosis gene Bcl-2. These results indicate that pharmacological doses of PLP inhibit pituitary cell proliferation and hormone secretion, in part mediated through PLP-induced cell-cycle arrest and apoptosis. Pyridoxine may therefore be appropriate for testing as a relatively safe drug for adjuvant treatment of hormone-secreting pituitary adenomas.

• Authors: Song-Guang Ren, Shlomo Melmed
• Journal: Endocrinology (Endocrinology) Vol. 147 Issue 8 Pg. 3936-42 (Aug 2006) ISSN: 0013-7227 [Print] United States
• PMID: 16690808 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-bcl-2
• Vitamin B Complex
• Pyridoxal Phosphate
• Prolactin
• Growth Hormone

Topics

• Adenoma
• Animals
• Apoptosis (drug effects)
• Cell Division (drug effects)
• Cell Line, Tumor
• G1 Phase (drug effects)
• Growth Hormone (metabolism)
• Mice
• Pituitary Gland, Anterior (cytology, drug effects, metabolism)
• Pituitary Neoplasms
• Prolactin (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Pyridoxal Phosphate (pharmacology)
• Rats
• Rats, Sprague-Dawley
• S Phase (drug effects)
• Vitamin B Complex (pharmacology)