Effects of progesterone and 18-methyl levonorgestrel on osteoblastic cells.
OBJECTIVE
To study the effects of progesterone (P) and 18-methyl levonorgestrel (LNG) on the expression of P receptors (PRA and PRB), c-fos, c-jun, and osteocalcin in the human osteosarcoma cell line MG-63 and human normal osteoblasts in order to understand the mechanism of progestin action on the proliferation and differentiation of osteoblasts.


METHODS
Cell proliferation was tested by MTT assay. The expression of PR, c-fos, c-jun, and osteocalcin was measured by semi-quantitative RT-PCR, Western immunoblot or immunocytochemistry.


RESULTS
Progesterone and LNG (10(-10)-10(-6)M) stimulated cell proliferation in a dose-dependent manner. Progesterone and LNG did not affect the expression of PRA and PRB mRNA and protein, but c-fos and c-jun mRNA and protein were upregulated in a dose-dependent manner. The expression of osteocalcin mRNA was also increased in human osteoblasts in a dose and time-dependent manner with greater effects of LNG than P, while the expression of osteocalcin mRNA in MG-63 cells was not changed by P or LNG.


CONCLUSIONS
Progesterone and LNG promote osteocalcin gene transcription by stimulating the expression of c-fos and c-jun, and result in osteoblast proliferation and differentiation.
Liang
Min
M
Institute of Endocrinology & Metabolism, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.
Liao
Er-Yuan
EY
Xu
Xin
X
Luo
Xiang-Hang
XH
Xiao
Xin-Hua
XH
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D011374:Progesterone / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D015675:Osteocalcin; D011374:Progesterone; D016912:Levonorgestrel