Effects of levonorgestrel, medroxyprogesterone acetate, norethindrone, and 17beta-estradiol on vascular endothelial growth factor isomers 121 and 165 in Ishikawa cells.
OBJECTIVE
To determine the effect of 17beta-E(2), levonorgestrel, medroxyprogesterone acetate, and norethindrone on the expression of vascular endothelial growth factor (VEGF) isoforms 121 and 165 in Ishikawa cells in vitro.


METHODS
Prospective basic research study.


METHODS
Basic research laboratory.


METHODS
None.


METHODS
Ishikawa cells were cultured in vitro. After 24 hours' incubation in serum-free media, 1.0, 0.1, and 0.01 microM concentrations of E(2), levonorgestrel, medroxyprogesterone acetate, and norethindrone were added for a further 24 hours of incubation.


METHODS
Isolation and identification of VEGF isoforms 121 and 165 using semiquantitative polymerase chain reaction, gel electrophoresis, with beta-actin as an internal control.


RESULTS
Estradiol stimulated VEGF isoforms 121 and 165. The progestins studied increased mRNA for VEGF isoforms 121 and 165 at all doses. Medroxyprogesterone acetate resulted in the greatest increase in both VEGF 121 and 165 compared with norethindrone and levonorgestrel.


CONCLUSIONS
Estradiol and progestins increased VEGF 121 and 165 isoform mRNA in Ishikawa cells in vitro. We hypothesize that differences in VEGF expression may be associated with the irregular bleeding during progestin use in clinical situations.
Archer
David F
DF
The Clinical Research Center, The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA. archerdf@evms.edu
Navarro
Francisco J
FJ
Leslie
Susan
S
Mirkin
Sebastian
S
D000230:Adenocarcinoma; D016889:Endometrial Neoplasms; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D009640:Norethindrone / Q000494:pharmacology*; D011446:Prospective Studies; D020033:Protein Isoforms / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D020033:Protein Isoforms; D012333:RNA, Messenger; D011980:Receptors, Progesterone; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol; D016912:Levonorgestrel; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone