PROGESTERONE-RECEPTOR EXPRESSION IN HUMAN SAPHENOUS VEINS

Background Clinical and epidemiological observations regarding varicos e veins, such as their predominance in women and the occurrence of ven ous stasis during sex-hormone therapy, the luteal phase of the menstru al cycle, and pregnancy, suggest a sex hormone-dependency of this veno us pathology. In the present study, analysis of steroid receptors was used to determine if these effects were due to a direct hormonal actio n on the saphenous vein. Methods and Results Biopsy samples were obtai ned from patients undergoing stripping removal of varicose saphenous v eins. Patients were men (n=5) and premenopausal (n=15) or postmenopaus al (n=10) women. Progesterone receptors (PR) and estrogen receptors (E R) were determined by both enzyme immunoassay (EIA) and immunocytochem istry by use of monoclonal antibodies. Ninety percent of the biopsy sa mples showed PR positivity by EIA (range, 5 to 53 fmol/mg cytosol prot ein). When present, PR staining was observed in the cell nuclei of the tunica media and the subendothelial layer (neointima). No significant variation was observed in the PR content of different regions within the same saphenous vein. In contrast, no ER or extremely low levels of ER (<5 fmol/mg cytosol protein) were detected by EIA in 25 of 30 vari cose biopsy samples. Reverse transcription-polymerase chain reaction ( RT-PCR) was used to analyze PR and ER mRNAs in biopsy samples that wer e PR positive/ER negative. With primers to the hormone-binding region encoded by PR mRNA, a RT-PCR product of the expected size was detected and its identity confirmed by Southern blot by use of a PR cDNA probe . In contrast, no RT-PCR product could be detected by use of primers t o the DNA-binding domain, the hinge region, and the ligand-binding dom ain encoded by ER mRNA. Conclusions These results indicate that human saphenous veins from both sexes express PR, as previously described fo r arterial blood vessels. This observation suggests that progesterone acts directly on these veins via a classic receptor-mediated pathway.