Progesterone Receptor Expression in Human Saphenous Veins

Abstract

Clinical and epidemiological observations regarding varicose veins, such as their predominance in women and the occurrence of venous stasis during sex-hormone therapy, the luteal phase of the menstrual cycle, and pregnancy, suggest a sex hormone-dependency of this venous pathology. In the present study, analysis of steroid receptors was used to determine if these effects were due to a direct hormonal action on the saphenous vein. Biopsy samples were obtained from patients undergoing stripping removal of varicose saphenous veins. Patients were men (n = 5) and premenopausal (n = 15) or postmenopausal (n = 10) women. Progesterone receptors (PR) and estrogen receptors (ER) were determined by both enzyme immunoassay (EIA) and immunocytochemistry by use of monoclonal antibodies. Ninety percent of the biopsy samples showed PR positivity by EIA (range, 5 to 53 fmol/mg cytosol protein). 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 varicose biopsy samples. Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze PR and ER mRNAs in biopsy samples that were 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 to the DNA-binding domain, the hinge region, and the ligand-binding domain encoded by ER mRNA. These results indicate that human saphenous veins from both sexes express PR, as previously described for arterial blood vessels. This observation suggests that progesterone acts directly on these veins via a classic receptor-mediated pathway.