Progesterone Receptor Expression in Human Saphenous Veins

Perrot-Applanat, M.; Cohen‐Solal, Karine; Milgröm, Edwin; Finet, M.

doi:10.1161/01.cir.92.10.2975

Cited by 57 publications

(45 citation statements)

References 27 publications

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“…The role of progestogens in the alteration of vessels blood flow and in the development of varicose veins warrants further study. 36 One potential limitation of our study is that observational studies are subject to bias. The validity of the ESTHER study has been discussed.…”

Section: Discussionmentioning

confidence: 96%

“…28 The occurrence of venous stasis during luteal phase or pregnancy, together with the presence of estrogen and progesterone receptors in the venous wall, 36 suggests that venous blood flow may be directly modulated by steroid hormones. Therefore, norpregnane derivatives, which have a high progestational activity, might increase the VTE risk through venous stasis via a progesterone receptormediated pathway.…”

Section: Discussionmentioning

confidence: 99%

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Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

et al. 2007

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After adjustment for potential confounding factors, odds ratios (ORs) for VTE in current users of oral and transdermal estrogen compared with nonusers were 4.2 (95% CI, 1.5 to 11.6) and 0.9 (95% CI, 0.4 to 2.1), respectively. There was no significant association of VTE with micronized progesterone and pregnane derivatives (OR, 0.7; 95% CI, 0.3 to 1.9 and OR, 0.9; 95% CI, 0.4 to 2.3, respectively). In contrast, norpregnane derivatives were associated with a 4-fold-increased VTE risk (OR, 3.9; 95% CI, 1.5 to 10.0). Conclusions-Oral but not transdermal estrogen is associated with an increased VTE risk. In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. If confirmed, these findings could benefit women in the management of their menopausal symptoms with respect to the VTE risk associated with oral estrogen and use of progestogens. (Circulation.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

et al. 2007

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“…27 The occurrence of venous stasis, especially observed during pregnancy and the luteal phase, could be modulated by steroid sex hormones via progesterone receptors which are present in the venous wall. 40 Therefore, an increase in progestational activity of progestins, especially norpregnanes, compared to micronized progesterone might further alter blood flow and increase thrombotic risk.…”

Section: Discussionmentioning

confidence: 99%

Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism

Canonico

Fournier

Carcaillon

et al. 2010

ATVB

238

125

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Objective-Oral estrogen therapy increases venous thromboembolism risk among postmenopausal women. Although recent data showed transdermal estrogens may be safe with respect to thrombotic risk, the impact of the route of estrogen administration and concomitant progestogens is not fully established. Methods and Results-We used data from the E3N French prospective cohort of women born between 1925 and 1950 and biennially followed by questionnaires from 1990. Study population consisted of 80 308 postmenopausal women (average follow-up: 10.1 years) including 549 documented idiopathic first venous thromboembolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional models. Compared to never-users, past-users of hormone therapy had no increased thrombotic risk (HRϭ1.1; 95% CI: 0.8 to 1.5). Oral not transdermal estrogens were associated with increased thrombotic risk (HRϭ1.7; 95% CI: 1.1 to 2.8 and HRϭ1.1; 95% CI: 0.8 to 1.8; homogeneity: Pϭ0.01). The thrombotic risk significantly differed by concomitant progestogens type (homogeneity: PϽ0.01): there was no significant association with progesterone, pregnanes, and nortestosterones (HRϭ0.9; 95% CI: 0.6 to 1.5, HRϭ1.3; 95% CI: 0.9 to 2.0 and HRϭ1.4; 95% CI: 0.7 to 2.4). However, norpregnanes were associated with increased thrombotic risk (HRϭ1.8; 95% CI: 1.2 to 2.7). Conclusions-In this large study, we found that route of estrogen administration and concomitant progestogens type are 2 important determinants of thrombotic risk among postmenopausal women using hormone therapy. Transdermal estrogens alone or combined with progesterone might be safe with respect to thrombotic risk.

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“…Direct effects of sex steroids on human veins have been postulated by a number of investigators [1,2,3,4,5,6] . Karas et al reported the presence of ER in smooth muscle cells of human saphenous vein, although at a low level [4] but Perrot-Applanat et al reported that ER and its mRNA were undetectable in 80% of saphenous veins examined [6].…”

Section: Discussionmentioning

confidence: 99%

“…VARIOUS clinical and epidemiological observations suggest that sex steroids play an important role in the function and pathology of human veins [1][2][3]. Karas et al recently demonstrated the presence of estrogen receptor (ER) in smooth muscle cells cultured from surgical specimens of non-pathological human saphenous veins removed for coronary artery bypass surgery [4].…”

mentioning

confidence: 99%

Aromatase and Sex Steroid Receptors in Human Vena Cava.

et al. 1999

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Abstract.Among sex steroids, especially estrogen metabolism has been considered to play a role in the function and pathology of human veins. We investigated the expression and activity of the estrogen-producing enzyme aromatase and estrogen receptor (ER) in human vena cava to assess possible in situ biosynthesis of estrogens and their modes of action. We first examined aromatase expression by immunohistochemistry in human inferior vena cava obtained from 29 autopsy cases (11 males, 18 females, 63.6±3.0 years old). We then semiquantitated the level of aromatase mRNA by reverse transcriptase-polymerase chain reaction in 24 cases and aromatase activity by 3H-water assay in 15 cases to examine whether or not and in which cell types aromatase was expressed. We also studied alternative use of multiple exon is of its gene and immunolocalization of 17,0-hydroxysteroid dehydrogenase type I (173-HSD I), which converts estrone produced by aromatase to estradiol, a biologically active estrogen and ER. Aromatase and 17p-HSD I immunoreactivity were both detected in smooth muscle cells (SMC) of the media in all the cases and in endothelial cells (EC) in 20 and 22 cases, respectively. ER immunoreactivity was detected in SMC of vena cava in 21 cases. The amount of aromatase mRNA was significantly greater in the cases utilizing is (I.3) or id (P.11) of exon 1 (9 cases, 191.1 ±26.3 attomol/ng total RNA) than those utilizing l b (1.4) as the promoter (14 cases, 50.6± 13.0 attomol/ng total RNA) (p < 0.01). Significant correlation (p < 6.05) was observed between the amount of aromatase mRNA and aromatase activity in 15 cases examined. No significant correlation was detected between the amount of aromatase mRNA or aromatase labeling index and the ER status. These results suggest that estrone and estradiol are produced in the human vena cava and that their production is mediated by aromatase and 17,0-HSD I, respectively but not all of these locally synthesized estrogens may not work directly in situ. In postmenopausal women and men, estrogen biosynthesis is mainly peripheral, through conversion of androstenedione or C19 steroids from the adrenal cortex, ovary and/or testis [7]. This conversion is catalyzed by the enzyme complex cytochrome P450 aromatase.In humans, aromatase has been detected in numerous extragonadal tissues including adipocytes [8]

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Progesterone Receptor Expression in Human Saphenous Veins

Abstract: 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.

Cited by 57 publications

References 27 publications

Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism

Aromatase and Sex Steroid Receptors in Human Vena Cava.

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