endothelin-1 and estrone-sulfate

To establish levels of plasma endothelin-1 in postmenopausal women with increased CV risk as compared with healthy premenopausal women and to measure the effects of different forms of estrogen replacement on plasma endothelin-1.. Prospective randomized study.. University of Southern California Medical Center.. We studied 18 postmenopausal women (mean age 53.4 +/- 4.9 years) with total cholesterol levels > 240 mg/dL divided into those with and without hypertension as well as in 10 healthy premenopausal women.. The postmenopausal women were randomized to receive oral estrone sulfate, transdermal E2, or placebo for 30 days.. We measured the endothelin-1 levels and total cholesterol at baseline and after 30 days of estrogen treatment.. In the postmenopausal women, endothelin-1 was higher (4.58 +/- 0.46 pg/mL) compared with premenopausal levels (2.80 +/- 0.46 pg/mL). In hypertensive postmenopausal women, endothelin-1 was 5.56 +/- 0.44 pg/mL. After estrogen, plasma endothelin-1 values decreased from 5.38 +/- 0.66 to 4.82 +/- 0.9 pg/mL with oral estrone sulfate, 4.84 +/- 0.25 to 4.54 +/- 0.49 pg/mL with transdermal E2, and did not change after placebo 4.76 +/- 0.71 to 4.81 +/- 0.46 pg/mL. In evaluating hypertensive women alone with estrogen therapy, plasma endothelin-1 showed the greatest decrement from 5.39 +/- 0.49 to 4.4 +/- 0.59 pg/mL (18.4%). The decrease in endothelin-1 with estrogen, which was statistically significant for the entire group, did appear to be influenced by the route of administration. Baseline plasma endothelin-1 levels were correlated positively to plasma cholesterol levels with a correlation coefficient of 0.632.. These data provide another potential mechanism explaining the cardioprotective effects of hormone replacement therapy.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Cardiovascular Diseases; Cholesterol; Endothelin-1; Estrogen Replacement Therapy; Estrogens; Estrone; Female; Humans; Hypertension; Middle Aged; Postmenopause; Premenopause; Prospective Studies; Reference Values; Risk Factors

To study effects of estrogens on endothelin-1 (ET-1) mRNA expression in the androgen-sensitive LNCaP-FGC cell line and its androgen-resistant derivative LNCaP-r. Further, if effects of estrone sulfate (E1S) are mediated via conversion to estradiol-17beta (E2). Estrogens have been shown to down-regulate ET-1, a mediator of the osteoblastic response of bone to metastatic prostate cancer.. Cells were grown in steroid-depleted medium and incubated for 2-4 and 48 hours with 0, 1, 10, and 100 nM of either E1S or E2. mRNA levels were measured with an RT-PCR technique. Estrogen metabolism by LNCaP-FGC cells was studied by incubation with estrone (E1) and E1S at the same conditions, followed by determination of E1 and E2.. ET-1 mRNA expression in LNCaP-FGC cells was significantly suppressed by E2 and E1S following incubation for 2-4h but after 48 h only by E2 at 1 and 10nM and in LNCaP-r cells only by E2 at 100 nM following 2-4h of incubation. ET-1 mRNA expression was significantly higher in untreated LNCaP-r than in untreated LNCaP-FGC cells. E1 was efficiently transformed into E2 by LNCaP-FGC cells but very little to E1 and no E2 was formed from E1S.. ET-1 mRNA expression in LNCaP-FGC can be inhibited by E2, but also by its prehormone E1S. The lack of formation of E2 from E1S suggests a mode of action not related to classical steroid receptors. The higher level of ET-1 mRNA expression found in LNCaP-r cells may reflect the capability of a hormone refractory tumor to maintain activity on its own, independently of known regulatory mechanisms such as sex steroids.

Topics: Biomarkers, Tumor; Endothelin-1; Estradiol; Estrogen Receptor beta; Estrone; Gene Expression; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured