title: Estrogen replacement suppresses function of thrombin stimulated platelets by inhibiting Ca(2+) influx and raising cyclic adenosine monophosphate.
abstract: OBJECTIVE
  Estrogen replacement therapy (ERT) in postmenopausal women reduces the risk of cardiovascular diseases. Beneficial changes in lipid profiles account for only one part, thereby raising the question of other estrogen induced benefit that may be lost at menopause. The purpose of this study was to determine the effects of estrogen replacement therapy (ERT) on platelet function of postmenopausal women.
  
  
  METHODS
  The effect of 4 weeks ERT (conjugated estrogens 0.625 mg/day) on platelet function was evaluated ex vivo in 18 postmenopausal women (mean age 53 +/- 5 years, after menopause 3.8 +/- 1.9 years).
  
  
  RESULTS
  After ERT, (1) plasma concentrations of estrone and estradiol significantly increased (estrone: 16 +/- 7-211+/- 80 pg/ml, estradiol: 14+/- 3-125 +/- 49 pg/ml, P<0.05) and LDL-cholesterol decreased (129 +/- 23-94 +/- 25 mg/dl, P<0.05). Plasma 6-keto-PG F(1) alpha significantly increased (7.2 +/- 3.4-13.3 +/- 6.7 pg/dl, P<0.05). (2) platelet aggregation and positive staining for P-selectin in thrombin- (0.1 and 1.0 U/ml) stimulated platelets were inhibited (Th 0.1 U/ml: 4.0 +/- 0.9-2.4 +/- 1.0/control, P<0.05), but positive staining for GP IIb-IIIa complex did not alter significantly. (3) Ca(2+) influx induced by thrombin decreased (Th 0.3 U/ml: 345 +/- 29-298 +/- 24 nmol/l, P<0.05). The baseline [Ca(2+)](i), the release of Ca(2+) from internal stores induced by thrombin and the size of internal Ca(2+) stores did not alter. (4) platelet c-AMP increased (Th 0.3 U/ml: 66.4 +/- 9.4-82.6 +/- 13.0 fmol/l, P<0.05), but platelet nitrite/nitrate (NO(x)) or c-GMP did not alter significantly.
  
  
  CONCLUSIONS
  These results suggest that modulation of platelet function by decreasing Ca influx and increased production of c-AMP may account in part for the cardiovascular benefit of ERT.
authors.affiliation: Department of Clinical Laboratory Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. nakano@mcai.med.hiroshima-u.ac.jp
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oshima
authors.forename: Ryoji
authors.initials: R
authors.lastname: Ozono
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ueda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Oue
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuura
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Sanada
authors.forename: Koso
authors.initials: K
authors.lastname: Ohama
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kambe
mesh_terms: D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D000242:Cyclic AMP / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D017698:Postmenopause / Q000378:metabolism*; D013917:Thrombin
chemical_list: D008078:Cholesterol, LDL; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D004970:Estrone; D004958:Estradiol; D000242:Cyclic AMP; D013917:Thrombin; D002118:Calcium