title: Progesterone withdrawal causes endothelin release from cultured human uterine microvascular endothelial cells.
abstract: BACKGROUND
  Current theories on the physiology of menstrual bleeding in humans offers an explanation for the shedding of the endometrium as a result of a breakdown of the extracellular matrix due to an inflammatory reaction. The link between the fall in progesterone levels and these events is not clear. Neither has an explanation been presented for the vasoconstriction in the coiled arteries occurring during menses. We have hypothesized a chain of events where the fall in progesterone levels induces an upregulation of the thrombin receptor in the small uterine arteries leading to an increased thrombin response and subsequent endothelin release.
  
  
  METHODS
  Endothelial cells from human umbilical cord (HUVECs) and from human small uterine arteries (UtMVECs) were cultured under conditions partly resembling the female hormonal cycle with progesterone withdrawal.
  
  
  RESULTS
  Following progesterone increase and subsequent withdrawal, we found an increased production of thrombin receptor and an increased release of endothelin from UtMVECs compared with HUVECs.
  
  
  CONCLUSIONS
  Endothelin release in response to progesterone withdrawal in UtMVECs can offer an explanation for the vasoconstriction seen in the coiled arteries during menses in humans.
authors.affiliation: Department of Women and Child Health, Karolinska Institutet and Hospital, S-171 76 Stockholm, Sweden. mans.edlund@ks.se
authors.forename: Måns
authors.initials: M
authors.lastname: Edlund
authors.forename: Eva
authors.initials: E
authors.lastname: Andersson
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fried
mesh_terms: D001158:Arteries; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D008833:Microcirculation; D011374:Progesterone / Q000008:administration & dosage* / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000378:metabolism; D018179:Receptors, Thrombin / Q000378:metabolism; D014470:Umbilical Cord / Q000098:blood supply; D014599:Uterus / Q000098:blood supply*
chemical_list: D016232:Endothelins; D011980:Receptors, Progesterone; D018179:Receptors, Thrombin; D011374:Progesterone