Changes in thrombospondin-1 levels in the endothelial cells of the anterior pituitary during estrogen-induced prolactin-secreting pituitary tumors.
Thrombospondin-1 (TSP-1), a multifunctional matrix glyco-protein, has been shown to control tumor growth by inhibiting angiogenesis in various tissues. However, the role of this glycoprotein in pituitary angiogenesis is not well studied. In this report, we determined the changes in the production and action of TSP-1 on endothelial cells in anterior pituitary following estradiol treatment, which is known to increase prolactin-secreting tumor growth and vascularization in this tissue. We showed that TSP-1 immunoreactive protein is distributed in the anterior pituitary, particularly in the endothelial cells. Estradiol treatment for 2 and 4 weeks decreased the total tissue immunoreactive level of TSP-1 as well as the endothelial cell-specific immunoreactive level of this protein in the anterior pituitary. The steroid treatment also decreased the protein levels of TSP-1 in anterior pituitary tissues and in purified pituitary endothelial cells in primary cultures. Determination of the effects of TSP-1 on proliferation and migration of pituitary-derived endothelial cells in primary cultures elucidated an inhibitory action of TSP-1 on these vascular cell functions. These results suggest that locally produced TSP-1 may regulate estrogen angiogenic action on the pituitary.
Sarkar
Abby J
AJ
Endocrinology Program and Department of Animal Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, New Jersey 08901, USA. sarkar@aesop.rutgers.edu
Chaturvedi
Kirti
K
Chen
Cui Ping
CP
Sarkar
Dipak K
DK
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western / Q000379:methods; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation / Q000379:methods; D003864:Depression, Chemical; D042783:Endothelial Cells / Q000378:metabolism*; D004958:Estradiol / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D015175:Prolactinoma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D019700:Thrombospondin 1 / Q000032:analysis / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol