title: Vascular endothelial growth factor in the rat pituitary: differential distribution and regulation by estrogen.
abstract: Vascular endothelial growth factor (VEGF), an endothelial cell mitogen and permeability factor, participates in tumor angiogenesis, but less is known about its regulation or function in normal vascular homeostasis. In the uterus, which undergoes cyclic changes in its vasculature, VEGF is induced by estrogen. Since the pituitary gland contains highly permeable capillaries and is estrogen-responsive, our objectives were to localize VEGF expression within the pituitary and to determine whether it is regulated by estrogen in both the pituitary and the somatolactotrope cell line, GH(3). Ovariectomized rats were injected with estradiol, and pituitaries and uteri were subjected to in situ hybridization or quantitative reverse transcription-polymerase chain reaction (RT-PCR). VEGF expression was strong and punctate in the neural lobe, weaker and diffuse in the anterior lobe and undetectable in the intermediate lobe. Two VEGF isoforms, 164 and 120, were detected in all tissues. In the posterior pituitary, VEGF expression was 3- to 6-fold higher than in the anterior pituitary or uterus and was unaltered by estrogen. In contrast, anterior pituitary VEGF was induced by estrogen within 1 h, peaked at 3 h, and returned to basal levels by 24 h. Similar dynamics, albeit 10-fold higher, were seen in the uterus. Translated VEGF proteins were detected by Western blot in both the anterior pituitary and uterus. GH(3) cells also showed a dose- and time-dependent induction of VEGF expression by estrogen.
  
  
  CONCLUSIONS
  (1) VEGF expression is higher in the neural lobe than in the anterior lobe and is undetectable in the intermediate lobe, (2) the expression of VEGF164 and VEGF120 is rapidly upregulated by estrogen in the anterior pituitary but is unchanged in the posterior pituitary, and (3) the pituitary lactotrope cell line, GH(3), also increases VEGF expression in response to estradiol.
authors.affiliation: Department of Cell Biology, University of Cincinnati Medical School, Cincinnati, Ohio 45267, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Ochoa
authors.forename: N A
authors.initials: NA
authors.lastname: Mitchner
authors.forename: C D
authors.initials: CD
authors.lastname: Paynter
authors.forename: R E
authors.initials: RE
authors.lastname: Morris
authors.forename: N
authors.initials: N
authors.lastname: Ben-Jonathan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D017403:In Situ Hybridization; D008222:Lymphokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014599:Uterus / Q000737:chemistry / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004958:Estradiol