The periphery of the human fetal adrenal gland is a site of angiogenesis: zonal differential expression and regulation of angiogenic factors.
BACKGROUND
Although the inner fetal zone (FZ) of the mid-gestation human fetal adrenal (HFA) produces dehydroepiandrosterone sulfate, the function of the outer definitive zone (DZ) remains less clear. We have proposed that the DZ phenotype is that of a pool of progenitor cells, many of which are mitotically active. Recently, we studied HFA expression of a family of vascular endothelial cell-specific angiogenic factors, the angiopoietins (Angs), and demonstrated that Ang2 was localized predominantly in the periphery of the gland. Ang1 stabilizes, whereas Ang2 destabilizes, vessels, increasing responsiveness to angiogenic stimuli such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF)-2.


OBJECTIVE
Our objective was to test the hypothesis that the periphery of the HFA is a site of angiogenesis.


METHODS
Studies were conducted involving RNA, frozen sections, and primary cell cultures from midgestation HFAs.


METHODS
Immunofluorescence, laser capture microdissection, and real-time quantitative RT-PCR were used.


RESULTS
Double immunostaining demonstrated that proliferating endothelial cells were limited to the DZ and DZ/FZ border. Ang2 mRNA was primarily expressed in the DZ, whereas Ang1 mRNA was primarily in the FZ. VEGF-A and FGF-2 mRNA levels were higher in the DZ. FGF-2 (10 ng/ml) induced Ang2 mRNA by 4-fold in both zones of cells (P < 0.01, at 24 h), but not Ang1 or VEGF-A mRNA.


CONCLUSIONS
Data suggest that angiogenesis occurs at the periphery of the HFA. The DZ-predominant expression of Ang2 may be explained, in part, by the parallel pattern of FGF-2 expression.
Ishimoto
Hitoshi
H
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California-San Francisco, San Francisco, CA 94143-0556, USA.
Minegishi
Kazuhiro
K
Higuchi
Takayuki
T
Furuya
Masataka
M
Asai
Satoshi
S
Kim
Seon Hye
SH
Tanaka
Mamoru
M
Yoshimura
Yasunori
Y
Jaffe
Robert B
RB
D000311:Adrenal Glands / Q000098:blood supply* / Q000196:embryology* / Q000378:metabolism; D042501:Angiogenic Proteins / Q000235:genetics* / Q000378:metabolism*; D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism; D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D042501:Angiogenic Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II; D000803:Angiotensin I