| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 12, 2005
Accepted on February 10, 2006
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences (H. I., R.B.J.), and Genomic Analysis Core Facility, Comprehensive Cancer Center (D.G.G.), University of California, San Francisco, San Francisco, CA 94143
CONTEXT: ACTH is the key tropic hormone for the human fetal adrenal (HFA). As vascular development must be coordinated with organ growth, ACTH may regulate local angiogenic factors, thereby influencing HFA angiogenesis. We previously demonstrated that ACTH up-regulates vascular endothelial growth factor (VEGF) in HFA cortical cells. A newer angiogenic factor family, the angiopoietins (Ang's), also plays critical roles: Ang1 stabilizes, while Ang2 destabilizes, vessels, increasing responsiveness to angiogenic stimuli.
OBJECTIVE: To investigate expression and ACTH regulation of Ang's and their receptor Tie2 in the HFA.
DESIGN, SETTING, AND PATIENTS: Studies were conducted involving RNA, frozen sections, and primary cell cultures from HFA's (14-24 wk), and human adult adrenal RNA. MAIN OUTCOME MEASURES: Ang's and Tie2 mRNA levels determined by real-time quantitative RT-PCR (qRT-PCR); Ang2 and Tie2, localized by immunostaining; and ACTH regulation of Ang's, investigated by qRT-PCR, Western blot and ELISA.
RESULTS: Mean HFA Ang2/Ang1 mRNA ratio was 6.3-fold higher than adult adrenals (P < 0.001). Ang2 was localized predominantly in the HFA periphery while Tie2 demonstrated endothelial localization. In isolated HFA cortical cells, ACTH up-regulated Ang mRNA levels in a time- and dose- dependent manner, with the balance favoring Ang2. Ang2 protein levels were elevated in ACTH-stimulated HFA cortical cells and conditioned medium. 8-Br-cAMP and forskolin mimicked ACTH effects on the Ang's.
CONCLUSIONS: Higher HFA Ang2/Ang1 ratios may reflect greater vascular remodeling than in the adult. Ang's, particularly Ang2, in concert with VEGF, may mediate ACTH tropic action, ensuring coordination of HFA growth, steroidogenesis and angiogenesis.
This article has been cited by other articles:
 |
|
 |
|
  H. Ishimoto, K. Minegishi, T. Higuchi, M. Furuya, S. Asai, S. H. Kim, M. Tanaka, Y. Yoshimura, and R. B. Jaffe The Periphery of the Human Fetal Adrenal Gland Is a Site of Angiogenesis: Zonal Differential Expression and Regulation of Angiogenic Factors J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2402 - 2408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ishimoto, M. O. Muench, T. Higuchi, K. Minegishi, M. Tanaka, Y. Yoshimura, and R. B. Jaffe Midkine, a Heparin-Binding Growth Factor, Selectively Stimulates Proliferation of Definitive Zone Cells of the Human Fetal Adrenal Gland J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4050 - 4056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ishimoto, D. G. Ginzinger, T. Matsumoto, Y. Hattori, M. Furuya, K. Minegishi, M. Tanaka, Y. Yoshimura, and R. B. Jaffe Differential Zonal Expression and Adrenocorticotropin Regulation of Secreted Protein Acidic and Rich in Cysteine (SPARC), a Matricellular Protein, in the Midgestation Human Fetal Adrenal Gland: Implications for Adrenal Development J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3208 - 3214. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
