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Endocrine Reviews 18 (3): 378-403
Copyright © 1997 by The Endocrine Society

Developmental and Functional Biology of the Primate Fetal Adrenal Cortex1

Sam Mesiano and Robert B. Jaffe

Reproductive Endocrinology Center, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143-0556

I. Introduction
II. Development
A. Embryonic adrenal development
B. Fetal adrenal development
C. Neonatal adrenal development
D. Growth
E. Functional development
1. Ontogeny of steroidogenic activity
2. Functional zonation and ontogeny of steroidogenic enzyme expression
3. Responsiveness to ACTH
III. Regulation
A. The fetal pituitary and ACTH
B. Growth factors
1. Basic fibroblast growth factor (bFGF)
2. Epidermal growth factor (EGF)
3. Insulin-like growth factors I and II (IGF-I and IGF-II)
4. Activin/inhibins
5. TGFß
C. Nuclear receptors/transcription factors
D. Placental factors
1. Human CG (hCG)
2. Placental CRH and ACTH
3. Indirect effect of placental glucocorticoid metabolism
4. Placental estrogens
IV. Physiology
A. Placental estrogen formation
B. Timing of parturition and fetal maturation
V. Summary




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Biol Reprod, February 1, 2002; 66(2): 282 - 290.
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C. Martinerie, C. Gicquel, A. Louvel, M. Laurent, P. N. Schofield, and Y. Le Bouc
Altered Expression of novH Is Associated with Human Adrenocortical Tumorigenesis
J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3929 - 3940.
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R. C. Ribeiro, F. Sandrini, B. Figueiredo, G. P. Zambetti, E. Michalkiewicz, A. R. Lafferty, L. DeLacerda, M. Rabin, C. Cadwell, G. Sampaio, et al.
An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma
PNAS, July 31, 2001; 98(16): 9330 - 9335.
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N. Hiroi, G. P. Chrousos, B. Kohn, A. Lafferty, M. Abu-Asab, S. Bonat, A. White, and S. R. Bornstein
Adrenocortical-Pituitary Hybrid Tumor Causing Cushing's Syndrome
J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2631 - 2637.
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E. Chamoux, L. Bolduc, J.-G. Lehoux, and N. Gallo-Payet
Identification of Extracellular Matrix Components and Their Integrin Receptors in the Human Fetal Adrenal Gland
J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2090 - 2098.
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 Mol. Endocrinol.Home page
N. A. Hanley, W. E. Rainey, D. I. Wilson, S. G. Ball, and K. L. Parker
Expression Profiles of SF-1, DAX1, and CYP17 in the Human Fetal Adrenal Gland: Potential Interactions in Gene Regulation
Mol. Endocrinol., January 1, 2001; 15(1): 57 - 68.
[Abstract] [Full Text]

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R. Gitau, N. M. Fisk, J. M. A. Teixeira, A. Cameron, and V. Glover
Fetal Hypothalamic-Pituitary-Adrenal Stress Responses to Invasive Procedures Are Independent of Maternal Responses
J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 104 - 109.
[Abstract] [Full Text]

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 Toxicol PatholHome page
T. J. Rosol, J. T. Yarrington, J. Latendresse, and C. C. Capen
Adrenal Gland: Structure, Function, and Mechanisms of Toxicity
Toxicol Pathol, January 1, 2001; 29(1): 41 - 48.
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L. Ibáñez, J. DiMartino-Nardi, N. Potau, and P. Saenger
Premature Adrenarche--Normal Variant or Forerunner of Adult Disease?
Endocr. Rev., December 1, 2000; 21(6): 671 - 696.
[Abstract] [Full Text]

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 EndocrinologyHome page
L. Breault, E. Chamoux, J.-G. LeHoux, and N. Gallo-Payet
Localization of G Protein {{alpha}}-Subunits in the Human Fetal Adrenal Gland
Endocrinology, December 1, 2000; 141(12): 4334 - 4341.
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J. R.G. Challis, S. G. Matthews, W. Gibb, and S. J. Lye
Endocrine and Paracrine Regulation of Birth at Term and Preterm
Endocr. Rev., October 1, 2000; 21(5): 514 - 550.
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P. C. White and P. W. Speiser
Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency
Endocr. Rev., June 1, 2000; 21(3): 245 - 291.
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F. Wilkin, N. Gagné, J. Paquette, L. L. Oligny, and C. Deal
Pediatric Adrenocortical Tumors: Molecular Events Leading to Insulin-Like Growth Factor II Gene Overexpression
J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 2048 - 2056.
[Abstract] [Full Text]

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 Arch. Dis. Child. Fetal Neonatal Ed.Home page
P C Ng
The fetal and neonatal hypothalamic-pituitary-adrenal axis
Arch. Dis. Child. Fetal Neonatal Ed., May 1, 2000; 82(3): 250F - 254.
[Full Text]

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 Biol. Reprod.Home page
C. L. Coulter, D. A. Myers, P. W. Nathanielsz, and I. M. Bird
Ontogeny of Angiotensin II Type 1 Receptor and Cytochrome P450c11 in the Sheep Adrenal Gland
Biol Reprod, March 1, 2000; 62(3): 714 - 719.
[Abstract] [Full Text]

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M. C. Zatelli, R. Rossi, and E. C. degli Uberti
Androgen Influences Transforming Growth Factor-{beta}1 Gene Expression in Human Adrenocortical Cells
J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 847 - 852.
[Abstract] [Full Text]

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E. Chamoux
Involvement of the Angiotensin II Type 2 Receptor in Apoptosis during Human Fetal Adrenal Gland Development
J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4722 - 4730.
[Abstract] [Full Text]

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 EndocrinologyHome page
E. D. Albrecht, J. S. Babischkin, W. A. Davies, M. G. Leavitt, and G. J. Pepe
Identification and Developmental Expression of the Estrogen Receptor {alpha} and {beta} in the Baboon Fetal Adrenal Gland
Endocrinology, December 1, 1999; 140(12): 5953 - 5961.
[Abstract] [Full Text]

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A. Chakravorty, S. Mesiano, and R. B. Jaffe
Corticotropin-Releasing Hormone Stimulates P450 17{alpha}-Hydroxylase/17,20-Lyase in Human Fetal Adrenal Cells via Protein Kinase C
J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3732 - 3738.
[Abstract] [Full Text] [PDF]

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M. G. Leavitt, E. D. Albrecht, and G. J. Pepe
Development of the Baboon Fetal Adrenal Gland: Regulation of the Ontogenesis of the Definitive and Transitional Zones by Adrenocorticotropin
J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3831 - 3835.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
T. Tajima, X.-M. Ma, S. R. Bornstein, and G. Aguilera
Prenatal Dexamethasone Treatment Does Not Prevent Alterations of the Hypothalamic Pituitary Adrenal Axis in Steroid 21-Hydroxylase Deficient Mice
Endocrinology, July 1, 1999; 140(7): 3354 - 3362.
[Abstract] [Full Text]

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 Biol. Reprod.Home page
R. B. Billiar, M. G. Leavitt, P. Smith, E. D. Albrecht, and G. J. Pepe
Functional Capacity of Fetal Zone Cells of the Baboon Fetal Adrenal Gland: A Major Source of {alpha}-Inhibin
Biol Reprod, July 1, 1999; 61(1): 142 - 146.
[Abstract] [Full Text]

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 EndocrinologyHome page
M. Freemark
Editorial: The Fetal Adrenal and the Maturation of the Growth Hormone and Prolactin Axes
Endocrinology, May 1, 1999; 140(5): 1963 - 1965.
[Full Text]

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 EndocrinologyHome page
M. M. Weber, C. Fottner, P. Schmidt, K. M. H. Brodowski, K. Gittner, H. Lahm, D. Engelhardt, and E. Wolf
Postnatal Overexpression of Insulin-Like Growth Factor II in Transgenic Mice Is Associated with Adrenocortical Hyperplasia and Enhanced Steroidogenesis
Endocrinology, April 1, 1999; 140(4): 1537 - 1543.
[Abstract] [Full Text]

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S. J. Spencer, S. Mesiano, J. Y. Lee, and R. B. Jaffe
Proliferation and Apoptosis in the Human Adrenal Cortex during the Fetal and Perinatal Periods: Implications for Growth and Remodeling
J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 1110 - 1115.
[Abstract] [Full Text]

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 Biol. Reprod.Home page
P. J. Burton and B. J. Waddell
Dual Function of 11ß-Hydroxysteroid Dehydrogenase in Placenta: Modulating Placental Glucocorticoid Passage and Local Steroid Action
Biol Reprod, February 1, 1999; 60(2): 234 - 240.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. L. Coulter and R. B. Jaffe
Functional Maturation of the Primate Fetal Adrenal in Vivo: 3. Specific Zonal Localization and Developmental Regulation of CYP21A2 (P450c21) and CYP11B1/CYP11B2 (P450c11/Aldosterone Synthase) Lead to Integrated Concept of Zonal and Temporal Steroid Biosynthesis
Endocrinology, December 1, 1998; 139(12): 5144 - 5150.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. Smith, S. Mesiano, E.-C. Chan, S. Brown, and R. B. Jaffe
Corticotropin-Releasing Hormone Directly and Preferentially Stimulates Dehydroepiandrosterone Sulfate Secretion by Human Fetal Adrenal Cortical Cells
J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2916 - 2920.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
N. Boulle, A. Logié, C. Gicquel, L. Perin, and Y. Le Bouc
Increased Levels of Insulin-Like Growth Factor II (IGF-II) and IGF-Binding Protein-2 Are Associated with Malignancy in Sporadic Adrenocortical Tumors
J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1713 - 1720.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
J. L. Shifren, S. Mesiano, R. N. Taylor, N. Ferrara, and R. B. Jaffe
Corticotropin Regulates Vascular Endothelial Growth Factor Expression in Human Fetal Adrenal Cortical Cells
J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1342 - 1347.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
G. W. Aberdeen, M. G. Leavitt, G. J. Pepe, and E. D. Albrecht
Effect of Maternal Betamethasone Administration at Midgestation on Baboon Fetal Adrenal Gland Development and Adrenocorticotropin Receptor Messenger Ribonucleic Acid Expression
J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 976 - 982.
[Abstract] [Full Text]

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G. Cao, C. K. Garcia, K. L. Wyne, R. A. Schultz, K. L. Parker, and H. H. Hobbs
Structure and Localization of the Human Gene Encoding SR-BI/CLA-1. EVIDENCE FOR TRANSCRIPTIONAL CONTROL BY STEROIDOGENIC FACTOR 1
J. Biol. Chem., December 26, 1997; 272(52): 33068 - 33076.
[Abstract] [Full Text] [PDF]


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