| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 21, 2004
Accepted on May 18, 2005
Departments of Pediatrics (M.B., E.G., M.H., D.B.W.) and Molecular Biology & Pharmacology (I.B., D.B.W.), Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110; Children's Hospital, Program for Developmental and Reproductive Biology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland (H.P., M.H.); Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland (N.R.); Department of Physiology, Univ. of Oulu, 90220 Oulu, Finland (J.L.)
* To whom correspondence should be addressed. E-mail: wilson_d{at}wustl.edu.
In response to prepubertal gonadectomy certain inbred mouse strains, including DBA/2J, develop sex steroid-producing adrenocortical neoplasms. This phenomenon has been attributed to a lack of gonadal hormones or a compensatory increase in gonadotropins. To assess the relative importance of these mechanisms, we created a new inbred model of adrenocortical neoplasia using female NU/J nude mice. These mice developed adrenocortical neoplasms in response to either gonadectomy or gonadotropin elevation from xenografts of hCG-secreting CHO cells. In each instance the adrenal tumors resembled the neoplasms found in gonadectomized DBA/2J mice and were composed of spindle-shaped A cells and lipid-laden B cells. Both cell populations were defined by ectopic expression of GATA-4 and an absence of the adrenocortical markers melanocortin-2-receptor and steroid 21-hydroxylase, but only B cells expressed the gonadal steroidogenic markers inhibin-
, LH receptor, P450c17, and P450c19. Expression of sex steroidogenic markers was attenuated in the neoplastic adrenal cortex of hCG-treated vs. gonadectomized mice. While neoplastic adrenals were an obvious source of estradiol in gonadectomized mice, ovaries appeared to be the major source of this hormone in hCG-treated mice. Gonadectomy and hCG-treatment elicited comparable increases in serum estradiol, but testosterone levels increased significantly only in hCG-treated mice. We conclude that chronic gonadotropin elevation, caused either by gonadectomy or hCG administration, signals a population of cells in the adrenal subcapsular region of permissive mice to undergo differentiation along a gonadal rather than an adrenal lineage. Thus, NU/J nude mice can be used as a model to study both neoplasia and adrenogonadal lineage specification.
This article has been cited by other articles:
 |
|
 |
|
  M. Doghman, J. Cazareth, and E. Lalli The T cell factor/{beta}-Catenin Antagonist PKF115-584 Inhibits Proliferation of Adrenocortical Carcinoma Cells J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3222 - 3225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vuorenoja, A. Rivero-Muller, A. J Ziecik, I. Huhtaniemi, J. Toppari, and N. A Rahman Targeted therapy for adrenocortical tumors in transgenic mice through their LH receptor by Hecate-human chorionic gonadotropin {beta} conjugate Endocr. Relat. Cancer, June 1, 2008; 15(2): 635 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Clugston, W. Zhang, and J. J. Greer Gene expression in the developing diaphragm: significance for congenital diaphragmatic hernia Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L665 - L675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bernichtein, E. Petretto, S. Jamieson, A. Goel, T. J. Aitman, J. M. Mangion, and I. T. Huhtaniemi Adrenal Gland Tumorigenesis after Gonadectomy in Mice Is a Complex Genetic Trait Driven by Epistatic Loci Endocrinology, February 1, 2008; 149(2): 651 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Doghman, T. Karpova, G. A. Rodrigues, M. Arhatte, J. De Moura, L. R. Cavalli, V. Virolle, P. Barbry, G. P. Zambetti, B. C. Figueiredo, et al. Increased Steroidogenic Factor-1 Dosage Triggers Adrenocortical Cell Proliferation and Cancer Mol. Endocrinol., December 1, 2007; 21(12): 2968 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Looyenga and G. D. Hammer Origin and Identity of Adrenocortical Tumors in Inhibin Knockout Mice: Implications for Cellular Plasticity in the Adrenal Cortex Mol. Endocrinol., November 1, 2006; 20(11): 2848 - 2863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. K Johnsen, M. Slawik, I. Shapiro, M. F Hartmann, S. A Wudy, B. D Looyenga, G. D Hammer, M. Reincke, and F. Beuschlein Gonadectomy in mice of the inbred strain CE/J induces proliferation of sub-capsular adrenal cells expressing gonadal marker genes. J. Endocrinol., July 1, 2006; 190(1): 47 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Anttonen, H Parviainen, A Kyronlahti, M Bielinska, D B Wilson, O Ritvos, and M Heikinheimo GATA-4 is a granulosa cell factor employed in inhibin-{alpha} activation by the TGF-{beta} pathway. J. Mol. Endocrinol., June 1, 2006; 36(3): 557 - 568. [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 |
