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This version published online on February 24, 2005
Endocrinology, doi:10.1210/en.2004-1290
A more recent version of this article appeared on June 1, 2005
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Submitted on October 1, 2004
Accepted on February 16, 2005

Development, Maintenance, and Function of the Adrenal Gland in Early Postnatal Pro-opiomelanocortin Null Mutant Mice

Jason Karpac, Dirk Ostwald, Stephanie Bui, Peggy Hunnewell, Malini Shankar, and Ute Hochgeschwender*

Molecular, Cell and Developmental Biology Program, Oklahoma Medical Research Foundation, 825 13th Street, Oklahoma City, OK 73104, USA

* To whom correspondence should be addressed. E-mail: Ute-Hochgeschwender{at}omrf.ouhsc.edu.

Adult mouse mutants homozygous for an engineered POMC null allele lack macroscopically distinct adrenal glands and circulating adrenal hormones. To understand the basis for this adrenal defect, we compared the development of adrenal primordia in POMC null mice and littermate controls. POMC null mutant mice are born with adrenal glands morphologically indistinguishable from those of their wild-type littermates. However, in mutants adrenal cells fail to proliferate postnatally and adrenals atrophy until they have disappeared macroscopically in the adult. While present, mutant adrenals are differentiated as evidenced by the presence of enzymes for the final steps in the synthesis of corticosterone, aldosterone, and catecholamines. However, in contrast to adrenals of wild-type littermates, adrenals of POMC null mutants do not produce corticosterone, not even in response to acute stimulation with exogenous ACTH. They do produce aldosterone, however at reduced levels correlating with adrenal size. Transplantation of POMC null mutant adrenals to adrenalectomized wild-type littermates results in adrenals with normal morphology and production of both corticosterone and aldosterone. These findings demonstrate that POMC peptides are not required for prenatal adrenal development, and that POMC peptides in addition to ACTH are required for postnatal proliferation and maintenance of adrenal structures capable of producing both glucocorticoids and mineralocorticoids.
Key words: N-terminal POMC peptides • MSH • adrenal development • transplantation




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