The Effects of Proopiomelanocortin Deficiency on Murine Adrenal Development and Responsiveness to Adrenocorticotropin

Abstract

The mature adrenal cortex is dependent upon proopiomelanocortin (POMC)-derived peptides for the maintenance of its size, structure, and endocrine function. Recent studies in mice genetically deficient in POMC have suggested that early exposure to POMC-derived peptides might also be necessary for the development of a functionally competent adrenal. We examined adrenal morphology and function in an independent line of mice lacking all POMC-derived peptides (Pomc-/-). Adrenal glands were found in all mice, although the glands of Pomc-/- mice had markedly reduced weight compared with control animals (0.5 +/- 0.1 vs. 2.1 +/- 0.1 mg, respectively; P < 0.05) and had disrupted cortical architecture. In Pomc-/- mice, plasma corticosterone was undetectable, and plasma aldosterone was significantly reduced compared with wild-type mice (498 +/- 88 vs. 1845 +/- 168 nmol/liter, respectively; P< 0.001). Heterozygous mice (Pomc+/-) had smaller adrenal glands with significantly lower levels of corticosterone both basally and in response to CRH and ACTH than wild-type mice, indicating that two functional copies of the Pomc gene are necessary to support the fully normal function of the hypothalamic-pituitary-adrenal axis. Three-month-old Pomc-/- mice were treated for 10 d with a highly specific ACTH analog. This treatment restored adrenal weight, cortical morphology, and plasma corticosterone to the levels seen in wild-type littermates. In conclusion, murine adrenal glands can develop without exposure to endogenous POMC-derived peptides during fetal and neonatal life. Although such glands are atrophic and hypofunctional, exposure to ACTH alone can restore their size, morphology, and corticosterone secretion.

In vivo alternative assessment of the chemicals that interfere with anterior pituitary POMC expression and interrenal steroidogenesis in POMC: EGFP transgenic zebrafish

“…For instance, the processing of POMC in anterior pituitary corticotrophs results in the generation of pro-γ-MSH, ACTH, and β-LPH (Bicknell, 2008). These POMC-derived hormones regulate many physiological processes including steroidogenesis, skin pigmentation, food intake, and energy balance (Coll et al, 2004(Coll et al, , 2005Coll and Tung, 2009). ACTH is the most important pituitary-derived peptide-controlling steroidogenesis in the adult adrenal gland (Hinson and Raven, 2006;Coll and Tung, 2009).…”

Differential mRNA expression of genes in the porcine adrenal gland associated with psychosocial stress

“…Besides its principal role in the regulation of steroid hormone synthesis and secretion, ACTH is also involved in the control of adrenal growth and functional architecture (Coll et al 2004, Karpac et al 2005. Accordingly, ACTH affects expression of transcripts associated with cell structure, adhesion and proliferation (Schimmer et al 2006, Hazard et al 2008.…”

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

“…ACTH: Despite the opposing effects that have been observed in the presence of acute and chronic ACTH, there is no doubt that this hormone is involved in the normal, physiological regulation of ALDO production [209][210][211].…”