Effect of a melanocortin type 2 receptor (MC2R) antagonist on the corticosterone response to hypoxia and ACTH stimulation in the neonatal rat
| Autor: | Adam J Goldenberg, Ashley L. Gehrand, Mack Jablonski, Emily Waples, Hershel Raff, Brian Hoeynck |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty endocrine system Time Factors Physiology Endogeny Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Hormone Antagonists Adrenocorticotropic Hormone Corticosterone Stress Physiological 030225 pediatrics Physiology (medical) Internal medicine Adrenal Glands medicine Animals Receptor Hypoxia Acth stimulation Neonatal rat Chemistry Antagonist Age Factors Hypoxia (medical) Phosphoproteins Disease Models Animal 030104 developmental biology Endocrinology Animals Newborn Gene Expression Regulation medicine.symptom Melanocortin Biomarkers Receptor Melanocortin Type 2 Research Article |
| Zdroj: | American journal of physiology. Regulatory, integrative and comparative physiology. 315(1) |
| ISSN: | 1522-1490 |
| Popis: | The adrenal stress response in the neonatal rat shifts from ACTH-independent to ACTH-dependent between postnatal days 2 (PD2) and 8 (PD8). This may be due to an increase in an endogenous, bioactive, nonimmunoreactive ligand to the melanocortin type 2 receptor (MC2R). GPS1574 is a newly described MC2R antagonist that we have shown to be effective in vitro. Further experimentation with GPS1574 would allow better insight into this seemingly ACTH-independent steroidogenic response in neonates. We evaluated the acute corticosterone response to hypoxia or ACTH injection following pretreatment with GPS1574 (32 mg/kg) or vehicle for GPS1574 in PD2, PD8, and PD15 rat pups. Pretreatment with GPS1574 decreased baseline corticosterone in PD2 pups but increased baseline corticosterone in PD8 and PD15 pups. GPS1574 did not attenuate the corticosterone response to hypoxia in PD2 pups and augmented the corticosterone response in PD8 and PD15 pups. GPS1574 augmented the corticosterone response to ACTH in PD2 and PD15 pups but had no significant impact on the response in PD8 pups. Baseline adrenal Mrap and Star mRNA increased from PD2 to PD15, whereas Mrap2 mRNA expression was low and did not change with age. The data suggest that GPS1574 is not a pure MC2R antagonist, but rather acts as a biasing agonist/antagonist. Its ability to attenuate or augment the adrenal response may depend on the ambient plasma ACTH concentration and/or developmental changes in early transduction steroidogenic pathway genes. |
| Databáze: | OpenAIRE |
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