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1 Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA
2 Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA
* To whom correspondence should be addressed. E-mail: kellerwd{at}cop.ufl.edu.
The present study was performed to identify the changes in genomic expression of critical components of the hypothalamus-pituitary-adrenal axis in the second half of gestation in fetal sheep. We isolated mRNA from pituitary, hypothalamus, hippocampus, and brainstem in fetal sheep that were 80, 100, 120, 130, 145 days gestation, and 1 and 7 days postnatal (n=4-5/group). Using real-time RT-PCR, we measured mRNA expression levels of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), serum and glucocorticoid induced kinase-1 (sgk1), proopiomelanocortin (POMC), corticotropin releasing hormone (CRH), and arginine vasopressin (AVP). Both MR and GR were highly expressed in pituitary and hippocampus; in all tissues GR was more highly expressed than MR. AVP was more highly expressed than CRH in hypothalamus. MR, GR, and sgk1 expression were increased postnatally in brainstem and sgk1 expression was increased postnatally in hypothalamus. GR expression was reduced in pituitary in term fetuses compared to younger ages. Hypothalamic CRH expression was increased at the end of gestation compared to younger ages, and AVP expression was increased in newborn lambs. Pituitary POMC was increased at 100 days gestation compared to 80 days; hypothalamic POMC was increased at 120 days. Overall, the results demonstrate the expression of both MR and GR in brain regions important for control of the HPA axis. Decreases in expression of GR in pituitary at the end of gestation might contribute to the decreased corticosteroid negative feedback sensitivity at term in this species.
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