Hypothalamic Glucocorticoid Implants Prevent Fetal Ovine Adrenocorticotropin Secretion in Response to Stress*

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Abstract
We evaluated the role of the hypothalamic paraventricular nucleus (PVN) in control of ACTH secretion in fetal sheep. Dexamethasone (DEX, 700 .mu.g) (n=6) or cholesterol (CHOL, 700 .mu.g) (n=5) implants were placed bilaterally 2 mm lateral to PVN of fetal sheep at 108 to 111 days of gestation (dga). After 5 days recovery, fetuses were challenged with: 1) hypotension (50% drop of blood pressure), 2) hypoxemia (fall of > 5 mm Hg in fetal PaO2), and 3) corticotropin-releasing hormone (CRH) (10 .mu.g iv, single injection to fetus). Hypotension and hypoxemia were repeated after 125 dga. Compared with CHOL, DEX fetuses had lower average concentrations of ACTH in plasma after hypotension [23 .+-. 0.5 vs. 149 .+-. 83.8 and 31 .+-. 13.1 vs. 101 .+-. 31.3 pg ml-1 at less than 125 and more than 125 dga, respectively (mean .+-. SEM, P < 0.05)] and during hypoxemia [11 .+-. 1.6 vs. 292 .+-. 152.8 and 33 .+-. 9.4 vs. 304 .+-. 91.3 pg ml-1 at less than 125 and more than 125 dga, respectively (P < 0.05)]. DEX and CHOL responses to CRH at 122 to 127 dga (10 .mu.g iv) were not different (38 .+-. 23.9 vs. 92 .+-. 26.7 pg ml-1, respectively). Immunocytochemistry demonstrated that CRH was decreased in PVN and eliminated from median eminence in DEX, but not in CHOL fetuses. Arginine vasopressin (AVP) immunostaining of PVN of DEX and CHOL fetuses was similar; however, unlike CHOL, DEX fetuses showed no AVP immunostaining of the external zone of median eminence. These results show that, fetal sheep, high concentrations of glucocorticoid near the fetal PVN prevent increases in plasma ACTH secretion seen in controls in response to hypotension and hypoxemia and exert at least part of their effect at the level of the CRH- and AVP-producing neurons located in the PVN.

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