McDonald T J, Hoffmann G E, Myers D A, Nathanielsz P W
Department of Physiology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
Endocrinology. 1990 Dec;127(6):2862-8. doi: 10.1210/endo-127-6-2862.
We evaluated the role of the hypothalamic paraventricular nucleus (PVN) in control of ACTH secretion in fetal sheep. Dexamethasone (DEX, 700 micrograms) (n = 6) or cholesterol (CHOL, 700 micrograms) (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 greater than 5 mm Hg in fetal PaO2), and 3) corticotropin-releasing hormone (CRH) (10 micrograms 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 less than 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 less than 0.05)]. DEX and CHOL responses to CRH at 122 to 127 dga (10 micrograms 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, in 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.
我们评估了下丘脑室旁核（PVN）在调控胎羊促肾上腺皮质激素（ACTH）分泌中的作用。在妊娠108至111天（dga）时，将地塞米松（DEX，700微克）（n = 6）或胆固醇（CHOL，700微克）（n = 5）双侧植入胎羊PVN外侧2毫米处。恢复5天后，对胎儿进行如下刺激：1）低血压（血压下降50%），2）低氧血症（胎儿动脉血氧分压下降超过5毫米汞柱），3）促肾上腺皮质激素释放激素（CRH）（静脉注射10微克，单次注射给胎儿）。在125 dga后重复进行低血压和低氧血症刺激。与CHOL组相比，DEX组胎儿在低血压后血浆ACTH平均浓度较低[分别在小于125 dga和大于125 dga时为23±0.5 vs. 149±83.8以及31±13.1 vs. 101±31.3皮克/毫升（平均值±标准误，P＜0.05）]，在低氧血症期间也较低[分别在小于125 dga和大于125 dga时为11±1.6 vs. 292±152.8以及33±9.4 vs. 304±91.3皮克/毫升（P＜0.05）]。在122至127 dga时，DEX组和CHOL组对CRH（静脉注射10微克）的反应无差异（分别为38±23.9 vs. 92±26.7皮克/毫升）。免疫细胞化学显示，DEX组胎儿PVN中CRH减少，且正中隆起处无CRH，而CHOL组胎儿则无此现象。DEX组和CHOL组胎儿PVN的精氨酸加压素（AVP）免疫染色相似；然而，与CHOL组不同，DEX组胎儿正中隆起外侧区无AVP免疫染色。这些结果表明，在胎羊中，胎儿PVN附近的高浓度糖皮质激素可阻止对照组中因低血压和低氧血症而出现的血浆ACTH分泌增加，且至少部分作用于位于PVN的产生CRH和AVP的神经元水平。
