Raff Hershel, Jacobson Lauren, Cullinan William E
Endocrinology and Diabetes, St. Luke's Physician's Office Bldg., 2801 W. KK River Pkwy., Suite 245, Milwaukee, WI 53215, USA.
Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R1224-30. doi: 10.1152/ajpregu.00259.2003. Epub 2003 Jul 10.
Hypoxia is a common cause of neonatal morbidity and mortality. We have previously demonstrated a dramatic ACTH-independent activation of adrenal steroidogenesis in hypoxic neonatal rats, leading to increases in circulating corticosterone levels. The purpose of the present study was to determine if this ACTH-independent increase in corticosterone inhibits the ACTH response to acute stimuli. Neonatal rats were exposed to normoxia (control) or hypoxia from birth to 5 or 7 days of age. At the end of the exposure, plasma ACTH and corticosterone were measured before and after either ether vapors were administered for 3 min or CRH (10 microg/kg) was given intraperitoneally. Thyroid function, pituitary pro-opiomelanocortin (POMC) mRNA and ACTH content, and hypothalamic corticotropin-releasing hormone (CRH), neuropeptide Y (NPY), and AVP mRNA were also assessed. Hypoxia led to a significant increase in corticosterone without a large increase in ACTH, confirming previous studies. The ACTH responses to ether or CRH administration were almost completely inhibited in hypoxic pups. Hypoxia did not affect the established regulators of the neonatal hypothalamic-pituitary-adrenal axis, including pituitary POMC or ACTH content, hypothalamic CRH, NPY, or AVP mRNA (parvo- or magnocellular), or thyroid function. We conclude that hypoxia from birth to 5 or 7 days of age leads to an attenuated ACTH response to acute stimuli, most likely due to glucocorticoid negative feedback. The neural and biochemical mechanism of this effect has yet to be elucidated.
缺氧是新生儿发病和死亡的常见原因。我们之前已经证明，在缺氧的新生大鼠中，肾上腺类固醇生成存在显著的促肾上腺皮质激素（ACTH）非依赖性激活，导致循环皮质酮水平升高。本研究的目的是确定这种皮质酮的ACTH非依赖性增加是否会抑制对急性刺激的ACTH反应。新生大鼠从出生到5或7日龄暴露于常氧（对照）或缺氧环境。在暴露结束时，在给予3分钟乙醚蒸气或腹腔注射促肾上腺皮质激素释放激素（CRH，10微克/千克）之前和之后，测量血浆ACTH和皮质酮水平。还评估了甲状腺功能、垂体前阿黑皮素原（POMC）mRNA和ACTH含量，以及下丘脑促肾上腺皮质激素释放激素（CRH）、神经肽Y（NPY）和精氨酸加压素（AVP）mRNA。缺氧导致皮质酮显著增加，而ACTH没有大幅增加，这证实了之前的研究。在缺氧的幼崽中，对乙醚或CRH给药的ACTH反应几乎完全受到抑制。缺氧不影响新生儿下丘脑-垂体-肾上腺轴的既定调节因子，包括垂体POMC或ACTH含量、下丘脑CRH、NPY或AVP mRNA（小细胞或大细胞），或甲状腺功能。我们得出结论，从出生到5或7日龄的缺氧会导致对急性刺激的ACTH反应减弱，最可能是由于糖皮质激素的负反馈作用。这种效应的神经和生化机制尚待阐明。
