Effect of the long-term administration of corticotropin-releasing factor on the pituitary-adrenal and pituitary-gonadal axis in the male rat.
Effect of the long-term administration of corticotropin-releasing factor on the pituitary-adrenal and pituitary-gonadal axis in the male rat.
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DOI：
10.1172/jci111748
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发表时间：
1985-02
期刊：
影响因子：
--
通讯作者：
C. Rivier;W. Vale
中科院分区：
文献类型：
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作者：
C. Rivier;W. Vale
在成年雄性大鼠中测量了持续暴露于绵羊促肾上腺皮质激素释放因子（oCRF）的影响。在 24 小时内向完整大鼠静脉输注 0.75 nmol oCRF/h，伴随着在释放因子给药的前 90 分钟内出现 ACTH 和皮质酮分泌的峰值，随后下降至较低但仍高于对照值。此外，促肾上腺皮质激素释放因子（CRF）治疗的大鼠血浆睾酮水平降低。对完整大鼠皮下注射 0.075 或 0.75 nmol oCRF/h 持续 7 天，也导致血浆 ACTH 和皮质酮水平升高，与暴露于释放因子 24 小时后测量的水平相当，以及剂量相关的肾上腺肥大和垂体 ACTH 含量增加。在这些动物中，CRF 显着抑制黄体生成素 (LH)（但不影响卵泡刺激素 [FSH]）、睾酮和 PRL 分泌，并降低精囊重量。 CRF 的所有作用均由外源性 ACTH 模拟。相比之下，除了 CRF 略微升高 FSH 分泌外，CRF 和 ACTH 都不能显着改变肾上腺切除动物的生殖参数，这表明外周施用 CRF 诱导的肾上腺类固醇循环水平升高是 CRF 诱导的生育力抑制的主要介质。这些结果表明，在大鼠中，外周给药的 CRF 对垂体-肾上腺轴的持续刺激导致垂体-肾上腺轴某种程度的脱敏，但仍然伴随着 ACTH 和皮质类固醇的循环水平持续升高。据信，经 CRF 治疗的大鼠肾上腺类固醇分泌增加，参与了在这些大鼠中观察到的生殖参数的破坏。
The effect of the continuous exposure to ovine corticotropin-releasing factor (oCRF) was measured in adult male rats. The intravenous infusion of 0.75 nmol oCRF/h to intact rats over a 24-h period was accompanied by a peak of ACTH and corticosterone secretion that occurred during the first 90 min of administration of the releasing factor, followed by a decrease to lower, but still above control, values. Additionally, corticotropin-releasing factor (CRF)-treated rats had decreased plasma testosterone levels. The subcutaneous administration of 0.075 or 0.75 nmol oCRF/h to intact rats for 7 d also resulted in elevations of both plasma ACTH and corticosterone levels comparable to those measured after a 24-h exposure to the releasing factor, as well as dose-related hypertrophy of the adrenals and increases in pituitary ACTH content. In these animals, CRF markedly inhibited luteinizing hormone (LH) (but not follicle-stimulating hormone [FSH] ), testosterone, and PRL secretion and decreased seminal vesicle weights. All the effects of CRF were mimicked by exogenously administered ACTH. By contrast, with the exception of FSH secretion, which was slightly elevated by CRF, neither CRF nor ACTH were able to significantly modify reproductive parameters in adrenalectomized animals, which suggests that the elevation of circulating levels of adrenal steroids induced by peripherally administered CRF represents major mediators of CRF-induced inhibition of fertility. These results indicate that in the rat, the continuous stimulation of the pituitary-adrenal axis by peripherally administered CRF causes some degree of desensitization of the pituitary-adrenal axis, but is still accompanied by persistent elevations of the circulating levels of both ACTH and corticosteroids. The increased secretion of adrenal steroids by CRF-treated rats is believed to participate in the disruption of reproductive parameters observed in these rats.