Lebouille J L, Burbach J P, De Kloet E R, Wiegant V M, Sweep C G, De Wied D
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
Neuroendocrinology. 1988 Jan;47(1):7-12. doi: 10.1159/000124883.
The influence of adrenalectomy and corticosterone substitution was investigated on Leu-Phe cleaving endopeptidase activity and on the levels of gamma-endorphin and beta-endorphin in the pituitary gland and the brain. The enzyme activity was quantitated by a specific radiometric assay based on the cleavage of the Leu17-Phe18 bond in a NH2- and COOH-terminally protected synthetic substrate which was analogous to beta-endorphin-(15-19). This activity may mimick the formation of gamma-endorphin. beta-Endorphin and gamma-endorphin were measured by specific radioimmunoassays. After 14 days of adrenalectomy enzyme activity had increased in anterior (15%) and neurointermediate lobes of the pituitary gland (30%), hypothalamus (25%), and liver (15%). This increase was prevented when the adrenalectomized animals were subjected to chronic corticosterone substitution by subcutaneous implantation of a pellet of 100 mg. Extirpation of only the adrenal medulla did not affect the Leu-Phe cleaving activity. Enzyme activity in the septum, hippocampus, and cerebellum had not changed after adrenalectomy. Determination of immunoreactive levels of gamma- and beta-endorphins showed that in the anterior pituitary gland gamma- and beta-endorphins had increased by 275 and 300%, respectively, 14 days after adrenalectomy. No significant changes were observed in endorphin levels of the intermediate lobe of the pituitary gland, hypothalamus, hippocampus, and septum. The results indicate that Leu-Phe cleaving endopeptidase activity in sensitive to glucocorticoids in tissues containing proopiomelanocortin-producing cells, i.e., anterior and neurointermediate pituitary gland and the hypothalamus. In the anterior pituitary gland it is correlated with the levels of gamma- and beta-endorphins.
研究了肾上腺切除术和皮质酮替代对亮氨酸 - 苯丙氨酸裂解内肽酶活性以及垂体和大脑中γ-内啡肽和β-内啡肽水平的影响。该酶活性通过基于在NH2和COOH末端保护的合成底物中Leu17 - Phe18键的裂解的特定放射性测定法定量，该底物类似于β-内啡肽 - (15 - 19)。这种活性可能模拟γ-内啡肽的形成。β-内啡肽和γ-内啡肽通过特定的放射免疫测定法测量。肾上腺切除术后14天，垂体前叶（15%）、神经中间叶（30%）、下丘脑（25%）和肝脏（15%）的酶活性增加。当通过皮下植入100mg丸剂对肾上腺切除的动物进行慢性皮质酮替代时，这种增加被阻止。仅切除肾上腺髓质不影响亮氨酸 - 苯丙氨酸裂解活性。肾上腺切除术后，隔区、海马和小脑的酶活性没有变化。γ-和β-内啡肽免疫反应水平的测定表明，肾上腺切除术后14天，垂体前叶中γ-和β-内啡肽分别增加了275%和300%。垂体中间叶、下丘脑、海马和隔区的内啡肽水平没有观察到显著变化。结果表明，亮氨酸 - 苯丙氨酸裂解内肽酶活性在含有促阿片黑素皮质素产生细胞的组织中，即垂体前叶、神经中间叶和下丘脑，对糖皮质激素敏感。在垂体前叶中，它与γ-和β-内啡肽的水平相关。
