Martensz N D
Neuroscience. 1985 Nov;16(3):625-40. doi: 10.1016/0306-4522(85)90197-6.
Puberty in the female rat is accompanied by a marked attenuation of the opioid inhibition of luteinizing hormone secretion. One factor which may contribute to this altered role is a change in the metabolism of opioid peptides during sexual maturation. beta-Endorphin undergoes a considerable degree of metabolism through both C-terminal proteolysis and N-acetylation, and these metabolites do not possess opioid activity. The processing of beta-endorphin in the hypothalamus and in the anterior and neurointermediate lobes of the pituitary gland in prepubertal and adult female rats was studied using gel filtration and high performance liquid chromatography coupled with radioimmunoassay. In the anterior lobe, high molecular weight precursors of beta-endorphin (pro-opiomelanocortin and beta-lipotropin) were present in prepubertal (28 days old) rats, but little authentic beta-endorphin was detected. In contrast, only beta-lipotropin and beta-endorphin were present in mature (70 days old) animals. Only beta-endorphin-sized peptides were present in the neurointermediate lobes of both prepubertal and adult rats. However, the proportion of N-acetylated metabolites was higher in sexually mature animals. In the hypothalamus, only beta-endorphin-sized peptides were present in both juvenile and adult animals. However, C-terminal proteolysis increased with age (no acetylated metabolites were detectable in this tissue). The proportion of the total beta-endorphin-like immunoreactivity attributable to beta-endorphin was lower in young adult (first dioestrus after vaginal opening) (55%) and mature (dioestrus, 61-64 days old) rats (56%) compared to prepubertal (30 days old) animals (75%) and the proportions of non-acetylated metabolites [beta-endorphin-(1-27) in young adults and beta-endorphin-(1-26) in adults] were increased concomitantly. These changes were correlated with a reduced luteinizing hormone response to the opiate antagonist naloxone in adult compared to prepubertal rats. beta-Endorphin is processed differently in the two lobes of the pituitary gland and in the hypothalamus and the degree of metabolism increases as the rat reaches sexual maturity. The increased metabolism of beta-endorphin in the hypothalamus, the site most likely to be involved in the control of luteinizing hormone secretion, results in a reduction in the relative proportion of the opioid active parent peptide. Thus, increased inactivation of beta-endorphin may contribute to the attenuation of the opioid inhibition of luteinizing hormone secretion observed during puberty.
雌性大鼠的青春期伴随着阿片类物质对促黄体生成素分泌抑制作用的显著减弱。导致这种作用改变的一个因素可能是性成熟过程中阿片肽代谢的变化。β-内啡肽通过C末端蛋白水解和N-乙酰化经历了相当程度的代谢，并且这些代谢产物不具有阿片活性。使用凝胶过滤、高效液相色谱结合放射免疫分析法研究了青春期前和成年雌性大鼠下丘脑以及垂体前叶和神经中间叶中β-内啡肽的加工过程。在垂体前叶中，青春期前（28日龄）大鼠存在β-内啡肽的高分子量前体（阿片促黑素皮质素原和β-促脂素），但检测到的真实β-内啡肽很少。相比之下，成熟（70日龄）动物中仅存在β-促脂素和β-内啡肽。青春期前和成年大鼠的神经中间叶中仅存在β-内啡肽大小的肽段。然而，性成熟动物中N-乙酰化代谢产物的比例更高。在下丘脑中，幼年和成年动物中均仅存在β-内啡肽大小的肽段。然而，C末端蛋白水解随年龄增加（该组织中未检测到乙酰化代谢产物）。与青春期前（30日龄）动物（75%）相比，年轻成年（阴道开口后的第一次发情期）大鼠（55%）和成熟（发情期，61 - 64日龄）大鼠（56%）中归因于β-内啡肽的总β-内啡肽样免疫反应性比例较低，并且非乙酰化代谢产物的比例（年轻成年大鼠中的β-内啡肽-(1 - 27)和成年大鼠中的β-内啡肽-(1 - 26)）相应增加。与青春期前大鼠相比，这些变化与成年大鼠中促黄体生成素对阿片拮抗剂纳洛酮的反应降低相关。β-内啡肽在垂体的两个叶和下丘脑中的加工方式不同，并且随着大鼠达到性成熟，代谢程度增加。下丘脑是最可能参与促黄体生成素分泌控制的部位，其中β-内啡肽代谢的增加导致阿片活性母肽的相对比例降低。因此，β-内啡肽失活增加可能导致青春期期间观察到的阿片类物质对促黄体生成素分泌抑制作用的减弱。
