Culler M D, Valenca M M, Merchenthaler I, Flerkó B, Negro-Vilar A
Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Endocrinology. 1988 May;122(5):1968-76. doi: 10.1210/endo-122-5-1968.
The structures of the complementary DNA (cDNA) that encode the rat and human hypothalamic LHRH prohormones were recently determined and the corresponding amino acid sequences deduced. In addition to the LHRH decapeptide, the prohormone contains a 56-amino acid peptide sequence which has been designated gonadotropin-releasing hormone associated peptide (GAP). In the present study we examined the effect of orchidectomy on LHRH prohormone processing in three brain regions known to contain the various elements of the LHRH neuronal system; the preoptic-anterior hypothalamic area, the hypothalamus (HYP), and the median eminence. Both LHRH-like and GAP-like immunoreactivities (LHRH-LI and GAP-LI) were quantitated in these regions in intact male rats and male rats orchidectomized for 1, 2, 3, 5, 7, 14, or 40 days. In addition, the LHRH and GAP immunoreactivities were localized and the effects of orchidectomy examined using immunocytochemical techniques. One day after orchidectomy, a small decrease in GAP-LI and an increase in LHRH-LI were evident in extracts of the preopticanterior hypothalamic area which resulted in a significant decrease in the GAP/LHRH molar ratio. A similar selective decrease in GAP-LI and in the GAP/LHRH molar ratio was also observed in extracts of the HYP, but not until 2 days after orchidectomy. The GAP/LHRH ratio in both regions gradually returned to that of the intact controls. In both the HYP and median eminence, GAP-LI and LHRH-LI gradually declined in parallel through 14 days after orchidectomy. The gradual loss of immunoreactivity in these regions was evident by both RIA quantification and immunocytochemistry. These observations suggest that 1) production and processing of both LHRH and its prohormone are affected by testicular factors, 2) that divergent enzyme and/or transport systems, regulating LHRH and GAP processing, may exist at the level of the perikarya, and 3) long term orchidectomy results in decreased biosynthesis of the prohormone and/or in parallel increases in LHRH and GAP degradation or transport.
编码大鼠和人类下丘脑促黄体激素释放激素（LHRH）原激素的互补DNA（cDNA）结构最近已被确定，并推导了相应的氨基酸序列。除了LHRH十肽外，原激素还包含一个56个氨基酸的肽序列，该序列被命名为促性腺激素释放激素相关肽（GAP）。在本研究中，我们研究了去势对三个已知含有LHRH神经元系统各种成分的脑区中LHRH原激素加工的影响；视前区-下丘脑前部区域、下丘脑（HYP）和正中隆起。在完整雄性大鼠以及去势1、2、3、5、7、14或40天的雄性大鼠的这些区域中，对LHRH样和GAP样免疫反应性（LHRH-LI和GAP-LI）进行了定量。此外，对LHRH和GAP免疫反应性进行了定位，并使用免疫细胞化学技术研究了去势的影响。去势后一天，视前区-下丘脑前部区域提取物中GAP-LI略有下降，LHRH-LI增加，导致GAP/LHRH摩尔比显著降低。在HYP提取物中也观察到GAP-LI和GAP/LHRH摩尔比类似的选择性降低，但直到去势后2天。两个区域的GAP/LHRH比值逐渐恢复到完整对照组的水平。在HYP和正中隆起中，去势后14天内GAP-LI和LHRH-LI平行逐渐下降。通过放射免疫分析定量和免疫细胞化学，这些区域免疫反应性的逐渐丧失是明显的。这些观察结果表明：1）LHRH及其原激素的产生和加工受睾丸因素影响；2）在核周水平可能存在调节LHRH和GAP加工的不同酶和/或转运系统；3）长期去势导致原激素生物合成减少和/或LHRH和GAP降解或转运平行增加。
