Responsiveness of immature versus adult male rat hypothalami to dibutyryl cyclic AMP- and forskolin-induced LHRH release in vitro.
Responsiveness of immature versus adult male rat hypothalami to dibutyryl cyclic AMP- and forskolin-induced LHRH release in vitro.
复制标题
未成熟雄性大鼠下丘脑与成年雄性大鼠下丘脑对二丁酰环 AMP 和毛喉素诱导的体外 LHRH 释放的反应性。
DOI：
10.1159/000124118
复制
发表时间：
1985
影响因子：
4.1
通讯作者：
Ramirez,VD
中科院分区：
文献类型：
--
作者：
Hartter,DE;Ramirez,VD
本研究观察了间歇性二丁酰环磷酸腺苷（dbcAMP，5 × 10 ~（-8）M）、丁酸盐（5 × 10 ~（-8）M）和毛喉素（10 ~（-4）M）对灌流25、30、45和60-75日龄（成年）雄性大鼠下丘脑碎片中免疫反应性促黄体生成素释放激素（LHRH）释放的影响。结果表明，在25天的年龄，雄性大鼠下丘脑是最响应于环AMP（162%的预输液基础LHRH释放），由30天的年龄，dbcAMP也引起增加LHRH释放（120%的基础）。到45日龄，dbcAMP对体外LHRH释放的影响略有抑制（基础的78%）;然而，到成年期，这种环核苷酸对LHRH释放的影响微乎其微（基础的92%）。丁酸盐还诱导雄性大鼠下丘脑体外LHRH释放的年龄依赖性改变，在25日龄时丁酸盐递送后略有增加（115%），在30日龄（82%）和45日龄（68%）时略有减少，成年期变化不大（94%）。后一发现强调了使用丁酸盐作为环AMP的丁酰衍生物的对照的重要性，已知其释放丁酸作为母体化合物的水解产物。要解决的可能性，缺乏有效性的dbcAMP在老年动物制剂是完全由于增加敏感性的雄性大鼠中基底下丘脑片段丁酸，我们研究了毛喉素（10- 4 M），腺苷酸环化酶刺激剂，对LHRH释放的影响。在30日龄的雄性大鼠制备，连续输注毛喉素诱发LHRH释放显着增加，其特征在于由情节浪涌;相反，这种化合物是相对无效的诱导LHRH浪涌在成年雄性大鼠的条件。该研究还表明，虽然下丘脑LHRH浓度在45日龄时达到最大水平，但LHRH的自发体外释放作为雄性大鼠供体的年龄（从25日龄到成年）的函数以接近线性的方式增加，从而表明自发LHRH神经元活性和dbcAMP刺激的LHRH释放之间的分离。总之，可以得出结论，下丘脑神经LHRH装置的环AMP（无论是外源性应用或通过刺激腺苷酸环化酶产生）的反应性降低大鼠成熟，没有响应接近青春期和成年期。此外，成熟的LHRH释放和LHRH浓度的变化，灌流中基底部的下丘脑片段从完整的雄性大鼠可以推断使用这种体外灌流系统。
In the present study, we have investigated the effects of intermittent dibutyryl cyclic AMP (dbcAMP, 5 × 10–8M), butyrate (5 × 10–8M) and forskolin (10–4M) on immunoreactive luteinizing hormone-releasing hormone (LHRH) release from superfused hypothalamic fragments from intact male rats of age 25, 30, 45, or 60–75 day (adult). The results indicate that at 25 days of age, male rat hypothalami were most responsive to cyclic AMP (162% of preinfusion basal LHRH release); by 30 days of age, dbcAMP also elicited increased LHRH release (120% of basal). By 45 days of age, the dbcAMP effect on in vitro LHRH release was slightly inhibitory (78% of basal); however, by adulthood, the effect of this cyclic nucleotide on LHRH release was minimal (92% of basal). Butyrate also induced age-dependent modifications in in vitro LHRH release from male rat hypothalami, with slight increases following butyrate delivery at 25 days of age (115%), slight decreases at 30 (82%) and 45 days of age (68%), and little change in adulthood (94%). This latter finding emphasizes the importance of using butyrate as a control for butyryl derivatives of cyclic AMP, which are known to liberate butyric acid as a product of hydrolysis of parent compounds. To address the possibility that the lack of effectiveness of dbcAMP in the older animal preparations was solely due to an increasing sensitivity of male rat medio-basal hypothalamus fragments to butyrate, we examined the effect of forskolin (10–4M), an adenylate cyclase stimulator, on LHRH release. In the 30-day-old male rat preparation, continuous infusion of forskolin evoked marked increases in LHRH release, characterized by episodic surges; in contrast, this compound was relatively ineffective in inducing LHRH surges in the adult male rat condition. This study also shows that while hypothalamic LHRH concentration reached maximal levels by 45 days of age, spontaneous in vitro release of LHRH increased in a near-linear fashion as a function of age of male rat donor (from 25 days of age to adult), thus indicating a dissociation between spontaneous LHRH neuronal activity and dbcAMP-stimulated LHRH release. In sum, it can be concluded that the responsivity of the hypothalamic neural LHRH apparatus to cyclic AMP (either exogenously applied or generated through stimulation of adenylate cyclase) decreases as the rats mature, with no response close to puberty and during adulthood. In addition, maturational changes in LHRH release and LHRH concentration in superfused medio-basal hypothalamus fragments from intact male rats can be inferred using this in vitro superfusion system.