Ogilvie K, Rivier C
Ligand Pharmaceuticals, Department of Pharmacology, San Diego, California 92121, USA.
Endocrinology. 1998 Jul;139(7):3088-95. doi: 10.1210/endo.139.7.6090.
The present work extends our previous report that the intracerebroventricular (i.c.v.) injection of interleukin-1beta(IL-1beta, 80 ng) significantly blunted the testosterone response to 1 U/kg human CG (hCG), an effect that we attributed to the stimulation of inhibitory pathways connecting the hypothalamus to the testes. Systemic blockade of prostaglandin-dependent pathways with ibuprofen (alpha-methyl-4-[2-methylpropyl]benzeneacetic acid; sodium salt), which did not, in itself, alter the stimulatory effect of hCG on testosterone release in control rats, modestly, but significantly (P < 0.05) reversed the inhibitory influence of IL-1beta. In contrast, blockade of brain receptors for CRF was unable to alter the effect of IL-1beta, as were lesions of the ventromedial hypothalamic nucleus, a brain area implicated in the control of ovarian function. Blockade of beta-adrenergic receptors significantly prevented the decrease in testicular responsiveness induced by the i.c.v. injection of IL-1beta. Finally, the central injection of the beta-adrenergic agonist isoproterenol, as well as that of norepinephrine, mimicked the ability of icv IL-1beta to blunt testicular secretory activity and produced a marked (P < 0.01) decrease in the response to hCG within 5 min of their administration. We propose that the explanation that best fits our findings is that the i.c.v. injection of IL-1beta activates a neural, catecholamine-dependent pathway that connects the brain and the testes independently of the pituitary.
本研究扩展了我们之前的报告，即脑室内（i.c.v.）注射白细胞介素-1β（IL-1β，80 ng）可显著减弱对1 U/kg人绒毛膜促性腺激素（hCG）的睾酮反应，我们将这种效应归因于连接下丘脑与睾丸的抑制性通路的激活。用布洛芬（α-甲基-4-[2-甲基丙基]苯乙酸；钠盐）对前列腺素依赖性通路进行全身阻断，其本身并不改变hCG对对照大鼠睾酮释放的刺激作用，但能适度且显著地（P < 0.05）逆转IL-1β的抑制作用。相比之下，阻断促肾上腺皮质激素释放因子（CRF）的脑受体无法改变IL-1β的作用，腹内侧下丘脑核的损伤也不能改变其作用，腹内侧下丘脑核是一个与卵巢功能控制有关的脑区。阻断β-肾上腺素能受体可显著防止i.c.v.注射IL-1β引起的睾丸反应性降低。最后，脑室内注射β-肾上腺素能激动剂异丙肾上腺素以及去甲肾上腺素，模拟了脑室内注射IL-1β减弱睾丸分泌活性的能力，并在给药后5分钟内使对hCG的反应显著降低（P < 0.01）。我们认为，最符合我们研究结果的解释是，脑室内注射IL-1β激活了一条独立于垂体连接脑和睾丸的神经、儿茶酚胺依赖性通路。
