Pu S, Kalra P S, Kalra S P
Department of Neuroscience, University of Florida College of Medicine, Gainesville 32610, USA.
J Neuroendocrinol. 1998 Aug;10(8):617-25. doi: 10.1046/j.1365-2826.1998.00245.x.
The aim of this study was to evaluate the relationship between cyclic LH hypersecretion and nitric oxide (NO) release in the medial preoptic area (MPOA), the hypothalamic site implicated in induction of LH hypersecretion. The MPOA extracellular cyclic GMP (cGMP) efflux (an index of NO release), was monitored by microdialysis. Quite unexpectedly, we observed a daily afternoon rise in the MPOA cGMP efflux in cycling female rats on proestrus and diestrus II, in ovariectomized (ovx) rats and in ovx rats treated with ovarian steroids to induce the LH surge. The daily rise in cGMP efflux occurred earlier in diestrous and in estradiol benzoate (EB)-treated ovx rats than in ovx rats. Progesterone (P) injection to estrogen-primed ovx rats further advanced the onset of the rise close to the earliest time of rise as seen on proestrus. The afternoon increase in the cGMP efflux in proestrous rats was abolished by pentobarbital treatment that blocked the LH surge. Intracerebroventricular (i.c.v.) injection of 1 H-[1,2,4]oxadiazo[4,3-a]quinoxalin-one (ODQ), a selective inhibitor of soluble guanylyl cyclase, suppressed the P-induced LH surge in EB-primed ovx rats, but not basal LH secretion in unprimed ovx rats. Analysis of brain NOS (bNOS) levels in the POA by Western blotting showed that the morning bNOS levels were higher in the POA of EB-treated rats than in unprimed ovx rats. Further, with the exception of ovx rats treated with sequential EB and P treatment, the POA bNOS levels rose significantly in the afternoon in unprimed ovx and EB-treated ovx rats. Collectively, these findings reveal a diurnal rhythm in the MPOA cGMP/NO efflux that is ovarian steroid-independent. Ovarian steroids apparently shift the timing of the afternoon rise in cGMP/NO efflux to synchronize with the activation of steroid-dependent neuronal systems responsible for the LH surge.
本研究的目的是评估促黄体生成素（LH）周期性分泌过多与内侧视前区（MPOA）一氧化氮（NO）释放之间的关系，MPOA是下丘脑的一个部位，与LH分泌过多的诱导有关。通过微透析监测MPOA细胞外环磷酸鸟苷（cGMP）流出（NO释放的指标）。非常出乎意料的是，我们观察到在发情前期和动情后期II的周期性雌性大鼠、去卵巢（ovx）大鼠以及用卵巢类固醇处理以诱导LH峰的ovx大鼠中，MPOA的cGMP流出在每天下午都会升高。cGMP流出的每日升高在动情期和苯甲酸雌二醇（EB）处理的ovx大鼠中比在ovx大鼠中出现得更早。向雌激素预处理的ovx大鼠注射孕酮（P）进一步提前了升高的起始时间，使其接近发情前期最早的升高时间。戊巴比妥处理阻断LH峰后，发情前期大鼠下午cGMP流出的增加被消除。脑室内（i.c.v.）注射1H-[1,2,4]恶二唑[4,3-a]喹喔啉-1（ODQ），一种可溶性鸟苷酸环化酶的选择性抑制剂，抑制了EB预处理的ovx大鼠中P诱导的LH峰，但不影响未预处理的ovx大鼠的基础LH分泌。通过蛋白质免疫印迹分析视前区（POA）的脑一氧化氮合酶（bNOS）水平表明，EB处理的大鼠POA中早晨的bNOS水平高于未预处理的ovx大鼠。此外，除了接受序贯EB和P处理的ovx大鼠外，未预处理的ovx大鼠和EB处理的ovx大鼠POA中的bNOS水平在下午显著升高。总的来说，这些发现揭示了MPOA中cGMP/NO流出的昼夜节律，该节律不依赖于卵巢类固醇。卵巢类固醇显然改变了下午cGMP/NO流出升高的时间，以与负责LH峰的类固醇依赖性神经元系统的激活同步。
