Abstract. It has recently been shown that neurokinin B, a tachykinin, is associated with GnRH pulse generation in sheep and goats. The aim of the present study was to clarify the role of tachykinin receptors in the control of LH secretion in rats. To this end, we evaluated the effect of CS-003, an antagonist for all three neurokinin receptors (NK1, NK2 and NK3 receptors), on pulsatile LH secretion in both sexes of rats with different routes of administration. Both oral and third ventricular administration of CS-003 suppressed LH secretion in both sexes of gonadectomized animals. Furthermore, intact male rats with oral administration of CS-003 showed decreased serum testosterone levels, which might be due to suppressed LH secretion. None of the three subtype-specific neurokinin receptor antagonists showed a significant effect on LH secretion in ovariectomized rats when each antagonist was singly administered. The present results suggest that neurokinins play a role in the control of pulsatile GnRH/LH secretion via multiple neurokinin receptors in both male and female rats. Key words: Luteinizing hormone, Neurokinin, Rat, Receptor (J. Reprod. Dev. 57: [409][410][411][412][413][414][415] 2011) ulsatile gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release is indispensable for regulation of gonadal functions, such as folliculogenesis, spermatogenesis and steroidogenesis, in rodents [1], ruminants [2,3] and primates [4]. The mechanism generating GnRH/LH pulses, called the GnRH pulse generator, has been suggested to be localized in the hypothalamus [5]. Recent studies have revealed that kisspeptin neurons located in the hypothalamus play a central role in regulating GnRH release [6,7]. Kisspeptin neurons have two populations in the hypothalamus [8]: One is located in the hypothalamic arcuate nucleus (ARC), and the other is located in the anteroventral periventricular nucleus (AVPV). Of these two populations, the AVPV kisspeptin neurons have been reported to be involved in the regulation of GnRH/LH surge [9,10]. On the other hand, the role of ARC kisspeptin neurons is still unclear, but several lines of evidence suggest that the population is associated with GnRH pulse generation [11].Recent studies have shown an interesting and essential aspect of the ARC kisspeptin neurons. Most kisspeptin neurons have neurokinin B (NKB) and dynorphin (Dyn) in sheep [12], goats [13] and rodents [14], and thus the neurons have been called KNDy neurons [15]. Colocalization of those three neuropeptides in the ARC neurons might be associated with GnRH pulse generation. It has recently been reported that mutations of genes encoding NKB and its receptor are associated with gonadotropin deficiency in humans [16], and central administration of a selective NKB receptor agonist stimulates LH secretion in sheep [17] and monkeys [18]. These reports indicate the significance of NKB/NK3 signaling in GnRH/gonadotropin release in these animal species. In addition to neurokinin B, nor-BNI, a κ-opioid receptor antagonist (KOR), rev...

No abstract

Inflammation of the cardiac coronary artery in ICR mice is occasionally observed in toxicity studies; however, this has not been well explored histologically. Herein, we investigated the detailed histology of the associated lesions in 6–8-week-old ICR mice. Coronary artery inflammation in the right ventricular wall was observed in 10 of 142 mice (7.0%). Histopathological examination revealed hypertrophy of the vascular smooth muscle cells and perivascular infiltration of macrophages in mild cases. In moderate to marked cases, single-cell necrosis of vascular smooth muscle cells, hemorrhage of the tunica media, and fibrinoid necrosis of the vessel wall were observed, in addition to the changes seen in mild cases. Electron microscopic examination of moderate cases revealed a discontinuous internal elastic lamina suggestive of rupture, and vascular smooth muscle cells beneath the elastic lamina showed degeneration and necrosis. These findings suggest that the lesions developed as a rupture of the internal elastic lamina and necrosis of vascular smooth muscle cells, while leaked plasma components caused vascular and perivascular inflammation. In ICR mice, dystrophic calcinosis (DCC) is known to occur rarely in the right ventricle. DCC is defined as focal calcification in necrotic myocardial fibers, the pathogenesis of which is considered to involve ectopic calcification. Since calcification was not observed in any part of the heart, including the inflammation region, the pathophysiology of cardiac arterial inflammation seen in our ICR mice was considered to differ from that of DCC.