| L-Glutamate is a major excitatory neurotransmitter in the central nervous system. It has been suggested that A^-methyl-D-aspartate (NMDA) receptors are important for neuroendocrine system. However, only little information is available about the involvement of NMDA receptors in the neuroendocrine regulation responding to stress.The present study was aimed to investigate the release of pituitary hormones during restraint, in concerning of the involvement of NMDA receptors. At first, adult male rats (12-weeks of age) were employed for experiment. AP-5, a competitive NMDA receptor antagonist, or MK-801, a non-competitive NMDA receptor antagonist, was administered either by intracerebroventricular (icv) injection or by intravenous (iv) injection at 15 minutes before (-15 min) a restraint of 3 hours. At 0 min before and at 15, 30, 60, 120 and 180 min during the restraint, the blood samples were separately collected through a jugular vein cannula. The plasma concentrations of prolactin (PRL), adrenocorticotropic hormone (ACTH), corticosterone (CORT), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) were respectively measured by radioimmunoassay. Secondly, to compare the role of NMDA receptors during the sexual maturation and aging, peripubertal (45-days of age) and middle-aged (16-months of age) male rats were adopted for restraint experiment and the role of NMDA receptors in restraint-induced release of above hormones were evaluated by pretreatment of MK-801. Additionally, the adaptation of pituitary hormone responses induced by repeated restraint was investigated, in concerninig of the time-course of the restraint.The results are as follows:1. The involvement of NMDA receptors in the release of pituitary hormones during restraint in the adult male rat.1) The restraint induced a marked rise in plasma PRL by at least 7-folds at 15 min. The ACTH level elevated by more than 6-folds at 15 min of restraint, and the CORT concentration was trebled at 60 min. As restraint continued, the hormone levels tended to fall back, but did not return to pre-stress levels at 180 min. In contrast, the restraint induced a swift increase of LH and T levels, and a slight increase of FSH level, at 15 min, which were soon followed by falling back.2) The restraint-induced release of PRL was prevented by MK-801 (50 ug/rat, icv; or 5 mg/kg, iv). The PRL release at 15 min was partially inhibited by AP-5 (50 or 100 ug/rat, z'cv), and the plasma levels of PRL at 180 min were lowered than time-matched control. However, PRL release during restraint was not affected by systemic treatment of AP-5 (10 mg/kg, iv).3) Pretreatment of AP-5 (50 (ig/rat, icv) or MK-801 (5 mg/kg, iv; 50 fig/rat, icv), significantly inhibited the ACTH response at 15 min, however AP-5 had only an insignificant inhibitive effect at 15 min when administered by iv injection. In each treatment, the plasma CORT changed following ACTH.4) A single injection of AP-5 (100 fig/rat, icv) significantly blocked the restraint-induced release of LH and T at 15 min, as MK-801 (50 fig/rat, icv) partially attenuated it. Systemic treatment of AP-5 (10 mg/kg, iv) or MK-801 (5 mg/kg, iv) did not alter the increase of plasma LH and T during restraint. None of the above treatments altered the FSH release.2. The involvement of NMD A receptors in restraint-induced release of pituitary hormones in the peripubertal male rat.In the peripubertal rat, PRL responded to the restraint with a robust increase at 15 min in a magnitude similar to that in adult rats, which was prevented by a single injection of MK-801 (5 mg/kg, iv). However, only a moderate increase of ACTH was observed with the peak appeared at 30 min, as the CORT response was comparable to that in the adult rat. MK-801 (5 mg/kg, iv) decreased the peak level of ACTH at 30 min of the restraint.In contrast to that in the adult rat, the restraint significantly decreased plasma levels of LH and T respectively at 15 min and 30 min, but produced a slight increase of FSH at 15 min. After MK-...
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