Abbud R, Smith M S
Department of Physiology, University of Pittsburgh School of Medicine, PA 15261.
Neuroendocrinology. 1993 Oct;58(4):454-64. doi: 10.1159/000126576.
We have used excitatory amino acids as tools to elucidate changes in hypothalamic function associated with lactation, focusing on the regulation of luteinizing hormone (LH) and prolactin secretion. In these studies, we have compared the responsiveness to NMA (N-methyl-D,L-aspartate), an agonist for the N-methyl-D-aspartate (NMDA) receptor, with that of kainate, an agonist for another type of glutamate receptor, the kainate receptor. To address the issue of the permeability of the blood-brain barrier to either NMA or kainate, systemic and central administration of the drugs were compared. Four injections of either drug were administered at 10-min intervals to cycling or lactating rats suckling 8 pups. All of these treatment significantly stimulated LH secretion in cycling rats. However, neither systemic injections of NMA (40 mg/kg) or kainate (2.5-3.5 mg/kg), nor third-ventricular administration of NMA (2 micrograms/2 microliters) or kainate (0.2-0.3 micrograms/2 microliters) stimulated LH secretion during lactation. In contrast, LH responses to NMA were observed in lactating animals suckling 2 pups. These data demonstrate that the intensity of the suckling stimulus determines the degree of gonadotropin-releasing hormone (GnRH) neuronal inhibition during lactation. Recovery of the LH response to NMA in animals suckling 8 pups was not observed after treatment with RU 486 to block the effects of progesterone. Thus, the elevated levels of progesterone during lactation do not appear to play a role in inhibiting GnRH neuronal responsiveness. Removal of the 8-pup suckling stimulus for 24 h also did not restore the LH response to NMA. However, treatment with RU 486 and removal of the suckling stimulus for 24 h did restore LH responses to NMA, suggesting that progesterone may play a role in prolonging the recovery of GnRH neuronal responsiveness. The prolactin responses to NMA and kainate changed with the reproductive state of the animal and the site of administration. Central injections of either drug stimulated prolactin release in both cycling and lactating animals. In contrast, whereas systemic administration of NMA stimulated prolactin secretion in cycling animals, kainate had no effect. In the lactating animals, systemic administration of either drug inhibited prolactin secretion. Thus, the difference in the prolactin responses to systemic administration of the drugs may not only be due to a difference in the distribution of kainate and NMDA receptors but also to the steady state level of activity of the prolactin-releasing and -inhibiting factors which is determined by the reproductive state of the animal.(ABSTRACT TRUNCATED AT 400 WORDS)
我们使用兴奋性氨基酸作为工具，以阐明与泌乳相关的下丘脑功能变化，重点关注促黄体生成素（LH）和催乳素分泌的调节。在这些研究中，我们比较了N-甲基-D，L-天冬氨酸（NMA，一种N-甲基-D-天冬氨酸（NMDA）受体激动剂）与另一种谷氨酸受体即海人酸受体激动剂海人酸的反应性。为了解决血脑屏障对NMA或海人酸的通透性问题，我们比较了药物的全身给药和中枢给药。以10分钟的间隔对哺乳8只幼崽的发情期或哺乳期大鼠进行4次药物注射。所有这些处理均显著刺激了发情期大鼠的LH分泌。然而，无论是全身注射NMA（40mg/kg）或海人酸（2.5 - 3.5mg/kg），还是第三脑室注射NMA（2微克/2微升）或海人酸（0.2 - 0.3微克/2微升），在哺乳期均未刺激LH分泌。相反，在哺乳2只幼崽的哺乳期动物中观察到了对NMA的LH反应。这些数据表明，哺乳刺激的强度决定了哺乳期促性腺激素释放激素（GnRH）神经元抑制的程度。在用RU 486阻断孕酮作用后，未观察到哺乳8只幼崽的动物对NMA的LH反应恢复。因此，哺乳期孕酮水平升高似乎在抑制GnRH神经元反应性方面不起作用。去除8只幼崽的哺乳刺激24小时也未恢复对NMA的LH反应。然而，用RU 486处理并去除哺乳刺激24小时确实恢复了对NMA的LH反应，这表明孕酮可能在延长GnRH神经元反应性的恢复中起作用。催乳素对NMA和海人酸的反应随动物的生殖状态和给药部位而变化。两种药物的中枢注射均刺激了发情期和哺乳期动物的催乳素释放。相反，虽然NMA的全身给药刺激了发情期动物的催乳素分泌，但海人酸无此作用。在哺乳期动物中，两种药物的全身给药均抑制了催乳素分泌。因此，药物全身给药时催乳素反应的差异可能不仅归因于海人酸和NMDA受体分布的差异，还归因于由动物生殖状态决定的催乳素释放和抑制因子的稳态活性水平。（摘要截取自400字）
