Schagen F H, Knigge U, Kjaer A, Larsen P J, Warberg J
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
Neuroendocrinology. 1996 Jun;63(6):550-8. doi: 10.1159/000127084.
We have previously shown that histaminergic neurons participate in mediation of the prolactin (PRL), adrenocorticotropin (ACTH) and oxytocin responses to physiological stimuli such as stress and dehydration. Since suckling is a potent stimulus for the secretion of these three hormones, we investigated the mediating role of neuronal histamine in suckling-induced release of oxytocin, PRL and ACTH in conscious lactating rats. The animals were pretreated with the histamine synthesis inhibitor alpha-fluoromethylhistidine, the H1 receptor antagonist mepyramine, the H2 receptor antagonist cimetidine or the H3 receptor agonist R (alpha) methylhistamine, which by binding to H3 autoreceptors inhibits histamine release and synthesis. After the lactating rats were separated from their pups for 240 min, the pups were returned for a suckling period of 20 min. Thereafter the mothers were sacrificed by decapitation and trunk blood was collected for determination of hormones. Lactating rats not exposed to suckling served as controls. Suckling increased oxytocin 2-fold, PRL 50-fold and ACTH 5-fold. Blockade of histamine synthesis by alpha-fluoromethylhistidine or histamine release by R(alpha)methylhistamine reduced the suckling-induced secretion of the three hormones significantly. Blockade of postsynaptic H1 receptors by mepyramine inhibited the hormone responses to suckling, while the blockade of postsynaptic H2 receptors by cimetidine decreased the suckling-induced oxytocin and PRL release but did not affect the ACTH release. None of the compounds affected oxytocin, PRL or ACTH secretion in lactating mothers not exposed to suckling. In addition, suckling significantly increased the mRNA of the histamine synthesizing enzyme histidine decarboxylase in the ventrolateral tuberomammillary nucleus by 1.5-fold, indicating that the stimulus of suckling enhances the neuronal histamine synthesis. We conclude that suckling increases neuronal histamine synthesis and that histaminergic neurons by activation of postsynaptic H1 and H2 receptors are involved in the hypothalamic mediation of oxytocin, PRL and ACTH responses to suckling. These findings further substantiate a role of neuronal histamine in the neuroendocrine regulation of pituitary hormones in response to physiological stimuli.
我们之前已经表明，组胺能神经元参与介导催乳素（PRL）、促肾上腺皮质激素（ACTH）和催产素对诸如应激和脱水等生理刺激的反应。由于哺乳是这三种激素分泌的有力刺激因素，我们研究了神经元组胺在清醒泌乳大鼠中对哺乳诱导的催产素、PRL和ACTH释放的介导作用。动物预先用组胺合成抑制剂α-氟甲基组氨酸、H1受体拮抗剂美吡拉敏、H2受体拮抗剂西咪替丁或H3受体激动剂R（α）甲基组氨酸进行预处理，后者通过与H3自身受体结合抑制组胺释放和合成。泌乳大鼠与幼崽分离240分钟后，将幼崽放回进行20分钟的哺乳期。此后，通过断头处死母鼠并采集躯干血以测定激素。未接受哺乳的泌乳大鼠作为对照。哺乳使催产素增加2倍、PRL增加50倍、ACTH增加5倍。α-氟甲基组氨酸对组胺合成的阻断或R（α）甲基组氨酸对组胺释放的阻断显著降低了哺乳诱导的这三种激素的分泌。美吡拉敏对突触后H1受体的阻断抑制了对哺乳的激素反应，而西咪替丁对突触后H2受体的阻断降低了哺乳诱导的催产素和PRL释放，但不影响ACTH释放。这些化合物均未影响未接受哺乳的泌乳母鼠的催产素、PRL或ACTH分泌。此外，哺乳使腹外侧结节乳头核中组胺合成酶组氨酸脱羧酶的mRNA显著增加1.5倍，表明哺乳刺激增强了神经元组胺合成。我们得出结论，哺乳增加神经元组胺合成，并且组胺能神经元通过突触后H1和H2受体的激活参与下丘脑对催产素、PRL和ACTH对哺乳反应的介导。这些发现进一步证实了神经元组胺在垂体激素对生理刺激的神经内分泌调节中的作用。
