McKee De'Nise T, Poletini Maristela O, Bertram Richard, Freeman Marc E
Department of Biological Science, Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.
Endocrinology. 2007 Oct;148(10):4649-57. doi: 10.1210/en.2007-0646. Epub 2007 Jul 5.
Cervical stimulation induces two daily rhythmic prolactin surges, nocturnal and diurnal, which persist for several days. We have shown that a bolus injection of oxytocin initiates a similar prolactin rhythm, which persists despite low levels of oxytocin after injection. This suggests that oxytocin may trigger the cervical stimulation-induced rhythmic prolactin surges. To investigate this hypothesis, we infused an oxytocin antagonist that does not cross the blood-brain barrier for 24 h before and after cervical stimulation and measured serum prolactin. We also measured dopaminergic neuronal activity because mathematical modeling predicted that this activity would be low in the presence of the oxytocin antagonist. We thus tested this hypothesis by measuring dopaminergic neuronal activity in the tuberoinfundibular, periventricular hypophyseal, and tuberohypophyseal dopaminergic neurons. Infusion of oxytocin antagonist before cervical stimulation abolished prolactin surges, and infusion of oxytocin antagonist after cervical stimulation abolished the diurnal and significantly decreased the nocturnal surges of prolactin. The rhythmic prolactin surges returned after the clearance of the oxytocin antagonist. Hypothalamic dopaminergic activity was elevated in antiphase with prolactin surges, and the antiphase elevation was abolished by the oxytocin antagonist in the tuberoinfundibular and tuberohypophyseal dopaminergic neurons, consistent with the mathematical model. These findings suggest that oxytocin is a physiologically relevant prolactin-releasing factor. However, the cervical stimulation-induced prolactin surges are maintained even in the absence of oxytocin actions at the lactotroph, which strongly suggests the maintenance of prolactin surges are not dependent upon oxytocin actions at the pituitary gland.
子宫颈刺激会引发每日两次的催乳素激增,分别在夜间和白天,这种情况会持续数天。我们已经表明,一次大剂量注射催产素会引发类似的催乳素节律,尽管注射后催产素水平较低,但这种节律仍会持续。这表明催产素可能触发子宫颈刺激诱导的催乳素节律性激增。为了研究这一假设,我们在子宫颈刺激前后24小时内输注一种不能穿过血脑屏障的催产素拮抗剂,并测量血清催乳素。我们还测量了多巴胺能神经元的活动,因为数学模型预测在存在催产素拮抗剂的情况下这种活动会较低。因此,我们通过测量结节漏斗部、室周垂体部和结节垂体部多巴胺能神经元中的多巴胺能神经元活动来检验这一假设。在子宫颈刺激前输注催产素拮抗剂可消除催乳素激增,在子宫颈刺激后输注催产素拮抗剂可消除白天的催乳素激增,并显著降低夜间的催乳素激增。在催产素拮抗剂清除后,节律性催乳素激增又恢复了。下丘脑多巴胺能活动与催乳素激增呈反相升高,在结节漏斗部和结节垂体部多巴胺能神经元中,催产素拮抗剂消除了这种反相升高,这与数学模型一致。这些发现表明催产素是一种生理上相关的催乳素释放因子。然而,即使在催乳素细胞不存在催产素作用的情况下,子宫颈刺激诱导的催乳素激增仍会维持,这强烈表明催乳素激增的维持不依赖于催产素在垂体的作用。