Bertram Richard, Egli Marcel, Toporikova Natalia, Freeman Marc E
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
Am J Physiol Endocrinol Metab. 2006 Mar;290(3):E573-82. doi: 10.1152/ajpendo.00428.2005.
For the first 10 days of pregnancy and the first 12 days of pseudopregnancy, the secretion of prolactin (PRL) from pituitary lactotrophs is rhythmic, with two surges/day. This rhythm can also be triggered by bolus injection of oxytocin (OT). We describe a mathematical model for the initiation, maintenance, and termination of the OT-induced PRL rhythm. In our model, the mechanism for this circadian rhythm is mutual interaction between lactotrophs and neuroendocrine dopamine (DA) neurons. This rhythm is, under normal lighting conditions, entrained by the suprachiasmatic nucleus (SCN) but persists in the absence of input from the SCN. We postulate that OT injection triggers the rhythm by activating a population of bistable hypothalamic neurons that innervate and inhibit DA neurons. The bistable nature of these neurons allows them to act as a memory device, maintaining the rhythm long after OT has been cleared from the blood. The mechanism for this memory device and the arguments supporting it are detailed with computer simulations. Finally, we consider potential targets for a rhythm-terminating factor and make predictions that may be used to determine which mechanism is operational in terminating the OT- or mating-induced PRL rhythm.
在怀孕的前10天以及假孕的前12天,垂体催乳素细胞分泌的催乳素(PRL)呈节律性,每天有两次分泌高峰。这种节律也可由大剂量注射催产素(OT)触发。我们描述了一个关于OT诱导的PRL节律的起始、维持和终止的数学模型。在我们的模型中,这种昼夜节律的机制是催乳素细胞与神经内分泌多巴胺(DA)神经元之间的相互作用。在正常光照条件下,这种节律受视交叉上核(SCN)的调节,但在没有SCN输入的情况下仍会持续。我们推测,OT注射通过激活一群支配并抑制DA神经元的双稳态下丘脑神经元来触发这种节律。这些神经元的双稳态特性使它们能够充当记忆装置,在OT从血液中清除后很长时间仍维持这种节律。通过计算机模拟详细阐述了这种记忆装置的机制及其支持论据。最后,我们考虑了节律终止因子的潜在靶点,并做出了一些预测,这些预测可用于确定在终止OT或交配诱导的PRL节律中起作用的是哪种机制。