A Two-Pathway Mathematical Model of the LH Response to GnRH that Predicts Self-Priming

[摘要] An acute response of LH to a stimulatory pulse ofGnRH is modelled as a result of a pathway (Pathway I) thatconsists of two compartments including a single (rate limiting)intermediate. In addition, a second pathway (Pathway II) wasadded, consisting of an intermediate transcription factor and subsequently a synthesised protein. Pathway II had a delayedeffect on LH release due to the time taken to produce theintermediate protein. The model included synergism betweenthese two pathways, which yielded an augmented response. The model accounts for a number of observations, includingGnRH self-priming and the biphasic pattern of LH response. The same model was used to fit the data of the LH responsewhen gonadotrophs responded to the addition of oxytocin in theresponse with a shoulder on the profile. Pathway I is able to beconceptualised as the basic Ca2+-mediated pathway. Pathway IIcontains features characteristic of the cAMP-mediated pathway. Thus, we have provided an explanation for details of the nature ofthe profile of LH secretion and additionally enabled incorporationof cAMP in an integrating model. The study investigated thepossibility of two interacting pathways being at the basis of boththe shoulder on the LH surges and self-priming, and the modelillustrates that this appears to be highly likely.

[学科分类] 内分泌与代谢学