Egli, Bertram, Sellix, Freeman, 2004

Model Status

This model has been curated and is known to run in PCEnv 0.2 and COR and give the results described in the published paper. A PCEnv session file is also available for this model and reproduces the set of graphs in Figure 6 of the publication.

Model Structure

Prolactin (PRL) is a hormone which is synthesised and secreted by lactotrophs in the anterior lobe of the pituitary gland. It plays an important role in lactation, and also contributes to a wide range of physiological functions. Its release is inhibited by dopamine (DA), and is stimulated by oxytocin (OT). Neurons in the paraventricular nucleus of the hypothalamus are major sites of OT synthesis, and they themselves are influenced by the secretion of vasoactive intestinal polypeptide (VIP) by the suprachiasmatic nucleus (SCN). The SCN is also part of the hypothalamus, and is known for its pacemaker function, often regulating the timing of circadian rhythms in mammals.

In the paper described here, Egli et al. present a mathematical model of the mechanisms regulating the rhythmic secretion of prolactin in rats (see figure below). In this model the SCN acts as a pacemaker, controlling the activity of the hypothalamic DA and OT neurons via its rhythmic VIP secretion. In turn, the activity of these DA and OT neurons combine to determine the PRL secretory pattern.

Schematic diagram of the network proposed to be involved in the regulation of prolactin (PRL) secretion in response to uterine cervical stimulation (CS). Vasoactive intestinal polypeptide (VIP) is secreted from the suprachiasmatic nucleus and relays the time of day to DAergic and OTergic neurosecretory cells via inhibition. x represents an additional stimulatory input which feeds into the OT neurons. DA neurons provide an inhibitory input while OT neurons provide a stimulatory input to the lactotrophs to regulate the synthesis and secretion of PRL.

The complete original paper reference is cited below:

Rhythmic secretion of prolactin in rats: action of oxytocin coordinated by vasoactive intestinal polypeptide of suprachiasmatic nucleus origin, 2004, Marcel Egli, Richard Bertram, Michael T. Sellix, and Marc E. Freeman. Endocrinology , 145, 3386-3394. (Full text and PDF versions of the article are available to journal subscribers on the Endocrinology website.) PubMed ID: 15033917

The authors highlight that the original code they wrote for this model can be downloaded here.