A mathematical model of pulse-coded hormone signal responses in pituitary gonadotroph cells

• This new mathematical model describes pulsed-signal decoding in pituitary cells.
• The model is based on experimental results published previously.
• Model structure is drawn from techniques common in control system engineering.
• Virtual experiments performed by simulation match the cell culture experiments.
• Model shows how a network of simple biochemical processes can decode pulse signals.

Cells in the pituitary that synthesize luteinizing and follicle-stimulating hormones regulate the relative production of these two key reproductive hormones in response to signals from the hypothalamus. These signals are encoded in the frequency of gonadotrophin-releasing-hormone pulses. In vitro experiments with a murine-derived cell line have identified key elements of the processes that decode the signal to regulate transcription of the subunits encoding these hormones. The mathematical model described in this paper is based on the results of those experiments and advances quantitative understanding of the biochemical decoder. The model consists of non-linear differential equations for each of six processes that lead to the synthesis of follicle-stimulating hormone. Simulations of the model exhibit key characteristics found in the experiments, including a preference for follicle-stimulating hormone synthesis at low pulse frequencies and a loss of this characteristic when a mutation is introduced.