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Endocrine Abstracts (2010) 21 SB1.3

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Mathematical modelling and endocrine research

Julian Davis

Manchester University, Manchester, UK.

Endocrine systems are dynamically changing and complex systems. Quantitative measurements of hormones over time became possible with the development of sensitive immunoassays, and it rapidly became clear that hormone release is often pulsatile. The timing of ultradian hormone pulses and circadian variation turns out to be a central characteristic of many systems, and this has required increasing use of mathematical analysis.

Regulation of gene expression has traditionally been analysed using RNA and protein preparations derived from large numbers of cells. However these types of analyses using ‘averaged’ data from cell lines can give an impression that all cells behave similarly and uniformly in space and time, but this is clearly not the case in real life. We have studied the regulation of pituitary gene promoter activity using the luciferase reporter gene: the luminescence signal can be readily measured in cell lysates using a luminometer, but advances in luminescence microscopy allow measurements from individual living cells over time. Surprisingly, promoter activity in single cells fluctuates dramatically, and we have utilized mathematical modelling to analyse the characteristics of the cycles of gene expression among individual cells and propose hypotheses about how they might be generated.

While endocrine cells display individual intrinsic rhythmic properties, in a tissue they must be co-ordinated in space and time to achieve the synchronized secretion of a large pulse of hormone over a short period. Some of this coordination may be explained by neural influences, but some appears to be due to the autonomous behaviour of intact tissues. Analysis of this coordination requires more detailed spatio-temporal mathematical modelling than before, and this will hold the next challenge. ‘Systems biology’ has involved interactions between two very distinct specialties, which brings the reward of new ways of seeing biological phenomena, and lead to new hypotheses about how endocrine systems operate.

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