Diffusion-Mediated Regulation Endocrine Networks

Author: Petrasek, Danny

Year: 2002

Degree: Dissertation (Ph.D.)

Advisor: Bruno, Oscar P.

Committee Members: Cohen, Donald S.; Bruno, Oscar P.; Fraser, Scott E.; Hou, Thomas Y.; Meiron, Daniel I.

Option: Applied And Computational Mathematics

DOI: 10.7907/776t-vs55

Abstract

In endocrine glands, vigorous and coordinated responses are often elicited by modest changes in the concentration of the organist molecule. The mammalian parathyroid gland is a representative case. Small (5%) changes in serum calcium result in tenfold (1000%) changes in glandular parathyroid hormone (PTH) release. In vitro, single isolated cells are observed to secrete fewer hormones than cells residing within a connected group, suggesting that a network has emergent regulatory properties. In PTH secreting tumors however, the ability to quickly respond to changes in calcium is strongly damped. A unifying hypothesis that accounts for these phenomena is realized by extra-cellular modulation of calcium diffusivity. A theoretical model and computational experiments demonstrate qualitative agreement with published experimental results. Our results suggest that in addition to the cellular mechanisms, endocrine glandular networks may have regulatory prowess at the level of interstitial transport. The extra-cellular diffusional mechanism proposed provides a consistent argument for 1) higher secretion of single cells in a connected network compared to isolated cells, 2) the rapid nonlinear response seen in healthy glands as well as 3) the pathological responses seen in hyperplasia and adenoma. Since the proposed diffusional regulation strongly depends on the existence of a connected cell network (gland), it also suggests a rationale for the advantages of cell networks as organs versus a dispersed system of isolated cells (in the case of the parathyroid gland).

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