Evidence for Synergetic Dynamics in a Mammalian Pituitary Cell Perifusion System

Abstract

Two recent studies of the release of gonadotropin luteinizing hormone (LH) by cultured pituitary cells in vitro in response to continuous perifusion with hypothalamic luteinizing hormone-releasing factor (LRF) have demonstrated a progressive decrease in levels of LH release, a desensitization response usually attributed to the down-regulation of pituitary cell membrane receptors for the secretagogue [1,2]. In contrast, in our laboratory over the past year, continuous perifusion of a similar preparation of pituitary cells revealed statistically consistent patterns of sustained, large-amplitude oscillations in growth hormone (GH) release in nearly 100 experiments. In addition to the potential clinical relevance of such a finding (self-organized, near periodic behavior may become resistant to regulatory input [3]), these data suggest the presence of a dynamical system with such features as nonlinear responses to linear changes in experimental conditions and the potential for the emergence of a variety of time-dependent behavior beyond stimulation or inhibition of release and receptor desensitization [4]. In fact, the biphasic behavior reported for some experiments in [2] may be an example of such bifurcations. Here we describe the oscillatory phenomena, present evidence that the cell culture behaves in many ways like a coupled system of relaxation oscillators, and report experiments suggesting that cAMP may, as in the case of the slime mold [5], play a role in its synergetic dynamics. The oscillatory patterns reported here were not observed previously [1,2] because of low sampling rates.