Medium flow rate modulates autocrine-paracrine feedback of GH and PRL release by perifused GH3 cells

Summary We previously documented both the spontaneous acceleration of growth hormone (GH) and prolactin (PRL) production by GH₃ cells during periffusion and the suppression of their production during plate culture. We here present the role played by medium flow itself in this differential behavior. Increasing rates of perifusion flow (pump rates of 1 to 5 ml/h, equivalent to chamber flow rates of 0.19 to 1.3 μl·min⁻¹·mm⁻² of cross-sectional area) were associated with enhanced GH and PRL secretion. Flow rate-dependent basal hromone secretion rates were established quickly and were stable for the first 10 to 14 h of perifusion. The previously documented independent, spontaneous, and continuously accelerating production of both hormones that followed during the subsequent 40 (PRL) to 60 (GH) h of perifusion was also shown to be flow-rate related. Any time the rate of medium flow was changed within an experiment, the rate of hormone secretion was modulated. However, that modulation did not interrupt ongoing flow-associated acceleration of hormone production once the latter had begun. In addition, GH₃ cell product(s) from one cell column reversibly inhibited secretion from cells in a downstream column. The inhibition did not occur when cells in the downstream column had been exposed to trypsin. Other work had suggested that neither GH, PRL, insulinlike growth factor-I, leucine, nor nutrient exhaustion were responsible for the effect. These data are consistent with autocrine-paracrine feedback regulation of GH₃ cells by a secretory product(s). Feedback would thus provide a mechanism to effect flow-rate-dependent modulation of GH and PRL release, and to explain accelerating hormone production during perifusion. This work was supported by a grant to M. E. S. from the National Institutes of Health (DK33388), Bethesda, MD, and in part, by the Medical Research Service of the Veterans Administration.