SECRETORY CHARACTERISTICS AND PHENOTYPIC PLASTICITY OF GROWTH HORMONE-PRODUCING AND PROLACTIN-PRODUCING CELL-LINES

Considerable information regarding the regulation of GH and prolactin (PRL) release has been generated using pituitary cell lines as model s ystems. Inasmuch as these cultures have been derived from single cells by clonal selection ithas frequently been assumed that they are compo sed of homogeneous populationsof hormone secretors. However, experienc e with GH(3) cells clearly demonstrates that such is not the case, sin ce this GH- and PRL-producing line is comprised of a mixture of cells that are bihormonal, secrete only GH, or secrete neither hormone. Inte restingly, the relative amount of these phenotypic subpopulations is n ot fixed, but can be altered by treatment with established regulators of GH and PRL secretion. This potential for secretory heterogeneity an d phenotypic plasticity prompted us to examine the cellular compositio n of other commonly used GH- and/or PRL secreting cell lines under con trol and treatment conditions. First, GH(4)C(1), GH(1), GC, MMQ and P- 0 cells were maintained according to established media and culture pro tocols and the relative abundance of GH and PRT secretors was assessed by reverse haemolytic plaque assays. As shown previously for GH(3) ce lls, two cell lines were found to be functionally heterogeneous. Speci fically,GH(4)C(1) and GH(1) were comprised of mixed populations of GH (25.9 +/- 1.1% and 51.3 +/- 6.5% (S.E.M.) respectively) and PRL (44.8 +/- 3.7% and 66.1 +/- 4.1% respectively) secretors. However, MMQ and G C cell cultures were relatively homogeneous with respect to hormone se cretion in that the MMQ cells released PRL (72.2 +/- 4.9%) but not GH, while GC cells released GH (93.6 +/- 1.4%) but not PRL. Similarly, P- 0 cell cultures contained predominantly GH-secreting cells (96.4 +/- 1 .2%), but a few cells weredetected that released PRL, (1.1 +/- 0.1%). We then tested whether cortisol or oestradiol-17 beta (OE(2)) could al ter the secretory composition ofcell. lines identified as reasonably h omogeneous (GC, MMQ and P-0) by treating cultures with steroids at dos es ranging from 0.001 to 1000 nmol/l for up to 144 h. The presence of steroids in GC and MMQ lines did not affect the percentage of GH and P RL secretors. However, treatment of P-0 cells with 0.001 to 1000 nmol OE(2)/1 for 24, 48 and 144 h resulted in adramatic increase in PRL cel ls when compared with controls. These increases occurred without alter ations in GH percentages and in the absence of significant cell prolif eration In fact, OE(2) suppressed the proliferation of P-0 cells to 20 % of the control rate (P<0.05), suggesting that OE(2) induced pre-exis ting GH-secreting cells to release both GH and PRL. Taken together, th ese results clearly indicate that clonal origin does not guarantee hom ogeneity of function, and alteration in the culture environment can ha ve profound effects on the secretory cell composition of acidophilic c ell lines. These considerations have important implications for the in terpretation ofresults generated with GH- and/or PRL-secreting cell li nes.