STEROIDS CAN MODULATE TRANSDIFFERENTIATION OF PROLACTIN AND GROWTH-HORMONE CELLS IN BOVINE PITUITARY CULTURES

Fluctuations in the proportions of pituitary acidophils (cells that release GH and PRL, either separately or concurrently) have been correlated with dynamic changes in the steroid hormone milieu. Since modulation of these acidophilic subtypes can occur without appreciable alterations in the total number of acidophils, it has been proposed that GH- and PRL- secreting cells can actually transdifferentiate (gain or lose the ability to release GH or PRL). To test this hypothesis, we examined the effects of steroids on the proportions of cells that released GH, PRL, or both hormones (i.e. mammosomatotropes) in bovine pituitary cell cultures. Specifically, anterior pituitary cells from castrated males were cultured for 6 days in the absence (controls) or presence of 17-beta-estradiol, cortisol, or progesterone. Reverse hemolytic plaque assays revealed that 6.64 +/- 1.2% of all pituitary cells released GH, while 68.8 +/- 5.3% were PRL secretors in control cultures. Cortisol and progesterone induced and increment in the proportions of GH-secreting cells (10 nM cortisol, +11.7 +/- 2.4%; 1000 nM cortisol, +10.5 +/- 4.7%; 1000 nM progesterone, +2.87 +/- 1.5%) above control values while decreasing the relative abundance of cells that released PRL (10 nM cortisol, -7.6 +/- 1.7%; 1000 nM cortisol, -6.6 +/- 1.2%; 1000 nM progesterone, -5.5 +/- 1.3%) below control values. However, 17-beta-estradiol was ineffective in this regard at doses of 0.1-1000 nM. A more critical examination of the steroid-induced changes revealed that they were attributable to increases in the proportions of cells that released GH alone and both hormones simultaneously along with a concomitant decrease in the fraction that secreted only PRL. Two lines of evidence discount the possibility that these effects were due to selective cell proliferation. First, the mitotic rate of cultures (assessed by immunofluorescent detection of bromodeoxyuridine incorporation) was only about 1% of all cells in both control and steroid-treated cultures. Second, blocking cell proliferation by the addition of cytosine arabinoside (100-mu-M) did not inhibit the cortisol-induced augmentation of GH-releasing cells. Taken together, these results substantiate the hypothesis that acidophilic subpopulations are capable of transdifferentiation given an appropriate hormonal signal.