Thyroid hormone controls glucocorticoid action in cultured GH₁ cells

Abstract

WE have demonstrated that L-triiodothyronine (T3) stimulates growth hormone synthesis three to four-fold^1–3 and inhibits prolactin secretion¹ in cultured GH₁ cells, which constitute a rat pituitary cell line. Others have shown that cortisol also stimulates growth hormone production in GH₁ cells⁴. In GH₃ cells, a closely related cell line, cortisol stimulates growth hormone production four- to eightfold and inhibits prolactin secretion approximately fourfold⁵. Thus, thyroid and glucocorticoid hormones seem to control similar growth hormone and prolactin responses in GH₁ and GH₃ cells. Studies of the effects of glucocorticoids in these cell lines^4,5, however, have used commercial serum preparations containing physiological concentrations of thyroid hormone⁶. To examine the intrinsic response of these cells to glucocorticoid, therefore, it is necessary to use medium supplemented with serum which contains very low thyroid hormone levels. Using culture medium supplemented with hypothyroid calf serum, we have examined the influence of T3 and cortisol on the induction of growth hormone synthesis in GH₁ cells. We report here that in the absence of T3, the cells seem unresponsive to glucocorticoids, whereas in its presence cortisol markedly enhanced growth hormone production. The apparent requirement of T3 for expression of the cortisol response seems independent of any influence of T3 on total cell steroid receptor levels or the nuclear-cytoplasmic distribution of the steroid receptor, and of any effect of cortisol in modulating the level of the T3 nuclear receptor.