Metabolic effect of 3,3',5'-triiodothyronine in cultured growth hormone-producing rat pituitary tumor cells. Evidence for a unique mechanism of thyroid hormone action.

Abstract

Physiologic levels of 3,3',5'-triiodothyronine (rT3) are generally believed to have minimal metabolic effects in the pituitary gland and other tissues. In the present studies, the regulatory role of rT3 and other thyroid hormones on iodothyronine 5'-deiodinase (15D) activity was studied in a growth hormoneproducing rat pituitary tumor cell line (GH3 cells). O5D activity was thiol-dependent and displayed nonlinear reaction kinetics suggesting the presence of two enzymatic processes, one having a low Michaelis constant (K. for thyroxine IT41 of 2 nM) and a second with a high K. value (0.9 MM). Growth of cells in hormone-depleted medium resulted in a two-to 3.5-fold increase in low K. 151D activity (P < 0.001). The addition of thyroid hormones to the culture medium resulted in a rapid, dosedependent inhibition of low K. 151) activity with the following order of analogue potency: rT3 2 T4> 3,5,3'-triiodothyronine (T3). Using serum-free culture conditions rT3 was -50 times more active than Tj. These inhibitory effects were noted within 15 min of hormone addition and could not be attributed to substrate competition with T4. These findings suggest that the control of T4 to T3 conversion by thyroid hormones in the anterior pituitary gland is mediated by a unique cellular mechanism that is independent of the nuclear T3 receptor, and under some circumstances, rT3 may play a regulatory role in controlling this enzymatic process.

Expression of Type 2 Iodothyronine Deiodinase in Corticotropin-Secreting Mouse Pituitary Tumor Cells Is Stimulated by Glucocorticoid and Corticotropin-Releasing Hormone

“…Because it was reported that D2 activity was present in GH3 rat pituitary tumor cells (20,21), effects of DEX and cAMP on D2 expression in GH3 cells were also studied. As shown in Fig.…”

Thyroid endocrine system disruption by pentachlorophenol: An in vitro and in vivo assay

“…In addition, gene transcription can be measured based on the modulation of basal GH and PRL secretion in GH3 cells, which is related directly to regulation of GH and PRL mRNA expressions (Tamura et al, 2000). Furthermore, GH3 cells possess both deiodinase 1 (Dio 1) and 2 (Dio 2) activity (St Germain, 1985;Mori et al, 2007), and are responsive to T3 (Baur et al, 1997). Both deiodinases have an important role for maintaining local T3 levels in the brain and pituitary in vivo.…”

Brain Cortex Reverse Triiodothyronine (rT3) and Triiodothyronine Concentrations under Steady State Infusions of Thyroxine and rT3

“…and rT 3 in particular, are also capable of inhibiting the activity of this enzyme in cell cultures in the absence of thyroid hormones (22)(23)(24).…”