THE EFFECT OF OLEIC-ACID ON THE SECRETION OF THYROTROPIN AND GROWTH-HORMONE BY CULTURED RAT ANTERIOR-PITUITARY-CELLS

Elevation of non-esterified fatty acids (NEFA) in vivo is associated with abnormal control of TSH. To determine whether TSH secretion is directly inhibited by NEFA, as has been reported for GH, cultured rat anterior pituitary cells were exposed for 20 h to oleic acid in medium containing 7.7 x 10(-5) mol/l bovine serum albumin (BSA). In a molar ratio with albumin of 1.2 (total oleic acid 9 x 10(-5) mol/l), or greater, oleic acid inhibited basal GH secretion (maximum inhibition to 40% of control) while basal TSH was less affected, a ratio of 3 (2.3 x 10(-4) mol/l oleic acid) or greater causing a smaller degree of inhibition (maximum inhibition to 80% of control). In the presence of 10(-9) mol/l growth hormone-releasing hormone or 10(-8) mol/l TRH, inhibition was achieved at a ratio of 12 (9 x 10(-4) mol/l oleic acid) or greater. Basal TSH was less sensitive to inhibition by thyroxine (T-4) in the presence of oleic acid/albumin at a ratio of 6 or greater, and inhibition by oleic acid was less than additive with T-4 at a ratio of 6 or greater. Responses to tri-iodothyronine (T-3) were unaffected at a ratio of 6 (4.6 x 10(-4) mol/l oleic acid), but a ratio of 12 inhibited the effects of both T-3 and T-4 on TSH. Oleic acid had less effect in the presence of TRH, a ratio of 12 causing a small increase in the threshold concentration of T-3 and T-4 for TSH inhibition. Further studies are required to determine the mechanism by which oleic acid inhibits the response of basal TSH to T-4 as well as the reason for a reduced effect of oleic acid in the presence of TRH. In some critically ill patients, total serum NEFA/albumin ratios from 1.5 to 6 have been reported, indicating that the direct inhibitory effects on TSH observed in vitro occur at free NEFA concentrations achieved in vivo. However, the direct inhibitory effect on TSH may be offset to some extent by reduced responsiveness to T-4 at higher oleic acid concentrations. Hence other sites of action of NEFA in vivo may also be important in limiting TSH secretion. Further studies should examine the hypothalamic hormones like TRH and somatostatin, which control the thyrotrophs, as potential sites of action of NEFA.