Antidepressants inhibit the glucocorticoid stimulation of thyrotropin releasing hormone expression in cultured hypothalamic neurons.

BACKGROUND

The pituitary thyroid axis is frequently effected in human depression possibly due to alteration in hypothalamic thyrotropin releasing hormone (TRH) secretion. Since clinical recovery is associated with normalization of thyroid function, the direct effect of antidepressants on TRH expression in a well established fetal rat hypothalamic neuronal culture system was investigated.

METHODS

Fetal rat hypothalamic neurons (day 17) in culture were treated with different concentrations of antidepressants with or without glucocorticoids for 7 days following which TRH content was measured by radioimmunoassay (RIA).

RESULTS

The results showed that Imipramine (IMIP), a tricyclic antidepressant (TCA), decreased the TRH content in a dose-dependent manner (from 80.7 +/- 4.9, at 10(-9) mol/L, to 14.1 +/- 0.6, at 10(-5) mol/L, fmol/well; P < 0.05). Desipramine (DESI), another tricyclic antidepressant, also decreased the TRH content (from 63.6 +/- 2.5, at 10(-9) mol/L, to 12.6 +/- 0.4, at 10(-5) mol/L, fmol/well; P < 0.05). Sertraline (SERT) and Fluoxetine (FLUO), serotonin selective reuptake inhibitors (SSRI), also decreased TRH content in a dose dependent manner (from 83.9 +/- 7.9, at 10(-10) mol/L, to 7.6 +/- 0.4, at 10(-5) mol/L, and from 41.66 +/- 2.5, at 10(-8) mol/L, to 17.54 +/- 0.92, at 10(-6) mol/L, fmol/well, respectively; both P < 0.05). We then tested the effect of these antidepressants on the Dex stimulation of TRH content. IMIP, DESIP and FLUO at 10(-6) mol/L reduced the TRH response to glucocorticoid stimulation (36.4 +/- 4.0, 56.6 +/- 2.4, 23.75 +/- 4.0, respectively vs 107 +/- 7.5 fmol/well; P < 0.05).

CONCLUSION

This raises the possibility that the enhanced thyroid function in depression, which we postulate, may result in part from glucocorticoid stimulation of TRH gene expression, can be reversed by antidepressants through a direct effect on the TRH neuron. However, other mechanisms may need to be invoked in addition since basal TRH content was also reduced.