Rationale: 5-Hydroxytryptamine(1A) (5-HT(1A)) receptor function has been shown to be attenuated by corticosteroid hormones in a variety of animal experimental paradigms. It has been suggested that this effect may be central to the pathophysiology of severe depressive illness in humans, a condition in which 5-HT(1A) receptor function is reduced and corticosteroid hormone levels are elevated. Evidence suggests that the hormonal response to L-tryptophan ( L-TRP) is mediated by 5-HT(1A) receptors. This response has been shown to be reduced following acute administration of hydrocortisone, and we hypothesised that sub-chronic administration of hydrocortisone would also blunt it.
Objectives: To examine the effects of sub-chronic administration of hydrocortisone on hormonal and psychological responses to L-TRP infusion in healthy male subjects. To ascertain whether cortisol was exerting effects on prolactin release directly at the pituitary rather than via hypothalamic 5-HT(1A) receptors, a thyroid-releasing hormone (TRH) challenge test was performed.
Methods: Fourteen healthy male volunteers took part in a random-order, double-blind, placebo-controlled study, in which 20 mg hydrocortisone or placebo was administered twice daily for 7 days before infusion of L-TRP. A TRH challenge was administered to eight of the subjects following the L-TRP infusion.
Results: Pre-treatment with hydrocortisone significantly reduced the growth hormone (GH) and cortisol responses, but not the prolactin (PRL) response to the infusion. TRH administration caused a robust increase in PRL, but this response was not attenuated by hydrocortisone pre-treatment. The TSH response to TRH was blunted. There was no effect of pre-treatment on psychological responses to L-TRP.
Conclusions: The attenuation in GH response following hydrocortisone pre-treatment could indicate a reduction in 5-HT(1A) receptor function, although it is probable that it is attributable to the action of hydrocortisone at the pituitary level. More precise, non-neuroendocrine models of 5-HT(1A) receptor function are necessary to clarify this.