The effects of sub-chronic administration of hydrocortisone on hormonal and psychological responses to L-tryptophan in normal male volunteers.
BACKGROUND
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.


OBJECTIVE
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.
Porter
Richard J
RJ
Department of Psychological Medicine, Christchurch School of Medicine, Christchurch, New Zealand.
Gallagher
Peter
P
Watson
Stuart
S
Lunn
Brian S
BS
Young
Allan H
AH
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D006728:Hormones / Q000097:blood*; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D011388:Prolactin / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D006728:Hormones; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D019382:Human Growth Hormone; D013973:Thyrotropin-Releasing Hormone; D014364:Tryptophan; D011388:Prolactin; D006854:Hydrocortisone