[Melatonin reduces cortisol response to ACTH in humans].
BACKGROUND
Melatonin receptors are widely distributed in human tissues but they have not been reported in human adrenal gland.


OBJECTIVE
To assess if the human adrenal gland expresses melatonin receptors and if melatonin affects cortisol response to ACTH in dexamethasone suppressed volunteers.


METHODS
Adrenal glands were obtained from 4 patients undergoing unilateral nephrectomy-adrenalectomy for renal cancer. Expression of mRNA MT1 and MT2 melatonin receptors was measured by Reverse TranscriPtase Polymerase Chain Reaction (RT-PCR). The effect of melatonin on the response to intravenous (i.v.) ACTH was tested (randomized cross-over, double-blind, placebo-controlled trial) in eight young healthy males pretreated with dexamethasone (1 mg) at 23:00 h. On the next day, at 08:00 h, an i.v. line was inserted, at 08:30 h, and after a blood sample, subjects ingested 6 mg melatonin or placebo. At 09:00 h, 1-24 ACTH (Cortrosyn, 1 microg/1.73 m2 body surface area) was injected, drawing samples at 0, 15, 30, 45 and 60 minutes after. Melatonin, cortisol, cortisone, progesterone, aldosterone, DHEA-S, testosterone and prolactin were measured by immunoassay.


RESULTS
The four adrenal glands expressed only MT1 receptor mRNA. Melatonin ingestion reduced the cortisol response to ACTH from 14.6 +/- 1.45 microg/dl at 60 min in the placebo group to 10.8 +/- 1.2 microg/dl in the melatonin group (p < 0.01 mixed model test). It did not affect other steroid hormone levels and abolished the morning physiological decline of prolactin.


CONCLUSIONS
The expression of MT1 melatonin receptor in the human adrenal, and the melatonin reduction of ACTH-stimulated cortisol production suggest a direct melatonin action on the adrenal gland.
Campino
Carmen
C
Departamento de Endocrinología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Lira 85, S degrees piso, Santiago, Chile. ccampino@med.puc.cl
Valenzuela
Francisco
F
Arteaga
Eugenio
E
Torres-Farfán
Claudia
C
Trucco
Cristián
C
Velasco
Alfredo
A
Guzmán
Sergio
S
Serón-Ferré
María
M
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000494:pharmacology; D004311:Double-Blind Method; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis*; D007118:Immunoassay; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D044122:Receptor, Melatonin, MT1 / Q000032:analysis* / Q000187:drug effects; D044123:Receptor, Melatonin, MT2 / Q000032:analysis* / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D055815:Young Adult
D005938:Glucocorticoids; D012333:RNA, Messenger; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D008550:Melatonin; D006854:Hydrocortisone