[Melatonin reduces cortisol response to ACTH in humans]

Rev Med Chil. 2008 Nov;136(11):1390-7. doi: 10.4067/s0034-98872008001100004.
[Article in Spanish]


Background: Melatonin receptors are widely distributed in human tissues but they have not been reported in human adrenal gland.

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

Material and 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / drug effects*
  • Adrenal Glands / metabolism
  • Adrenocorticotropic Hormone / administration & dosage
  • Adrenocorticotropic Hormone / pharmacology*
  • Adult
  • Cross-Over Studies
  • Dexamethasone / pharmacology
  • Double-Blind Method
  • Glucocorticoids / pharmacology
  • Humans
  • Hydrocortisone / biosynthesis*
  • Immunoassay
  • Male
  • Melatonin / administration & dosage
  • Melatonin / pharmacology*
  • RNA, Messenger / analysis
  • Receptor, Melatonin, MT1 / analysis*
  • Receptor, Melatonin, MT1 / drug effects
  • Receptor, Melatonin, MT2 / analysis*
  • Receptor, Melatonin, MT2 / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Young Adult


  • Glucocorticoids
  • RNA, Messenger
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Melatonin
  • Hydrocortisone