Circadian Rhythms in Urinary Steroids in Response to a 36-Hour Sustained Metyrapone Administration in Eight Young Men

Abstract

Eight apparently healthy human males, ˜ 16 years of age volunteered to collect urines every 4 hours: a) during 24 hours (control); b) during 36 hours with 0.75 g metyrapone ingested every 4 hours (total dose 7.50 g); c) again 36 hours without medication. Subjects’ synchronization: lights on at 07.15 h; lights off at 23.00 h. Spontaneous diet with meals at 07.30 h, 11.30 h, 15.30 h. and 18.30 h. Circadian changes in urinary 17-hydroxycorticosteroids (17-OHCS), tetrahydro-11-deoxycortisol (THS), 17-ketosteroids (17-KS) and the estimated portion of 11-hydroxylated tetrahydrocorticosteroids (11-OHCS) were documented and analysed by the cosinor method among others. The 17-OHCS circadian rhythm (p <0.05) has its acrophase (circadian peak time) located at 14.30 h in the three experimental circumstances (a, b, and c above) while a statistically significant rise in both mesor (24-hour rhythm adjusted mean) and amplitude values occurs for b and c in comparison with a. Only traces of THS are excreted during a, without rhythm detection. During (b) and after (c) metyrapone administration, a THS circadian rhythm is validated (p <0.05) with an acrophase at ˜ 14.30 h and a great amplitude. The 17-KS circadian rhythm shows also a rise of the mesor value during b and c while the acrophase s are located at ˜ 13.30 h.

Since the drug was given at fixed dose and regular time intervals, the validated circadian rhythm can be viewed as a circadian change in the response to metyrapone of the pituitary-adrenal system among other biosystems.

Key words

Metyrapone - Adrenals and Biorhythm - 17-Hydroxycorticosteroids - 17-Ketosteroids - Creatinine