THE INVITRO EFFECT OF METYRAPONE ON STEROID-SYNTHESIS IN MICE ADRENALS AT DIFFERENT CIRCADIAN STAGES

The circadian rhythm of the in vitro biosynthesis of cortisol and cortisone in mice adrenals has been documented in the absence and presence of 0.1-mu-mol metyrapone, an inhibitor of steroid 11-beta-monooxygenase. After 3 weeks of synchronization with 12 h light: 12 h darkness, adrenalectomy was performed at eight circadian stages: 0, 4, 9, 10, 13, 16, 21, and 22 h after light onset (HALO). Because it has been shown that mice adrenals could convert exogenous 11-deoxycortisol, the synthesis of 11-oxysteroids (cortisol + cortisone) in adrenal homogenates was studied from tritiated precursor. The pattern of steroid synthesis showed a maximum around the end (10 HALO) and a minimum at the beginning of the resting period (0 HALO), the variation was approximately 10%. A similar pattern was observed in the presence of a approximately 50% inhibiting dose of metyrapone. On the other hand, the percent inhibition of 11-oxysteroids synthesis was greater at the beginning of the resting period (0 HALO) and minimum around the end of the activity span (21 HALO), with an overall variation of 20%. However, the variations were statistically insignificant (unpaired t test).