An ultrastructural morphometric study of the effects of chronic melatonin administration on the zona fasciculata of rat adrenal cortex.

The effects of a long-term administration of melatonin on the adrenal zona fasciculata were investigated both in 'normal' rats and in animals whose hypothalamo-hypophyseal-adrenal axis had been interrupted by a prolonged infusion with dexamethasone or dexamethasone plus maintenance doses of ACTH. In the 'normal' rats, melatonin caused a notable atrophy of zona fasciculata cells, coupled with a significant lowering in the plasma concentration of corticosterone. On the contrary, in dexamethasone- or dexamethasone plus ACTH-infused animals, melatonin induced an evident hypertrophy of zona fasciculata cells which, however, was not associated with a rise in the corticosterone blood level. The hypothesis is advanced that the direct stimulatory effect of melatonin on the growth of zona fasciculata in 'normal' rats can be masked by the concurrent inhibition of the hypophyseal release of ACTH. The possible mechanism of the direct effect of melatonin on the zona fasciculata is discussed in the light of evidence indicating that this hormone enhances the intracellular catabolism of corticosterone, which is well-known to exert a powerful direct depression of the growth and steroidogenic capacity of rat adrenocortical cells.