Morphological and functional stimulation of adrenal reticularis zone by dopaminergic blockade in dogs

In order to investigate factors affecting adrenal maturation leading to adrenarche, the effect of dopaminergic blockade on the morphology and function of the adrenal reticularis zone was studied in fourteen preadrenarchal dogs. Seven animals of 7 weeks of age (adrenarche at 11 weeks) were treated with domperidone (DOM) 3 times/day p.o. (3 mg/kg) at 09.00 h, 14.00 h, and 21.00 h, plus an additional injection of DOM s.c. (0.6 mg/kg) at 21.00 h for 15 days. Seven control animals received diluent. Twelve hours after the last injection, dogs received 0.25 mg ACTH i.m. and were sacrificed 60 min later. Blood was collected and adrenals removed. After histological evaluation, the percent of the reticularis, fasciculata, and glomerulosa zones with respect to the total cortex was calculated. Plasma androstenedione (A), dehydroepiandrosterone (DHA), 17-OH-progesterone (17P), and cortisol (F) levels in response to ACTH were also assessed. DOM-treated dogs show a significant development of the zona reticularis compared to control animals (19.2 +/- 0.6% vs 8.8 +/- 2.09% respectively, X +/- SE, P less than 0.01). In the same animals, the DHA response to ACTH (9.0 +/- 1.6 ng/dl) was significantly higher than in placebo-treated dogs (3.8 +/- 1.1 ng/dl, P less than 0.05) while no significant differences were found in F, A, and 17P levels between the two groups. Finally the post-ACTH A/DHA ratio of DOM-treated dogs (1.33 +/- 0.28) was significantly decreased in respect to the placebo-treated animals (5.49 +/- 2.54, P less than 0.01). These data demonstrate that the morphological and functional development of zona reticularis may be subject to dopaminergic control and this could represent an important step in the initiation of adrenarche. However, the cellular mechanism responsible remains to be clarified.