Thyroxine replacement after hypophysectomy alters the pattern of enkephalin localisation in the adrenal medulla of the fetal sheep.

It has been suggested that a pituitary-derived or -dependent factor may suppress enkephalin peptide synthesis in the central noradrenaline- containing cells of the sheep adrenal medulla in late gestation. We have investigated the effect of thyroxine (T4) replacement after fetal hypophysectomy on the localisation of enkephalin peptides within the peripheral adrenaline- and central noradrenaline-containing regions of the adrenal medulla of the fetal sheep. Fetal hypophysectomy (HX) was performed in 12 fetal sheep at 105-108 days gestation (term = 145 +/- 3 days gestation). T4 (40 micrograms/kg/24h) (HX + T4) or saline (HX + Sal) were infused between 110 and 140 days gestation. Adrenal glands were collected from the HX + T4, HX + Sal groups and from a group of intact fetal sheep (n = 4) for immunohistochemistry using anti- met-enkephalin and an avidin-biotin staining system. In adrenals from intact fetal sheep, there was intense positive staining for met-enkephalin in the peripheral adrenaline-containing region and sparse staining for enkephalins in the central noradrenaline-containing region. In contrast, in the HX + Sal group, enkephalin staining was uniformly present throughout the peripheral and central regions of the adrenal medulla. In the HX + T4 group, however, the staining density of met-enkephalin was higher within the adrenaline cells of the peripheral rim of the medulla than in the central medullary region. We have demonstrated that T4 replacement after fetal hypophysectomy restores the normal ontogenetic pattern of localisation of enkephalin peptides within the fetal adrenal. We postulate that T4 acts either indirectly via neural mechanisms or directly at the noradrenaline-containing cells to mediate the suppression of enkephalin staining within the central noradrenaline-containing region of the adrenal medulla of the fetal sheep in late gestation.