CORTICOSTEROID RELEASE BY ADRENAL TISSUE FROM FOETAL AND NEWBORN LAMBS IN RESPONSE TO CORTICOTROPHIN STIMULATION IN A PERIFUSION SYSTEM IN VITRO

Abstract

Adrenal glands from 24 foetal lambs (100–145 days gestation) and eight postnatal lambs (birth to 25 days of age) were used to study developmental changes in the responsiveness of the lamb adrenal to stimulation by synthetic adrenocorticotrophin (ACTH). A continuous flow incubation system in vitro (perifusion) was used in these studies. Addition of ACTH to the perifusion medium (0·3 μg Synacthen/ml) significantly increased the rate of corticosteroid release (as measured by a protein-binding assay) by adrenal tissue from foetuses of all ages studied. With tissue from foetuses of 137 days gestation or less, corticosteroid release during ACTH stimulation was < 2 μg/100 mg tissue in the 3 h following addition of ACTH to the perifusion medium. With tissue from foetuses older than this, the rate of corticosteroid release stimulated by ACTH increased as foetal age increased. At 145 days gestation (just before birth) release was 6·8 μg/100 mg tissue and in postnatal lambs less than 1 day old it was 12·3 μg/100 mg tissue during the 3 h following the start of stimulation. This increase in the response of the foetal adrenal to ACTH stimulation paralleled the increases in adrenal weight and plasma corticosteroid concentration which occurred before birth. With tissue from older lambs ACTH-stimulated corticosteroid release was 5·5 μg/100 mg tissue/3 h, a value comparable to that of 5·6 μg/100 mg tissue/3 h obtained with adrenal tissue from adult sheep. Separation of corticosteroids in the perifusion medium by chromatography on LH 20 Sephadex indicated that adrenals from younger foetuses (< 137 days gestation) released approximately equal amounts of cortisol and corticosterone, whereas adrenals from older foetuses and postnatal lambs released mainly cortisol. Pituitary tissue from all foetuses stimulated corticosteroid release from adrenal tissue of adult sheep, implying that foetal pituitary stores of ACTH do not limit development of foetal adrenal cortex function during the last third of gestation. The results indicate that there is a marked increase during the last week of gestation in the responsiveness of the foetal adrenal to ACTH stimulation and that this increase is related to maturation of corticosteroid biosynthetic pathways during this period.