Changes in the Ratio of Bioactive to Immunoreactive Adrenocorticotropin-Like Activity Released by Pituitary Cells from Ovine Fetuses and Lambs

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Abstract
We have compared the biological (B) and immunological (I) ACTH-like activities (ALA) released by short term cultured pituitary cells from fetal (63-144 days old) and young lambs (7-150 days old) both under basal conditions, and when stimulated by ovine(o)CRF-(1-41) or arginine vasopressin (AVP), separately or in combination. The bioassay was based on the production of corticosteroids by cultured adrenal cells from adult sheep. The standard used in both the RIA and the bioassay was synthetic ACTH-(1-24). Under every condition, curves for dilution of the incubation media were parallel to the standard curves in both the RIA and the bioassay. When expressed per 5 .times. 105 pituitary cells, B-ALA output increased with gestational age and remained high after birth. During fetal life, B-ALA released was always lower than I-ALA. However, the B/I ratios increased with gestational age from 0.29 .+-. (SE) 0.04 at 63 days to 0.70 .+-. 0.04 at 144 days. Conversely, for postpartum animals, the B/I ratio were not different from 1, except in the case of stimulation by AVP alone, when they were significantly higher than 1. A 4-day treatment of pituitary cells from 120- to 126-day-old fetuses by AVP or cortisol resulted in an 1.5-fold enhancement of the B/I ratio of the ALA secreted under AVP stimulation. These results indicate that during development of the sheep I-ACTH levels are probably not representative of the corticotropic activity released by the pituitary. Furthermore, they suggest that the prepartum increase in fetal cortisol does result, in part, from an enhanced trophic drive to the fetal adrenal.