Development of the pituitary adrenal axis in fetal sheep twins

Plasma cortisol increases in fetuses at term and is important for overall development. This study was designed to determine whether cortisol increases synchronously in twin fetal sheep and whether differences between twins contribute to the respective timing. Catheters were surgically implanted in fetal arteries in twins, the amniotic sac, and a maternal artery and vein. Blood was drawn daily until labor was imminent or the twins were delivered. Fetal pituitaries and adrenals were removed for in vitro measurements. Analyses included blood gases and cortisol (daily) and plasma cortisol, adrenocorticotropic hormone (ACTH), and estrogens (at completion). Twins were assigned retrospectively to group A or B, depending on which cortisol was first elevated (group A) above baseline. Group A fetuses consistently had higher cortisol until term. All group A fetuses also first had elevated ACTH. In four of four sets of twins of both sexes, the male was in group A. There were no differences between fetuses in plasma estrogens or pituitary ACTH response to stimulation, but adrenal cells from group A fetuses were more responsive. These data suggest that adrenal activity is increased in one twin consistently, with the difference being attributable to the responsiveness of adrenal cells to ACTH rather than pituitary responsiveness to either corticotropin-releasing hormone or vasopressin. Difference between sexes may also be involved.