ONTOGENY AND ULTRADIAN RHYTHMS OF ADRENOCORTICOTROPIN AND CORTISOL IN THE LATE-GESTATION FETAL HORSE

Fetal maturation and the timing of parturition in both sheep and primates are thought to be controlled by the hypothalamic-pituitary-adrenal axis but little is known about the endocrinology of the equine fetus. We investigated the ontogeny of plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol and corticosteroid binding capacity in the late-gestation fetal horse. We also wished to determine whether there is ultradian rhythmic release of ACTH and cortisol in fetal horses and we compared fetuses to maternal and non-pregnant adult horses. Six fetuses, 278-304 days gestation (term approximate to 335), were catheterized and sampled daily until delivery. Mean (+/-S.E.M.) ACTH concentrations increased significantly from 159+/-21 to 246+/-42 pg/ml over the last 2 days before parturition. Fetal cortisol increased significantly from 3.1+/-1.0 to 13.4+/-3.7 ng/ml (mean+/-S.E.M.) over the last 9 days before delivery. The slope of regressions for ACTH and cortisol concentrations with respect to time were positive in all subjects and statistically significant in 3 of 6 for ACTH and 5 of 6 for cortisol. Fetal corticosteroid binding capacity declined from 49.5+/-20.5 to 16.1+/-2.2 ng/ml (mean+/-S.E.M.) over the last 10 days before parturition. However, the greatest changes in ACTH, cortisol and corticosteroid binding capacity occurred very late in gestation, during the last 48 to 72 h before parturition. Significant peaks and nadirs in plasma ACTH concentration were detected in all 20 experiments and in plasma cortisol concentration in 17 of 20 experiments using Cluster analysis. We found statistically significant periods of oscillation between 11 and 64 min in plasma ACTH (19 of 20 experiments) and cortisol (15 of 20 experiments) using power spectral density analysis. Statistically significant periods between 11 and 17 min were detected in 11 of 20 experiments for ACTH and in 8 of 20 for cortisol. We conclude that: 1) at the end of gestation, equine fetal plasma ACTH and cortisol concentrations increase while corticosteroid binding capacity decreases suggesting that there is a disproportionately large increase in unbound cortisol at this time; 2) the secretion of ACTH and cortisol is rhythmic in both fetal and adult horses; 3) most animals exhibit a period of oscillation between 11 and 17 min; and 4) there is no apparent developmental change from late gestation to adulthood in the ultradian oscillator influencing ACTH and cortisol secretion in this species.