STUDIES ON THE ROLE OF ACTH IN THE REGULATION OF ADRENAL RESPONSIVENESS AND THE TIMING OF PARTURITION IN THE OVINE FETUS

A dramatic late-gestation increase in fetal plasma cortisol concentrat ions is critical for the timing of parturition in the sheep. This incr ease appears to depend upon an intact hypothalamo-pituitary unit and i s characterised by increasing responsiveness of the fetal adrenal glan d to ACTH. ACTH has been postulated as the critical determinant of the late-gestation cortisol increase; however, recent evidence has sugges ted that other factors, including the ACTH precursor, pro-opiomelanoco rtin, may also be involved. To further define the role of ACTH in dete rmining the tinting of parturition and the responsiveness of the fetal adrenal gland, intact (INT/ACTH) and hypophysectomised (HX/ACTH) fetu ses received a continuous infusion of ACTH((1-24)) from the time of su rgery (similar to 115 days gestational age (GA)) at a rate we have pre viously shown to generate normal fetal cortisol concentrations and ter m parturition in HX fetuses. A third group of saline-infused intact fe tuses (INT/SAL) served as the control group. Adrenal responsiveness wa s assessed by cortisol responses to ACTH((1-24)) challenges at 120, 13 0 and 140 days GA. There were no differences between the three groups of fetuses in the timing of parturition, the late-gestation increase i n cortisol concentrations or the size of the adrenal cortex. In both I NT/SAL and INT/ACTH fetuses, there were significant increases in basal immunoreactive-ACTH concentrations with advancing GA, although no suc h increase was observed in HX/ACTH fetuses. The proportion of total AC TH immunoreactivity present in low molecular weight (LMW) forms in INT /ACTH fetuses was greater than that in INT/SAL fetuses, while the leve l of LMW ACTH in HX/ACTH fetuses was intermediate. Both ACTH((1-24))-i nfused groups of fetuses had dramatically enhanced adrenal responsiven ess to ACTH((1-24)) at all GAs tested when compared with INT/SAT, fetu ses and there was a correlation tin rank order) between the proportion of LMW ACTH immunoreactivity and adrenal responsiveness. From these o bservations it appears that there is a separate regulation of adrenal responsiveness from basal cortisol concentrations and that an increase in basal cortisol concentrations can occur in the absence of an incre ase in basal ACTH concentrations. Furthermore, an increase in adrenal responsiveness does not appear to predict the timing of parturition no r basal cortisol concentrations. Taken together with previous studies it appears that ACTH plays an essential role in maintaining the growth of the fetal adrenal and enhancing its responsiveness, but a late-ges tation increase in ACTH concentrations is not required to regulate bas al cortisol concentrations or the timing of parturition.