The role of fetal adrenal hormones in the switch from fetal to adult globin synthesis in the sheep

The switch from γ (fetal) to β (adult) globin production was studied by the analysis of globin synthesis in chronically cannulated ovine fetuses and newborn lambs. The γ/α globin synthesis ratio decreased from 0.98 ± 0.11 (S.D.) (n = 4 samples) at 100-120 days of gestation to 0.15 ± 0.07 (n = 4) in lambs of 150-156 days post-conception, and the β/α synthesis ratio increased from 0.04 ± 0.06 (n = 4) to 1.13 ± 0.21 (n = 4) over the same period. In bilaterally adrenalectomized fetuses, which survived in utero until 151-156 days, the γ/α and β/α synthesis ratios were 0.64 ± 0.14 (n = 3) and 0.25 ± 0.07 (n = 3) respectively in the 150- to 156-day period. Bilateral adrenalectomy did not affect the time of onset of β globin synthesis, but significantly decreased the rate. In one bilaterally adrenalectomized fetus the infusion of increasing concentrations of cortisol restored the rate of β globin synthesis to normal. Treatment of three intact fetuses with 100 μg cortisol/h for 3 weeks, from 100 to 121 days, did not affect the timing or rate of switch from γ to β globin synthesis. Thus fetal adrenal secretions, probably cortisol, affected the rate of change of γ to β globin synthesis but other factors must have been involved in the initiation of the switch.