The Development of Corticotrophs in the Fetal Sheep Pars Distalis: The Effect of Adrenalectomy or Cortisol Infusion*

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Abstract
At 90 days gestation a uniquely fetal-type and an adult-type corticotroph have been observed in the fetal sheep pars distalis (term .apprx. 147 days). Between 90 and 130 days gestation the fetal type is predominant, and its numbers decline toward term. In this study the effect of the endogenous cortisol surge on the change in the population of corticotrophs in the pars distalis was investigated in sheep fetuses after bilateral adrenalectomy at 120 days gestation or after an infusion of 2 mg cortisol/day between 109 and 115 days gestation. The total proportion of corticotrophs, expressed as a percentage, decreased significantly (P < 0.01) from 115 days in saline-infused controls (21.09 .+-. 1.10%) and 135 days in intact controls (14.59 .+-. 1.12%). The percentage of adult-type corticotrophs increased significantly (P < 0.01) from 5.65 .+-. 0.77 at 115 days, to 11.93 .+-. 1.41 at 135 days. The percentage of fetal-type corticotrophs decreased significantly (P < 0.001) from 14.91 .+-. 0.35 at 115 days to 2.33 .+-. 0.48 at 135 days. A small proportion of ACTH-immunoreactive cells could not be defined as either adult- or fetal-type corticotrophs. These changes in the corticotroph population had not occurred at 135 days in fetuses that had been adrenalectomized at 120 days; the percentage of corticotrophs relative to unstained cells (21.70 .+-. 0.46%), the percentage of adult-type corticotrophs (6.42 .+-. 0.29%), and the percentage of fetal-type corticotrophs (14.65 .+-. 0.49%) were similar to those in 115-day-old fetuses, indicating that the normal change in the corticotroph population between 115 and 135 days gestation was dependent upon the presence of the fetal adrenal. In fetuses exposed to exogenous cortisol between 109 and 115 days gestation, the percentage of corticotrophs relative to unstained cells (16.53 .+-. 1.68%), the percentage of adult-type corticotrophs (12.40 .+-. 1.34%), and the percentage of fetal-type corticotrophs (3.78 .+-. 0.58%) were similar to those at 135 days. This indicates that a short period of increased fetal plasma cortisol can bring about premature maturation of the corticotrophs in the fetal sheep pars distalis. We have also described an ACTH-immunoreactive cell which has characteristics of both an adult- and a fetal-type corticotroph. Its morphological appearance suggests that it may be a transitional stage from the fetal- to the adult-type corticotroph. We conclude that cortisol produced by the fetal adrenal results in the change from a predominantly fetal-type to an adult-type corticotroph population between 115 and 135 days gestation in the pars distalis. This study demonstrates a previously undescribed developmental feedback relationship between the adrenal cortex and the pars distalis of the fetal sheep.