Effect of Adrenalectomy or Long Term Cortisol or Adrenocorticotropin (ACTH)-Releasing Factor Infusion on the Concentration and Molecular Weight Distribution of ACTH in Fetal Sheep Plasma*

Abstract

It is unclear whether the maturation of corticotrophs from the fetal to the adult type in the fetal sheep pituitary in late gestation is associated with changes in the sensitivity of the fetal pituitary to corticotrophic secretagogues and in the form of ACTH-containing peptides (IR-ACTH) secreted into the circulation. The maturation of the pituitary corticotroph population is known to be accelerated by intrafetal cortisol infusion and delayed by bilateral fetal adrenalectomy. We have therefore investigated the mol wt profile of IR-ACTH present in fetal sheep plasma from 110 days gestation until term (147 +/- 3 days) and determined whether intrafetal cortisol infusion between 105-117 days (2.5 mg cortisol/day), or bilateral fetal adrenalectomy can alter the mol wt profile of IR-ACTH in fetal sheep plasma. We have also investigated whether prior exposure to cortisol alters the subsequent responsiveness of the fetal pituitary to a long term infusion of ovine (o) CRF (10 micrograms oCRF/day). In the control group, the proportion of IR-ACTH which eluted in the low-mol wt (LMW) range (i.e. less than 12K) was significantly higher between 121-125 days (43.9 +/- 4.2%) than between 126-139 days (26.8 +/- 9.3%) but not different to that after 140 days gestation (29.9 +/- 5.5%). Between 110-117 days, cortisol infusion had no effect on the proportion of IR-ACTH in the LMW range (43.9 +/- 5.7%, saline infused; 44.1 +/- 2.4%, cortisol infused). Between 121-125 days, the proportion of IR-ACTH in the LMW range in the CRF-infused groups (with or without prior exposure to cortisol) was significantly lower (27.4 +/- 2.1%) than in the saline-infused control group. In contrast, after fetal adrenalectomy, the proportion of IR-ACTH in the LMW range between 126-139 days was significantly higher (48.0 +/- 6.7%) than in intact control animals (23.8 +/- 3.5%). We conclude that the change in the mol wt profile of IR-ACTH in fetal plasma after 125 days may be a consequence of changes in the morphological and/or functional characteristics of the corticotrophic cells in the fetal pituitary. Infusion of oCRF appears to accelerate the normal maturation of the fetal pituitary-adrenal relationship, and oCRF acting either directly or via secretion of cortisol may play a role in the posttranslational processing of POMC in the fetal sheep pituitary after 125 days gestation.