Age-dependent changes in the processing of corticotropin-containing peptides in pituitary cells of the foetal sheep.

sheep of 118-135 days increase sharply their cortisol output in response to low corticotropin concentrations. At 140145 days (term = 145 days) the response of adrenal cells to corticotropin stimulation was essentially the same with a small increase only over total output at 118-135 days. Corticosterone production from the foetal adrenal was always no more than half of that for cortisol, and fell between 120 and 143 days; it gave an essentially similar dose-response curve to corticotropin as did cortisol. These data suggest that the steroidogenic capacity of the foetal sheep adrenal in response to corticotropin stimulation does not show a pronounced increase over the latter third of gestation, although it does rise through the growth of the gland. Thus the changes in the activity of the gland in vivo are more likely to be caused by changes in circulating factors. We have shown that the large-molecular-weight precursor forms of corticotropin are present in high concentrations in the plasma of foetal sheep, and that the ratio of these to corticotropin(I-39)-peptide falls at the time of increased adrenal activity (Jones & Roebuck, 1980). Moreover, these corticotropincontaining molecules inhibit the steroidogenic effects of corticotropin-( 1-391-peptide on the adrenal (Jones & Roebuck, 1980; Roebuck et al., 1980), and thus could be at least one of the factors modulating adrenal activity in utero.