Development of responsiveness of dispersed rabbit adrenocortical cells to synthetic adrenocorticotropic hormone [ACTH-(1-24)] and alpha melanocyte-stimulating hormone.

Although there is a considerable body of evidence suggesting increased activity of the fetal and neonatal adrenal in the rabbit, the mechanism responsible for this increased activity has not yet been determined. This report provides data on the function of dispersed fetal, neonatal, and adult rabbit adrenocortical cells in vitro. During the period between 22-29 days gestation, the fetal rabbit adrenal cortex increases its cell number and three features of in vitro activity: basal corticoid production, responsiveness to synthetic ACTH-(1-24), and maximum corticoid secretory capacity. None of these variables is significantly altered during the first 3-5 days of neonatal life or in adult rabbits. At no time was any corticoid response observed to alpha MSH.

Responsiveness and maximum secretory capacity of isolated fetal lamb adrenocortical cells throughout the last third of gestation.

Although considerable evidence implicates increased fetal adrenal function as a major factor in the initiation of parturition in the sheep, the mechanism responsible for this increased activity has not yet been determined. We have investigated the development of the function of fetal lamb adrenal cortical cells dispersed in vitro. There was no change in the sensitivity of the cells to synthetic ACTH (ACTH1-24), as demonstrated by the concentraton of ACTH1-24 producing a 50% maximum response in corticoid secretion. This finding does not support the suggestion that there is a qualitative change in fetal adrenal receptor function as term approaches. No stimulation of corticoid was observed after the administration of alpha MSH or PRL in vitro at any gestational age or of alpha MSH in vivo in four fetuses at 125--130 days gestation. Both the maximum output and the 50% maximum response in corticoid secretion of adrenal cells from term fetuses were similar to those of adrenal cells from adult ewes. A significant increase in the maximum output of corticoids per cell in response to ACTH1-24 occurs as early as 107 days gestation and continues steadily to term.

Time trend analysis of plasma unconjugated and sulfoconjugated estrone and 3 beta-delta 5-steroids in fetal and maternal sheep plasma in relation to spontaneous parturition at term.

Parturition in the sheep is preceded by a complex series of changes in both fetal and maternal plasma-steroid hormone concentrations. Using the chronically catheterized fetal sheep preparation, we measured unconjugated and sulfoconjugated pregnenolone, 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, and estrone in fetal and maternal plasma over the final 20 days before spontaneous vaginal delivery at term. Where appropriate, third degree polynomial functions were fitted to the changing plasma hormone concentration profile. Fetal and maternal plasma pregnenolone and pregnenolone sulfate both fell from maximum values in the last 4 days of gestation. Fetal and maternal plasma estrone and estrone sulfate concentrations underwent a terminal rise over the last 4 days of gestation that was a mirror image of the fall in plasma pregnenolone and pregnenolone sulfate. Maternal 17 alpha-hydroxypregnenolone rose over the last 4 days of gestation. Fetal 17 alpha-hydroxypregnenolone, maternal and fetal plasma dehydroepiandrosterone sulfate, and fetal plasma dehydroepiandrosterone sulfate, and fetal plasma dehydroepiandrosterone showed no trend during the period of study. Maternal plasma dehydroepiandrosterone rose over the last 4 days of gestation. These results support the view that increased activity of placental 17 alpha-hydroxylase and 17-20-desmolase is responsible for the conversion of C-21 steroids to estrogens at term. delta 5-Steroids are present in very high plasma concentrations in fetal sheep plasma and may constitute a more important precursor pool for estrogen biosynthesis than does circulating plasma progesterone.

Time-trend analysis of plasma cortisol concentrations in the fetal sheep in relation to parturition.

Using a cortisol RIA carefully validated for specificity in fetal ovine plasma, we studied plasma cortisol time-trend changes in eight chronically catheterized sheep fetuses in the last 22 days of gestation before the spontaneous onset of labor. Best fit exponential type curves were drawn for each individual fetus to define the time before the onset of labor at which fetal plasma cortisol was rising at different rates. Fetal plasma cortisol increased at a rate of 0.5 ng ml-1 day-1 as early as 17.1 days before labor in one fetus, whereas the mean value for all eight fetuses occurred 11.8 +/- 1.0 (SEM) days before labor. The rate of increase doubled to 1.0 ng cortisol ml-1 day-1 as early as 14.4 days before labor in one fetus, whereas the mean value for all eight fetuses occurred 9.3 +/- 0.9 days before labor. These findings suggest that the regulatory mechanisms responsible for the prelabor increase in fetal cortisol production are activated earlier in gestation than we previously thought.