DEVELOPMENTAL REGULATION OF CORTICOSTEROID-BINDING GLOBULIN BIOSYNTHESIS IN THE BABOON FETUS

The present study determined the roles of estrogen and cortisol in mat ernal and fetal corticosteroid-binding globulin (CBG) levels and fetal hepatic messenger RNA (mRNA) expression in the baboon. Samples of fet al liver, kidney, and brain were obtained from untreated control anima ls at early (day 60; n = 4), mid (day 100; n = 8), and late (day 165; n = 5) gestation (term = day 184). Maternal and umbilical blood sample s were collected on day 100 from baboons in which betamethasone was ad ministered sc to the mother (n = 6) on days 60-99 of gestation and on day 165 from animals (n = 4) in which the fetus was administered betam ethasone on days 150-164 of gestation. Maternal serum cortisol concent rations were similar at mid (43 +/- 2 mu g/dl) and late (42 +/- 3 mu g /dl) gestation and decreased (P < 0.05) at midgestation (1 +/- 1 mu g/ dl) and term (31 +/- 4 mu g/dl) after betamethasone treatment. Umbilic al serum cortisol levels were also reduced (P < 0.05) at both mid (1 /- 1 mu g/dl) and late (14 +/- 5 mu g/dl) gestation by betamethasone t reatment. Fetal serum CBG levels in untreated animals were lower (P < 0.05) on day 165 (444 +/- 29 pmol/ml) than on day 100 (844 +/- 35 pmol /ml) and increased (P < 0.05) at midgestation (1098 +/- 64 pmol/ml), b ut not at term (551 +/- 24 pmol/ml), after betamethasone treatment. In contrast, maternal serum CBG levels (range, 528-770 pmol/ml) were not altered by gestational age or betamethasone. The human CBG complement ary DNA hybridized to a single mRNA species of 1.8 kilobases in baboon fetal liver; however, CBG was not expressed in fetal kidney and was d etectable in fetal brain and pancreas only by reverse transcription-PC R. In untreated baboon fetuses, the mRNA levels of hepatic CBG, expres sed as a ratio of 18S RNA, progressively decreased (P < 0.05) in early (1.83 +/- 0.17), mid (0.97 +/- 0.12), and late (0.51 +/- 0.04) gestat ion. These results demonstrate that fetal hepatic CBG mRNA expression and serum CBG concentrations were elevated early in baboon gestation a nd exhibited a progressive decline during the course of advancing preg nancy. We suggest that the increased levels of fetal CBG in the early stages of gestation reflect stimulation of hepatic CBG synthesis by ma ternal cortisol, which we previously demonstrated to occur in the fetu s as a result of preferential 11 beta-hydroxysteroid dehydrogenase-cat alyzed glucocorticoid reduction across the placenta. The decline in fe tal CBG may reflect the developmental increase in catabolism of cortis ol to bioinactive cortisone in target tissues of the fetus such as the liver.