Abstract
This study examined changes in the blood concentration of corticosterone with the onset and progression of pregnancy in the rat. To identify the source of variation in blood corticosterone, the metabolic clearance rate (MCR) and production rate of corticosterone were also determined. Measurements were made in conscious rats (n=4–7 per group) in the morning of dioestrus and days 5, 10, 16 and 22 of pregnancy (term=day 23). Corticosterone levels were 713 ±38 nmol/l (mean±s.e.m.) in non-pregnant rats, remained unchanged to day 10 of pregnancy, then increased to 1036 ± 52 nmol/l by day 16 and remained high at day 22. The production rate of corticosterone appeared to increase during pregnancy from 25·6±1·7 μmol/day on day 10 to reach 36·3±3·3 mol/day on day 22, but this did not reach statistical significance (one-way ANOVA). The MCR of corticosterone was similar among all groups (overall mean 34·6±2·5 1/day), although a slight but non-significant fall was apparent at day 16. When account was taken of changes in maternal weight, the MCR decreased progressively from 139± 10 1/day per kg before pregnancy to reach a minimum of 88 ±7 1/day per kg on day 16. Transuterine extraction of corticosterone on day 22 of pregnancy was 19·2±3·1% and so, based on this and estimates of uterine blood flow, the uterus must account for around 15% of corticosterone clearance at this time. Because this uterine contribution is effectively additional clearance, it is likely that without it the MCR of corticosterone would have fallen during pregnancy. Administration of ACTH (1–24) (3·5 nmol) increased the production rate of corticosterone at dioestrus and at day 16 of pregnancy, but this effect was less marked in the pregnant group (134% and 41% increase respectively). The MCR of corticosterone also rose (17%) following ACTH(1–24) administration in pregnant but not dioestrous rats. This difference in the MCR response is likely to reflect pregnancy-induced changes in the relative levels of corticosterone, progesterone and corticosteroid-binding globulin.
In conclusion, this study shows that blood levels of corticosterone increase progressively during pregnancy in conscious rats. This increase apparently resulted from the net effects of increased production and decreased MCR, neither of which reached statistical significance. It would appear, however, that the trend toward increased production of corticosterone contributes more to the rise in blood corticosterone than does MCR, since the latter was more effectively maintained at pre-pregnancy levels. The demonstration of significant transuterine extraction of corticosterone at day 22 suggests that the maintenance of corticosterone clearance late in pregnancy is due, in part, to an additional contribution by the uterus and its contents.
Journal of Endocrinology (1994) 143, 183–190
Metabolic clearance rate and production rate of calcitriol in uremia