Summary. Secretion rates by the major sites of progesterone synthesis were measured during pregnancy in 3 ewes with single fetuses after autotransplantation of the left adrenal and the left ovary (containing the corpus luteum) to the neck. The total production of progesterone measured by tracer kinetics increased from 12·1 ±2·0 (s.e.m.) to 31·3 ± 2·4 μg/min between 66–103 and 133–145 days p.c. Ovarian and adrenal secretion rates measured directly at the same times decreased from 5·2 ± 0·9 to 2·1 ±0·9 μg/min (ovary), or remained unchanged, about 0·03 μg/min (adrenal). The difference between the total production of progesterone and ovarian and adrenal secretion showed that the contribution from other endocrine tissues (presumably the placenta) increased from 6·8 ± 1·5 to 29·2 ± 4·1 μg/min (P < 0·001) during this period.
F. A. Harrison and R. B. Heap
F. A. Harrison, R. B. Heap and N. L. Poyser
Summary. A uterine pouch was prepared surgically in ewes before mating to study the production and chemical composition of uterine secretions during pregnancy. Pregnancy was established in 6 sheep and in the first 55 days uterine fluid was present in small amounts (<5 ml), whereas between 109 days post coitum and 3 days post partum the volume ranged from 90 to 775 ml.
The chemical composition of uterine fluid in pregnancy differed from that of plasma especially in respect of its high concentration of total calcium (up to 83·5 mM) and prostaglandin (PG) F-2α (up to 1500 ng/ml). Progesterone was implicated as an important endocrine factor since uterine fluid (188 ml) with a high concentration of total calcium (53·5 mM) and PGF-2α (235 ng/ml) was recovered from a non-pregnant sheep treated with progesterone for 115 days.
J. Y. F. Paterson, Cecelia A. Bedford, F. A. Harrison and R. B. Heap
The rates of metabolism of progesterone and 20α-dihydroprogesterone (20α-diHP) in sheep have been measured during and after the infusion of tracer amounts of [3H]progesterone. There were significant differences in the blood concentration of [3H]progesterone between experiments, but these were not attributable to the stage of gestation or to the difference between pregnant and non-pregnant animals. The mean (±S.E.M.) metabolic clearance rate of progesterone was 3·277 ± 0·239 litres blood/min.
The simplest model of the distribution of progesterone was one containing two pools, V1[P] and V2[P], where [P] is the blood concentration of progesterone, and in 23 experiments on 7 sheep the mean pool dimensions were 7·8[P] μg and 70[P] μg, respectively. This model was developed to include the formation of 20α-diHP from progesterone. Progesterone appeared to be the major source of 20α-diHP, though this did not seem to be an obligatory metabolite. The parameters obtained gave comparably low residual deviations for both labelled steroids and were consistent with other observations made on progesterone clearance.
J. Y. F. Paterson, F. A. Harrison, E. L. Sheldrick and R. B. Heap
Summary. When [3H]progesterone is infused intravenously into ewes, blood 20α-dihydroprogesterone (20α-diHP) becomes labelled and the changes in [3H]20α-diHP activity with time are clearly related to that of [3H]progesterone. Concentrations of 20α-diHP in blood have now been estimated for these experiments. During the infusion, the specific radioactivity of 20α-diHP at steady state was only 53% of the specific radioactivity of progesterone, indicating that 20α-diHP was produced other than by C-20 reduction of secreted progesterone. The change in blood concentration of 20α-diHP during pregnancy in ewes suggests that the placenta is its source.
[3H]20α-dihydroprogesterone was infused into pregnant ewes and the specific radioactivity of 20α-diHP measured during and after infusion. Together with information from earlier experiments when [3H]progesterone was infused, there is now sufficient data to estimate, without constraint, the parameters of a four-pool model describing the distribution and metabolism of progesterone and 20α-dyhydro-progesterone in sheep.
J. R. G. CHALLIS, F. A. HARRISON, R. B. HEAP, E. W. HORTON and N. L. POYSER
We have reported elsewhere that the concentration of progesterone in the uterine venous blood of sheep decreases before the onset of parturition, whereas the concentration of total unconjugated oestrogens (predominantly oestrone) increases sharply within 48 hr before delivery (Challis, 1971a, b; Bedford, Challis, Harrison & Heap, 1972). In one of these ewes, concentrations of prostaglandin F2∝ (PGF2∝) in uterine venous blood have been measured, as well as those of progesterone and oestrogens, to define the temporal relations of these compounds in the same animal immediately before term. Recent work in the sheep has shown that the concentration of PGF2∝ in the uterine venous blood and the maternal caruncles increases at parturition which has been induced experimentally by infusion of dexamethasone into the fetus (Liggins & Grieves, 1971; Thorburn, Nicol, Bassett, Shutt & Cox, 1972) and it has been suggested that an elevated fetal cortisol level (Bassett & Thorburn, 1969) may provide a stimulus for PGF2∝ synthesis (Liggins, Grieves, Kendal & Knox,