SPLANCHNIC, UTERINE, OVARIAN AND ADRENAL UPTAKE OF PROGESTERONE AND 20α-Dihydroprogesterone IN THE PREGNANT AND NON-PREGNANT SHEEP

Abstract

SUMMARY The uptake and extraction of progesterone and 20α-dihydroprogesterone (20α-diHP) by the splanchnic region and by some extra-splanchnic organs was measured by the determination of the concentration of labelled progesterone and 20α-diHP in a carotid artery and in the portal, hepatic, uterine, ovarian and adrenal veins during continuous intravenous infusion of [3H]progesterone. The efficiency of splanchnic extraction of progesterone and 20α-diHP was 92 and 91%. The splanchnic clearance rates of progesterone and 20α-diHP were 1·210 and 1·223 l/min, respectively. Splanchnic clearance accounted for 27·1% of the metabolic clearance rate of progesterone. The efficiency of extraction of progesterone by some extra-splanchnic organs ranged from 7·9–45·9% across one uterine horn, 5·8–29·9% across one ovary and 30·9–33·3% across one adrenal. For the extraction of 20α-diHP the values were 6·1–9·4% (uterine horn), 15·5% (ovary) and 18·3% (adrenal). In some experiments there was a small production of 20α-diHP across the uterus and ovary. As the blood flow was a relatively small proportion of cardiac output, the clearance rate of progesterone by any one of these sites was less than 0·2% of the metabolic clearance rate. Labelled progesterone and labelled 5α-pregnanedione were retained in the endometrium (but not in the myometrium) at much higher concentrations than those found in arterial or uterine venous blood. The reduced form, 20α-dihydroprogesterone, was retained in neither the endometrium nor the myometrium. There was a high concentration of polar, conjugated metabolites of progesterone in both uterine tissues compared with that in blood. The results show that the high metabolic clearance rate of progesterone in the sheep is only partially due to splanchnic (mainly hepatic) uptake, and that over 70% of the progesterone produced is catabolized by extra-splanchnic organs.

Colostrum production in ewes: a review of regulation mechanisms and of energy supply

“…This conclusion supported previous studies on hepatic blood and clearance in cows (Wieghart et al, 1986) and ram lambs (Burrin et al, 1989). However, in contrast, Bedford et al (1974) attributed only 27% of the metabolic clearance of progesterone to hepatic uptake in the sheep, and Freetly and Ferrell (1994) did not detect any relationship between splanchnic clearance of progesterone and the level of nutrition.…”

Concomitant changes in progesterone catabolic enzymes, cytochrome P450 2C and 3A, with plasma insulin concentrations in ewes supplemented with sodium acetate or sodium propionate

“…Therefore, we believe the decreased cytochrome P450 2C and 3A activities in the sodium propionate-supplemented animals compared to the sodium acetate-supplemented animals are most likely due to the effect of elevated insulin concentrations at the time of biopsy. Bedford et al (1972 and1974) reported metabolic clearance rates (volume of blood cleared of progesterone per unit time) for progesterone to be approximately 3.5 to 4.3 l/min in sheep. Splanchnic clearance rate of progesterone could account for 30% of total progesterone metabolism, and 70% to 90% of the total clearance of progesterone in these splanchnic organs was cleared by the liver (Bedford et al, 1974).…”

“…Bedford et al (1972 and1974) reported metabolic clearance rates (volume of blood cleared of progesterone per unit time) for progesterone to be approximately 3.5 to 4.3 l/min in sheep. Splanchnic clearance rate of progesterone could account for 30% of total progesterone metabolism, and 70% to 90% of the total clearance of progesterone in these splanchnic organs was cleared by the liver (Bedford et al, 1974). In these studies, metabolic clearance rates were determined by infusing progesterone into the peripheral circulation via the jugular vein, which is different from the in vivo source of progesterone, primarily produced in the ovary or the gravid uterus both of which are part of the portal drained viscera.…”

Overfeeding during early pregnancy reduces peripheral progesterone concentration and pregnancy rate in sheep

“…In the former study this phenomenon occurred when ovariectomized ewes were given controlled daily doses of progesterone. This effect of nutrition on plasma progesterone concentrations may be due to a higher clearance rate of progesterone since blood flow to the liver of ewes increases with feeding (Bensadoun & Reid, 1962) and the liver is a major site of progesterone catabolism (Bedford et al, 1974). If compensatory changes in secretion rate from the ovary do not occur then the peripheral progesterone concentration would be altered, and some ewes, when overfed, would have peripheral progesterone concentrations below the threshhold necessary for embryo survival.…”