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.