Changes in the Blood Concentrations of Progesterone and 20α-Hydroxypregn-4-En-3-One during Late Pregnancy in the Conscious Rat: A Specific Role for Metabolic Clearance Rate1

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Abstract
Near term in the rat, the blood concentration of progesterone falls while that of 20α-hydroxypregn-4-en-3- one (20α-DHP) increases. This is generally attributed to changes in ovarian secretion alone, but altered rates of hormone metabolism could also have a role. In the present study, therefore, metabolic clearance rate (MCR), production rate, and peripheral interconversion of progesterone and 20α-DHP were measured on Day 16 of pregnancy, the time of maximal progesterone secretion, and on Day 22, one day prior to parturition. Conscious rats (n = 8 per group) were infused with either [3H]progesterone or [3H]20α-DHP and the dynamics of progestin metabolism were calculated from the resultant isotopic and endogenous progesterone and 20α-DHP concentrations. The blood concentration of progesterone declined by 69% between Day 16 (54 ± 2 ng/ml) and Day 22 (17 ± 2 ng/ml), and this was due to the combined effect of a 48% increase in the MCR and a 54% decrease in production rate of progesterone. In contrast, the production rate of 20α-DHP was twofold greater on Day 22 compared to Day 16. As a result, the blood concentration of 20α-DHP increased from 28 ± 3 ng/ml on Day 16 to 40 ± 6 nem! on Day 22, and this change would have been greater but for a concomitant increase (41%) in the MCR of 20α-DHP. Although peripheral conversion of progesterone to 20α-DHP was similar on Day 16 (transfer constant, 12.8 ± 0.6%) and Day 22 (12.3 ± 0.9%), the contribution of this conversion to total 20α-DHP production fell from 32% to 7% between the two days. Conversion of 20α-DHP to progesterone was not detectable on either day of pregnancy. In summary, the present study demonstrates that the fall in the blood concentration of progesterone just prior to parturition in the rat is not simply due to altered secretion. Rather, the increase in MCR of progesterone makes an important contribution to this decline and may have a specific role in facilitating luteolysis.