Abstract
BackgroundIn the rat, the maintenance of gestation is dependent on progesterone production from the corpora lutea (CL), which are under the control of pituitary, decidual and placental hormones. The luteal metabolism of progesterone during gestation has been amply studied. However, the regulation of progesterone synthesis and degradation during pseudopregnancy (PSP), in which the CL are mainly under the control of pituitary prolactin (PRL), is not well known. The objectives of this investigation were: i) to study the luteal metabolism of progesterone during PSP by measuring the activities of the enzymes 3beta-hydroxysteroid dehydrogenase (3betaHSD), involved in progesterone biosynthesis, and that of 20alpha-hydroxysteroid dehydrogenase (20alphaHSD), involved in progesterone catabolism; and ii) to determine the role of decidualization on progesterone metabolism in PSP.MethodsPSP was induced mechanically at 10:00 h on the estrus of 4-day cycling Wistar rats, and the stimulus for decidualization was provided by scratching the uterus on day 4 of PSP. 3betaHSD and 20alphaHSD activities were measured in the CL isolated from ovaries of PSP rats using a spectrophotometric method. Serum concentrations of progesterone, PRL, androstenedione, and estradiol were measured by radioimmunoassay (RIA).ResultsThe PSP stage induced mechanically in cycling rats lasted 11.3 ± 0.09 days (n = 14). Serum progesterone concentration was high until day 10 of PSP, and declined thereafter. Serum PRL concentration was high on the first days of PSP but decreased significantly from days 6 to 9, having minimal values on days 10 and 11. Luteal 3betaHSD activities were elevated until day 6 of PSP, after which they progressively declined, reaching minimal values at the end of PSP. Luteal 20alphaHSD activities were very low until day 9, but abruptly increased at the end of PSP. When the deciduoma was induced by scratching the uterus of pseudopregnant animals on day 4 (PSP+D), PSP was extended to 18 ± 2.2 days (n = 8). In PSP + D rats, serum progesterone and PRL levels, and luteal 3betaHSD activities were higher than in pseudopregnant rats on day 11. Decidualization also prevented the increase in luteal 20alphaHSD activities observed on day 11 of PSP. Administration of the dopaminergic agonist CB154 in PSP + D rats on day 10 of PSP induced a decline in both serum PRL and progesterone on day 11 of PSP, values that were not different from that of pseudopregnant controls.ConclusionsWe have established that during the final period of PSP a decline in progesterone biosynthesis occurs before the increase in progesterone catabolism. We have also shown that decidualization in pseudopregnant rats extends the life of the CL by prolonging the production of pituitary PRL, and by maintaining high 3betaHSD and low 20alphaHSD activities within the CL leading to sustained production of progesterone.
Highlights
In the rat, the maintenance of gestation is dependent on progesterone production from the corpora lutea (CL), which are under the control of pituitary, decidual and placental hormones
Progesterone is increased in systemic circulation throughout pregnancy and is exclusively produced by the CL that exhibit enhanced expression of enzymes involved in progesterone synthesis, such as P450 side chain cleavage (P450scc) needed for the formation of pregnenolone from cholesterol [3,4,5], and 3beta-hydroxysteroid dehydrogenase (3betaHSD) that converts pregnenolone to progesterone [6]. 20alpha-hydroxysteroid dehydrogenase (20alphaHSD), the enzyme that catabolizes progesterone giving rise to a metabolite without progestational capability, and, incapable of supporting pregnancy, has been shown to be negligible both, at the level of mRNA, and protein expression and activity throughout most of pregnancy [7,8]
Serum progesterone and prolactin concentrations and luteal 3betaHSD and 20alphaHSD activities during pseudopregnancy in rats Pseudopregnant rats sacrificed at 18:00 h showed elevated concentrations of circulating progesterone from days 3 to 9 of PSP, whereas the hormonal levels declined significantly after day 10 of PSP as compared with those measured on day 9 (Fig. 1A)
Summary
The maintenance of gestation is dependent on progesterone production from the corpora lutea (CL), which are under the control of pituitary, decidual and placental hormones. 20alpha-hydroxysteroid dehydrogenase (20alphaHSD), the enzyme that catabolizes progesterone giving rise to a metabolite without progestational capability, and, incapable of supporting pregnancy, has been shown to be negligible both, at the level of mRNA, and protein expression and activity throughout most of pregnancy [7,8] It is only before parturition, at a time when the tropic support of lactogenic hormones is interrupted due to the down regulation of luteal prolactin (PRL) receptors [8,9,10], that 20alphaHSD is abruptly expressed [8,11,12]. We have detected that early regression of the pregnant rat CL is characterized by the increase in 20alphaHSD luteal activity and by a decline in 3betaHSD luteal activity [19,20,21]
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