Effects of a 3 beta-hydroxysteroid dehydrogenase inhibitor on monocyte-macrophage infiltration into rat corpus luteum and on apoptosis: relationship to the luteolytic action of prolactin

The administration of prolactin to hypophysectomized rats results in regres sion of the corpora lutea, accompanied by immune-inflammatory events such a s infiltration of monocytes and macrophages. Recent reports indicate an aut ocrine role for progesterone during the lifespan of the corpus luteum. In t he present study, an inhibitor of 3 beta-hydroxysteroid dehydrogenase, Tril ostane, was used to investigate the hypothesis that a decrease in luteal ti ssue steroids precipitates the cascade of immune-inflammatory events leadin g to luteal regression in prolactin-treated hypophysectomized rats. Immatur e rats were induced to ovulate by administering eCG-hCG, and hypophysectomi zed on the day after ovulation (at 32 days of age). Rats were injected s.c. 9-11 days after hypophysectomy with (a) Trilostane (80 mg kg(-1) day(-1)), (b) ovine prolactin (500 mu g day(-1)), (c) Trilostane plus prolactin, or (d) vehicle. Plasma and luteal tissue progesterone and 20 alpha-dihydroprog esterone ('progestin') were quantified; luteal tissue monocytesmacrophages and apoptotic nuclei were counted, and luteal wet mass was determined. Rats treated with prolactin alone showed the expected markers of luteal regress ion: decreased plasma progestin, increased numbers of monocytes-macrophages and apoptotic nuclei in luteal tissue, and decreased luteal wet mass; howe ver, progestin concentration in luteal tissue was unchanged. Treatment with Trilostane reduced plasma and luteal tissue progestin, but did not result in an infiltration of monocytes-macrophages or increased numbers of apoptot ic nuclei in the corpora lutea, or any change in luteal wet mass. Trilostan e in combination with prolactin reduced plasma and luteal tissue progestin and produced the expected markers of regression, with the exception of lute al tissue mass, which remained unchanged. In conclusion, inhibition of ster oidogenesis does not initiate luteal regression or augment prolactin-induce d luteal regression in hypophysectomized rats. Prolactin-induced infiltrati on of monocytes-macrophages is not accompanied by a decrease in luteal tiss ue progestin, at least in the early stages of luteal regression.