Endometrial Secretory Products: Regulation of Hormonal Responsiveness of Rabbit Luteal Cells In Vitro

Abstract

In the rabbit, hysterectomy prolongs progesterone secretion from about 18 days to about 22 days (1,2), which suggests that both uterine and nonuterine (probably ovarian) mechanisms lead to luteal regression. If hysterectomized rabbits are treated with exogenous estradiol, the luteotropic hormone in this species (2), corpora lutea do not regress by day 22, and progesterone secretion remains elevated for greater than 33 days (1). More recent work (3) suggests that there are at least 3 uterine modulators of the corpus luteum: factor 1, secreted between days 10 and 11 of pseudopregnancy is associated with a reduction in progesterone secretion; factor 2, produced between days 11 and 13, prevents the “luteolytic effect” of factor 1; and factor 3 secreted after day 13, is associated with the final phase of luteal regression and correlates temporally with uterine PGF₂ secretion (4). Since inhibition of prostaglandin synthesis with indomethacin does not mimic the effect of hysterectomy in this animal model (3), we have proposed that factors 1 and 2, which are released at mid-pseudopregnancy, are crucial in signaling the initiation of luteal regression. In addition, 2D SDS polyacrylamide gel electrophoresis of proteins secreted by the endometrium during days 10–13 of pseudopregnancy revealed that the uterus undergoes dramatic changes in protein synthetic characteristics during this critical time of pseudopregnancy. Between days 10 and 11, at the time when uterine luteolytic activity was observed, there was a prominent loss of a group of acidic proteins of about 45,000 Da, pI 5.5–6.0, and a more variable reduction in another group of proteins of approximately 30,000 Da, pI of 4.0–4.5.