| Description |
Intrauterine progesterone administration is an effective method of contraception. The contraceptive effect is produce without alteration in systemic endocrine functions. Thus, the contraceptive action of intrauterine progesterone must reside within the uterus. Studies of uteri containing a progesterone-releasing intrauterine device (IUD) demonstrated significant alteration of endometrial histology and biochemistry. The mechanism of these changes is unknown. Therefore, this study was performed in an attempt to elucidate the mechanism of contraceptive action of intrauterine progesterone treatment. The uterus undergoes secretory transformation as a prerequisite for pregnancy, and this response in induced by progesterone. The response of the uterus to progesterone is mediated by specific progesterone receptors in the uterine cells. The concentration of these receptors determines the sensitivity of the uterus to circulating progesterone. Therefore, an alteration of progesterone receptor concentration could affect secretory transformation of the endometrium, resulting in the prevention of pregnancy. Accordingly, the uterine progesterone receptor content was investigated in rabbits implanted with a progesterone-releasing IUD. One essential component of uterine secretory transformation is the production of characteristic endometrial secretions. These secretions contain numerous proteins that serve to nourish the pre-implantation embryo and may play a role in nidation. Several of these secretory proteins are pregnancy specific, i.e. secretion corresponds to the uterine preparations for pregnancy. The protein composition of the uterine luminal fluid is controlled by ovarian steroids. Thus, intrauterine progesterone administration may alter the protein composition of the luminal fluid, which could be detrimental to the embryo and prevent the successful progress of pregnancy. Rabbits were implanted with placebo or Progestasert IUD's for 2 weeks. Pseudo-pregnancy was induced and the uteri were removed and frozen for subsequent progesterone receptor assay. The uterine luminal fluid was also collected and fractionated by gel filtration for both qualitative and quantitative characterization of protein components. In addition, one of the luminal proteins, unteroglobin, which is know to bind progesterone with high affinity, was investigated. The uteri were homogenized and cytosol and nuclear fractions were prepared for assay of progesterone receptors. The uterine progesterone receptor study was carried out on 5 groups of animals with different treatments: Group 1, control; Group 2, infusion of progesterone into the uterine cavity by an osmotic mini-pump; Group 3, placebo mini-pump; Group 4, Progestasert implant; and Group 5, placebo IUD. Analysis of the intrauterine luminal fluid revealed that the intraluminal administration of progesterone caused a 50% reduction in total protein content. Furthermore, the decrease in protein content of the uterine fluid was mot apparent for the albumin, beta-glycoprotein, and transferrin fractions, while unteroglobin content remained relatively constant. The progesterone binding characteristics and sedimentation coefficient of unteroglobin were not altered by intrauterine progesterone treatment. A significant decline in both cytosol and nuclear progesterone receptor concentration in uteri was observed in animals treated with progesterone. The depression of receptor content was observed in uteri infused with progesterone as well as those containing the progesterone-releasing IUD. In addition, the placebo IUD appeared to depress the nuclear progesterone receptor concentration. This may be related to a foreign body reaction in the uterus and suggests a mode of contraception for non-mediated IUD's. This investigation demonstrated significant alterations in the uterine environment due to chronic intrauterine progesterone administration. There is disruption of the uterine luminal fluid protein pattern and a reduction of uterine cytoplasmic and nuclear progesterone receptor levels. These alterations may be factors related to the contraceptive efficacy of the progesterone-releasing IUD.. |
