Catechol oestrogen induced initiation of implantation in the delayed implanting rat

In the rat oestrogen is essential for induction of implantation in a progesterone primed uterus. The ability of the catechol oestrogens, 4-hydroxy-oestradiol (4-OH-E2) and 2-hydroxy-oestradiol (2-OH-E2) to initiate the implantation process (blue reaction, indicative of increased endometrial capillary permeability at the location of the blastocyst) in hypophysectomized delayed implanting rats was compared to that of oestradiol-17β (E2). Delayed implantation was maintained by daily administration of 2 mg of progesterone. A single sc injection of 100 ng of E2 or 400 ng of 4-OH-E2 consistently initiated implantation in all animals. When delivered sc via osmotic minipumps at a constant release rate of 10 ng/μl/h, implantation of a full complement of embryos was obtained with E given for 6 or 24 h. This dose 4-OH-E2 was ineffective when administered for 24 h. However, 25 ng/μl/h for 24 h was effective. When the dose was increased to 50 mg/μl/h implantation was evident in the majority of animals exposed to the hormone for 6 or 8 h; all animals implanted when this dose was given for 24 h. In contrast, 2-OH-E2 given at 50 ng/μl/h for 24 h was totally ineffective. When the dose of the latter steroid was raised to 200 ng/μl/h implantation was achieved in half of the animals when exposure was 24 h. The results suggest that when administered systemically, 4-OH-E2 is less potent than E2, but more potent than 2-OH-E2, for initiating implantation. The lower potency of systemically administered catechol oestrogens probably results from their rapid metabolism and clearance for the circulation and target tissues.