Investigations on the re-establishment of the positive feedback of oestradiol during anoestrus in the bitch.

To test for the re-establishment of the positive feedback of oestradiol (E2) during anoestrus in the dog, the hypothalamo-pituitary-ovarian axis of five beagle bitches was challenged by treatments with oestradiol benzoate (EB), mimicking the course of the pro-oestric E2 secretion. Treatments in anoestrus started 7 days following the decline of progesterone (P) <1 ng/ml; they were repeated in 5 week intervals until onset of pro-oestrus; another treatment was performed during dioestrus 50 days after onset of the preceding pro-oestric bleeding. Each dog served as its own control by receiving vehicle-treatments in one of the following cycles. Each observation period covered a time window of 168 h and blood samples were collected for the determination of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and E2 in 6 (0-24 h) and 8 h (24-168 h) intervals. In the control periods and as indicated by the parameters area under curve (AUC), basal and maximal values, the availability of LH, FSH and E2 decreased from dioestrus to early anoestrus to increase again during the course of anoestrus (p < 0.05), indicating a gradual desensitization of the hypothalamus towards the negative feedback of oestradiol. At all times treatments with EB lowered the availability of FSH (decreased AUC and basal levels). A delay in the occurrence of the first LH peak after treatments with EB (p < 0.001) and decreased maximal values (p < 0.001) indicated a suppression of the LH-release. In no case treatment with EB led to a pre-ovulatory like LH-surge. In each dog the last trial with EB in anoestrus passed over into pro-oestrus/oestrus, with a reduced AUC and peak value of the pre-ovulatory LH-surge being the only differences to the control group. The observed differences in the response of LH and FSH to treatments with EB point towards subtle differences in the mechanisms controlling the release of these two hormones during anoestrus. From the data obtained, it may be concluded that the time window for E2 to act via a positive feedback seems to be very small and restricted to the end of anoestrus, and that full follicular function is a pre-requisite to allow for this phenomenon.