ESTRADIOL POTENTIATES A PROLONGED PROGESTERONE-INDUCED SUPPRESSION OFLH-RELEASE IN OVARIECTOMIZED COWS

Our working hypothesis was that the negative feedback effect of proges terone on LH secretion in ovariectomised cows is greatly enhanced by o estradiol when both hormones are administered intravaginally. Each of eight ovariectomised cows had a progesterone releasing device ('CIDR-1 '; Eazi-breed CIDR-B-TM, InterAg, Hamilton, New Zealand) inserted into the vagina for 3 days, followed by an injection of 1 mg oestradiol be nzoate (ODB) in peanut oil 24 h after device removal. The timing of th is injection was designated as Day 0. The CIDR-1 was reinserted concur rently with an injection of 0.4 mg ODB on Day 5. An additional device ('CIDR-2') was inserted 4 days later (Day 9). In four of the cows, an ODB capsule (CIDIROL(TM), Douglas Pharmaceuticals, Auckland, New Zeala nd) was placed into a groove on the surface of CIDR-2 preceding insert ion. CIDR-2 was withdrawn after 5 days (Day 14) and CIDR-1 was withdra wn 2 days later (Day 16). The treatment regimen was repeated in a cros s-over design where each cow received CIDR-2 with or without an ODB ca psule. Blood samples were collected at intervals of 15 min for a perio d of 16 h beginning 8 h before insertion of CIDR-2 to determine change s in LH secretion pattern, and then at intervals of 8 h until 48 h aft er removal of CIDR-1 to determine mean LH and steroid concentrations. Concentrations of progesterone in plasma reflected the effects of inse rting and removing each CIDR device. The insertion of CIDR-2 elevated progesterone from 2.0 +/- 0.1 ng ml(-1) to 4.9 +/- 0.1 ng ml(-1) withi n 30 min (P < 0.01) and maintained levels > 3 ng ml(-1). Withdrawal of CIDR-2 produced a new baseline level of 1.8 +/- 0.1 ng ml(-1) within 4 h (P < 0.01). Concentrations of oestradiol-17 beta in plasma increas ed from a baseline of < 1 pg ml(-1) to a maximum of 12.6 +/- 2.2 pg ml (-1) at 22 h after insertion of an ODB capsule. Initial pulse frequenc y of LH (1.2 +/- 0.05 pulses h(-1)) and mean concentration of LH (1.6 +/- 0.1 ng ml(-1)) declined (P < 0.05) to 0.2 +/- 0.1 pulses h(-1) and 0.5 +/- 0.1 ng ml(-1) during the period from 2 to 8 h following inser tion of CIDR-2. Mean concentrations recovered to pre-treatment levels (> 1 ng ml(-1)) within 48 h if CIDR-2 was inserted without an ODB caps ule. In contrast, LH levels remained less than 0.7 ng ml(-1) for 5 day s following this form of ODB treatment. A subsequent increase in mean LH of 1.4 +/- 0.2 ng ml(-1) (P < 0.05) was inversely synchronised with the precipitous decline in progesterone of 1.2 +/- 0.1 ng ml(-1), fol lowing removal of CIDR-2. The inclusion of an ODB capsule with inserti on of CIDR-2 reduced concentrations of FSH from 166 +/- 17 ng ml(-1) t o a new baseline of 105 +/- 16 ng ml(-1) within 24 h (P < 0.05). In co nclusion, an acute increase in progesterone induced a transient suppre ssion of LH lasting less than 48 h. This suppression was prolonged to 5 days by the concurrent insertion of a capsule containing 10 mg ODB. The subsequent recovery of LH was coincident with the decline in proge sterone following removal of CIDR-2.