Burke C R, Macmillan K L, Boland M P
Dairying Research Corporation (Ltd), Hamilton, New Zealand.
Anim Reprod Sci. 1996 Dec 2;45(1-2):13-28. doi: 10.1016/s0378-4320(96)01569-2.
Our working hypothesis was that the negative feedback effect of progesterone on LH secretion in ovariectomised cows is greatly enhanced by oestradiol when both hormones are administered intravaginally. Each of eight ovariectomised cows had a progesterone releasing device ('CIDR-1'; Eazi-breed CIDR-B. InterAg, Hamilton, New Zealand) inserted into the vagina for 3 days, followed by an injection of 1 mg oestradiol benzoate (ODB) in peanut oil 24 h after device removal. The timing of this injection was designated as Day 0. The CIDR-1 was reinserted concurrently 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), Douglas Pharmaceuticals. Auckland, New Zealand) was placed into a groove on the surface of CIDR-2 preceding insertion. CIDR-2 was withdrawn after 5 days (Day 14) and CIDR-1 was withdrawn 2 days later (Day 16). The treatment regimen was repeated in a cross-over design where each cow received CIDR-2 with or without an ODB capsule. Blood samples were collected at intervals of 15 min for a period of 16 h beginning 8 h before insertion of CIDR-2 to determine changes in LH secretion pattern, and then at intervals of 8 h until 48 h after removal of CIDR-1 to determine mean LH and steroid concentrations. Concentrations of progesterone in plasma reflected the effects of inserting 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 within 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 increased 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 frequency 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 insertion 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 capsule. In contrast, LH levels remained less than 0.7 ng ml-1 for 5 days 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, following removal of CIDR-2. The inclusion of an ODB capsule with insertion of CIDR-2 reduced concentrations of FSH from 166 +/- 17 ng ml-1 to a new baseline of 105 +/- 16 ng ml-1 within 24 h (P < 0.05). In conclusion, an acute increase in progesterone induced a transient suppression 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 progesterone following removal of CIDR-2.
我们的工作假设是,当通过阴道内给药同时给予孕酮和雌二醇时,孕酮对去卵巢母牛促黄体生成素(LH)分泌的负反馈作用会被雌二醇大大增强。八头去卵巢母牛中的每一头都在阴道内插入一个孕酮释放装置(“CIDR-1”;Eazi-breed CIDR-B,新西兰汉密尔顿InterAg公司)3天,然后在取出装置24小时后,于花生油中注射1毫克苯甲酸雌二醇(ODB)。此次注射时间定为第0天。在第5天,再次插入CIDR-1的同时注射0.4毫克ODB。4天后(第9天)插入另一个装置(“CIDR-2”)。在其中四头母牛中,于插入CIDR-2之前,将一个ODB胶囊(CIDIROL,新西兰奥克兰道格拉斯制药公司)放置在CIDR-2表面的凹槽中。5天后(第14天)取出CIDR-2,2天后(第16天)取出CIDR-1。采用交叉设计重复该治疗方案,即每头母牛接受带有或不带有ODB胶囊的CIDR-2。在插入CIDR-2前8小时开始,每隔15分钟采集一次血样,持续16小时,以确定LH分泌模式的变化,然后每隔8小时采集一次血样,直至取出CIDR-1后48小时,以确定LH和类固醇的平均浓度。血浆中孕酮的浓度反映了每次插入和取出CIDR装置的效果。插入CIDR-2后30分钟内,孕酮水平从2.0±0.1纳克/毫升升高至4.9±0.1纳克/毫升(P<0.01),并维持在>3纳克/毫升的水平。取出CIDR-2后4小时内,产生了新的基线水平1.8±0.1纳克/毫升(P<0.01)。在插入ODB胶囊后22小时,血浆中雌二醇-17β的浓度从<1皮克/毫升的基线水平升高至最高12.6±2.2皮克/毫升。在插入CIDR-2后的2至8小时内,LH的初始脉冲频率(1.2±0.05次脉冲/小时)和LH的平均浓度(1.6±0.1纳克/毫升)下降(P<0.05)至0.2±0.1次脉冲/小时和0.5±0.1纳克/毫升。如果插入不带ODB胶囊的CIDR-2,平均浓度在48小时内恢复到治疗前水平(>1纳克/毫升)。相比之下,在这种形式的ODB治疗后,LH水平在5天内一直低于0.7纳克/毫升。在取出CIDR-2后,LH平均水平随后升高1.4±0.2纳克/毫升(P<0.05),与孕酮急剧下降1.2±0.1纳克/毫升呈负相关。在插入CIDR-2时包含一个ODB胶囊,可使促卵泡生成素(FSH)浓度在24小时内从166±17纳克/毫升降至新的基线水平105±16纳克/毫升(P<0.05)。总之,孕酮的急性增加会导致LH短暂抑制,持续时间不到48小时。通过同时插入一个含有10毫克ODB的胶囊,这种抑制作用延长至5天。LH随后的恢复与取出CIDR-2后孕酮的下降同时发生。