46) Both orexin receptors are expressed in rat ovaries and fluctuate with the estrous cycle. Effects of orexin receptor antagonists on gonadotropins and ovulation

SILVEYRA, P; LUX-LANTOS VA; LIBERTUN C

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

Año: 2007 vol. 293 p. 977 - 985

0193-1849

Orexins are peptides controlling feeding, sleep and neuroendocrine functions. They are synthesized by the hypothalamus with projections throughout the brain. Orexins and their receptors OX1 and OX2 are present outside the CNS. Here the expression of preproorexin (PPO), OX1 and OX2 was studied in rat ovaries. PPO, OX1 and OX2 were determined by quantitative real-time RT-PCR in ovaries of cycling Sprague-Dawley rats on all days of the cycle. Serum hormones and food consumption were determined. Then, ovarian OX1 and OX2 expression was studied after ovulation blockade with Cetrorelix or Nembutal. Finally, proestrous rats were treated at 14:00 h and 19:00 h with a selective OX1 antagonist (SB- 334867-A) and/or a selective OX2 antagonist (JNJ-10397049) and hormone levels, ovulation and ovarian histology were studied. Both receptors expression increased in the ovary between 17:00 h and 23:00 h of proestrus exclusively, in coincidence with hormone peaks, but not with the dark-light cycle or food intake. PPO was not detected. Cetrorelix or Nembutal prevented the increases of OX1 and OX2 while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1 and OX2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.1 and OX2 are present outside the CNS. Here the expression of preproorexin (PPO), OX1 and OX2 was studied in rat ovaries. PPO, OX1 and OX2 were determined by quantitative real-time RT-PCR in ovaries of cycling Sprague-Dawley rats on all days of the cycle. Serum hormones and food consumption were determined. Then, ovarian OX1 and OX2 expression was studied after ovulation blockade with Cetrorelix or Nembutal. Finally, proestrous rats were treated at 14:00 h and 19:00 h with a selective OX1 antagonist (SB- 334867-A) and/or a selective OX2 antagonist (JNJ-10397049) and hormone levels, ovulation and ovarian histology were studied. Both receptors expression increased in the ovary between 17:00 h and 23:00 h of proestrus exclusively, in coincidence with hormone peaks, but not with the dark-light cycle or food intake. PPO was not detected. Cetrorelix or Nembutal prevented the increases of OX1 and OX2 while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1 and OX2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.1 and OX2 was studied in rat ovaries. PPO, OX1 and OX2 were determined by quantitative real-time RT-PCR in ovaries of cycling Sprague-Dawley rats on all days of the cycle. Serum hormones and food consumption were determined. Then, ovarian OX1 and OX2 expression was studied after ovulation blockade with Cetrorelix or Nembutal. Finally, proestrous rats were treated at 14:00 h and 19:00 h with a selective OX1 antagonist (SB- 334867-A) and/or a selective OX2 antagonist (JNJ-10397049) and hormone levels, ovulation and ovarian histology were studied. Both receptors expression increased in the ovary between 17:00 h and 23:00 h of proestrus exclusively, in coincidence with hormone peaks, but not with the dark-light cycle or food intake. PPO was not detected. Cetrorelix or Nembutal prevented the increases of OX1 and OX2 while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1 and OX2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.1 and OX2 expression was studied after ovulation blockade with Cetrorelix or Nembutal. Finally, proestrous rats were treated at 14:00 h and 19:00 h with a selective OX1 antagonist (SB- 334867-A) and/or a selective OX2 antagonist (JNJ-10397049) and hormone levels, ovulation and ovarian histology were studied. Both receptors expression increased in the ovary between 17:00 h and 23:00 h of proestrus exclusively, in coincidence with hormone peaks, but not with the dark-light cycle or food intake. PPO was not detected. Cetrorelix or Nembutal prevented the increases of OX1 and OX2 while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1 and OX2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.2 expression was studied after ovulation blockade with Cetrorelix or Nembutal. Finally, proestrous rats were treated at 14:00 h and 19:00 h with a selective OX1 antagonist (SB- 334867-A) and/or a selective OX2 antagonist (JNJ-10397049) and hormone levels, ovulation and ovarian histology were studied. Both receptors expression increased in the ovary between 17:00 h and 23:00 h of proestrus exclusively, in coincidence with hormone peaks, but not with the dark-light cycle or food intake. PPO was not detected. Cetrorelix or Nembutal prevented the increases of OX1 and OX2 while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1 and OX2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.1 antagonist (SB- 334867-A) and/or a selective OX2 antagonist (JNJ-10397049) and hormone levels, ovulation and ovarian histology were studied. Both receptors expression increased in the ovary between 17:00 h and 23:00 h of proestrus exclusively, in coincidence with hormone peaks, but not with the dark-light cycle or food intake. PPO was not detected. Cetrorelix or Nembutal prevented the increases of OX1 and OX2 while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1 and OX2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.2 antagonist (JNJ-10397049) and hormone levels, ovulation and ovarian histology were studied. Both receptors expression increased in the ovary between 17:00 h and 23:00 h of proestrus exclusively, in coincidence with hormone peaks, but not with the dark-light cycle or food intake. PPO was not detected. Cetrorelix or Nembutal prevented the increases of OX1 and OX2 while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1 and OX2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.1 and OX2 while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1 and OX2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.2 while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1 and OX2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.1 and OX2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.2, only during proestrous afternoon, and its hormone dependence but not on the darklight cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.