Both orexin receptors are expressed in rat ovaries and fluctuate with the estrous cycle: effects of orexin receptor antagonists on gonadotropins and ovulation

American Journal of Physiology - Endocrinology and Metabolism - Tập 293 Số 4 - Trang E977-E985 - 2007
Patricia Silveyra1, Victoria Lux‐Lantos, Carlos Libertun
1Instituto de Biología y Medicina Experimental-Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Argentina.

Tóm tắt

Orexins are peptides controlling feeding, sleep, and neuroendocrine functions. They are synthesized by the hypothalamus with projections throughout the brain. Orexins and their orexin 1 (OX1) and orexin 2 receptors (OX2) are present outside the central nervous system. 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. Ovarian OX1 and OX2 expression was then studied after ovulation blockade with Cetrorelix or Nembutal. Finally, proestrous rats were treated at 1400 and 1900 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 1700 and 2300 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 dependence on the dark-light cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.

Từ khóa


Tài liệu tham khảo

10.1124/jpet.102.048025

10.1016/S0196-9781(00)00369-7

10.1210/en.2005-0455

10.1007/s00418-003-0562-z

10.1046/j.1365-2826.2000.00559.x

10.1016/0031-9384(95)02003-9

10.1016/S0167-0115(00)00209-3

10.1210/en.2002-220958

10.1016/j.brainres.2003.08.016

10.1016/S0167-0115(01)00357-3

10.1210/endo-124-6-2944

10.1016/S0196-9781(99)00157-6

10.1016/S0169-328X(99)00317-4

10.1073/pnas.95.1.322

10.1054/npep.2002.0892

10.1093/humrep/12.6.1142

10.1016/S0091-3022(03)00028-1

10.1159/000048232

10.1096/fj.02-0933com

10.1016/j.neuroscience.2003.07.008

10.1016/S0896-6273(01)00293-8

10.1046/j.1365-2826.2001.00719.x

10.1006/bbrc.2001.4328

10.1016/S0304-3940(02)00176-3

10.1210/en.2002-0030

10.1210/endo.142.8.8299

10.1016/j.neulet.2004.06.068

10.1210/jc.2003-031778

10.1152/ajpendo.00351.2004

10.1210/jcem.86.9.7849

Kastin AJ, Akerstrom V. Orexin A but not orexin B rapidly enters brain from blood by simple diffusion. J Pharmacol Exp Ther 289: 219–223, 1999.

10.1016/S0006-8993(01)02157-6

10.1152/ajpendo.00060.2004

10.1152/ajpcell.00055.2002

10.1021/jm030982t

10.1081/IAS-120027225

10.1016/j.bmcl.2004.06.032

10.1016/S0959-4388(02)00331-8

10.1016/S0303-7207(03)00206-5

10.1016/S0006-8993(99)01336-0

Nowak KW, Strowski MZ, Switonska MM, Kaczmarek P, Singh V, Fabis M, Mackowiak P, Nowak M, Malendowicz LK. Evidence that orexins A and B stimulate insulin secretion from rat pancreatic islets via both receptor subtypes. Int J Mol Med 15: 969–972, 2005.

10.1016/0014-2999(90)90337-6

10.1095/biolreprod.104.034454

10.1530/rep.1.00910

10.1523/JNEUROSCI.18-23-09996.1998

10.1530/eje.0.1500737

10.1016/S0167-0115(98)00128-1

10.1210/jcem.86.10.7921

10.1210/endo.142.12.8558

10.1016/S0092-8674(00)80949-6

10.1159/000098333

10.1152/ajpregu.1999.277.6.R1780

10.1152/ajpendo.00467.2006

10.1210/en.2002-0041

10.1038/sj.bjp.0703953

10.1152/ajpgi.00218.2004

10.1006/bbrc.1999.1573

10.1177/153537020623101006

10.1016/S0014-5793(98)01266-6

10.1385/ENDO:22:2:127

10.1210/en.2004-1226

10.1002/cne.20859

10.1152/ajpregu.00704.2005

Thông tin
Thông tin xuất bản

American Journal of Physiology - Endocrinology and Metabolism

Tập 293 Số 4

E977-E985

Thông tin tác giả