Both Orexin Receptors Are Present in Rat Ovaries and Fluctuate with the Estrous Cycle, but Not with the Dark-Light Cycle or Food Intake; Effects of an OX1Receptor Antagonist.

PATRICIA SILVEYRA; VICTORIA A.R. LUX-LANTOS; CARLOS LIBERTUN

Toronto, Canada

Congreso; The Endocrine Society (USA). 89th Annual Meeting.; 2007

The Endocrine Society (USA).

[P1-318] Both Orexin Receptors Are Present in Rat Ovaries and Fluctuate with the Estrous Cycle, but Not with the Dark-Light Cycle or Food Intake; Effects of an OX1 Receptor Antagonist.Patricia Silveyra, Victoria AR Lux-Lantos, Carlos Libertun. Neuroendo, IBYME-CONICET, Buenos Aires, Argentina; Quimica Biol, FCEN-UBA, Buenos Aires, Argentina; Physiol, Fac de Med-UBA, Buenos Aires, ArgentinaOrexins are peptides controlling feeding, sleep, autonomic and neuroendocrine functions. They are synthesized by neurons of the lateral hypothalamus with projections throughout the brain. Orexins and their receptors OX1 and OX2 have been described outside the CNS. Here, the expression of preproorexin (PPO), OX1 and OX2 was studied in rat ovaries.Expression of PPO, OX1 and OX2 was determined by real-time RT-PCR in ovaries of cycling Sprague-Dawley rats at different times on all days of the cycle. Serum hormones and food consumption were also studied. Then, ovarian OX1 and OX2 expression was studied at 19:00 h of proestrus (P) after ovulation blockade with either Cetrorelix (CRX) or Nembutal (NEM) injected at 14:00 h (1). Finally, groups of P rats were treated at 14:00 h and 19:00 h with a selective OX1 antagonist (SB-334867-A; Tocris, USA) and hormone levels, ovulation and ovarian histology were evaluated.OX1 and OX2 expression was found in rat ovaries and increased between 17:00 h and 23:00 h of P (p<0.05 vs. 11:00 h), but not on any other day. This profile is coincident with the P afternoon gonadotropin and PRL peaks, but not with the dark-light cycle or food intake. PPO was not detected at any time.CRX and NEM treatments prevented gonad OX1 and OX2 increases at 19:00 h (p<0.01 vs. saline) while they blunted gonadotropin surges, suggesting that the expression of OX1 and OX2 in ovary was under the influence of the P hormonal status.All control rats ovulated (ova/rat: 15.2±0.5) while 25% of rats treated with SB-334867-A did not ovulate at all, and in the remaining 75% a clear reduction in ova number was recorded (8.5±1.9 ova/rat; p<0.01). SB-334867-A-treated rats showed a decrease in preovulatory gonadotropin and PRL surges. Ovaries from SB-334867-A-treated rats showed macro and microscopically an intense hyperemic reaction with more preovulatory follicles/field (control: 2.5±0.2; SB334867-A: 4.4±0.6, p<0.01) and less corpora lutea/field (control: 9.2±0.4; SB-334867-A: 5.7±0.6, p<0.01).Here we demonstrate for the first time the presence of both orexin receptors in rat ovary, their fluctuation with the estrous cycle with an increased expression of OX1 and OX2 only during the P afternoon and its dependence on gonadotropins, but not on the dark-light cycle or food intake. OX1 antagonist reduced serum gonadotropins and ovulation and induced an intense hyperemic reaction in the gonad.(1) Silveyra P at al., Am J Physiology 2007; In press.Supported by Consejo Nacional de Investigaciones Científicas y Técnicas; Agencia Nacional de Promoción Científica y Tecnológica (BID 1728/OC-AR PICT 2004 5-26307); Universidad de Buenos Aires, Argentina.