NCBI Summary:
The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein selectively binds the hypothalamic neuropeptide orexin A. A related gene (HCRTR2) encodes a G-protein coupled receptor that binds orexin A and orexin B. [provided by RefSeq, Jan 2009]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Steroid metabolism
Comment
Orexin A promotes granulosa cell secretion of progesterone in sheep. Li M et al. (2019) Orexin A, a small-molecule peptide, can regulate female hormones, but limited evidence for its mechanism of activity exists in ovine. The objective of this study was to investigate the effect of orexin A on progesterone (P4) secretion in cultured granulosa of sheep follicles. Sheep ovarian granulosa were isolated and identified, pre-incubated with luteinizing hormone (LH) (2.5 IU/ml), follicle-stimulating hormone (FSH) (2.5 IU/ml), or oestrogen (1 µg/ml); and cultured in vitro. The pretreated sheep ovarian granulosa were subsequently cultured with different concentrations (1 nM, 10 nM, 58 nM, 100 nM, and 145 nM) of orexin A for varying amounts of time (0 h, 24 h, 48 h, and 72 h). Then, the expression levels of P4, steroidogenic acute regulatory protein (StAR), 3β-Hydroxysteroid dehydrogenase (3β-HSD) and cytochrome P450 (CYP11) were determined. The results showed that the sheep ovarian granulosa were correctly identified. The different concentrations of orexin A promoted the secretion of P4 from granulosa in the ovine ovary compared with that in the control. The expression of StAR, 3β-HSD and P450 (CYP11) gradually increased, and then decreased with increasing concentrations of orexin A, but the expression of P450 (CYP11) decreased with the increase of time. These results revealed that orexin A promotes the secretion of P4 by regulating the expression of StAR, 3β-HSD, and P450 (CYP11). Understanding the mechanism underlying the promotion of P4 by orexin A could open new therapeutic possibilities in the treatment of hormone homeostasis.//////////////////
Effects of Orexins A and B on Expression of Orexin Receptors and Progesterone Release in Luteal and Granulosa Ovarian Cells. Cataldi NI et al. Orexin-A and Orexin-B are neuropeptides controlling sleep-wakefulness, feeding and neuroendocrine functions via their G protein-coupled receptors, Orexin-1R and Orexin-2R. They are synthesized in the lateral hypothalamus and project throughout the brain. Orexins and orexin receptors have also been described outside the brain. Previously we demonstrated the presence of both receptors in the ovary, their increased expression during proestrous afternoon and the dependence on the gonadotropins. Here we studied the effects of orexins on the mRNA expression of both receptors, by quantitative real-time PCR, on luteal cells from superovulated rat ovaries and granulosa cells from diethylstilbestrol-treated rat ovaries. Effects on progesterone secretion were also measured. In luteal cells, 1 nM of either Orexin-A or Orexin-B decreased progesterone secretion. Orexin-A treatment increased expression of both Orexin-1R and Orexin-2R mRNA. The effect on Orexin-1R mRNA expression was abolished by an Orexin-1R selective receptor antagonist SB-334867 and the effect on Orexin-2R mRNA expression was abolished by a selective Orexin-2R antagonist JNJ-10397049. Orexin-B did not modify Orexin-1R mRNA expression, but increased Orexin-2R mRNA expression. The effect of Orexin-B on Orexin-2R was abolished by a selective Orexin-2R antagonist. Neither the expression of orexin receptors nor progesterone secretions by granulosa cells were affected by orexins. FSH, as positive control, increased both steroid hormones secretion, but did not induce the expression of OX receptors in granulosa cells isolated from late preantral/early antral follicles.. Finally in ovaries obtained immediately after sacrifice, the expression of Orexin-1R and Orexin-2R was higher in superovulated rat ovaries compared to control or diethylstilbestrol treated rat ovaries. A selective presence and function of both orexinergic receptors in luteal and granulosa cells is described, suggesting that the orexinergic system may have a functional role in the ovary.
Expression regulated by
FSH
Comment
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 et al. 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 dark-light cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes. Key words: orexin receptors, gonadotropins, orexin 1 and orexin 2 receptor antagonists, ovary, ovulation.
Ovarian localization
Luteal cells
Comment
Expression of orexin receptors 1 (OX1R) and 2 (OX2R) in the porcine ovary during the oestrous cycle. Nitkiewicz A et al. Orexin A and B are neuropeptides which are synthesized mainly in the lateral hypothalamus and are associated with a variety of physiological functions such as energy homeostasis, sleep and wakefulness, feeding behavior, as well as the reproductive system. The orexins activate two G-protein-coupled receptors termed orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). The present study analyses OX1R and OX2R mRNAs and proteins expression in the porcine ovary on days 2-3, 10-12, 14-16 and 17-19 of the oestrous cycle. Using real-time PCR, higher OX1R mRNA expression was detected in porcine CLs (p<0.01) than in granulosa and theca cells. The expression peak of the OX2R gene occurred in granulosa cells (p<0.05 in comparison with CLs on days 2-3 and 10-12 of the oestrous cycle). The OX1R protein content was higher (p<0.01) in CLs isolated during the luteal phase in comparison with follicular cells. The OX2R protein level was more pronounced (p<0.05) in CLs on days 10-12 and 14-16 than in the remaining periods of the cycle. In conclusion, we demonstrated the presence of OX1R and OX2R genes and proteins in the ovary of the pig and the impact of the hormonal milieu on the expression of both receptors. Our results suggest that orexins may affect reproductive functions.