Orexin A and B levels in the hypothalamus of female rats: the effects of the estrous cycle and age

Porkka‐Heiskanen, Tarja; Kalinchuk, Anna V.; Alanko, Lauri; Huhtaniemi, I; Stenberg, Dag

doi:10.1530/eje.0.1500737

Cited by 85 publications

(46 citation statements)

References 40 publications

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“…The physiological concentration of orexin A in hypothalamic tissue has been shown to be dependent on the days of the estrous cycle in female rats [42]. The hypothalamic orexin A concentration was 0.25 n M on the days of estrus and 0.7 n M on the days of proestrus [42]. Therefore, the orexin A concentration used in our study is very close to the range of physiological concentrations of orexin A in the brain.…”

Section: Discussionsupporting

confidence: 64%

“…The most effective dose of orexin A that showed regulation of GnRH expression and release is 0.1 n M . The physiological concentration of orexin A in hypothalamic tissue has been shown to be dependent on the days of the estrous cycle in female rats [42]. The hypothalamic orexin A concentration was 0.25 n M on the days of estrus and 0.7 n M on the days of proestrus [42].…”

Section: Discussionmentioning

confidence: 99%

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Orexin A Induces GnRH Gene Expression and Secretion from GT1-7 Hypothalamic GnRH Neurons

et al. 2006

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Orexin A, a recently discovered hypothalamic peptide, has been shown to have a stimulatory effect on release of gonadotropin-releasing hormone (GnRH) from rat hypothalamic explants in vitro. However, it is presently unclear whether in vivo this effect is mediated directly at the level of the GnRH neuron, or via multiple afferent neuronal connections. Therefore, in the present study, we investigated the direct action of orexin A on GnRH neurons using the immortalized GnRH-secreting GT1-7 hypothalamic cells. Orexin-1 receptor (OX1R) expression was detected in GT1-7 cells by RT-PCR and Western blot. Results showed that 0.1–1 nM orexin A, when administered in culture media for 4 h, can significantly stimulate GnRH mRNA expression in GT1-7 cells (p < 0.05). Administration of 1 µM OX1R antagonist, SB-334867, completely blocked the observed orexin A responses in these cells, indicating that orexin A stimulation of GnRH neurons is specifically through OX1R. Moreover, 0.1 nM orexin A stimulated GnRH release after 30–45 min. To examine possible signal transduction pathways involved in mediating these effects, a MEK inhibitor (UO-126), PKC inhibitor (calphostin C), and PKA inhibitor (H-89), were used, with each blocking orexin A-induced GnRH transcription and release from immortalized cells. Collectively, our results show that orexin A is capable of directly stimulating GnRH transcription and neuropeptide release from these immortalized hypothalamic neurons, and that the effects of orexin A appear to be mediated via the OX1R, coupled with activation of the PKC-, MAPK- and PKA-signaling pathways. It is suggested that the stimulatory effect of orexin A on GnRH transcription and release may also occur directly at the level of GnRH neurons in vivo.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Orexin A Induces GnRH Gene Expression and Secretion from GT1-7 Hypothalamic GnRH Neurons

et al. 2006

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“…Immunoreactivity of orexin neurons changed during the estrous cycle in rats (Porkka-Heiskanen et al 2004). Orexin-A or orexin-B administered intracerebroventricularly reduces serum luteinizing hormone (LH) levels and suppresses the pulsatile secretion of LH (Irahara et al 2001, Kok et al 2004, indicating an involvement of orexins in the regulation of reproductive endocrine functions.…”

Section: Daily Food Intake (G)mentioning

confidence: 99%

Central and/or peripheral immunoreactivity of orexin-A in pregnant rats and women

Sun

Tian²,

Yao³

et al. 2006

Journal of Molecular Endocrinology

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Orexins (A and B) have been implicated in feeding behavior, energy balance and state of vigilance. During pregnancy, their involvement in feeding regulation and reproduction are poorly understood. In this study, we investigated orexin-A immunoreactivity in the hypothalamus and serum in pregnant rats and women by immunofluorescence staining, image analysis and radioimmunoassay, examined the correlation of serum orexin-A and leptin with gestational age in pregnant women by regression analysis, and explored the effect of leptin injected intracerebroventricularly (i.c.v.) on orexin-A immunoreactivity in the hypothalamus of normal rats by immunohistochemistry. The results showed that pregnant rats had significantly greater daily food intake on days 15 and 20 of pregnancy than virgin ones (+27·3%, P<0·01 and +38·6%, P<0·001 respectively), with significantly fewer number and lower mean staining intensity of orexin-A-immunoreactive (ir) neurons on days 16 (both P<0·05) and 21 (both P<0·01) of pregnancy. Moreover, serum levels of orexin-A exhibited 2·0-fold and 2·2-fold increases (both P<0·001) in rats on days 16 and 21 of pregnancy compared with those in virgin rats, and 1·9-fold and 2·0-fold increases (both P<0·001) in mid (13-26 weeks) and late pregnant women (27-40 weeks) compared with those in non-pregnant women. Simultaneously, serum levels of leptin showed a 2·3-fold and 2·2-fold increase (both P<0·001) in rats on days 16 and 21 of pregnancy, and a 3·3-fold and 4·3-fold increase (both P<0·001) in mid and late pregnant women. Serum levels of both orexin-A and leptin correlated positively with gestational age in pregnant women. Leptin injected i.c.v. significantly decreased the number (P<0·01) and mean staining intensity (P<0·01) of orexin-A-ir neurons in the hypothalamus, food intake (P<0·01) and body weight gain (P<0·001) compared with vehicle injection in normal rats. These results suggested that central and serum orexin-A might be involved in the regulation of feeding and energy metabolism during pregnancy. The change in central orexin-A immunoreactivity might be related to the increased serum leptin concentrations.

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“…OREXINS AND ADRENAL GLAND concentration in the rat hypothalamus has been demonstrated (Porkka-Heiskanen et al, 2004).…”

Section: A Expression Of Orexins and Their Receptorsmentioning

confidence: 98%

Orexins in the Regulation of the Hypothalamic-Pituitary-Adrenal Axis

Spinazzi

Andreis²,

Rossi³

et al. 2006

Pharmacological Reviews

162

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Orexin A and B levels in the hypothalamus of female rats: the effects of the estrous cycle and age

Cited by 85 publications

References 40 publications

Orexin A Induces GnRH Gene Expression and Secretion from GT1-7 Hypothalamic GnRH Neurons

Orexin A Induces GnRH Gene Expression and Secretion from GT1-7 Hypothalamic GnRH Neurons

Central and/or peripheral immunoreactivity of orexin-A in pregnant rats and women

Orexins in the Regulation of the Hypothalamic-Pituitary-Adrenal Axis

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