Effects of interleukin-1 beta on the steroid-induced luteinizing hormone surge: role of norepinephrine in the medial preoptic area.
ABSTRACT Interleukin-1beta (IL-1beta), a cytokine, is known to inhibit the preovulatory surge of luteinizing hormone (LH); however, the mechanism by which it does so is unclear. This study was done to see if this effect is mediated through hypothalamic catecholamines. Adult female Sprague-Dawley rats were ovariectomized and implanted with a push-pull cannula in the medial preoptic area (MPA) of the hypothalamus. They were injected subcutaneously with 30 microg of Estradiol on the day 8 after surgery and with 2mg of Progesterone on day 10 at 1000 h. On the day of perfusion (day 10), the rats were injected with IL-1beta or its vehicle at 1300 h. Perfusate samples from the MPA and blood samples from a jugular catheter were collected from 1300 to 1800 h. Catecholamine concentrations in the perfusate were measured using high performance liquid chromatography (HPLC)-EC and LH levels in the serum using RIA. Norepinephrine release in the MPA of control rats increased significantly at 1530, 1600, and 1630 h paralelling an increase in LH at 1600 h. In contrast, IL-1beta treatment blocked the LH surge and the rise in norepinephrine release in the MPA. No changes were observed in dopamine release, both in control and IL-treated animals. These results demonstrate for the first time that IL-induced suppression of the LH surge is probably mediated through inhibition of norepinephrine release in the MPA.
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ABSTRACT: AimsInterleukin-1β (IL-1β) is a cytokine that is known to activate the stress axis and suppress the reproductive axis. Different brain areas are involved in the regulation of these two axes. However, they are both under the stimulatory control of the catecholamine, norepinephrine (NE). Here, we hypothesized that IL-1β differentially affects these two axes by modulating NE levels in specific brain regions.Main methodsFemale Sprague–Dawley rats in proestrus were injected intraperitoneally with either PBS-1.0% BSA (control) or 5 μg of IL-1β at 1 pm. Groups of rats were sacrificed at 1, 3, and 5 pm and their brains were collected. Brain areas associated with reproduction as well as areas associated with stress axis activity were isolated and analyzed for NE concentrations using HPLC–EC. Trunk blood was analyzed for IL-1β, corticosterone and luteinizing hormone levels.Key findingsAs a general trend, treatment with IL-1β significantly decreased NE levels (p < 0.05) in the areas controlling reproductive functions when compared to the control group. In contrast, NE levels increased significantly (p < 0.05) in the stress associated areas. LH levels were markedly decreased with IL-1β treatment while corticosterone levels increased dramatically.SignificanceThe ability of IL-1β to produce differential effects on the stress and reproductive axis could be explained by modulation of NE levels in specific brain areas that are associated with these functions. This differential regulation of NE may be an adaptive phenomenon in response to a systemic immune challenge.Life sciences 10/2012; 91(s 17–18):878–884. · 2.56 Impact Factor
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ABSTRACT: The cytokine, interleukin-1β (IL-1β), is known to produce specific effects on the neuroendocrine system such as suppression of the reproductive axis and stimulation of the stress axis. The mechanism by which IL-1β produces these differential effects is not clear. Since norepinephrine (NE) is involved in these effects, we hypothesized that IL-1β acts on brainstem noradrenergic nuclei to affect gene transcription of NE synthesizing enzymes, cytokines and associated transcription factors. Adult female Sprague Dawley rats in proestrus were divided into two groups. Control animals received PBS-BSA and the treatment group received 5 μg of rat recombinant IL-1β i.p. at noon. They were sacrificed in groups at 1, 3 and 5 pm (n=6/group) for measurement of tyrosine hydroxylase (TH) mRNA by qPCR or at 3 pm for mRNA analysis by qPCR array. TH mRNA levels decreased gradually with time in both control and IL-1β-treated rats in the ventrolateral medulla. In the nucleus of solitary tract, TH mRNA levels were significantly reduced by IL-1β treatment at 5 pm. In the locus coeruleus, TH mRNA levels increased significantly at 5 pm with IL-1β treatment compared to controls. In the second set of animals analyzed by qPCR array, there were several fold increases in the expression of certain cytokines, chemokines, and transcription factors in specific noradrenergic nuclei. Systemic administration of IL-1β causes significant changes in the expression of tyrosine hydroxylase and several chemokines in brain stem noradrenergic nuclei, thereby mediating its neuroendocrine effects.Life sciences 01/2012; 90(1-2):77-81. · 2.56 Impact Factor
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ABSTRACT: The incidence of ovulatory disorders is common in obese animal models. The mechanism behind this effect is unclear. We hypothesised that a high-fat (HF) diet induces alterations in neuroendocrine mechanisms resulting in anovulation in diet-induced obese (DIO) animals. Adult female DIO and diet-resistant (DR) rats were fed either chow or a HF diet (45% calories from fat) for 6 weeks. Oestrous cyclicity and body weight were monitored regularly. At the end of treatment, rats were implanted with a jugular catheter to monitor luteinising hormone (LH) levels on the day of pro-oestrous. Rats were sacrificed on the next pro-oestrous, and their brains and ovaries were collected. Plasma from trunk blood was analysed for oestradiol and leptin concentrations. Ovaries were fixed and sectioned for histological analysis. Brains were removed, frozen and sectioned, and norepinephrine (NE) concentrations in discrete hypothalamic areas were measured using high-performance liquid chromatography with electrochemical detection. A HF diet exposure affected oestrous cyclicity in both DIO and DR rats, with the effect being more pronounced in DIO animals. HF diet exposure increased leptin levels in both DIO and DR rats. Oestradiol levels were low in the DIO-HF group. NE levels in the hypothalamus were unaffected by HF diet or genotype. A normal LH surge was observed in DR-Chow rats and LH levels were low in the remaining groups. These results lead to the conclusion that DIO rats have an inherently reduced reproductive capacity and exposure to a HF diet decreases it further. A reduction in oestradiol and LH surge levels could contribute to this effect; however, the underlying mechanisms need to be investigated further.Journal of Neuroendocrinology 12/2011; 24(5):748-55. · 3.33 Impact Factor