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.
- SourceAvailable from: Puliyur S Mohankumar[Show abstract] [Hide abstract]
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: We have previously reported that tumor necrosis factor-alpha (TNF-alpha) suppressed pulsatile secretion of luteinizing hormone (LH) in adrenalectomized (ADX) rats, which was restored by replacement of glucocorticoid. In the present study, we examined the role of glucocorticoid in inducing the preovulatory LH surge under conditions of infectious stress. Intravenous injection of TNF-alpha (1 microg) into the proestrous rats at 1300 h attenuated the LH surge and decreased the number of oocytes ovulated. The inhibitory effect of TNF-alpha on the LH surge was blocked by pretreatment with indomethacin, suggesting that the effects of TNF-alpha were mediated by prostaglandins (PGs). On the other hand, ADX markedly enhanced the inhibitory effect of TNF-alpha on the LH surge and subsequent ovulation, which was almost completely restored by pretreatment with a subcutaneous injection of corticosterone (10 mg). These results suggest that glucocorticoid counteracts the inhibitory effect of the cytokines on the preovulatory LH surge by suppressing PG synthesis, and thereby helps to maintain reproductive function under infectious stress conditions.Journal of Endocrinology 07/2004; 181(3):509-13. · 4.06 Impact Factor
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ABSTRACT: The neurons that produce gonadotrophin-releasing hormone (GnRH) are mainly found in the medial preoptic area (MPOA) and constitute a common final pathway to the control of luteinizing hormone (LH) surge on proestrus. The control of GnRH secretion depends on several neurotransmitters, such as serotonin (5-HT), noradrenaline (NA), dopamine (DA) and nitric oxide (NO). The aim of this work was to study the profile of 5-HT, catecholamines and their main metabolites in the MPOA throughout the estrous cycle and their interactions with NO system in this area to control LH surge. For this purpose, the following were evaluated: (I) the effect of pargyline (a monoamine oxidase inhibitor) acute treatment on plasma LH secretion throughout the estrous cycle, correlated with changes of 5-HT, DA and NA content as well as activity and expression of neuronal NO synthase (nNOS) within MPOA; (II) the effect of 5,7-dihydroxitriptamine (a drug that depletes 5-HT) microinjection into MPOA on plasma LH in ovariectomized rats treated with oil, estradiol (E(2)) or E(2) plus progesterone (P(4)). Pargyline prevented LH surge on proestrus without altering its basal secretion. Throughout the estrous cycle, pargyline augmented both 5-HT and DA contents in approximately 300% and NA content in 50% in the MPOA. During proestrus, pargyline stimulated nNOS activity at 9 h and inhibited it at 11 h. nNOS expression was inhibited by pargyline at 15 h. Depletion of 5-HT content in the MPOA increased LH secretion in ovariectomized rats treated with E(2) plus P(4), but it did not modify in rats treated with either oil or E(2). Therefore, the present data show that pargyline treatment can inhibit proestrus LH surge through a mechanism that may involve 5-HT and NO systems in the MPOA. Moreover, the effect of 5-HT in the MPOA for limiting LH surge seems to depend on plasma levels of E(2) and P(4).Brain Research 05/2007; 1142:37-45. · 2.88 Impact Factor