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1.
Ketosis is found in various pathophysiological conditions, including diabetes and starvation, that are accompanied by suppression of gonadal activity. The aim of the present study was to determine the role of ketone body in the brain in regulating pulsatile luteinizing hormone (LH) secretion in female rats. Injection of 3-hydroxybutyrate (3HB), a ketone body, into the fourth cerebroventricle (4V) induced suppression of pulsatile LH secretion in a dose-dependent manner in ovariectomized (OVX) rats with an estradiol (E2) implant producing diestrus plasma E2 levels. Plasma glucose and corticosterone levels increased immediately after the 4V 3HB injection, suggesting that the treatment caused a hunger response. The 3HB-induced suppression of LH pulses might be mediated by noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) because a local injection of α-methyl- p-tyrosine, a catecholamine synthesis inhibitor, into the PVN blocked 3HB-induced suppression of LH pulses and PVN noradrenaline release was increased by 4V 3HB injection in E2-primed OVX rats. These results suggest that ketone body sensed by a central energy sensor in the hindbrain may suppress gonadotropin release via noradrenergic inputs to the PVN under ketosis.  相似文献   

2.
The present study examined the effect of acute lipoprivation on pulsatile luteinizing hormone (LH) secretion in both normal-fat diet, ad libitum-fed and fasted female rats. To produce an acute lipoprivic condition, mercaptoacetate (MA), an inhibitor of fatty acid oxidation, was administered intraperitoneally to ad libitum-fed or 24-h fasted ovariectomized (OVX) rats with or without an estradiol (E2) implant, that produces a negative feedback effect on LH pulses. The steroid treatment was performed to determine the effect of estrogen on lipoprivic changes in LH release, because estrogen enhances fasting- or glucoprivation-induced suppression of LH pulses. Pulsatile LH secretion was suppressed by MA administration in a dose-dependent manner in the ad libitum-fed OVX and OVX+E2 rats. LH pulses were more severely suppressed in the 24-h-fasted OVX and OVX+E2 rats compared to the ad libitum-fed rats. Estrogen slightly enhanced lipoprivic suppression but the effect was not significant. In the present study, increased plasma glucose and free-fatty acid concentrations may indicate a blockade of fatty acid metabolism by the MA treatment, but food intake was not affected by any of the MA doses. Acute vagotomy did not block lipoprivic suppression of LH pulses. Thus, the present study indicates that lipid metabolism is important for maintenance of normal reproductive function even in rats fed a normal-fat diet and lipoprivation may be more critical in fasted animals that probably rely more heavily on fatty acid oxidation to maintain appropriate metabolic fuel levels. In addition, failure of blockade of lipoprivic LH inhibition by vagotomy suggests that lipoprivic information resulting in LH suppression is not transmitted to the brain via the vagus nerve.  相似文献   

3.
Previous studies have suggested the presence of a glucose-sensing mechanism in the hindbrain that appears to regulate reproductive function as well as feeding behavior. The ependymocytes lining the ventricular wall of the hindbrain showed immunoreactivities to pancreatic glucokinase (GK), a key enzyme for glucose sensing in pancreatic B cells. Our goal in the present study was to test whether the GK-immunopositive ependymocytes in the wall of the fourth cerebroventricle (4V) play a role in regulating gonadal activity. Our approach was to determine the effect of injecting alloxan, a GK inhibitor, into the 4V on pulsatile luteinizing hormone (LH) secretion. Estrogen-primed ovariectomized rats received an injection of alloxan (10 or 20 microg/animal) into the 4V and blood samples were collected every 6 min for 3 h for measurement of blood LH, corticosterone and glucose levels. Pulsatile LH secretion was suppressed after alloxan injection and all pulse parameters were significantly (P<0.05) inhibited by 20 microg alloxan. Plasma corticosterone levels were increased significantly (P<0.05) by 20 microg alloxan, suggesting that LH pulse suppression by alloxan may be at least partly mediated by activation of the hypothalamo-pituitary-adrenal axis. The present results suggest that acute suppression of GK activity in the hindbrain inhibits pulsatile LH secretion in female rats, and supports the idea that GK-immunopositive ependymocytes may sense glucose levels in the cerebrospinal fluid and play a role in regulation of LH secretion.  相似文献   

4.
The bed nucleus of the stria terminalis (BNST) is one of the brain areas densely innervated by noradrenergic neurons originating in the brain stem. The present study aims to determine the role of noradrenergic receptors in the BNST in regulating pulsatile luteinizing hormone (LH) secretion in female rats. Ovariectomized (OVX) or estrogen-primed OVX (OVX+E2) rats received three 1-h-interval injections of 0.05 micromol of noradrenaline (NA), phenylephrine (alpha1-adrenergic receptor agonist), clonidine (alpha2-agonist), or isoproterenol (beta-agonist) into the BNST. Injection of NA or alpha1-adrenergic agonist into the BNST strongly suppressed pulsatile LH secretion in OVX+E2 rats with a significant (P < 0.05) decrease in the mean LH level for 3 h and LH pulse frequency, but alpha2-and beta-agonists did not affect any of the LH pulse parameters. In OVX animals, alpha1- and alpha2-adrenergic agonists caused a significant change in LH pulse frequency and amplitude, respectively, though the effect was not as apparent as the NA- or alpha1-agonist-induced changes in OVX+E2 animals. These results indicate that NA inputs to the BNST suppress pulsatile LH secretion via alpha1-adrenergic receptors and that estrogen enhances this suppression.  相似文献   

5.
Accumulating evidence suggests that the arcuate nucleus (ARC) kisspeptin/neurokinin B (NKB)/dynorphin (KNDy) neurons play a role in estrogen negative feedback action on pulsatile gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release. The present study aimed to determine if dynorphin (Dyn) is involved in estrogen negative feedback on pulsatile GnRH/LH release. The effect of the injection of nor-binaltorphimine (nor-BNI), a kappa-opioid receptor (KOR) antagonist, into the third cerebroventricle (3V) on LH pulses was determined in ovariectomized (OVX) adult female rats with/without replacement of negative feedback levels of estradiol (low E2). The mean LH concentrations and baseline levels of LH secretion in nor-BNI-injected, low E2-treated rats were significantly higher compared with vehicle-treated controls. On the other hand, the nor-BNI treatment failed to affect any LH pulse parameters in OVX rats without low E2 treatment. These results suggest that Dyn is involved in the estrogen negative feedback regulation of pulsatile GnRH/LH release. The low E2 treatment had no significant effect on the numbers of ARC Pdyn (Dyn gene)-,Kiss1- and Tac2 (NKB gene)-expressing cells. The treatment also did not affect mRNA levels of Pdyn and Oprk1 (KOR gene) in the ARC-median eminence region, but significantly increased the ARC kisspeptin immunoreactivity. These findings suggest that the negative feedback level of estrogen suppresses kisspeptin release from the ARC KNDy neurons through an unknown mechanism without affecting the Dyn and KOR expressions in the ARC. Taken together, the present result suggests that Dyn-KOR signaling is a part of estrogen negative feedback action on GnRH/LH pulses by reducing the kisspeptin release in female rats.  相似文献   

6.
Glucoprivation induced by 2-deoxy-D-glucose (2DG) suppresses pulsatile luteinizing hormone (LH) secretion in female rats. The suppression is enhanced in the presence of estrogen. In the present study, 2DG-induced Fos expression was examined in the solitary tract nucleus (NTS), hypothalamic paraventricular nucleus (PVN), raphe obscurus nucleus (ROb) and raphe pallidus nucleus (RPa), which have been previously suggested to be involved in glucoprivation-induced suppression of LH secretion in female rats. Ovariectomized (OVX) or estrogen-primed ovariectomized (OVX+E(2)) rats were injected intravenously with 2DG (400 mg/kg BW). The brain was removed 1 h after the injection. The number of Fos-like-immunoreactive (Fos-li) cells in the PVN and NTS was significantly increased in OVX+E(2) rats compared with control groups, but did not show a significant increase in the OVX group. Few Fos-li cells were observed in the ROb and RPa in all groups. All of the Fos-li cells in the PVN and NTS were neurons because they had immunoreactivities to microtubule-associated protein 2. Some Fos-li cells (8.3%) had tyrosine hydroxylase-like immunoreactivities in the NTS in 2DG-treated OVX+E(2) rats. These results suggest that neurons in the PVN and NTS are involved in the estrogen-dependent neural cascade mediating glucoprivic suppression of LH secretion in female rats.  相似文献   

7.
Energy availability has been considered to regulate gonadal activity by modulating the release of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) at various reproductive phases, such as lactation and puberty in domestic as well as wild animals. Experimental models with rats and sheep have demonstrated that fasting or glucoprivation suppresses pulsatile LH release. From those experiments, the information on energy deficiency is considered to be detected by specific central sensors and conveyed to the hypothalamus to regulate LH release as well as food intake. Noradrenergic neurons, originating in the medulla oblongata and projecting to the hypothalamic paraventricular nucleus (PVN), is reported to be one of the pathways mediating the response of LH release to energy deficiency. The other component is considered to be an energy-sensing mechanism in the brain. Glucose or other oxidizable fuels may function as a metabolic signal to regulate LH release. Previous studies suggest the presence of a glucose-sensing mechanism in the rat hindbrain. From our previous results in the rat, the ependymocytes lining the wall of the cerebroventricle could possibly serve as a glucose sensor to regulate GnRH/LH release. Greater understanding of the nature of the energy-sensing mechanism in the brain will contribute to the nutritional manipulation of reproductive performance in domestic animals in various conditions.  相似文献   

8.
It has recently been shown that neurokinin B, a tachykinin, is associated with GnRH pulse generation in sheep and goats. The aim of the present study was to clarify the role of tachykinin receptors in the control of LH secretion in rats. To this end, we evaluated the effect of CS-003, an antagonist for all three neurokinin receptors (NK1, NK2 and NK3 receptors), on pulsatile LH secretion in both sexes of rats with different routes of administration. Both oral and third ventricular administration of CS-003 suppressed LH secretion in both sexes of gonadectomized animals. Furthermore, intact male rats with oral administration of CS-003 showed decreased serum testosterone levels, which might be due to suppressed LH secretion. None of the three subtype-specific neurokinin receptor antagonists showed a significant effect on LH secretion in ovariectomized rats when each antagonist was singly administered. The present results suggest that neurokinins play a role in the control of pulsatile GnRH/LH secretion via multiple neurokinin receptors in both male and female rats.  相似文献   

9.
AIMS: The aims of the present study were to characterise the renal effects of the alpha2-adrenergic agonist, xylazine, in the rat and to test the role of changes in glomerular filtration rate, glucosuria, and arginine vasopressin (AVP) in its mechanism of action. METHODS: Male Wistar rats were anaesthetised with pentobarbitone sodium (50 mg/kg), and polyethylene cannulae were surgically placed for blood pressure measurement and for blood and urine collection. Rats were given xylazine and other alpha2 agonists by bolus intravenous dose, and the effects of the drugs were monitored in the presence and absence of the selective alpha2 antagonist, yohimbine, the alpha1, alpha2B antagonist, prazosin, and the V2-receptor antagonist, d(CH2)5 [D-Ile2,Ile4,Ala-NH29]AVP. RESULTS: Xylazine at 2.5 mg/kg caused a significant and prolonged dose-dependent increase in urine flow rate and sodium excretion but had only short-lasting effects on blood pressure, heart rate, and glomerular filtration rate. Prazosin had no effect on the measured responses. Although plasma glucose concentration and glucose excretion rate were increased by xylazine, the magnitudes of these increases were insufficient to account for the diuresis observed. Xylazine, and 2 other alpha2 agonists, clonidine and oxymetazoline, increased urine flow and/or sodium excretion despite the presence of d(CH2)5 [D-Ile2,Ile4,Ala-NH29]AVP. CONCLUSIONS: Xylazine causes a diuretic and natriuretic alpha2A-adrenergic response in the rat that is independent of changes in glomerular filtration rate, the development of glucosuria, or AVP action on the distal nephron of the kidney. CLINICAL RELEVANCE: The adverse effects of xylazine on salt and water balance need to be considered and possibly compensated for by fluid replacement or post-surgical administration of alpha2-receptor antagonists.  相似文献   

10.
Reproductive function is suppressed during lactation owing to the suckling-induced suppression of the kisspeptin gene (Kiss1) expression in the arcuate nucleus (ARC) and subsequent suppression of luteinizing hormone (LH) release. Our previous study revealed that somatostatin (SST) neurons mediate suckling-induced suppression of LH release via SST receptor 2 (SSTR2) in ovariectomized lactating rats during early lactation. This study examined whether central SST-SSTR2 signaling mediates the inhibition of ARC Kiss1 expression and LH release in lactating rats during late lactation and whether the inhibition of glutamatergic neurons, stimulators of LH release, is involved in the suppression of LH release mediated by central SST-SSTR2 signaling in lactating rats. A central injection of the SSTR2 antagonist CYN154806 (CYN) significantly increased ARC Kiss1 expression in lactating rats on day 16 of lactation. Dual in situ hybridization revealed that few ARC Kiss1-positive cells co-expressed Sstr2, and some of the ARC Slc17a6 (a glutamatergic neuronal marker)-positive cells co-expressed Sstr2. Furthermore, almost all ARC Kiss1-positive cells co-expressed Grin1, a subunit of N-methyl-D-aspartate (NMDA) receptors. The numbers of Slc17a6/Sstr2 double-labeled and Slc17a6 single-labeled cells were significantly lower in lactating dams than in non-lactating rats whose pups had been removed after parturition. A central injection of an NMDA antagonist reversed the CYN-induced increase in LH release in lactating rats. Overall, these results suggest that central SST-SSTR2 signaling, at least partly, mediates the suppression of ARC Kiss1 expression and LH release by inhibiting ARC glutamatergic interneurons in lactating rats.  相似文献   

11.
It is known that water deprivation or injection of hypertonic saline induces anorexia. The present study examined the possible involvement of vasopressin in the suppression of food intake during high plasma osmolality. Intraperitoneal injection of vasopressin (20 microg/kg) into male rats significantly suppressed food intake for 1 hr. This anorectic effect of vasopressin was reversed by simultaneous injection of a peptide antagonist for V(1) receptor (40 microg/kg), but not for V(2) receptor (40 microg/kg). Intraperitoneal injection of hypertonic saline (20% NaCl, 2 ml/kg) similarly suppressed food intake for 2 hr, which was associated with a transient increase in plasma vasopressin concentrations. This hypertonic saline-induced suppression of food intake was blocked by a V(1) receptor antagonist. Vasopressin (40 ng/2 microl) directly administered into the third ventricle of the brain also suppressed food intake for 1 hr. These results suggest that vasopressin participates in the suppression of food intake during high plasma osmolality, the action of which is mediated by V(1) receptors in the brain.  相似文献   

12.
Background: Immune stress induced by lipopolysaccharide(LPS) influences the gonadotropin-releasing hormone(GnRH)/luteinizing hormone(LH) secretion. Presence of LPS interacting Toll-like receptor(TLR) 4 in the hypothalamus may enable the direct action of LPS on the GnRH/LH secretion. So, the aim of the study was to investigate the influence of intracerebroventricular(icv) injection of TLR4 antagonist on GnRH/LH secretion in anestrous ewes during LPS-induced central inflammation. Animals were divided into three groups icv-treated with: Ringer-Locke solution, LPS and TLR4 antagonist followed by LPS.Results: It was demonstrated that TLR4 antagonist reduced LPS-dependent suppression of GnRH gene expression in the preoptic area and in the medial basal hypothalamus, and suppression of receptor for GnRH gene expression in the anterior pituitary gland. It was also shown that TLR4 antagonist reduced suppression of LH release caused by icv injection of LPS. Central administration of LPS stimulated TLR4 gene expression in the medial basal hypothalamus.Conclusions: It was indicated that blockade of TLR4 prevents the inhibitory effect of centrally acting LPS on the GnRH/LH secretion. This suggests that some negative effects of bacterial infection on the hypothalamic-pituitary-gonadal axis activity at the hypothalamic level may be caused by central action of LPS acting through TLR4.  相似文献   

13.
Mature boars were subjected to chronic treatment with a gonadotropin-releasing hormone (GnRH) agonist, goserelin (D-Ser[But]6, Azgly-NH210), and serum luteinizing hormone (LH) and testosterone concentrations were measured. Ten sexually mature boars were randomly assigned to treatment (n = 5) or control (n = 5) groups. On day 0, boars were implanted sc (day 0) with 2 GnRH agonist implants (1 mg of GnRH/implant) or sham implants. Blood samples were collected at 12-hour intervals on days -2 and -1, at 6-hour intervals on days 0 through 4, and at 12-hour intervals on days 5 through 8. In addition, blood samples were collected at 15-minute intervals for 6 hours on days -1, 0, 4, and 8. Serum testosterone and LH concentrations were determined by radioimmunoassay. Maximal LH (7 +/- 1 ng/ml) and testosterone (26 +/- 3 ng/ml) concentrations were observed at 5 and 18 hours, respectively, after GnRH agonist treatment. Subsequently, LH and testosterone concentrations decreased to pretreatment values (0.3 +/- 0.1 ng/ml and 1.8 +/- 0.4 ng/ml, respectively) by 24 and 48 hours, respectively, after GnRH agonist implantation. Few differences in the characteristics of pulsatile LH release were observed between the groups. Testosterone and LH concentrations in samples collected at 6- and 12-hour intervals and pulsatile LH release did not change after sham treatment of control boars. Whereas previous reports indicated that chronic GnRH administration suppressed serum LH and testosterone concentrations in rams, rats, and dogs, our results indicate that chronic GnRH agonist treatment induced transitory increases, without subsequent suppression, in LH and testosterone concentrations in mature boars.  相似文献   

14.
The present study aimed to determine estrogen feedback action sites to mediate prepubertal restraint of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release in female rats. Wistar-Imamichi strain rats were ovariectomized (OVX) and received a local estradiol-17β (estradiol) or cholesterol microimplant in several brain areas, such as the medial preoptic area (mPOA), paraventricular nucleus, ventromedial nucleus and arcuate nucleus (ARC), at 20 or 35 days of age. Six days after receiving the estradiol microimplant, animals were bled to detect LH pulses at 26 or 41 days of age, representing the pre- or postpubertal period, respectively. Estradiol microimplants in the mPOA or ARC, but not in other brain regions, suppressed LH pulses in prepubertal OVX rats. Apparent LH pulses were found in the postpubertal period in all animals bearing estradiol or cholesterol implants. It is unlikely that pubertal changes in responsiveness to estrogen are due to a change in estrogen receptor (ER) expression, because the number of ERα-immunoreactive cells and mRNA levels of Esr1, Esr2 and Gpr30 in the mPOA and ARC were comparable between the pre- and postpubertal periods. In addition, kisspeptin or GnRH injection overrode estradiol-dependent prepubertal LH suppression, suggesting that estrogen inhibits the kisspeptin-GnRH cascade during the prepubertal period. Thus, estrogen-responsive neurons located in the mPOA and ARC may play key roles in estrogen-dependent prepubertal restraint of GnRH/LH secretion in female rats.  相似文献   

15.
The effect of the centrally acting α-adrenoceptor agonist, clonidine, on plasma LH and FSH was studied in oestradiol-primed and unprimed ewes and in oestrous ewes. In unprimed anoestrous ewes, clonidine stimulated LH and FSH release after a lag period of 18 h, and noradrenaline intracarotid injection or i.v. infusions immediately stimulated LH release. In oestradiol-infused anoestrous ewes, clonidine produced either a delay or inhibition of the gonadotrophin surge and noradrenaline i.v. infusion advanced the LH surge. In oestrous ewes treated with clonidine, there was marked delay in the LH surge, but the magnitude of the LH and FSH surges were unaffected. Intravenous administration of α-adrenoceptor blockers, phentolamine and phenoxybenzamine, blocked the oestradiol-induced gondotrophin surge in anoestrous ewes. The effect of phenoxybenzamine on gonadotrophin surge was dose dependent in oestrous ewes. Small doses (4 mg/kg i.v.) of phenoxybenzamine delayed the synchronous LH and FSH surges. There was complete blockade of the LH surge and partial blockade of FSH surges in ewes given phenoxybenzamine (8 mg/kg i.v.) before the expected synchronous gonadotrophin surges. After this experiment, the initial rise of plasma progesterone concentrations did not occur until day 6 of oestrous cycle. Administration of phenoxybenzamine before the expected second FSH surge had no effect on the second FSH surge. Gonadotrophin release induced by gonadotrophin-releasing hormone was attenuated by phenoxybenzamine, but not by clonidine. The results suggest that the LH surge is under α-adrenergic control and the first FSH surge is under partial α-adrenergic control, but the second FSH surge is not under α-adrenergic control. The results also suggest oestradiol modulation of α-adrenergic receptor action.  相似文献   

16.
In this study the anti-inflammatory properties of zilpaterol, a beta2-adrenergic receptor (AR) agonist specifically developed as a growth promoter in cattle were investigated. Although zilpaterol has a different structure compared with the beta2-AR agonists known to date, it was noted that it was able to bind to both the beta2-AR (Ki = 1.1 x 10(-6)) and the beta1-AR (Ki = 1.0 x 10(-5)). Using lipopolysaccharide (LPS)-exposed U937 macrophages, the production of cyclic adenosine-3',5'-cyclic monophosphate (cAMP) and tumor necrosis factor alpha (TNF-alpha) were investigated. Zilpaterol inhibited TNF-alpha release and induced intracellular cAMP levels in a dose-dependent manner. The inhibition of TNF-alpha release and induction of cAMP production was mainly mediated via the beta2-AR, as indicated by addition of beta1- and beta2-specific antagonists. The effects of zilpaterol were investigated in LPS-treated male Wistar rats after pretreatment with zilpaterol. Zilpaterol dosed at 500 microg/kg body weight reduced the TNF-alpha plasma levels. In conclusion, zilpaterol is a beta2-adrenergic agonist and an inhibitor of TNF-alpha production induced by LPS both in vivo and in vitro.  相似文献   

17.
An adult Holstein cow was inadvertently administered an overdose of xylazine hydrochloride. The cow became weak, collapsed, and developed severe bradycardia and intermittent heart block. Initial therapy for cardiovascular collapse consisted of rapid infusion of large volumes of intravenous fluids and intravenous injection of atropine sulfate. Yohimbine, an alpha 2-adrenergic antagonist, and tolazoline hydrochloride, an alpha 1- and alpha 2-adrenergic antagonist, were administered intravenously as antidotes for xylazine overdose. The cow recovered but calved prematurely 4 days later.  相似文献   

18.
The effects of morphine and the opiate receptor antagonist, naloxone, on the secretory pattern of luteinizing hormone (LH) were assessed in male sheep. Morphine infusion (250 mg/hr) abruptly stopped LH pulsatile secretion in castrates (wethers) and decreased mean serum LH concentrations by nearly 70 percent. Response of the pituitary to exogenous LH releasing hormone was not affected by morphine suggesting that the effects of morphine on LH secretion were mediated through the hypothalamus. Estradiol-implanted wethers, characterized by a nonpulsatile LH secretory pattern, responded to intravenous injection of naloxone (20, 50 and 200 mg Lv.) with an immediate release (pulse) of L.H. Similarly, LH release was significantly increased following naloxone infusion (200 mg/hr for four hours) in intact rams and wethers implanted with testosterone or estradiol. In contrast, naloxone infusion altered the pattern of LH secretion in wethers but without affecting mean serum LH concentrations. These results support the notion that LH secretion in male-sheep is tonically regulated by endogenous opiates and further suggests that opioid modulation of the hypothalamic-pituitary-LH axis in sheep involves an interaction with the steroid negative feedback system.  相似文献   

19.
Administration of endotoxin suppresses circulating concentration of luteinizing hormone (LH) in a number of species, including rats, sheep, cattle, and non-human primates. Specifically, endotoxin administration decreases circulating concentration of LH and LH pulses frequency in castrated male sheep. Endotoxin could alter circulating concentrations of LH via actions at the hypothalamus through altered GnRH production and/or release, or endotoxin could alter circulating concentrations of LH at the level of the pituitary via inhibition of LH production and release or inhibition of LH in response to GnRH. The site of endotoxin suppression of circulating concentrations of LH as well as possible mediators of endotoxin suppression of circulating concentrations of LH, including cortiocotropin-releasing hormone, arginine vasopressin, glucocorticoids, inflammatory cytokines, prostaglandins, and opioids, are discussed.  相似文献   

20.
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