The present study was designed to analyze in detail the effects of L-glutamate (L-Glu) and its agonists on the release of LHRH from arcuate nucleus-median eminence (AN-ME) fragments in vitro. Fragments from adult male rats were incubated in Krebs-Ringer bicarbonate buffer in the presence of different concentrations of L-Glu, kainate (KA), N-methyl-D-aspartic acid (NMDA), and quisqualate (QA). L-Glu at 10-20 mM evoked a significant increase in basal LHRH release, while D-glutamate at similar concentrations was ineffective. Partial depolarization with 14 mM K+ significantly augmented the release of LHRH induced by L-Glu. L-Glu-induced LHRH release was blunted in a dose-related manner by the specific KA/QA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione. Exposure to KA or QA significantly increased LHRH release at concentrations (1 mM) much lower than those required for L-Glu. In the presence of 14 mM K+ the potencies of KA and QA (0.075 and 0.1 mM, respectively) were significantly enhanced. 6,7-Dinitroquinoxaline-2,3-dione blocked KA-induced LHRH release, while AP-7, a competitive NMDA receptor antagonist, was inactive in preventing L-Glu- and KA-induced LHRH release. LHRH secretion from AN-ME fragments was unaffected by NMDA at concentrations up to 10 mM in the different media tested. A significant stimulatory effect of NMDA at 20 mM was observed when fragments were incubated in Mg2+-free medium. These results show the stereoselectivity of L-Glu to enhance LHRH release from AN-ME fragments in vitro. Moreover, in view of the respective potencies of excitatory amino acid agonists (KA = QA greater than L-Glu greater than NMDA) and the selective antagonism of excitatory amino acid effects, they provide evidence that non-NMDA receptors primarily mediate the excitatory actions of L-Glu on LHRH release from nerve terminals in the AN-ME.
The present study was designed to evaluate the relative contribution of endogenous excitatory amino acids to the control of the estradiol-induced LH surge using specific blockers for N-methyl-D-aspartic acid (NMDA) and non-NMDA receptor types. Adult female rats ovariectomized for 2-3 weeks were implanted with third ventricular cannulae one week before the experiments. Silastic capsules (3 cm active surface) containing estradiol benzoate (250 micrograms/ml dissolved in sesame oil) were implanted subcutaneously two days prior to bleeding. Blood samples were collected at hourly intervals (from 1300 to 2100 h) through indwelling atrial cannulae implanted the day before the bleeding. (+) 2-amino-7-phosphoheptanoic acid (AP-7), a NMDA receptor antagonist, and 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA receptor antagonist, were administered (10 and 20 nmole dissolved in 10 microliters 0.9% sodium chloride, respectively) at 1300 and 1400 h into the third ventricle. LH, FSH and PRL levels were assayed by RIA in plasma samples. AP-7 and DNQX administration completely blocked the estradiol-induced LH surge, whereas PRL and FSH secretion was not affected by the treatments. These results indicate that endogenous EAA play an important role in controlling LH secretion. Furthermore, the study reveals that both EAA receptor types; i.e. NMDA and non-NMDA, appear to be necessary for the physiological mechanism(s) triggering the estradiol-induced LH surge.
The levels of prolactin and LH in the plasma of rats were determined at various times after intraventricular injection of histamine. Doses of 5 and 60 μg histamine (free base) in male rats, anaesthetized with ether, induced an increase in the level of prolactin in the plasma, whilst producing a slight decrease in the concentration of LH. Injection of 5 μg histamine at 14.00 h into female rats at all stages of the oestrous cycle caused prolactin to be released; the effect was greatest at oestrus and at day 1 of dioestrus. Histamine also gave rise to a marked increase in the level of LH in the plasma when administered to pro-oestrous rats, but had no effect when injected at the other stages of the oestrous cycle. The effect of histamine on the release of prolactin in ovariectomized, oestradiol benzoate: progesterone-primed (OVX,OB:P) rats was found to be dose-related, and the level of LH in the plasma was increased by as little as 1·25 μg. Pretreatment with adrenergic (phenoxybenzamine and propranolol) and cholinergic (atropine) antagonists failed to block the stimulatory effects of histamine on prolactin secretion, but pretreatment with methysergide (serotonin antagonist) increased the histamine-induced release of prolactin in male rats. Antagonists did not modify the response of prolactin to histamine in OVX,OB:P-primed rats. The histamine-induced release of LH in OVX,OB:P-primed rats was slightly reduced by pretreatment with phenoxybenzamine, propranolol and atropine, but not by methysergide. These results indicate that histamine facilitates the release of prolactin. The stimulatory action of histamine on both pro-oestrous and OVX,OB:P-primed but not male rats suggests that histamine may be involved in LH release in the rat. Results obtained in animals pretreated with transmitter antagonists, which were unable to prevent histamine-induced hormone release, suggest that the actions of this amine are not mediated by cholinergic, noradrenergic or serotonergic mechanisms.
The effects of increasing brain GABA levels by administration of aminooxyacetic acid (AOAA), a GABA-transaminase inhibitor, on tonic and induced LH release were evaluated in ovariectomized rats.Pulsatile LH release was clearly inhibited by AOAA. Mean plasma LH levels fell, the frequently of pulses decreased, and the intervals between pulses increased. An absence of LH pulses was seen in some animals. Administration of the GABA antagonist, bicuculline, prevented these modifications. In addition, it enhanced mean plasma LH levels. AOAA blunted the rise of plasma LH levels produced by either oestradiol or progesterone in oestradiol-primed ovariectomized rats. In contrast, the AOAA treatment apparently facilitated the inhibitory feedback of oestradiol on LH release. The acute release of LH produced by LRH injection was not altered by AOAA.The results support the view that brain GABA exerts an inhibitory action on LH release in the rat.
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