摘要:

The fluid bathing pineal glands isolated from guinea pigs was collected serially and its melatonin content was estimated. Production was found to be high (500 pg/5 min) soon after isolation of the gland: it declined exponentially to a maintained lower level (50 pg/5 min) with a half-time of 16–20 min. A rapid increase could be produced by exposure of the gland to the β-adrenoceptor agonist orciprenaline or by stimulating it electrically. The time course and the extent of the responses to either form of stimulation were similar in glands that had been taken in the morning, at dusk or in mid-dark: the prestimulation peak was lower from glands taken at dusk. Thus the pineal gland of the guinea pig is capable of responding rapidly to stimulation of its β-adrenoceptors at any time. These responses parallel the depolarization observed intracellularly in this species when the pineal gland is stimulated electrically or exposed to β-adrenoceptor agon

ISSN:0028-3835    

DOI:10.1159/000125561

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The effect of aging on the release of gonadotropin-releasing hormone (GnRH) in vitro and of luteinizing hormone (LH) both in vivo and in vitro in ovariectomized (Ovx) rats was studied. Old (21–24 months) and young (3–4 months) rats were Ovx before use. They were injected subcutaneously with estradiol benzoate (25 µg/kg) or sesame oil for 3 days and then challenged with GnRH (0.5,2 or 10 µg/kg) via a jugular catheter. Blood samples were collected immediately before and at 5, 10, 20, 40 and 60 min following GnRH injection. For in vitro study, Ovx rats were decapitated. The anterior pituitary glands (APs) were incubated with GnRH (0.1 or 10 nM) and estradiol (0, 0.1, 1 or 10 nM) at 37 ¤C for 30 min. The mediobasal hypothalamus was superfused with Locke’s solution at 37 °C for 210 min, and stimulated with 60 mM KCl at 90 and 150 min. The medium samples were collected at 10-min intervals. Concentrations of GnRH and LH in plasma and medium samples were measured by radioimmunoassay. In all rats, the basal and GnRH-stimulated levels of plasma LH were lower in old than in young rats. The spontaneous release of LH in vitro from APs of Ovx rats was increased by aging, whereas GnRH-stimulated release of LH in vitro was lower in old than in young animals. The potassium-stimulated, but not spontaneous, release of GnRH was lower in old than in young Ovx rats. These results suggest that the reduction of plasma LH level in female rats during aging is in part due to a decrease in the K+-stimulated release of GnRH, and a reduction of pituitary responsiveness to GnRH and

ISSN:0028-3835    

DOI:10.1159/000125562

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The effect of corticotropin-releasing factor (CRF) on the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, the central neuronal system governing pulsatile pituitary luteinizing hormone (LH) secretion, was studied electrophysiologically in 6 ovariectomized rhesus monkeys bearing bilateral arrays of recording elecrodes implanted in the mediobasal hypothalamus. ‘Volleys’ of increased multiunit activity (MUA) were recorded for 6–10 h in animals placed in primate chairs. The circulating concentrations of LH and cortisol were determined by radioimmunoassay in blood samples taken every 10 min for 3–4 h prior to the administration of CRF (200 µg, i.v.) and for 3–6 h thereafter. CRF resulted in a significant decrease in the frequency of pulse generator activity in 4 of 6 animals, a significant decrease in the duration of MUA volleys and a rise in circulating cortisol levels in all 6 monkeys. Treatment with metyrapone (30 mg/kg, i.m.), an inhibitor of adrenal steroidogenesis that prevented the CRF-induced rise in serum cortisol levels, did not reverse the inhibitory effects of CRF on the frequency or duration of MUA volleys. The opiate antagonist naloxone (0.8 mg/kg, i.v., 10 min prior to CRF followed by 0.8 mg/kg/h infusion) blocked the effects of CRF on MUA volley frequency in 2 of 3 animals, but failed to block the effect of CRF on MUA volley duration, suggesting that endogenous opioids may mediate the action of CRF on pulse generator frequency but not o

ISSN:0028-3835    

DOI:10.1159/000125563

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Both the luteinizing-hormone-releasing hormone (LHRH) decapeptide and an LHRH fragment consisting of the last 6 amino acids of the decapeptide, Ac-LHRH5–10, have been shown to enhance lordosis behavior in ovariectomized, estradiol-benzoate treated female rats. Although the behavioral efficacy of the 2 peptides is similar, several lines of research suggest that the fragment and the decapeptide may act via different mechanisms. The present study attempted to differentiate the behavioral action of the 2 peptides by administering a long-acting LHRH antagonist analogue prior to infusion of either Ac-LHRH5–10 or LHRH. Without antagonist administration, the decapeptide and the fragment were equally effective in elevating lordotic posturing 90 min after bilateral infusion through cannulae positioned in the ventromedial nucleus of the hypothalamus (VMH). Infusion of a potent LHRH antagonist analogue [Ac-dehydro, Pro1, pCl, D-Phe2, DTrp3,6]-LHRH, into the VMH significantly reduced the lordosis-to-mount ratio in animals subsequently treated with the LHRH decapeptide, but had no significant effect on lordotic behavior when the animals were subsequently infused with the Ac-LHRH5–10 fragment. The results indicate that LHRH enhancement of mating behavior is a receptor-mediated event and suggest that the Ac-LHRH5–10 fragment enhances lordotic behavior via a mechanism that is distinct from that of the LHRH deca

ISSN:0028-3835    

DOI:10.1159/000125564

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Recent reports from several laboratories have implicated the excitatory neurotransmitter glutamate as a component in the neural regulation of sexual maturation. In the rat we have previously proposed that a hypothalamic opioid restraint mechanism may ultimately be overridden by maturation of an excitatory drive, culminating in first ovulation. We have now investigated whether glutamate may be the excitatory factor. Treatment of immature female rats with single, daily injections of two N-methyl-D-aspartate (NMDA) antagonists – dextrorphan (18 mg/kg) and MK-801 (0.1 mg/kg) – beginning on the 27th postnatal day, significantly delayed the timing of vaginal opening (VO). Interestingly, treated rats reached VO in spite of continued antagonist treatment. The antagonist effect was reversed by preinjection of NMDA, suggesting that endogenous glutamate exerts its effect via an NMDA-subtype glutamate receptor. Injection of NMDA alone (15 mg/kg; once daily) produced a striking synchronization of VO such that all treated rats showed VO over a 24-hour period compared to a normal distribution of several days for control rats. In a model of first ovulation, i.e. rats induced to ovulate by pregnant mare serum, MK-801 (1 mg/kg) arrested treated rats at proestrus. This was readily reversible after discontinuing injections. A lower dose of MK-801 (0.1 mg/kg/day) was ineffective in delaying ovulation. In a second series of experiments we studied the consequences of a neonatal hypothalamic lesion which destroys glutamate-sensitive neurons. Monosodium glutamate (MSG; 4 mg/g), injected on postnatal days 2 and 4, resulted in an acceleration of sexual maturation such that treated rats reached first ovulation on day 30.1 ± 0.2 compared to 34.8 ± 0.4 for control rats. The action of MSG was prevented by co-injection of MK-801. In conclusion, our data demonstrate that: (1) hypothalamic glutamate receptors represent a significant regulatory component of sexual maturation, and (2) the neurotoxin MSG probably removes an inhibitory, possibly opioid, factor which normally restrains the onset of pu

ISSN:0028-3835    

DOI:10.1159/000125565

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

In the aged rat, the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis was found to be increased. In fact, the plasma corticosterone concentrations in the aged (25 months) Sprague-Dawley rat were higher than in the young (3 months) Sprague-Dawley rat. To determine which component of the HPA axis principally contributes to this hyperactivity, an in vitro approach was applied. Neither the adrenal nor the pituitary revealed any age-induced modification in their basal or hormone-stimulated in vitro activity. Moreover, the ability of corticosterone to inhibit the in vitro stimulated pituitary adrenocorticotropic hormone release was preserved in aged rats. On the contrary, the in vitro hypothalamic activity was altered in aged rats. The basal and stimulated release of bioactive corticotropin-releasing factor were increased in aged rats. The results obtained in this study indicate that the hypercorticosteronemia of the aged Sprague-Dawley rat is associated with hypothalamic hyperactivity and with normal in vitro activity and reactivity of the adrenal and pituitary.

ISSN:0028-3835    

DOI:10.1159/000125566

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

N-methyl aspartic acid (NMA) was without effect on the pituitary growth hormone (GH) secretion of adult and neonatal rats in vitro. Administration of NMA resulted in a rapid rise of plasma GH levels in intact but not in arcuate-nucleus-lesioned adult rats, indicating that NMA stimulated GH-releasing hormone (GRH) secretion. In 2-day-old rats, both NMA and γ-aminobutyric acid (GABA) elevated plasma GH levels in a dose-related fashion; GRH administration was without effect. The elevation of plasma GH levels after NMA injection was reduced by administering an antibody to GRH. These results indicate that GH secretion is partly regulated by endogenous GRH in the newborn rat but that the elevation of plasma GH levels after GABA is not mediated by GRH. The high plasma GH levels seen in the newborn rat may result from the independent action of GABA and GRH but the effect of other factors cannot be excluded either

ISSN:0028-3835    

DOI:10.1159/000125567

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The effect of Al cell group electrical stimulation on the simultaneous release of endogenous noradrenaline (NA) and γ-aminobutyric acid (GABA) from the medial preoptic area (MPOA) was monitored with microdialysis. In ovariectomised (OVX) rats a 15-min period of Al stimulation induced an immediate increase in both NA and GABA release in the MPOA. Electrical stimulation lateral to the A1 region did not alter NA or GABA release. The addition of the α-adrenergic antagonist phenoxybenzamine to the perfusion medium resulted in a significant increase in basal NA levels, and electrical stimulation during this period further increased NA release while GABA levels were not significantly altered throughout. The effect of oestrogen on this pathway was examined in animals at a time of oestrogen-negative feedback on luteinising hormone (LH) secretion (OVX-EBn) and prior to the expected oestrogen-induced LH surge (OVX-EBp). Activation of Al neurones in OVX-EBn rats resulted in NA and GABA increases in the MPOA similar to that observed with OVX rats. In OVX-EBp animals, basal GABA levels were found to be significantly higher compared with OVX rats but NA release induced by Al stimulation had no effect on GABA levels. Depolarisation of the MPOA by increasing the potassium ion concentration of the perfusion medium evoked significantly greater GABA release from OVX-EBp rats compared with the OVX and OVX-EBn animals. Potassium-stimulated NA release was not significantly altered by oestrogen administration. These results demonstrate an excitatory α-adrenergic mediated noradrenergic input to GABA neurones in the MPOA. We provide evidence for oestrogen modulation of this pathway at the time of the LH surge and suggest that GABA neurones in the MPOA may mediate some of the known effects of NA on LH secreti

ISSN:0028-3835    

DOI:10.1159/000125568

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Previous studies have demonstrated that the adrenocorticotropic hormone (ACTH) and its 4–10 fragment are potent modulators of attention in humans. In these studies the Nd component (‘negative displacement’) of the stimulus-evoked brain potential (event-related potential, ERP), which is a neurophysiological indicator of selective attention, proved most sensitive to effects of these peptides. The Nd decreased in amplitude linearly with logarithmically increasing doses of ACTH 4–10 applied. Here we report results complementing these previous findings by establishing a time course of the effects of ACTH 4–10 on human attention. In a double-blind cross-over study, attention performance on a dichotic listening task was tested in 18 healthy volunteers, after having received intravenously either placebo or 1 mg ACTH 4–10. Tests took place 0, 30, 90, 180, 330, 600 min, 24, 48 and 72 h after drug intake and took about 15 min. Each subject was tested on 4 of these occasions, selected according to a random schedule. During task performance ERPs to the different task stimuli were recorded. ERPs were used to determine the Nd (an indicator of controlled processing of stimuli which the subjects selectively attended to) and the mismatch negativity (MMN) reflecting automatic processing of stimulus deviance. ACTH 4–10 diminished the Nd significantly at 30 min after treatment administration. On none of the other occasions significant changes in Nd occurred. MMN was not affected by the peptide. The results indicate a short-term action of ACTH 4–10 on selective attention, which takes about 30 min to develop and does not last longer than 90 min

ISSN:0028-3835    

DOI:10.1159/000125569

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The possible involvement of histamine (HA) in the stress-induced increase in plasma renin activity (PRA) was investigated in male rats. Intracerebroventricular (ICV) infusion of histamine (HA; 3.8–60 µg) increased PRA dose-dependently, and the Kd (dissociation konstant) of HA was estimated to approximately 30 µg. ICV infusion of HA (30 µg) as well as 5 min of restraint stress increased plasma renin activity (PRA) 2- and 3-fold, respectively (p < 0.01). These effects were abolished by prior ICV infusion of the H2-receptor antagonists cimetidine (100 µg) and ranitidine (125 µg) (p < 0.01), which reduced the PRA to subbasal levels (p < 0.05). When administered alone the H2-receptor antagonists had no effect on PRA. In contrast, the H1-receptor antagonist mepyramine (100 µg) increased the basal PRA level (p < 0.01) and slightly augmented the HA- and stress-induced increase in PRA (p < 0.05). HA as well as restraint stress increased the plasma levels of dopamine, norepinephrine and epinephrine almost 2-fold (p < 0.01). The effect of the two stimuli was prevented by prior ICV infusion of mepyramine or cimetidine (p < 0.01). Pretreatment with the β-adrenergic receptor blocker propranolol (7 mg/kg i.p.) abolished the HA-induced and inhibited by 70% the stress-induced PRA increase. The results indicate that histaminergic neurons participate in the cerebral regulation of renin secretion. The H2-receptor-mediated PRA-increasing effect of HA involves activation of sympathetic nerves. In addition, HA seems to exert a minor inhibiting effect on PRA via H1-r

ISSN:0028-3835    

DOI:10.1159/000125570

出版商:S. Karger AG    

年代:1990

数据来源: Karger