摘要:

Both γ-aminobutyric acid (GABA) and the endogenous opioid peptides have pervasive effects on neuroendocrine function. This study examined the effects of selective activation of GABAB and/or µ-opioid receptors on neurons of the arcuate nucelus (ARC) of the rat hypothalamus using intracellular recording of cells in a hypothalamic slice. Some recorded neurons were filled with biocytin allowing subsequent identification and immunocytochemical evaluation for the presence of β-endorphin. ARC neurons exhibited a broad array of active and passive conductances. Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGOL), a µ-opioid receptor agonist, inhibited spontaneous firing, hyperpolarized 68% of ARC cells in a dose-dependent manner and increased cell conductance. Baclofen, a GABAB receptor agonist, hyperpolarized all cells tested. The reversal potentials for both the DAGOL- and baclofen-induced currents were near that of a potassium conductance. Maximal activation by either of the agonists blocked the effects of the other agonist. Identified β-endorphin cells were inhibited by both DAGOL and baclofen. The results of these in vitro studies suggest that GABAB and µ-opioid receptors are coupled to the same set of potassium channels and that these channels directly and powerfully inhibit most ARC cells, including β-endorphin neurons. We propose that convergence of inhibitory influences at the ligand-gated potassium conductance described here may be an important site of interaction for opioidergic, GABAergic and other putative neurotransmitter systems in the control of neuroendocrine circuits by t

ISSN:0028-3835    

DOI:10.1159/000125979

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The influence of naloxone on the release in limbic brain areas of both oxytocin (OXT) and vasopressin, measured by radioimmunoassay, was studied in conscious parturient rats. Three consecutive 30-min push-pull perfusions (20 µl artificial CSF/ min) were made, via previously implanted guide cannulae, within the medio-lateral septum and dorsal hippocampus of parturient animals given saline or naloxone hydrochloride (5 mg/kg body weight) after delivery of the second pup. OXT release in the hippocampus, but not in the septum, was increased during parturition, compared to day 1 post partum. During the first 30-min collection period following naloxone administration, release of OXT was significantly elevated within the septum (445% compared to saline controls, p < 0.002), but not in the dorsal hippocampus; vasopressin release was not affected. In contrast, on day 1 post partum, naloxone, administered 5 min after starting two consecutive perfusions failed to alter OXT release in septum or hippocampus in conscious rats. Naloxone, known to increase the release of OXT also from the posterior pituitary during parturition, speeded the parturition process significantly between the birth of pups 4 and 8 during push-pull perfusion of septum or hippocampus. The data suggest that endogenous opioid inhibition is involved in the regulation of central OXT release, but not vasopressin release, during parturition. Together with previous studies on OXT release from the posterior pituitary, it seems that during parturition there is coordinated endogenous opioid action on the release of OXT both into blood and into the brain

ISSN:0028-3835    

DOI:10.1159/000125958

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

This study aimed at examining the effect of thyroid hormones on cholinergic transmission in isolated rat superior cervical ganglia (SCG). In SCG explants incubated with 3H-choline, thyroxine (T4) and 3,3’,5-triiodothyronine (T3) added to the medium before a second depolarization stimulus of 60 mM K+ resulted in a dose-dependent increase of S2/S1 ratio for 3H release. The concentration of hormone that produced 50% of maximal increase in K+-induced radioactivity release was 8 × 10–9 M for T4 and 1.6 × 10–8M for T3 while 3,3’,5,5’-tetraiodothyroacetic acid was almost ineffective. Preincubation of SCG with 10–7M iopanoic acid for 30 min before S2, although not affecting by itself S2/S1 ratio, effectively prevented the increase given by T4 or T3. 3H-acetylcholine release by SCG was augmented in a high K+ and the effect was amplified by T4 to a similar extent as that for total 3H release. When added to the incubation medium together with 60 mM K+ for 30 min, T4 (10–7M) increased significantly the activity of choline acetyltransferase (ChAT). T4 did not affect ChAT activity in SCG exposed to 4.7 mM K+, nor in SCG homogenates. 3H-choline uptake measured immediately after exposure of SCG to 60 mM K+ decreased by 25%, whereas it increased by 71% after a subsequent 30-min incubation with 4.7 mM K+. Addition of 10–7M T4 prevented the changes in choline uptake observed in a high K+ medium. These results indicate that T4 increases SCG choline

ISSN:0028-3835    

DOI:10.1159/000125959

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The stimulation of TSH secretion by TRH involves the phosphatidylinositol second messenger pathway via activation of phospholipase C. This effect is mediated by a GTP-binding protein and leads to a mobilization of intracellular Ca2+ stores and an activation of protein kinase C. However, TRH stimulation also results in an influx of extracellular Ca2+. Since we have previously demonstrated that a non-TRH fragment of the prepro-TRH molecule, the connecting peptide PS4 (prepro-TRH 160–169), was able to potentiate the TRH-induced TSH release in a dose-dependent manner, we attempted to determine whether this potentiation might be due to a Ca2+-dependent phenomenon and whether a specific class of voltage-dependent Ca2+ channels, the L type Ca2+ channels, might be involved in the effect of PS4. This was studied by perifusing normal pituitary fragments with medium containing either the Ca2+ ionophore, ionomycin, and Co2+ ions, or organic compounds well known to block L-type Ca2+ channels, and by measuring the TSH response to a pulse of TRH (10 nM) in the presence or absence of PS4 (100 nM). We show that PS4 potentiation of the TRH-induced TSH release (1) was blocked by Co2+ (3 mM), a concentration which did not modify significantly the TSH response, while ionomycin potentiated that response, (2) was completely reversed by the dihydropyridine (DHP) nifedipine (10 µM) as well as by the benzothiazepine diltiazem (1 µM) and strongly reduced by the phenylalkylamine verapamil (50 µM) (at the concentrations tested only diltiazem slightly reduced the TSH response to TRH), (3) was abolished by ω-conotoxin GVIA (100 nM), and (4) was completely reversed by perifusion of pertussis toxin (100 ng/ml). Altogether these observations strongly suggest that PS4 potentiation of the TSH response to TRH is a Ca2+ -dependent phenomenon, mediated by the activation of DHP- and ω-conotoxin-sensitive Ca2+ channels of the L type. A pertussis toxin-sensitive G protein seems to be involved in this p

ISSN:0028-3835    

DOI:10.1159/000125960

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

To investigate the role of vasopressin in prolactin (PRL) release during lactation, vasopressin antiserum (VP-Ab) was administered to lactating rats, giving it intravenously 15 min before permitting their previously isolated pups to suckle or to continuously suckled rats. The suckling-induced rise in plasma PRL levels was significantly less in VP-Ab-treated mothers than in rats receiving a similar amount of normal rabbit serum (NRS). The inhibitory effect of VP-Ab could not be detected on the next day. Angiotensin II antiserum (AII-Ab) had no effect on plasma PRL response induced by suckling. VP-Ab given to continuously suckled rats reduced the high amplitude oscillation of PRL concentration observed in NRS-injected rats. A transient increase of water intake was detected on the day of VP-Ab treatment only, which provides direct evidence for at least partial neutralization of vasopressin in the circulation. These findings suggest that vasopressin released from the neural lobe of the pituitary gland is essential for the normal PRL secretory response induced by suckling and the episodic pattern of PRL release in continuously suckled mother rats. Furthermore, these results support the assumption that disturbance in the regulation of water and electrolyte balance at the level of the neuro-intermediate lobe of the pituitary gland may alter PRL secretion during lactation.

ISSN:0028-3835    

DOI:10.1159/000125961

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Estrogen affects gonadotrophin levels and sex behavior in monkeys. This action could be via inhibitory GABA-ergic neurons in the hypothalamus. We tested for direct estrogen actions on such neurons. Seven days after ovariectomy (OVX) or OVX + estrogen treatment (10 mg estradiol valerate in 1 ml sesame oil s.c. on the day of OVX), light- and electron-microscopic double immunostaining procedures were used for simultaneous visualization of immunoreactivity for progesterone receptors (PR) and glutamic acid decarboxylase (GAD), and to detect ultrastructural changes in PR-containing neurons in the arcuate and ventrome-dial hypothalamic nuclei of colchicine- and noncolchicine-treated African green monkeys (Cercopithecus aethiops). Immunoreactivity for PR was found only in cell nuclei, and estrogen treatment enhanced the intensity of the immunostaining: in estrogen-treated monkeys in the arcuate nucleus 62%, while in the ventromedial nucleus 42% of the neurons contained PR-immunoreactive nuclei. All of the PR-containing neurons were immunopositive for GAD in colchicine-pretreated monkeys. OVX induced whorl body formation, while estrogen treatment of OVX animals resulted in a large number of nematosomes. While all of the whorl bodies and the majority of nematosomes were observed in PR-immunopositive GAD neurons, nematosomes were also found in non-PR-containing GAD-immunoreactive cells.

ISSN:0028-3835    

DOI:10.1159/000125962

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

We have studied the effects of gonadectomy and testosterone supplementation on the development of the vasopressin- and oxytocin-containing nucleus (VON) of the pig hypothalamus that shows a decrease in neuron number during the first weeks postnatally, followed by an increase during puberty. Neonatal gonadectomy caused a 2.5-fold increase in VON volume and neuron number in males and 3-fold in females at the age of 16 weeks, the onset of puberty. However, the difference between gonadectomized and nongonadectomized animals disappeared after puberty (38 weeks). Testosterone replacement from 16 weeks onwards induced a decrease in neuron number and volume of the VON. The present study indicates that the development of the VON is influenced by gonadal steroids although it seems improbable that these hormones affect the VON directly.

ISSN:0028-3835    

DOI:10.1159/000125963

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Evidence suggests that endogenous opioid peptides (EOP) inhibit pulsatile luteinizing hormone (LH) secretion during both the luteal and follicular phases of the ovine estrous cycle. Further data from sheep and other species indicate that the hypothalamus is the primary site of action for this EOP inhibition. The purpose of the following experiments was to determine which areas of the hypothalamus are involved in the EOP inhibition of pulsatile LH secretion. Regularly cycling ewes (n = 10) were stereotaxically implanted with guide tubes into the preoptic area (POA) and medial basal hypothalamus (MBH). Implants containing the EOP antagonist WIN 44,441–3 (WIN) were placed into each of these areas. Blood samples were collected at 12-min intervals for 3 h before and during WIN administration in the luteal phase and for 4 h before and during WIN administration in the follicular phase of the estrous cycle. During the luteal phase, WIN implants in either area increased (p < 0.01) LH pulse frequency (POA 1.4 ± 0.3/3 h before vs. 3.1 ± 0.4/3 h during; MBH 1.1 ± 0.2/3 h before vs. 2.8 ± 0.5/3 h during). There was no effect on LH pulse amplitude. In contrast, during the follicular phase, WIN implants selectively increased (p < 0.01) LH pulse frequency when implanted in the POA (3.2 ± 0.4/4 h before vs. 5.2 ± 0.6/4 h during) while increasing (p < 0.05) only LH pulse amplitude when placed in the MBH (0.7 ± 0.2 ng/ml before vs. 1.4 ± 0.3 ng/ml during). These results suggest that although EOP act in both POA and MBH to inhibit LH secretion, different populations of EOP neurons may be activated during different phases of the estr

ISSN:0028-3835    

DOI:10.1159/000125964

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Preproenkephalin A (ppEnk) mRNA has been identified in extracts of rat pineal gland using oligonucleotides complementary to nonoverlapping regions of this mRNA. The mRNA has an apparent molecular size of 1.4 kb, equivalent to that found in rat brain. Slot-blot analysis, used to determine the relative amount of ppEnk mRNA in serveral tissues, demonstrated that the pineal contains 70% of the concentration of ppEnk mRNA found in the hypothalamus. Using a highly specific radioimmunoassay, rat pineals were demonstrated to contain approximately 3.5 pg methionine-enkephalin (Met-Enk) per gland. Following enzymatic digestion to release cryptic Met-Enk from larger molecular forms, pineals contained approximately 160 pg Met-Enk per gland. Gel filtration analysis of pineal extracts demonstrated that the peak of the cryptic Met-Enk has a molecular weight of 32 kDa (presumably proenkephalin). These results suggest that in rat pineal ppEnk gene products may contribute to pineal functioning.

ISSN:0028-3835    

DOI:10.1159/000125965

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The aim of the present experiments was to determine whether some rationale for the presence of the several inhibitory neurotransmitters in the innervation to the toad melanotroph might be found in differences in their individual effects or in possible cooperative interactions affecting secretion. Measurements of peptide release from isolated, perifused neurointemediate lobes of the toad Xenopus laevis showed that each of the three identified inhibitory transmitters, dopamine, GABA and NPY, was able to inhibit secretion profoundly and no less effectively than omission of Ca. Moreover, the inhibitory effects were rather similar in onset, duration and recovery. Furthermore, there was no evidence of any cooperative interactions when the transmitters were given in various combinations. And finally, the inhibitory response to each of the transmitters was abolished by pretreatment with pertussis toxin. While not excluding differential postsynaptic effects on other parameters of melanotroph function, the similarities observed have encouraged alternative speculations on the significance of the apparent redundancy of inhibitory transmitters.

ISSN:0028-3835    

DOI:10.1159/000125966

出版商:S. Karger AG    

年代:1991

数据来源: Karger