摘要:

An iodine-labelled derivative of β-endorphin, 125I-Tyr27 βh-endorphin, was used in carrier-free form to study the binding of β-endorphin to brain opioid receptors. The experiments were carried out with rat cortex membranes in vitro under conditions that gave a high degree of naloxone reversible binding. βh-Endorphin and nonradioactive iodo-Tyr27 βh-endorphin were found to be identical in their ability to inhibit the binding of l25I-Tyr27 βh-endorphin. Competition experiments demonstrated the existence of binding sites with higher affinity for β-endorphin than for a variety of other opioids, including naturally occurring fragments of β-endorphin. The experiments show that 125I-Tyr27 β-endorphin possesses similar binding properties to the unmodified peptide and can be used with the advantages of iodine-125 as an isotope for the investigation of β-endorphin receptors in brain. In experiments employing 125I-Tyr27 β-endorphin 1 -27 as the radioiodinated ligand, binding curves were obtained which showed that β-endorphin 1–31 was more potent than β-endorphin 1–27 in inhibiting the binding of the labelled 27 residue peptide. With both the 27 and 31 residue radioligands, magnesium ion enhanced the specific binding whereas sodium ion and guanylyl-imidodiphosphate had a strong inhibitory effect. The data indicate that β-endorphin 1–27 binds with reduced affinity to the same receptors as β-endorphin 1–31 and like the 31 residue peptide exhibits properties charac

ISSN:0028-3835    

DOI:10.1159/000124592

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The diurnal secretion of melatonin from the pineal gland transduces information about day length to the reproductive axis of many seasonal breeders including the ewe. In the sheep the target for melatonin is thought to be neural, such that the hormone acts through the GnRH pulse generator to produce seasonal alterations in the frequency of pulsatile LH secretion. These effects on the pulse generating mechanism take approximately 50 days to become evident. It is possible that melatonin also exerts direct effects at the level of the pituitary gland to alter responsiveness to GnRH. Such effects have been noted in other species. The site of action of melatonin to regulate pulsatile LH secretion was assessed in the ewe by determining whether the animal’s endogenous melatonin acutely modifies pituitary responsiveness to sustained pulsatile administration of GnRH. Using an animal model in which endogenous GnRH was blocked, pituitary responsiveness to hourly pulses of exogenous GnRH was assessed under conditions of both high (dark period) and low (light period) melatonin. No evidence for acute effects of melatonin on pituitary response to GnRH was found. In another experiment, the amplitude and frequency of endogenously generated LH pulses in ovariectomized ewes was found not to change during the 24-hour light/dark cycle. These data lead to the conclusion that melatonin does not act at the pituitary gland to produce acute effects on LH secretion. Rather, our findings are consistant with the hypothesis that the action of melatonin, in this short-day breeder is long term, and is directed towards the neural elements of the hypothalamic pulse-generating mechanis

ISSN:0028-3835    

DOI:10.1159/000124593

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Vasoactive intestinal polypeptide (VIP) has been identified in hypothalamic tissue, is secreted into hypophysial portal blood, and stimulates prolactin (PRL) release in vivo and in vitro. It has been proposed, therefore, that VIP is a physiologic PRL-releasing factor. In this study, we confirm that VIP stimulates PRL release from rat pituitary cells in vitro, and demonstrate that an anti-VIP antiserum blocks VIP-induced PRL secretion. Surprisingly, the anti-VIP antiserum inhibited basal PRL secretion from rat pituitary cells in 3 separate experiments. Data from these experiments were pooled, as the responses were similar, revealing basal PRL release of 10.7 + 1.3 ng rPRL/105 cells (X ± SE), while anti-VIP antisera significantly inhibited release to 4.4 ±0.6 ng rPRL/105 cells (p < 0.001). PRL release in incubates containing control non-immune sera did not differ from basal release, 8.1 ng rPRL/105 cells. A further control experiment was conducted wherein cells were incubated with an anti-ACTH antiserum, representing another hyperimmune serum, which had no effect on PRL secretion. These data suggest that VIP, in addition to its possible role as a hypothalamic-derived PRL-releasing factor, may play a role within the pituitary as a regulator of basal PRL secretio

ISSN:0028-3835    

DOI:10.1159/000124594

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The development of acute insensitivity of pituitary LH secretion to LH-RH after a short exposure to LH-RH is described. In the first experiment, ovariectomized (OVX), phenobarbital-pretreated rats were given pulses of LH-RH (1.25 or 6.25 ng/100 g body weight (b.w.), intravenously). In rats given 1.25 ng at time 0,6.25 ng at 60 min, 1.25 ng at 80 min and 1.25 ng at 120 min, there was a substantial increase in plasma LH after the first two injections, no increase after the third injection and a relatively small increase after the fourth one. In other rats treated identically but not given a 1.25-ng dose at 80 min, the plasma LH rise in response to the 1.25-ng dose at 120 min was comparable to that seen after the 1.25-ng dose given at time 0. If the 1.25-ng LH-RH pulses given at times 0 and 80 min were replaced by a rat pituitary extract, the plasma LH rise in response to the 1.25-ng dose at 120 min was comparable to that seen after administration of pituitary extract. In the second experiment, OVX phenobarbital-pretreated rats were given 1.25 ng LH-RH/100 gb.w. at t = 0. They were then divided into three groups, each receiving 1.25, 3.75 or 6.25 ng LH-RH/100 g b.w. at t = 60 min. Each of these three groups was again divided into three groups which received 1.25 ng LH-RH/100 g b.w. at 80, 100 or 120 min. The response to 1.25 ng LH-RH/100 g b.w. was significantly depressed at t = 80 min in the animals that had received a dose of 3.75 or 6.25 ng LH-RH/100 gb.w. at t = 60 min. At t= 100 min a significantly decreased response was still observed in the animals which had been treated with a dose of 6.25 ng LH-RH/100 g b.w. at t = 60 min. It is concluded that, in the OVX rat, a single dose of LH-RH can induce short-term desensitization of pituitary gland LH release in response to LH-RH. The duration of this short-term desensitization is related to the dose of LH-RH that causes it. This desensitization may have physiological significance in establishing pulsatile rhythms of LH release.

ISSN:0028-3835    

DOI:10.1159/000124595

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

That growth hormone (GH) regulates its own secretion by negative feedback both directly and indirectly via somatomedins has been well-documented in the rat and assumed, on the basis of limited studies, to be true for man as well. Prior to proceeding with studies designed to investigate the nature of this feedback in various endocrine states, we sought first to confirm the existence of direct, short-latency GH feedback in normal individuals. Primed, continuous rate infusions of human GH in normal volunteers achieved a range of steady state GH levels. After 1 h of GH infusion, arginine HC1 (500 mg/kg) was infused over 30 min and the GH response assessed. Seven of 8 subjects achieved steady state GH levels in the 8–21 ng/ml range with an infusion rate of 0.0045 U/min following a 0.277 U bolus. After arginine, there was a significant increment of GH levels (range 11.6–69.5 ng/ml) in all 7 subjects. With a higher infusion rate of 0.009 U/min following a 0.54 U bolus, 1 of 2 subjects reached a steady state of 31.0 ng/ml and no response to arginine was demonstrable. Two subjects reached steady state levels of 45.0 and 58 ng/ml during a 0.018 U/min infusion after a 1.08 U bolus and had increments of 26.2 and 25.9 ng/ml following arginine. In 3 subjects achieving levels of 64.5, 107.0 and 132.0 ng/ml, there were increments of 55.0, 61.7 and 13.0 ng/ml during infusions of 0.036 U/min following boluses of 2.16 U. However, only in the first of these 3 was a true steady state achieved. Additionally, in these last 3 subjects, on a separate day, the primed continuous rate GH infusion was extended for 6 h prior to arginine infusion to try to stimulate the generation of somatomedin-C. These 3 subjects achieved steady state GH levels of 94.4 ±5.4, 108.5 ±8.5 and 125.9 ±5.8 ng/ml, and they had GH increments of 43.6, 21.8 and 7.1 ng/ml, respectively. Somatomedin-C levels did not change during the infusion. In all 14 GH infusions in which a steady state was reached, only 2 subjects did not demonstrate GH responses to arginine. In the 22 control arginine studies in these 11 subjects, 3 had absent GH responses to arginine. The numbers of absent responses in these control versus experimental conditions are not statistically different. We, therefore, were unable to detect significant blunting of the GH response to arginine and are unable to confirm previous reports of direct GH feedback

ISSN:0028-3835    

DOI:10.1159/000124599

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The effects of continuous intravenous infusion of naloxone or vehicle on the blood pressure and vasopressin responses to step-wise hemorrhage were examined in conscious, age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). Step-wise hemorrhage progressively lowered blood pressure and increased plasma vasopressin levels in both SHR and WKY. The WKY were relatively resistant to the hypotensive effect of hemorrhage. No significant differences were noted in blood pressure responses between naloxone-treated and vehicle-treated SHR while naloxone treatment attenuated hypotension only slightly in WKY. Plasma vasopressin levels were also elevated by naloxone treatment in SHR following a nonhypotensive hemorrhage equivalent to 0.5% of body weight. However, no differences were observed between plasma vasopressin levels in naloxone-treated and vehicle-treated SHR at greater degrees of hemorrhage. In addition, plasma vasopressin levels were similar at all times in hemorrhaged WKY, regardless of treatment. Plasma vasopressin levels were increased by naloxone in both time-control SHR and WKY. The data demonstrate that naloxone-sensitive systems exert only minimal effects on the immediate cardiovascular responses to hypovolemia in normotensive rats and no measurable effects in SHR. It does appear that naloxone-sensitive mechanisms contribute a small, but significant, tonic inhibitory influence over vasopressin secretion in both normotensive and hypertensive rats under basal conditions and in SHR in response to a small reduction in blood volume.

ISSN:0028-3835    

DOI:10.1159/000124600

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

We have previously shown that chelated copper stimulates the release of LHRH from explants of the median eminence area (MEA) incubated under in vitro conditions, and that this stimulation involves a ligand specific interaction. To further elucidate the mechanism of action of copper, we addressed two questions: (a) What is the divalent metal [metal(II)] specificity for this release process? (b) Is the stimulation of LHRH release by CuHis dependent on influx of extracellular calcium? MEA obtained from adult male rats were incubated for 15 min with one of the following divalent metals Cu, Ni, Fe, Zn, Cd or Mn (each complexed to histidine at an equimolar ratio; 100 µM) and then in the absence of metal for an additional period of 30 min. We found that CuHis and to a lesser extent NiHis stimulated LHRH release, and that FeHis, ZnHis, CdHis or MnHis did not do so. In addition, MEA were incubated for 15 min with CuHis in the presence or absence of CaCl2. Under these two conditions, the temporal pattern and magnitude of CuHis-stimulated LHRH release were identical, indicating that extracellular calcium is not required for copper action. Since, in this series of metals, Cu2+ and Ni2+ are the most potent oxidizing agents, our finding strongly supports our previous proposition that an oxidation reaction is involved in the process of copper stimulation of LHRH release. It has yet to be elucidated whether copper action is totally independent of an increase in intracellular calcium or whether copper leads to LHRH release via mobilization of calcium from intracellular stores

ISSN:0028-3835    

DOI:10.1159/000124601

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

To throw light onto the mechanism(s) by which the cholinergic system influences growth hormone (GH) release, the effects of two muscarinic receptor blockers, pirenzepine and atropine, and of an acetylcholinesterase inhibitor, pyridostigmine bromide, on the GH response to GHRH-44 were studied in 19 normal volunteers. Moreover, the effects of pirenzepine administration on plasma GH levels both in basal conditions and after stimulation by GHRH-44 and TRH were studied in 9 acromegalics. Both pirenzepine (0.6 mg/kg i.v., 5 min before GHRH) and atropine (1 mg i.m., 15 min before GHRH) blunted the GH response to GHRH (1 µg/kg i.v. bolus) (area under the response curve, AUC: 81.3 ± 17.3 vs. 481.2 + 211.3 ng/ml/h for pirenzepine and 100.2 ± 27.0 vs. 364.7 + 81.0 ng/ml/h for atropine; p < 0.01). Pyridostigmine (120 mg orally, 30 min before GHRH) induced a variable but significant (p < 0.02) rise in basal plasma GH levels and, furthermore, an unequivocal potentiation of the GH response to GHRH (AUC: 1044.6 + 245.3 vs. 481.2 + 211.3 ng/ml/h; p

ISSN:0028-3835    

DOI:10.1159/000124602

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The effects of the dopamine (DA) receptor antagonist metoclopramide on the plasma thyroid stimulating hormone (TSH) and prolactin (PRL) levels were studied in 8 patients with subclinical hypothyroidism (defined as absence of clinical signs of hypothyroidism with normal thyroid hormone levels, normal or slightly increased basal plasma TSH levels and increased and long-lasting TSH response to TRH) before and after l-thyroxine replacement therapy. Metoclopramide induced a significant (p < 0.01) TSH release in the subclinical hypothyroid patients. Two weeks after l-thyroxine replacement therapy (50 µg/day), the TSH response to metoclopramide was completely blunted in subclinical hypothyroidism. In these patients a significant (p < 0.01) inhibition of TSH response to intravenous thyrotropin-releasing hormone (TRH) was also observed after treatment with thyroid hormone. In analogy to the TSH behavior, plasma PRL secretion in response to metoclopramide and TRH administration was significantly (p < 0.05) inhibited in the subclinical hypothyroid patients after l-thyroxine replacement therapy

ISSN:0028-3835    

DOI:10.1159/000124603

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The purpose of these studies was to determine the effect of suckling on the plasma oxytocin (OT) concentration profile in conscious primiparous rats during midlactation. Comparisons were made with plasma prolactin (PRL) levels obtained in the same rats. OT levels in the majority of rats exhibited a single peak during the first 5–30 min, then fell rapidly during the course of a 45-min period of suckling. The plasma OT levels were sustained over a longer period in mothers suckling 8 rather than 6 pups; the amplitudes of the OT response were similar, however. By contrast, plasma PRL profiles indicated that a steady secretion of the hormone occurred throughout the suckling period, with suckling of 8 pups resulting in significantly higher plasma levels than suckling of 6 pups. A considerably greater increase in the peak plasma OT concentration resulted when hungry foster litters of 6 pups were suckled after the mothers’ own 6 pups had been suckled. Plasma PRL levels during the two sucklings, though, were similar. The rapid onset of the OT response to suckling was seen more clearly in urethane-anesthetized rats following mammary nerve stimulation. Plasma OT levels rose to a peak within 5 s after the onset, then fell to prestimulus levels by the end of the 65-second stimulation period. These results suggest that different regulating mechanisms are involved in the secretory responses of OT and PRL to suckling and that different thresholds of activation are likely to exist for the two hormo

ISSN:0028-3835    

DOI:10.1159/000124604

出版商:S. Karger AG    

年代:1986

数据来源: Karger