摘要:

The distribution of melatonin receptors in six discrete brain areas of mature (3–4 months old) and aged (>24 months old) male rats was recorded every 4 h during a 24-hour light: dark cycle (L:D 14:10 h). I25I-melatonin was used as a melatonin receptor probe. In the mature animals, specific binding of 125I-melatonin was found in all brain areas investigated, i.e. hypothalamus, medulla pons, hippocampus, cerebellum, parietal cortex and striatum. The density of 125I-melatonin-binding sites in the hypothalamus, medulla pons and hippocampus exhibited clear diurnal rhythms with different patterns and phases. No such rhythm was evident in the cerebellum, parietal cortex and striatum. The apparent affinity of the binding sites was similar in all the brain regions and did not change at any of the times recorded. In the old male rats, the density of 125I-melatonin binding sites in the hypothalamus was only 10% of that in the mature animals at 13 h after the onset of light and was vanishingly small throughout the 24-hour period. The 24-hour mean of the binding site density in the parietal cortex, hippocampus and medulla pons was significantly lower than in mature rats with no apparent diurnal variations. The age-related decrease in the density of melatonin-binding sites was less pronounced in the cerebellum and striatum. In all brain areas tested, apart from the hypothalamus, the decrease in receptor densities was not accompanied by changes in the apparent affinity towards the ligand. Serum concentrations of melatonin measured by radioimmunoassay exhibited a significant nocturnal rise in the rats, but in the aged this rise was about one third of that in the mature animals. The results clearly indicate diurnal rhythms in 125I-melatonin binding in the hypothalamus, medulla pons and hippocampus of mature rats, vanishing in the aged animals despite persistence of rhythm in circulating melatonin. In addition, a definite age-related decline in melatonin receptors is evident, particularly in the hypothalamus and hippocampu

ISSN:0028-3835    

DOI:10.1159/000125066

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Endogenous opioid peptides (EOPs) suppress pulsatile LH release during pregnancy in the rat, but the stimulatory effect of the EOP receptor antagonist naloxone on LH pulse frequency is reduced or eliminated on day 22 of gestation [13]. Plasma progesterone (P) levels are elevated through day 20 and fall by day 22. The aim of this study was to determine whether the decline in plasma P levels underlies the loss of EOP suppression of LH pulse frequency on day 22. Rats were bled on day 20 of pregnancy while being infused with 0.9% saline (0.5 ml/h) for 3 h, or implanted with empty or P-filled silastic capsules on day 20 and bled on day 22 while being infused first with saline for 3 h and then naloxone (0.5 mg/kg/h) for 3 h. Plasma P levels in the P-capsule group did not differ significantly from day 20 values, whereas P values in the empty capsule group were markedly decreased compared to day 20 levels and to values in the P-capsule group. Plasma estradiol values did not vary significantly between the two capsule-implanted groups. Mean blood LH levels increased between day 20 and day 22 due to an increase in LH pulse frequency and a small but significant increase in LH pulse amplitude. On day 22, mean blood LH levels, pulse amplitude and pulse frequency values during the saline infusion period in the P-capsule group were less than in the empty capsule group, and did not differ from values in the day 20 group. Naloxone infusion increased mean blood LH levels and pulse amplitude in both the empty and the P-capsule groups. However, no increase in LH pulse frequency was observed in the empty capsule group in response to naloxone infusion, whereas pulse frequency during naloxone infusion in the P-capsule group increased markedly. In another study, pituitary responsiveness to LHRH was measured during saline infusion on day 22 and was greater in rats bearing empty than P-filled silastic capsules. Since the stimulatory effect of naloxone on LH pulse frequency was only seen in the P-capsule group, which had the lowest LH response to LHRH, this rules out the possibility that low pituitary responsiveness to LHRH on day 22 contributed to the reduced effectiveness of naloxone in increasing LH pulse frequency at this time. Overall, the data suggest that as P levels decline rapidly on day 22, P-dependent EOP suppression of LH pulse frequency is diminished, allowing an increase in this parameter of pulsatile LH secretion, and eliminating the stimulatory effect of naloxone on pulse frequency. In contrast, naloxone was able to stimulate LH pulse amplitude in both capsule-implanted groups, indicating that EOP suppression of pulse amplitude is not dependent on the presence of high plasma P levels and is still active at the end of gestation in the rat.

ISSN:0028-3835    

DOI:10.1159/000125067

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Catecholaminergic innervation of luteinizing hormone-releasing hormone (LHRH) and glutamic acid decarboxylase (GAD) immunoreacitve neurons in the rat medial preoptic area (MPO) was studied using electron-microscopic (EM) double-label immunostaining and combinations of single- and double-label immunostaining with acute axonal degeneration. The EM double-immunostaining experiments included double staining for either tyrosine hydroxylase (TH) and LHRH, or TH and GAD. Analysis of TH and LHRH double-immunostained material revealed synaptic connections between TH immunoreactive axons and LHRH immunopositive neurons. The TH and GAD double-staining experiments also demonstrated synaptic connections between axons immunoreactive for TH and GAD immunopositive neurons. Two days following unilateral surgical transection of the ventral and dorsal noradrenergic bundles, synaptic connections were found between degenerated boutons and GAD immunoreactive neurons in the ipsilateral MPO. However, no synapses could be observed in the same area between degenerated axons and the LHRH immunopositive neurons. Following the same operation and immunostaining for TH, a moderate number of degenerating TH immunopositive axons as well as a large number of nondegenerated TH immunoreactive boutons were observed. Double immunostaining for TH and GAD in MPO sections ipsilateral to the operation revealed synaptic connections between the degenerating TH immunopositive axons and GAD immunoreative neurons. These results suggest that there are direct synaptic connections between catecholaminergic axons and GAD and LHRH immunoreactive neurons in the medial preoptic area of the rat. Some of the connections between TH immunopositive afferents and GAD immunoreactive neurons may represent connections from noradrenergic neurons in the brain stem, while the majority of TH-GAD and TH-LHRH connections may represent innervation of GABA and LHRH neurons from local dopamine-containing cells.

ISSN:0028-3835    

DOI:10.1159/000125068

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Inhomozygous (di/di) Brattleboro rats, pro-opiomelanocortin (POMC) synthesis and processing, and the release of its products, is by definition not under the control of hypothalamic arginine vasopressin (AVP) in contrast with normal rats or heterozygote (di/ +) littermates. To explore the role of AVP on these parameters, we have compared homozygotes and heterozygotes in terms of POMC mRNA levels, pituitary content of immunoreactive (ir)-ACTH, ir-β-endor-phin (β-EP), α-melanocyte-stimulating hormone (α-MSH) and ir-N-acetyl-EP (NacEP), plasma levels of ir-ACTH and ir-β-EP, and RP-HPLC profiles of the various forms of ir-α-MSH and ir-NacEP. Homozygous rats had immeasurably low levels of hypothalamic ir-AVP, in contrast with their heterozygote littermates; hypothalamic ir-corticotropin releasing factor did not differ between strains. No difference between-strains was seen in levels of POMC mRNA; elevated levels of all pituitary peptides, except ir-ACTH, were found in di/di rats; plasma levels of both ir-ACTH and ir-β-EP were lower in di/di rats; pituitary ir-α-MSH RP-HPLC profiles were similar in both strains, but those for ir-NacEP showed a striking increase in Nacα-EP in di/di rats. We interpret these data as evidence for decreased degradation/retarded release of POMC products from the di/di anterior pituitary, for increased processing of POMC products to shorter forms in both anterior pituitary and neuro-intermediate lobe, and thus for a role of AVP in the processing of POMC, as well as POMC synthesis and ACTH/β-E

ISSN:0028-3835    

DOI:10.1159/000125069

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Loperamide is a peripheral opiate agonist able to inhibit ACTH secretion. In this work, the interactions between loperamide and two ACTH secretagogues, lysine vasopressin (LVP) and corticotropin-releasing hormone (CRH), were investigated in patients with Addison’s disease. After loperamide (16 mg orally) or placebo administration, 5 patients received LVP (0.06 IU/kg i.v. over 1 h) and 6 patients received oCRH (1 µg/kg i.v. as bolus). In all patients loperamide induced a significant fall in plasma ACTH levels. LVP increased ACTH levels after both loperamide (from 48 ± 17.3 to a peak of 95 + 21 pmol/l) and placebo (from 231 ± 59.5 to 365 ± 86.6 pmol/l): the interaction between treatments and time was not significant. CRH caused a rise in plasma ACTH after both loperamide (from 30 ± 16.6 to a peak of 108 ± 31 pmol/l) and placebo (from 98.5 ± 47 to 211 ± 61.7 pmol/l): the interaction between treatments and time was significant, and the first phase of CRH-induced ACTH secretion was significantly lower after loperamide. These data demonstrate that loperamide differently modifies the stimulatory action of LVP and CRH on ACTH secretion: namely, LVP and loperamide act in an additive manner, while CRH and loperamide interact in a non additive way. Although these findings might be explained by the involvement of different intracellular ACTH-secreting mechanisms, an influence of loperamide on some suprapituitary factors modulating the ACTH response is

ISSN:0028-3835    

DOI:10.1159/000125070

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Infusion of the three human prepro-VIP derived peptides [vasoactive intestinal peptide (VIP), peptide histidine methionine (PHM) and the newly discovered peptide histidine valine (PHV-42)] at a constant nominal rate of 5 pmol/kg/min in 6 healthy volunteers for 60 min resulted in plateau plasma levels of 56,475 and 1,052 pmol/l, respectively. Although these values were above those found in the circulation under physiological conditions, only VIP caused a significant rise of prolactin (PRL) during, and postinfusion. Circulating luteinizing hormone and cortisol concentrations remained unchanged. As peptide histidine isoleucine, the porcine equivalent of PHM, has been postulated to be a potent hypophyseal portal pituitary PRL-releasing factor in the rat, we suggest that in man, VIP is more active than either PHM or PHV-42, and is likely to be a better candidate.

ISSN:0028-3835    

DOI:10.1159/000125071

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

We had previously shown that the hypothalamo-neurohypophyseal vasopressin secreting system is suppressed in aged rats. In the present study, using aged (26 months) male Fischer 344 (F344) rats, we showed that in contrast to vasopressin, oxytocin plasma concentration and hypothalamic content were unaltered in comparison with young (2–3 months) rats; however, based on data from our past and current studies, the neurohypophyseal concentrations of both hormones were found to be decreased in aged rats. We also compared the effect of aging on the oxytocin and vasopressin in secretory functions. Superfusion technique was employed to examine oxytocin and vasopressin release from isolated neural lobes of young (2–3 months) and old (26 months) male F344 and young (2–3 months), middle-aged (12 months) and old (30 months) Sprague-Dawley (SD) rats. Aging affected basal release of oxytocin and vasopressin in a differential manner. Expressed per gland, basal release of oxytocin increased in aged rats of both strains; whereas vasopressin release decreased in SD, and did not change in F344, old rats. The vasopressin responses to electrical stimulation, 56 mM K+ and initial traumatic release were decreased in aged rats; whereas oxytocin responses were either unaltered or decreased much less. All age-related changes were more pronounced in SD than in F344 rats. Thus, while the aging process is associated with a significant impairment in the vasopressin secretory function, the oxytocin secretory function is much less affected by that process. Significant strain differences were observed in the effects of aging on oxytocin and vasopressin re

ISSN:0028-3835    

DOI:10.1159/000125072

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Effects of plasma glucose and free fatty acid (FFA) concentrations on bovine growth hormone-releasing factor (bGRF)-induced release of growth hormone (GH) were examined in ovariohysterectomized sheep. In experiment 1, the effects of an infusion of insulin (0.025 U/kg BW·h–1), glucose (40 mg/kg BW·· h–1), insulin plus glucose or saline on the subsequent effects of bGRF on plasma GH concentrations were determined. Insulin-induced hypoglycemia inhibited GRF effects on plasma GH concentrations while glucose infusion enhanced bGRF actions. Infusing a higher glucose dose (120 mg/kg BW·h–1) had no effect on GRF actions. Subsequently, infusion of FFA (0.25 g/kg/·h–1), nicotinic acid (50 mg/kg BW) or saline for 1 h prior to bGRF injection demonstrated that FFA inhibited GRF actions but FFA depletion by nicotinic acid infusion had no effect on GRF actions. Nicotinic acid (40 mg/kg BW·h–1) infused for 2 h prior to bGRF injection significantly enhanced bGRF-stimulated GH secretion. Finally, to determine whether central nervous system glucopenia produced similar effects to insulin-induced hypoglycemia, 2-deoxyglucose (500 mg) was injected into the lateral ventricle followed in 1 h by the i.v. injection of bGRF. The central glucopenia produced by 2-DG inhibited GRF-stimulated GH release. These data demonstrate that decreased peripheral or central nervous system glucose availability and exogenous administration of FFA antagonized GRF-induced release of GH. And, pharmacologic depletion of circulating FFA for at least 2 h facilitated GRF-induce

ISSN:0028-3835    

DOI:10.1159/000125073

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

To investigate the dopaminergic role in the sleep-associated changes of luteinizing hormone (LH) pulsatile pattern, 11 normal cycling women were studied in the early follicular phase (EF, days 3 and 4) of their cycles before and after the administration of metoclopramide (MCP), a dopamine receptor antagonist. Twenty-four-hour infusions of either saline (NaCl 150 mmol/l–50 ml/h) or metoclopramide (MCP, 30 µg/kg/h) were conducted in a random sequence. Pulsatile LH activities were assessed in blood samples obtained at 15-min intervals for 48 h. Sleep was electrophysiologically confirmed by EEG during night hours (23.00–07.00 h). Significant sleep-associated decreases in LH pulse frequency (p < 0.05) and mean LH serum levels (p < 0.001) with a concurrent increase in LH pulse amplitude (p < 0.01) were observed during the saline control studies. MCP infusion failed to significantly modify the LH pulsatile activity during either the wake or sleep periods. In particular, it did not prevent the changes in LH pulsatility during sleep. This observation suggests that a dopaminergic mechanism does not critically contribute to the sleep-related changes in LH pulsatile activity in women during the early follicular p

ISSN:0028-3835    

DOI:10.1159/000125074

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Thyrotropin-releasing hormone (TRH), but not histidyl-proline diketopiperazine (cyclo[His-Pro]), induced transient hyperglycemia associated with hyperglucagonemia and marked hyperinsulinemia when placed intracerebroventricularly (i.c.v.) in anesthetized rats. This TRH-induced hyperglycemia was prevented by acute adrenalectomy. However, adrenalectomy did not prevent TRH-induced hyperinsulinemia or hyperglucagonemia. In streptozotocin-induced diabetic rats, i.c.v. administration of TRH caused progressive and pronounced hyperglycemia. i.c.v. TRH-induced hyperinsulinemia was abolished by vagotomy and by systemic administration of hexamethonium or atropine. These results suggest that TRH induces hyperglycemia mediated by stimulation of the sympathetico-adrenal system and hyperinsulinemia by stimulation of the vagus nerve, and that the rapid decline of plasma glucose levels following transient hyperglycemia is due to hyperinsulinemia.

ISSN:0028-3835    

DOI:10.1159/000125075

出版商:S. Karger AG    

年代:1988

数据来源: Karger