摘要:

AbstractActivation of gonadotrophin‐releasing hormone (GnRHJ pathways is a pivotal event in the process of sexual maturation, however the regulatory influences that precipitate this change and lead to the onset of puberty remain poorly understood. Recent studies indicate that neuropeptide Y (NPY) may participate in the regulation of luteinizing hormone secretion by modulating the pattern of GnRH secretion and by directly altering the pituitary responsiveness to GnRH stimulation. To determine whether NPY plays a role in puberty‐associated changes in hypothalamic function, levels of NPY‐like immunoreactivity (NPY‐IR) were measured in a fragment of the hypothalamus encompassing the median eminence and medial portion of the arcuate nucleus (ME‐AN), and also in the remainder of the hypothalamus from male rats of different ages. To identify changes in hypothaiamic NPY linked to the process of sexual development, the effect of delaying sexual maturation by daily afternoon administration of 100 μg melatonin (MT) from 20 to 40 days was investigated. In the hypothalamus and ME‐AN, total NPY content increased progressively with age. Expressed as a concentration (fmol/μg extracted protein), peak values for the ME‐AN (55.4 ± 7.0) were observed at 30 days of age followed by a decline to lower levels (30.2 ± 1.9) at 40 days. Daily afternoon administration of MT from 20 days of age resulted in significant increases (P<0.01) in the levels of NPY‐IR in the ME‐AN compared to control values at 30 and 40 days of age. MT was without effect on NPY‐IR levels in the remainder of the hypothalamus. When MT was administered in the early morning, a procedure which does not delay sexual maturation, NPY‐IR values for the ME‐AN region were not different from control rats indicating that the MT‐induced changes in NPY were related to the effects on sexual maturation. Using pituitary luteinizing hormone content and seminal vesicle weight as indices of sexual development, significant inverse correlation coefficients (P<0.001) between these parameters and the NPY concentration in the ME‐AN were observed (r =−0.79 and −0.70, respectively). From published data it is not possible to conclude whether the main effects of NPY are exerted at the hypothalamic or pituitary level. However, the changes in the NPY content of the ME‐AN observed during the onset of puberty, and the influence of MT on these changes, support assertions that NPY is involved i

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1992.tb00337.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractWhile the pharmacology of noradrenaline effects on growth hormone (GH) secretion has been extensively studied, the precise localization of noradrenergic neurons involved remains unclear. In the present work, we investigated whether A6 noradrenergic neurons located in the locus coeruleus can play a role in the rhythmic pattern of GH secretion or in the sensitivity of the hormone response to different external challenges. Three weeks after bilateral 6‐hydroxydopamine injections (8μg/3μl) into the locus coeruleus, hypothalamic noradrenaline concentrations were reduced by 60%. Pulsatile GH secretory patterns were observed in unanaesthetized, freely moving control, sham‐operated or locus coeruleus‐lesioned male rats. The amplitude of the pulses and the area under the curves during the 6‐ or 12‐h sampling period were twice as high in locus coeruleus‐lesioned than in control and sham‐operated rats. In contrast, trough levels of GH and intervals between GH peaks were similar in all groups. Prolactin, adrenocorticotrophin, thyroid‐stimulating hormone and luteinizing hormone plasma levels were not affected by the lesion. GH responses to two centrally acting drugs i.e. clonidine (2.5, 5 and 10μg/100g body wt) and morphine (200μg/100g body wt) were also highly amplified in locus coeruleus‐lesioned rats. In contrast, GH responses to two peptides directly acting on somatotrophs i.e. GH‐releasing factor (0.05 and 1.25μg/100g body wt) and vasoactive intestinal peptide (1.5μg/100g body wt) were the same in sham‐operated and lesioned animals.These data suggest that noradrenergic inputs from the locus coeruleus exert a selective inhibitory influence on GH secretion through ce

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1992.tb00338.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractGlucocorticoid actions in the brain, particularly in the hippocampus and the hypothalamus, are critically involved in the response of the organism to stress. The key molecules in this process are the corticosteroid receptors, which upon activation, migrate and act in the nucleus. We have investigated the effect of stress on the activated form of the cytosolic glucocorticoid receptor from the above brain areas, using anion exchange chromatography. Exposure of rats to chronic stress resulted in the disappearance of the chromatographic peak, which corresponds to the activated form (DE II) of the hormone‐receptor complex. For this phenomenon to occur, 1) the animal must be exposed to chronic, and not to acute stress, and 2) the adrenals of the animal must be intact. The disappearance of the activated form of the hormone‐receptor complex (DE II) following chronic stress is most probably due to proteolysis of the receptor molecule, since it is specifically inhibited by the protease inhibitor leupeptin. This phenomenon may represent an adaptive mechanism which helps the organism cope with a repeated stres

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1992.tb00339.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractProopiomelanocortin (POMC) gene transcription in the anterior pituitary varies during stress and glucocorticoid feedback. These changes appear to parallel alterations in peptide release. The diurnal rhythm of the hypothalamo‐pituitary‐adrenal axis also involves the periodic excursion of adrenocorticotropin (ACTH) levels in plasma, but it is not clear whether the diurnal release is accompanied by changes at the transcriptional level. In the present study, we have initially characterized the heteronuclear species of POMC (hnPOMC) RNA found in the anterior pituitary by a Northern blot analysis and subsequently used this method to quantitate relative changes in the levels of heteronuclear transcript during diurnal stimulation. Two species of RNA migrating at 6.0 kb and 4.1 kb were found in the nuclear fraction of the anterior pituitary. Successive probing by various POMC cRNAs indicated that the 6.0 kb fragment was the primary transcript and the 4.1 kb fragment corresponded to the intron A‐containing processing intermediate of POMC.The nuclear species were quantitated after acute swim stress and during the diurnal ACTH secretion. Acute swim increased plasma ACTH levels by 243% after 30 min. This was paralleled by a 214% increase in the primary transcript RNA levels. Endogenous circadian stimulation in the evening produced a smaller rise of plasma ACTH (79%), and was accompanied by a 34% increase in POMC hnRNA levels. Nuclear processing intermediate (4.1 kb) and the mRNA levels did not vary during the evening. These results suggest that the diurnal mechanism transiently increases ACTH release as well as POMC gene transcription in the anterior pituitary. Release and transcription appear to be tightly coupled during circadian activation as well as during s

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1992.tb00340.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractIn the rat, there is a marked but transient increase in hypothalamic aromatase activity during the last week of fetal life. The present study was undertaken to gain insight into the regulation of this developmental pattern. Hypothalamic fragments comprising the medial basal hypothalamus and the suprachiasmatic region (henceforth referred to as preoptic area) were explanted and cultured in serum‐free medium for 2 to 5 days. Aromatase activity was measured by the formation of3H2O, utilizing either [1ß‐3H]androstene‐dione or [1ß‐3H]testosterone as substrate. Maximal rates of activity were obtained at a saturating concentration of 0.3 μM [1ß‐3H]testosterone. Confirmation of the identity of the [3H]estradiol formed was demonstrated by recrystallization of the derivatized estradiol to constant specific activity following incubation with [1,2,6,7‐3H]testosterone. In agreement with previous reports,in vivohypothalamic aromatase activity was negligible before gestational day (GD) 16, increased strikingly by GD19 (>5.0 pmol/h/mg protein) and decreased, thereafter, to low levels at GD22 (∼1.0 pmol/h/mg protein). Medial basal hypothalamus‐preoptic area fragments explanted before GD17 failed to develop aromatase activityin vitro. If the tissue was explanted on GD17 or 18 (i.e. when the in vivo rate of activity was increasing), the enzyme activity did not continue to increase, but it was rather maintained for 2 days before decreasing in a manner that closely mimicked the decline observed in vivo. A similar, butimmediate decline was observed when the tissue was explanted on GD19 (i.e. at the time when theactivity peaksin vivo). Exposure of explants to either growth factors (insulin‐like growth factor II, epidermal growth factor, and basic or acidic fibroblast growth factor), or steroids (estradiol‐17ß, progesterone, testosterone, dihydrotestosterone and corticosterone) failed to either increase aromatase activity before the peak at GD19 or ameliorate its perinatal decline. Increase of Ca2+fluxes with the ionophore A23187 or activation of the cyclic AMP, cyclic GMP, or protein kinase C pathways were similarly ineffective, as was angiotensin II, a recently proposed stimulator of neural aromatase. In contrast, aromatase activity was suppressed 2‐ to 4‐fold by activation of the cyclic AMP pathway (with either forskolin or 8‐bromo‐cyclic AMP) or by the androgens, testosterone and dihydrotestosterone.These results suggest that: 1) the appearance of aromatase activity in the rat hypothalamus before GD17 requires the unfolding of extrahypothalamic events, 2) the increase in aromatase activity that occurs before GD19 also requires extrahypothalamic inputs and does not involve any of the known intracellular signal transduction pathways, and 3) the decline in activity observed after GD19 is regulated within the hypothalamus, and appears to be determined, at least in part, by the activation of cyclic AMP formation. A potential

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1992.tb00341.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractThe aim of this study was to investigate which characteristics of the nocturnal melatonin signal, in addition to its duration, convey photoperiodic information to the reproductive axis. To achieve control over the pattern of circulating melatonin, male Syrian hamsters held under stimulatory long daylengths (16h light:8h dark) were pinealectomized to remove the principal source of circulating endogenous hormone and then fitted with chronic subcutaneous cannulae through which programmed infusions of melatonin solution or vehicle could be delivered. Experiment 1 tested whether long intervals between successive melatonin signals impaired the photoperiodic response. Animals which received a short day‐like melatonin infusion of 10 h duration once every 24 h (T = 24) for 6 weeks underwent gonadal atrophy. When the same number of signals (42) was delivered at a frequency of once every 32 h (T = 32), they were ineffective and animals remained gonadally active. Two infusion patterns were used to determine if the loss of response to 10 h signals given at T = 32 h was a consequence of the frequency per se or the long interval between signals (22 h). In the first, a ‘chimaeric’ signal which combined a long duration i.e. short day‐like 18 h melatonin signal with a short day‐like melatonin‐free interval of 14 h (combined signal T = 32 h) was able to induce significant, but only partial, gonadal atrophy. Second, when the 22‐h interval between 10‐h melatonin signals was interrupted by a short (2 h) melatonin pulse, significant but partial gonadal regression again occurred. Moreover, the response depended upon the timing of the 2 h pulse. When this fell early in the melatonin‐free interval, leaving a large portion of it intact, it had no effect on gonadal condition. In contrast, a pulse delivered in the middle of the interval, which divided it up into two short day‐like segments of 10 h each, was partially effective in restoring a short day response. The second experiment tested whether melatonin signals delivered at a high frequency would induce a photoperiodic response. A 10 h infusion delivered once every 24 h caused gonadal atrophy. The same melatonin infusion delivered at a periodicity of 20 h (T = 20) was also very potent as a short day stimulus. However, when 10‐h signals were delivered at the higher frequencies of once every 18 or 16 h, they were less effective. Only a minority of animals exhibited gonadal atrophy and overall the group means were not significantly different from those of saline‐infused controls, but were significantly greater than those of the 24 and 20 h groups. These data demonstrate that the photoperiodic response to the melatonin signal is sensitive to the frequency at which the signal is received. However, there is no evidence for a circadian basis to this sensitivity, nor a dependence upon the relationship between the endocrine stimulus and the light‐dark cycle, insofar as signals encountered at a non‐circadian period of 20 h are very effective. Moreover, the effectiveness of signals encountered at longer periodicities can be modified by manipulation of the uninterrupted duration of the interval free of melatonin, demonstrating a role in photoperiodic time measurement for the duration of t

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1992.tb00342.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractThe distribution and development of delta sleep‐inducing peptide (DSIP) in the guinea‐pig brain were studied in 2‐ to 60‐day‐old animals by using the indirect immunofluorescence method. DSIP‐immunoreactive perikarya were observed in the olfactory bulb and tubercle, diagonal band of Broca, septum, preoptic area, anterior and lateral hypothalamus, arcuate nucleus and hippocampus. In addition to the densest innervation of the median eminence, DSIP‐immunoreactive fibres were widely localized from forebrain to mesencephalon. The field of immunoreactive fibre endings appeared to be in close association with either the blood vessels of brain, ventricles, subarachnoid space or immunolabelled perikarya. Furthermore, throughout development the topographic distribution pattern of immunolabelled neuronal elements seemed to be similar. However, a generalized increase in number, immunofluorescence intensity and varicosities of DSIP fibres was displayed with the growth. The present results provide an anatomical basis for understanding multiple actions of DSIP in the central nervous system and future research for DSIP o

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1992.tb00343.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractThere is evidence for involvement of vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in control of prolactin secretion. In fact VIP‐ and PHI‐like immunoreactivities have been demonstrated in the hypotha/amic paraventricular nucleus and at the median eminence level. Using immunohistochemistry we have compared the distribution of immunoreactive VIP and PHI in the hypothalamus of male Sprague‐Dawley rats and BS rats, a rat strain which has a deficient release of prolactin after stressful stimuli. Quantitative information was obtained by radioimmunoassay for VIP. VIP‐ and PHI‐positive cell bodies were found in the parvocellular part of the paraventricular nucleus in colchicine‐treated rats and in nerve fibres within the median eminence of untreated rats to the same extent in both strains. Furthermore, intravenous injection of VIP caused a significant increase in serum prolactin tevets in both strains. However, at the median eminence level in BS rats, the blood vessels located in the lateral aspects of the median eminence did not show the dense VIP/PHI innervation seen in Sprague‐Dawley rats. Also, a thick VIP/PHI‐positive nerve bundle present on the surface of the median eminence of Sprague‐Dawley rats could not be seen in BS rats. Radioimmunoassay analysis revealed that VIP levels in the median eminence were twice as high in Sprague‐Dawley as compared to BS rats. Taken together, these results suggest that the defect in the prolactin release mechanism present in BS rats is not confined to the paraventricular system or the pituitary, but could be due to a deficit in VIP/PHI in fibres associated with portal vessels at the me

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1992.tb00344.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractSince the gonadotropin‐releasing hormone‐associated peptide (GAP) has been reported to be capable of inhibiting prolactin release from normal lactotrophs, with the present study we have examined thein vitroeffects of GAP on prolactin release in an estrone‐induced, dopamine‐sensitive rat pituitary adenoma and two malignant, transplantable and dopamine‐resistant rat pituitary tumors, 7315a and MtTW15. Enzymatically dispersed cells obtained from the three types of tumor were cultured in multiwell dishes for 4 days. On the fifth day, the cells were exposed for 4 h to human GAP 1–56 or to the analog GAP 42–56 or to rat GAP 1–53, at various concentrations. In some experiments, the effect of a pretreatment of the cells for 16 h with pertussis toxin before exposure to human GAP was also evaluated. In the three tissues, rat GAP was able to inhibit prolactin release in a dose‐dependent manner. Human GAP 1–56 and GAP 42–56 were able to inhibit prolactin release in a dose‐dependent manner in all cells except those of the MtTW15 tumor. Furthermore, in adenomatous cells, the inhibitory effects of these peptides were suppressed by pretreatment of the cells with pertussis toxin. These findings indicate that GAP is capable of inhibiting prolactin release even in dopamine‐resistant pituitary tumors. This inhibition is exerted through a pertussis toxin‐sensitive G‐protein‐dependent signaling

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1992.tb00345.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractThe effect of enhancement of cholinergic tone by pyridostigmine on the growth hormone (GH) response to thyrotropin‐releasing hormone (TRH) or glucose‐induced acute hyperglycaemia was tested in six adult unanaesthetized beagle dogs. Both TRH (5μg/ kg iv) and glucose (2 g/kg orally) did not significantly alter baseline GH levels but reduced the GH response to GH‐releasing hormone (GHRH) (2 μg/kg iv), although this effect was more clear‐cut with TRH than with glucose. Pretreatment with pyridostigmine (2 mg/kg orally) counteracted the inhibitory effect of hyperglycaemia on the GHRH‐induced GH release, but had no effect on the inhibition induced by TRH. In summary, these results indicate that: 1) acute hyperglycaemia and TRH play an inhibitory role on GHRH‐stimulated GH secretion in dogs; 2) the inhibitory effect of acute hyperglycaemia is mediated via hypothalamic cholinergic neurotransmission, whereas other neurotransmitter pathways would be. involved in the

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1992.tb00346.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY