摘要:

Rat pineal serotonin N‐acetyltransferase (EC 2.3.1.87) activity is isolated in two molecular forms (Mr≅ 10,000 95,000) by high performance size exclusion liquid chromatography in the presence of ammonium acetate (0.1 M, pH 6.5). In the presence of sodium citrate (0.1 M, pH 6.5), however, it is eluted as a single peak of intermediate size (Mr= 30,000). A highly enriched preparation of one of the molecular forms has been obtained by a two‐step purification procedure involving disulfide‐exchange anion‐exchange chromatography. The N‐acetyltransferase in 250 pineal glands obtained from isoproterenol‐treated rats can be purified about 80‐fold in 1 day; recovery is about 3%. Polyacrylamide gel electrophoresis of the final preparation indicates that a single major b(Mr≅ 11,000) is present; this appears to be serotonin N

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1987.tb00861.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Anterior‐posterior and lateral skull roentgenograms of 1,044 children aged 0–18 yr were examined for pineal gland calcification. Eighty children with pineal calcification were identified. Cranial computed tomograms (CCT) existing for half of the 80 cases provided confirmation. In contrast to existing reports on pineal calcification in the first decade of life, we found a significant percentage of “physiological” calcification even between 0 and 6 yr of age (range 2.9–4.2%). Contrary to current opinion we were not able to detect any signs of pineal gland tumors in these cases. We were able to confirm other reports which note a steep rise of the incidence of pineal calcification during the second decad

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1987.tb00862.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Melatonin is metabolised by hydroxylation to form 6‐hydroxy‐melatonin by demethylation to form N‐acetyl‐serotonin, which are excreted as sulphate glucuronide conjugates. We required these metabolites as pure powders therefore undertook their isolation characterisation. Three volunteers ingested 1 g each of melatonin, their urine was collected pooled. For the sulphate conjugates, a Lichoprep column was used to concentrate the metabolites to remove most of the urea. The sulphate conjugates were separated from the glucuronides on a Florisil column further purified on a fractogel column. They were separated by high‐performance liquid chromatography (HPLC) resulting in white powders of 6‐hydroxy‐melatonin sulphate (SaMT) N‐acetyl‐serotonin sulphate (SNAS). For the glucuronide conjugates, an aliquot of the pooled urine was taken to dryness, the residue was dissolved in methanol, the solution was filtered. The methanol filtrate was taken to dryness, the residue was applied to a Florisil column. The isolated glucuronide conjugates were recrystallized prior to separation by HPLC, which gave pure white powders of N‐acetyl‐serotonin glucuronide (GNAS) 6‐hydroxy‐melatonin glucuronide (GaMT). Characterisation was achieved by using infrared ultraviolet spectroscopy, thin‐layer chromatography (TLC), gas chromatography‐mass spectrometry (GCMS). These techniques unambiguously confirmed the assigned structures for SaMT SNAS fully supported the assigned structures for GNAS GaMT. Three TLC solvent systems were used, in each case the individual conjugated metabolite appeared as a discreet spot. Purity, as assessed by GCMS, was shown to be greater than 95% for SNAS,

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1987.tb00863.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Pineals from male Long‐Evans rats (60–65 days old; adapted to a 0700–1900 photoperiod) were cultured for 6 h either in light (1200–1800) or in dark (1800–2400). The objective was to ascertain the effects of tryptophan (trp) phenylalanine (phe) levels ratios in the culture medium on melatonin levels in the pineals their respective media. Total culture (pineal + medium) melatonin levels, determined by RIA, were similar under all conditions. However, in cultures during the early dark phase (1800–2400) lower trp:phe ratios in the medium led to lower pineal:medium ratios of melatonin content. In cultures during the late light phase (1200–1800) the trp:phe ratio had little impact on the pineal:medium distribution of melatonin. Trp:phe ratio rather than absolute level of either amino acid appeared responsible for this effect. Functionally this means that during early dark phase, but not late light phase, movement of melatonin from cultured pineal to medium is progressively facilitated by lower trp:phe ratios. It remains to be determined to what extent darkness per se and/or endogenous pineal rhythmic mechanisms have a permissive role in the action of trp:phe ratio on pineal melatonin release. A melatonin compartmentalization/release effect of these or other amino acids, or their ratios, has not been reported previously may possibly contribute to mechanisms for melatonin's transport or rel

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1987.tb00864.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

The aim of the present study was to determine the diurnal secretion of melatonin, cortisol, prolactin, calcitonin during chronic parathyroid hormone‐dependent hypercalcemia. Eight women, aged 40–76 years, with primary hyperparathyroidism (PHPT) were studied before after surgical removal of a parathyroid adenoma. The hormone concentrations in blood were determined at 08, 12, 16, 22, 02, 04, 06 h. Concomitantly, the excretion of melatonin cortisol in urine between 07–19 h 19–07 h, the clearance of calcium creatinine were measured.Nyctohemeral serum prolactin calcitonin were unaffected by moderate parathyroid hormone‐dependent hypercalcemia. In contrast, serum cortisol melatonin were significantly higher during active disease than after surgical cure. Mean 24‐h variation of serum cortisol was 349 ± 34 nmol/liter vs. 223 ± 17 nmol/liter mean serum melatonin was 0.13 ± 0.04 nmol/liter vs. 0.06 ± 0.02 nmol/liter. Endogenous creatinine clearance was similar before after surgery, while the clearance of melatonin cortisol significantly increased after surgery, indicating an increased tubular reabsorption of both hormones during active disease. Fasting morning glucose concentrations were also significantly decreased after successful surgery, 6.1 ± 0.6 vs. 5.2 ± 0.5 mmol/liter. It is suggested that the relative hypercortisolism may be the cause of the glucose intolerance in primary hyperparathyroidism.Three to 4 months after surgical cure the serum melatonin levels were significantly lower than those seen in age‐matched controls, indicating a melatonin insufficiency in patients successfully treated for PHPT. The meaning of this finding is not yet understood but might be of importance in the development of primary

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1987.tb00865.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

The present study analyzes the participation of pineal stalk superior cervical ganglia (SCG) in the conduction of photic evoked potentials (PEP) to the pineal body (PB) in unanesthetized freely moving rats implanted with semimicroelectrodes. The PEPs were recorded in PB, lateral hypothalamus (LH), habenular complex (HC). In some rats the pineal stalk was lesioned either by electrolysis or by surgical means. Recordings were begun 3 days after electrode implantation; three recording sessions were performed before after extirpation of SCG or lesion of pineal stalk. The PEPs recorded in LH HC were characterized by 3 components (positive‐negative‐positive: PNP). The average latency of the first wave was 35.3 ± 1.7 38.8 ± 1.6 ms for LH HC, respectively. The peaks of PEPs in PB showed different polarity (NPN), the first component had a latency of 36.1 ± 1.2 ms. The PEPs persisted in all three structures after extirpation of SCG after electrolytic lesion or transection of the pineal stalk. These results show that the PEPs recorded in PB are not generated in this structure, since they persist after interrupting its connections with the rest of the central nervous system; this suggests that PEPs could be the result of electrotonic transmission from neighboring stru

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1987.tb00866.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

The effect of inhibitory cations on hydroxyindole‐O‐methyltransferase (HIOMT) was investigated in order to elucidate the mechanisms involved. Copper inhibition of HIOMT can be classified as partial, classic noncompetitive inhibition with respect to S‐adenosyl methionine and as partial, mixed noncompetitive inhibition with respect to N‐acetylserotonin. Binding of copper to the enzyme impaired but did not prevent catalysis, and the difference in inhibitory pattern observed with both substrates may be due to the obligatory order of substrate binding to HIOMT. Calcium and magnesium were uncompetitive inhibitors of HIOMT with respect to both substrates and binding of these cations to the enzyme prevents catalysis. The cations presumably bind to HIOMT in the vicinity of the catalytic site and in some way prevent or impair the catalytic process, possibly by interfering with substrate binding to the enzyme, interfering with methyl transfer or product release after catalysis, or a combination of these effects. The different inhibitory patterns observed may result from differences in molecular size or outer electron shell valence of the

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1987.tb00867.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

After reversing a 12:12‐h light‐dark regimen of environmental lighting, pineal retinal melatonin levels of white leghorn chicks recorded at the first mid‐darkness were greatly enhanced reached maximum levels after three more days; those recorded during the light periods indicate gradual decline but were far from the nadir of the original light period, even at the end of the experiment.The first mid‐darkness serum melatonin levels recorded after photoperiod reversal were not much different from their original mid‐light values. However, on continuing with the reversed regimen, the next mid‐darkness levels were sharply increased, maximum levels were reached after a further 2 days. Under the same experimental conditions light had much more drastic effects, 6 h on the reversed regimen were sufficient to bring down completely the high value of the original mid‐darkness period to the level of the starting mid‐light nadir.Retinal N‐acetylserotonin (NAS) measured simultaneously had a pattern similar to that of melatonin, but the pineal NAS rhythm did invert completely, albeit gradually.Eye covering did not prevent inversion of pineal serum melatonin rhythms, which were identical in eye‐covered sighted control chicks on the reversed regimen of light. However, retinal melatonin values of the light periods were significantly less depressed in eye‐covered than in sighted control chicks. Moreover, eye covering completely prevented the retinal NAS depression under light but did not affect pineal NAS. During darkness retinal pineal NAS elevation was sluggish in t

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1987.tb00868.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

The purpose of this study was to investigate the effect of bright artificial light exposure on the rhythms of 6‐sulphatoxy melatonin cortisol excretion in urine. Six healthy males were exposed to light (>3,000 lux) from 1900 to 0200 h (sunset 1928 h) on one occasion. The artificial light delayed the onset of 6‐sulphatoxy melatonin excretion. On the next evening the onset of 6‐sulphatoxy melatonin excretion in normal light/darkness was delayed by 1 h. The timing of the peak excretion of cortisol was not affected by the light treatment; however, cortisol excretion rate was maintained at a signficantly higher rate in the morning afternoon after the treatment. These results demonstrate the inhibitory action of high intensity light in humans suggest that one 6‐h period of extra light in the evening can phase delay the melatoni

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1987.tb00869.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Conventional antiandrogen therapy for prostatic cancer generally results in the death of androgen‐dependent cells, resulting in shrinkage of the tumor, followed by regrowth of the tumor as androgen‐insensitive cells take over. Because of reported antigonadotropic antineoplastic effects of the pineal hormone melatonin (MEL), we hypothesized that this indole might provide an effective therapy for prostate cancer, as it would be effective against both populations of tumor cells. We used three sublines of the Dunning R3327 rat prostatic adenocarcinoma to determine whether MEL could suppress the growth of these tumors and, if so, by what mechanisms this occurs. In one experiment, we compared the growth of a well‐differentiated slow‐growing Dunning tumor in rats given MEL combined with the potentiating procedure olfactory bulbectomy (BULBX), with that in rats pinealectomized (PINX) or untreated. Tumor growth in BULBX‐MEL rats was significantly suppressed over that in the other two groups, as were the weights of the gonads accessory sex glands. Tumor morphology, DNA concentration, androgen receptor concentration distribution were identical in untreated controls in BULBX‐MEL rats, suggesting that the treatment affected all populations of tumor cells equally. With another strain of well‐differentiated slow‐growing Dunning tumor, we examined the effects of MEL in rats with without BULBX. Reproductive parameters were not suppressed in BULBX‐MEL rats and, while there was a trend toward slower tumor growth in this group, this was not significant. Intact rats given MEL grew larger tumors than did control rats but, again, differences were not significant. In a third experiment, we examined a fast‐growing androgen‐insensitive anaplastic Dunning tumor. PINX was without effect on this tumor, but BULBX‐MEL resulted in a significant suppression of one of the constants in the logistic equation fitted to the growth curves. This indicates that there were some direct antitumor effects of BULBX‐MEL on this tumor strain. We conclude that MEL suppresses growth of s

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1987.tb00870.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY