摘要:

Abstract:The orphan receptors RZRoα, RZRβ, RORod, RZRα2, RORα3, and RORγform a subfamily within the superfamily of nuclear hormone receptors. Recently, experimental evidence that the pineal gland hormone melatonin is the natural ligand for these nuclear receptors has come to light. This discovery is rather surprising, given that most people in the field believed melatonin acts exclusively through membrane receptors. However, these new findings establish a nuclear signalling pathway for melatonin, i.e., direct ligand‐induced control of target gene transcription, which most probably mediates part of the physiological functions of the hormone. Interestingly, the very recently identified first RZR/melatonin responding gene, 5‐Iipoxygenase, is not expressed in the brain and is not involved in circadian rhythmicity, but rather acts in the periphery, mainly in myeloid cells, as one of the key enzymes of allergic and inflammatory reactions. Thus, nuclear melatonin signalling opens up a new perspective in understanding the actions of the pineal gland

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00157.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The mammalian pineal gland serves as a neuroendocrine interface to convert environmental lighting conditions into a humoral message, the nocturnally elevated synthesis of melatonin. Regulation and fine tuning of the circadian melatonin production in response to external cues requires complex interactions of transsynaptic signalling. These requirements are fulfilled by a high degree of plasticity on all levels between receptor activation and cellular response. Many receptors on pinealocytic membranes and enzymes involved in melatonin synthesis are linked to the second messenger cAMP. Cross talk between second and third messengers converges in the pineal gland—as in other tissues—eventually on a modulated activity of transcription factors. Of fundamental importance for genes involved in the transsynaptic signalling to create a circadian profile in melatonin synthesis is the cAMP‐inducible promoter element, the CRE (cAMP responsive element). Indeed, the CRE is shared by many pineal genes that are of physiological importance. Recently, the deciphering of molecular determinants regulating expression of cAMP‐inducible genes in the mammalian pineal gland, like NAT, c‐jun, or the β‐adrenergic receptor, suggests a modulation in their transcription by a dual regulatory mechanism: posttransiational activation of theearlythird messenger CREB (cAMP responsive element binding protein) stimulates, cis‐acting cAMP‐induced transcriptional upregulation of thelatethird messenger 1CER (inducible cAMP early repressor) inhibits

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00158.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Previously it has been found that rat small bowel crypt cell hyperplasia occurred several weeks after pinealectomy. To determine if this effect was longer‐lasting (because of the possible role of the pineal in bowel malignancy) the crypt cell proliferation rate was determined in rat small bowel and colon 6 months after pinealectomy, using a stathmokinetic technique. Although the hyperproliferative effect of pinealectomy was well maintained in the small bowel crypts after 6 months, the hyper proliferative effect in the colonic crypts was much less marked. There is no obvious explanation for these findings, although it is possible that regional differences in levels of gut neuropeptides or melatonin are involved. The mechanism of the effect of pinealectomy on the crypts remains unexplained—in particular, why the effect is so prolon

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00159.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:We have studied the postnatal evolution of the glial cells in the rat pineal gland after its chemical pre‐ and perinatal denervation, by the assessment of the immunocytochemical expression of three antigens characteristic of glial cells i.e., vimentin (VIM), glial fibrillary acidic protein (GFAP), and S‐100 protein. The neurotoxic agents we applied consisted of 6‐hydroxydopamine (6‐OHDA) administered during the first 5 postnatal days, and N‐(2‐chloroethyl)‐N‐ethyl‐2‐bro‐mobenzylamine (DSP‐4) injected to pregnant rats in the 15th gestational day. VIM immunoreactivity was detected in pineal glial cells from the first postnatal day, both in denervated and control groups. However, in denervated glands, the maturation process of the glial cells is considerably accelerated, since they appear completely detached of the connective tissue septa at day 15. From day 30, the number of VIM‐positive structures progressively increases until adulthood, when a large number of immunoreactive cell processes produces a reticular appearance to the denervated pineal gland. The first GFAP and S‐100 protein immunoreactive cells were observed earlier in denervated animals (5th postnatal day for S‐100 protein, and 10th postnatal day for GFAP) compared with controls. In the experimentally denervated groups, the population of positive cells, as well as their size and the number of their cell processes, is considerably higher and progressively increased. They were always characteristically located in the proximal half of the gland. From day 45, this region of the gland shows a notable amount of hypertrophic positive cells with thick processes, showing a gliotic aspect. This increase in the immunoreactive structures to the glial antigens we applied, and the acceleration of their expression in denervated animals, are interpreted as a functional reaction of the glial component of the gland that would enhance the synthesis and liberation of neurotrophic factors (such as nerve growth factor) to adapt to this particular experimental cond

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00160.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:With some exceptions, in most of the mammals the pituitary pars tuber‐alis and the hypothalamic suprachiasmatic nuclei are reportedly the main targets for the pineal hormone melatonin. However, it is not known if the conspicuous diversity in the distribution pattern of melatonin binding sites in these areas depicts differences in reproductive behavior observed in the seasonally breeding species in the temperate zones. We explored the distribution and the characteristics of melatonin binding sites in the hypothalamus and pituitary of three species (bovine, horse, and donkey) different in terms of seasonal reproductive competence. The topographical localization, investigated by in vitro autoradiography, revealed 2‐[125I]iodomelatonin binding sites only in the pituitary gland in all three species, primarily in the pars tuberalis (PT), but also in the pars distalis (PD) and pars intermedia (PI). Kinetic, inhibition, and saturation studies, performed by means of in vitro binding, revealed presence of a single class high affinity binding sites. The Kdvalues, melatonin, and 2‐iodomelatonin Kjvalues were in the low picomo‐lar range. Coincubation with GTP7S inhibited 2‐[125I]iodomelatonin binding, demonstrating that these putative receptors are linked to a G protein in their signal‐transduction pathway. The hypothalamus was devoid of specific binding. In conclusion, the results suggest that in these species, the hypophysis may be a principal target for the melatonin action on the reproduc

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00161.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The activities of the enzymes N‐acetyltransferase (NAT) and hydroxyin‐dole‐O‐methyltransferase (HIOMT) and the hormone melatonin were studied in the optic lobe of the subadult giant tiger shrimpPenaeus monodon. Compared with the level in other species, a relatively high level of NAT activity that was temperature‐ and pH‐dependent were observed. The NAT enzyme had a relatively high maximum velocity (Vmax, 100 pmol/hr/μg protein) and low Michaelis constant (Km, 22 μM), when tryptamine is used as substrate. In contrast to the high level of NAT activity, HIOMT activity and melatonin levels were low in the optic lobe of the giant tiger shrimp. Sex differences in the levels of NAT activity and melatonin, which are observed in a freshwater speciesMacrobrachium rosenber‐gii, were not noticeable in the saltwater speciesP. monodon, at least not when they were in their

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00162.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Singlet oxygen (O2[1Δg]) is a very reactive molecule that can be produced by living cells and may contribute to cytotoxicity. The pineal hormone melatonin has been reported to possess potent antioxidant activity, and to be capable of scavenging O2(1Δg). We investigated whether melatonin might reduce the neurotoxic action of O2(lΔg). The cytotoxic effect of singlet oxygen was studied in primary cultures of cerebellar granule neurons pretreated with a photosensitive dye, rose bengal, and exposed to light—a procedure that generates O2(1Δg). We found that this procedure triggers neuronal death, which is preceded by mitochondrial impairment (assayed by the rate of the reduction of MTT, 3‐[4,5‐di‐methylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide, into formazan), and by DNA fragmentation—a marker of apoptosis. DNA fragmentation was determined in situ by terminal deoxynucleotidyl transferase assay; cell death was assayed with 0.4% trypan blue solution—viable cells with an intact membrane are not permeable to trypan blue; dead cells are, and thus, they are stained blue. Neuroprotection was obtained with the pineal hormone melatonin. In a cell‐free system, melatonin also protected the enzyme creatine kinase (EC 2.7.3.2) from the rose bengal‐induced injury. The results suggest that melatonin might counteract the cytotoxic action of singlet oxygen. Further studies are needed to clarify the exact role singlet oxygen and melatonin might play in

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00163.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY