Subject: melatonin/iron/pineal/endocrine

query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8264970&dopt=Abstract 
   
   [_] 1: Neurosci Lett 1993 Sep 3;159(1-2):211-4 Related Articles,
   Books, LinkOut
   
          Effect of iron and estrogen on melatonin secretion by the
          chicken pineal gland.
          Pablos MI, Agapito MT, Recio JM, Perez-Gallardo L, Cordova MD,
          Mori JO
          Departamento Bioquimica, Biologia Molecular y Fisiologia,
          Facultad de Ciencias, Valladolid, Spain.
          Estrogen effects on pineal secretion of melatonin are
          controversial. Some feel that estrogen inhibits melatonin
          output in vitro but not in vivo. Melatonin levels vary with the
          age in chickens where circulating estrogen levels also vary.
          Laying hens have minimal melatonin levels and maximal serum
          iron concentrations. Thus, we reasoned that iron released by
          estrogen may inhibit melatonin secretion from the chick pineal
          gland. The present study shows that perifusion of
          estrogen-treated chick pineal glands with several
          concentrations of iron greatly inhibited melatonin secretion.
          PMID: 8264970, UI: 94088947
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Subject: melatonin


                        Melatonin - The Sleep Master
                                      
   An emerging role for this over-the-counter supplement in the treatment
                                 of autism.
                                      
                            Jaak Panksepp, Ph.D.
                       Bowling Green State University
                             Bowling Green, OH
                                      
   One of the most common and most troubling times we experience is when
   we or our children cannot fall asleep effectively. Autistic children
   appear to be especially prone to this problem, and in has been
   estimated that more than half exhibit some disturbance in sleep
   patterns. This suggests some form of deficit in the brain systems that
   normally promote sleep. During the past decade there has been great
   progress in understanding the normal brain mechanisms which sustain
   restful sleep. Since a great number of sleep promoting substances
   exist in the brain and body, any of them might be deficient in
   neurological condition we call autism. Here we will focus on one of
   the major factors, melatonin, which is presently proving to be a
   remarkably effective natural sleeping aid not only for restless
   autistic children but also their often bedraggled parents.
   
   As many parents have already discovered, this natural sleep molecule
   is presently available over-the-counter at many health food stores and
   distributors (although the ever present danger exists that
   special-interests will succeed in coaxing the FDA into taking this
   safe and effective aid off the shelves, as has already been done for
   several other important supplements, most notably tryptophan). Of
   course, as with any powerful and effective substance, there are
   certain guidelines that one should follow to maximize benefits and
   avoid problems. Although there are sound theoretical reasons for
   believing that autistic children may be manufacturing either too much
   melatonin (see Chamberlain & Herman, 1990) or too little, our own
   viewpoint has been that many kids do not secrete enough (see Panksepp,
   Lensing, Leboyer & Bouvard, 1991).
   
   Unfortunately, there presently is simply not enough good data to
   decide which viewpoint is correct. However, the fact that melatonin
   can stabilize and promote normal sleep and daily bodily rhythms is
   presently certain. However, it is important to learn how to use this
   remarkably safe and powerful substance wisely. After briefly
   summarizing how melatonin works in the brain, we will share some
   important advice in the proper use of melatonin (including when it
   should be given, how much should be given, and what to do if melatonin
   stops working, as sometimes does happen). The first thing that is
   important to know is that our brains contain a wonderful clock-like
   mechanisms that normally keeps time with about a 24 Hr. period, but
   its accuracy is controlled by many factors such as light (i.e.,..,
   day-night cycles) and various brain chemicals, especially melatonin.
   This clock-like control center is situated in two small clusters of
   neurons at the base of the brain called the suprachiasmatic nuclei
   (SCN) which, as the name implies, are situated directly above the
   optic chiasm, the place where half the nerves from each of our eyes
   cross over to the opposite halves of our brains. The many output
   pathways from the SCN control practically all behavioral rhythms that
   have been studied, from feeding to sleep. When both nuclei are
   destroyed, animals scatter their behavior haphazardly throughout the
   day instead of maintaining a well-patterned routine of daily
   activities. Our own natural melatonin secretions, which normally occur
   during the early morning hours when we have our deepest sleep,
   coordinates the accuracy of the SCN clock. People who have lost their
   sight, and hence are unable to coordinate their bodily clock via the
   influence of natural day-night cycles, are able to stabilize their
   rhythms by taking small amounts of melatonin at exactly the same time
   each day. And that is really the secret to proper melatonin use--it
   should be given only once a day in small amounts, and the proper time
   is about half an hour before one's normal sleep-time.
   
   Within our bodies, melatonin is naturally produced within the pineal
   gland, a glandular organ nestled between the cerebral hemispheres,
   that the great French philosopher Descartes once proposed to be the
   "seat of the soul." In that gland, melatonin is synthesized in two
   steps from the precursor neurotransmitter serotonin. Pineal stores of
   melatonin are typically released into the circulation when
   illumination diminishes, and may help explain why most of us sleep
   better when the lights are off. During those morning hours when
   melatonin levels begin to diminish, birds begin to sing and we also
   tend to wake up, restored, to start our daily activities. It is easy
   to understand why lack of sleep might increase behavioral and
   psychological problems during the day. In addition, melatonin does a
   remarkable number of beneficial tasks in the body: Not only is it a
   powerful inducer of sleep, but it also regulates a variety of other
   bodily processes ranging from brain maturation to the vigor of our
   immune responses. It has been found to retard the growth of some
   cancers, and quite independently of that beneficial effect, it can
   also alleviate certain forms of anxiety and depression. Most
   remarkably, given in the drinking water, it has increased life-span in
   various experimental animals by about 20%. It also helps control the
   onset of puberty during adolescence.
   
   In short, melatonin exerts many beneficial effect on the brain and
   body, but parents are well advised to follow certain guidelines in its
   use as a sleep-promoting agent:
    1. WHEN? It should be given only once a day, about half an hour
       before the regular sleep-time. Supplementing with additional
       melatonin in the middle of the night may be effective, but it is
       not a smart policy, for that can shift the biological clock in
       chaotic and undesirable ways.
       
    1. HOW MUCH? Although melatonin is very safe (people have consumed
       grams each day for many day with no ill effects), very small
       amount can go a long way. Commercially available preparations
       usually come in 2.5 or 3 milligram (mg) tablets, and a young child
       should do well on a third of this amount. The higher amounts will
       produce deeper sleep, but the hormone may still be circulating at
       quite high levels in the morning, and there are reasons to believe
       that is undesirable.
       
    1. POTENCY CHANGE? Melatonin usually does not diminish in its effects
       even with prolong use, but for unknown reasons, this is not the
       case in all individuals. If a low dose of melatonin that has been
       effective for some time seems to be losing its effect (i.e.,
       tolerance is setting in), one is wiser to stop giving the
       supplement for a while rather than increasing the dose. Some
       parents seek to restore the desired effects by increasing the
       doses, but that only seems to intensify the tolerance process. It
       is better to take a week to a month off, and then see whether
       sensitivity has returned. In our experience, sensitivity is
       usually restored in this way. Many autistic children that have
       been receiving melatonin on a regular schedule appear to exhibit
       benefits above and beyond the improvements in sleep. They are more
       "with it" during the day. These may be the side-benefits of the
       still mysterious restorative processes that sleep provides for all
       of us. Additional benefits may arise from the stabilization of
       body rhythms that may have been out of synch before the melatonin
       supplementation.
       
    1. Although we do know that melatonin and sleep have many bodily
       benefits, we do not have adequate evidence about the many "hows
       and whys." Our knowledge of such matters has not progressed much
       beyond Shakespeare's speculation that the function of sleep is "to
       knit up the raveled sleeve of care" even though modern thinkers
       are more likely to suggest that "sleep restores brain
       neurochemistries and other bodily resources that have been
       depleted by waking activities." Melatonin appears to be a prime
       guardian of such restorative processes, and without it, our lives
       become raveled indeed. It is likely that the for presently unknown
       reasons, the brains of some autistic children are deficient in
       this important chemistry. If so, early supplementation with this
       hormone may be essential for normalizing development.
       Unfortunately we know little about such matters, and only future
       research can give us the answers that we desperately need now.
       
   Chamberlain, R.S., & Herman, B.H. (1990) A novel biochemical model
   linking dysfunction in the brain melatonin, proopiomelanocortin
   peptides, and serotonin in autism. Biological Psychiatry, 1990, 28,
   773-793.
   
   Panksepp, J., Lensing, P., Leboyer, M., & Bouvard, M.P. (1991)
   Naltrexone and other potential new pharmacological treatments of
   autism. Brain Dysfunction, 4, 281-300.
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