Dr. Sebastiano
Venturi
investigator on Iodine Deficiency Disorders
and Iodine metabolism
|
-Iodine in biology |
Dr. Sebastiano Venturi C.V. |
 |
Published in Thyroid, 2000 Aug;10 (8):727-9.
ENVIRONMENTAL IODINE DEFICIENCY: A CHALLENGE TO THE EVOLUTION OF TERRESTRIAL LIFE?
Sebastiano Venturi, Francesco M. Donati, Alessandro Venturi and Mattia Venturi
Servizio di Igiene, AUSL n.1, Regione Marche. PENNABILLI (PS), Italy
KEYWORDS : antioxidant, evolution, iodide, iodine deficiency, selenium, thyroid
Iodine is the heaviest and richest in electrons among
essential elements required in the diet. Inorganic iodides are necessary
for all living vegetal and animal cells, but only the Vertebrates have
the thyroid gland and its iodinated hormones. In humans the total amount
of iodine is about 30-50 mg and less than 30 % is present in thyroid gland
and in its hormones. About 60-80 % of total iodine is non-hormonal and
it is concentrated in extrathyroidal tissues, but its biological role
is still unknown. Recently we have hypothesized that iodide might have
an ancestral antioxidant function in all iodide-concentrating cells from
primitive Algae to more recent Vertebrates (1-7). Into these cells iodide
acts as an electron donor in the presence of H2O2
and peroxidase (8), the remaining iodine readily iodinates the tyrosine
and (more slowly) the histidine or some specific lipid (9), and so, neutralizes
its own high oxidant power.
IODINE, THYROXINE AND THYROID EVOLUTION
Over three billion years ago, blue-green algae (Cyanobacteria), which
are the most primitive oxygenic photosynthetic organisms, ancestors of
multicellular eukaryotic algae, that contain the highest amount of iodine,
were the first living cells to produce oxygen, which was toxic at that
time, in the terrestrial atmosphere. So, algal cells required a protective
antioxidant action in which iodides might have had this specific role.
In fact iodides are greatly present and available in sea-waters, where
algal phytoplankton acts as a biological accumulator of iodides. Recently
our hypothesis of the ancestral antioxidant action of iodides has experimentally
been confirmed in some algae by an important study carried out by Kupper
et al.(10). Since about 700 million years ago thyroxine (T4) is
present in fibrous exoskeletal scleroproteins of the lowest invertebrates
(Porifera and Anthozoa)(11), without showing any hormonal action. When
some primitive marine vertebrates started to emerge from the iodine-rich
sea and transferred to iodine-deficient fresh water and finally land,
their diet became iodine deficient and also harboured vegetal iodide-competitors
such as nitrates, nitrites, thiocyanates and some glycosides (12). Hence
these animals needed an efficient thyroid gland as reservoir of iodine.
Therefore we believe that, during progressive slow adaptation to terrestrial
life, the primitive Chordates learned to use the primitive, but not antagonized,
T4 in order to transport antioxidant iodide into the cells. So, the remaining
triiodothyronine (T3), the real active hormone, became active in the metamorphosis
and thermogenesis for a better adaptation of the organisms to terrestrial
environment ( fresh water, atmosphere, gravity, temperature and diet ).
By the way, in a previous work (4) we reported a primitive biochemical
cooperation among thyroid cells (producing thyroid homone), C cells (producing
calcitonin), parathyroid cells (producing parathyroid hormone) and pituitary
cells (producing growth hormone), which all derived from primitive iodide-concentrating
foregut. In fact, all these hormones cooperate to strengthen antigravity
action of the skeleton. The new hormonal action of T3 was made possible
by the formation of T3- receptors in the cells of vertebrates. Firstly,
about 600-500 million years ago, in primitive Chordata appeared the alpha
T3-receptors with a metamorphosing action and then, about 250-150 million
years ago, in the Birds and Mammalia appeared the beta T3-receptors
with metabolic and thermogenetic actions. In water the iodine concentration
decreases step by step from sea-water (about 60 micrograms (mcg) per liter)
to estuary and source of rivers (less than 0.26 mcg / litre in some Triassic
mountain regions of northern Italy), and in parallel, salt-water fishes
(herring) contain about 520 mcg of iodine per Kg compared to fresh-water
trouts about 20 mcg per Kg (1). So, some iodine-deficient fresh-water
trouts (and some migratory fishes) may suffer thyroid hypertrophy (13)
or related metabolic disorders. During human embryogenesis alpha
T3-receptor genes are expressed before the beta T3-receptors. Gastric
iodide-pump, phylogenetically more primitive than the thyroidal one, has
lower affinity for iodide and does not respond to more recent TSH (Thyrotropin).
In fact, in a pregnant mouse, fetal gastric mucosa shows iodine-concentrating
ability earlier than fetal thyroid (14). On the other hand, from a biochemical
point of view, as inhibitors of lipid peroxidation, by 5’-monodeiodinase
activity (a seleno-enzyme), T4 and reverse-T3 (but not T3) became and
were found to be more effective in this antioxidant activity than vitamin
E, glutathione and ascorbic acid (15). In fact maternal T4, and not T3,
plays a crucial role in protecting fetal brain from damages caused by
hypothyroidism (16). Virgili et al. (17) reported that treatment
with thyroxine protects from peroxidative intestinal damage, induced by
zinc-deficiency in rats. Dietary iodides are able to defend brain cells
from lipid peroxidation in rats (18). The antioxidant action of iodides
has also been described in isolated rabbit eyes (19). Rieger et al.
(20), Winkler et al.(21) and Buchberger et al. (22) reported
a beneficial and antioxidant action of iodides in many cronic diseases
and in eye cataractogenesis. Researchers reported the cooperation between
antioxidant selenium and iodine. In fact selenium is present also in cellular
peroxidases and deiodinases, which are able to oxidate iodides and the
latter enzymes produce iodides from iodothyronines. Thyroid-peroxidase
is an important selenium-glutathione-enzyme which utilizes iodides in
order to transfer electrons to the oxygen of hydrogen peroxide. Thyroid
gland and marine fishes have the highest concentration of selenium and
iodine. Furthermore there is an interesting chemical gradient of electronegativity,
according to Pauling-scale units, among Oxygen (3.44), Iodine (2.66),
Selenium (2.55) and Hydrogen (2.20). This gradient might clear up the
possible role of iodides in electron tranfer.
NONTHYROIDAL IODIDE-CONCENTRATING ORGANISMS
Iodide uptake is present in Algae, plants, Porifera, Antozoa, and arthropods
without showing any hormonal or biological action. In the Mammalia several
extrathyroidal organs share the same gene expression of sodium / iodide
symporter of thyroidal iodide-pump and particularly stomach mucosa, lactating
mammary gland and salivary glands (23). Thymus, epidermis, choroid plexus
and articular, arterial and skeletal systems (24) have iodide-concentrating
ability too. But what role does iodine play in animal cells? We may chronologically
differentiate on the basis of the phylogenesis and embryogenesis three
ways of action of iodine :
1) an ancient and direct action, on endodermal fore-gut and stomach
and on ectodermal epidermis, where inorganic iodides probably act as antioxidants.
2) a recent and direct action, on fetal prehormonal thyroid and
on salivary and mammary glands, thymus, ovary and on nervous, arterial
and skeletal systems, where inorganic iodides are active.
3) a recent and indirect action of the thyroid and its iodinated
hormones, on all vertebrate cells, which makes use of specific organic
iodine-compounds: thyroxine (T4) and triiodothyronine (T3), which act
in very small quantities and utilize T3-receptors. Indeed thyroid hormones
contain less than 1 mg of iodine and less than 1/30 - 1/50 of total iodine
amount.
We believe that all these actions of iodine may still take place
into the cells of modern vertebrates (3-4, 6). In fact, Evans et al.
(25) reported that 5 mg of potassium iodide (daily injected)
acts as 0.25 micrograms of L-thyroxine in recovering the impaired functions
of many organs of thyroidectomized rats. Thyroid cells phylogenetically
derived from primitive iodide-concentrating gastroenteric cells which,
during evolution, migrated and specialized in uptake of iodides and storage
and elaboration of iodine compounds, in order to adapt to iodine-deficient
terrestrial life. The thyroid gland, with a progressively more developed
morphology, is a modern organ and its function started and was improved
from primitive Chordata to more recent marine and fresh-water fishes,
Amphibia, Reptliles, Birds and finally Mammals in which the thyroidectomy
and hypothyroidism might be considered like a sort of phylogenetical and
metabolical regression to a former stage of "reptilian life".
In fact, reptilian features seem to be restored in hypothyroid humans
such as a dry, hairless, scaly, cold skin and a general slowdown of metabolism,
digestion, heart rate, nervous reflexes with lethargic cerebration, hyperuricemia
and hypothermia. In conclusion, we believe that environmental iodine deficiency
might be an important evolutionary factor of terrestrial life. Moreover,
we should point out that extrathyroidal action of iodide might be an important
new area for investigation.
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