|
Protein tyrosine phosphorylation influences
adhesive junction assembly and follicular organization of
cultured thyroid epithelial cells
Yap A.S.; Stevenson B.R.; Cooper V.; Manley S.W.
Dr. A.S. Yap, Dept. of Physiology and Pharmacology,
University of Queensland, St. Lucia, Brisbane, QLD 4072
Australia
Endocrinology (USA), 1997, 138/6 (2315-2324)
The follicular histoarchitecture of the thyroid forms the
anatomical basis for thyroid physiology and is commonly
disturbed in diseases of the thyroid. We have used cultured
porcine thyroid cells to study thyroid epithelial
morphogenesis and its regulation. When cultured in the
presence of TSH, freshly isolated thyroid cells reorganize to
form follicles within three-dimensional cell aggregates.
However, when established follicles are washed into TSH-free
medium, thyroid cells spread and migrate to convert follicles
into confluent epithelioid monolayers, activating
morphogenetic mechanisms, such as cell locomotility, that may
be relevant to thyroid inflammation and tumor invasiveness.
The phenomenon of follicle to monolayer conversion, therefore,
provides an opportunity to identify morphogenetic mechanisms
that 1) must be tonically inhibited to maintain follicular
organization and 2) may contribute to pathogenetic
disturbances of follicular architecture when functioning
aberrantly. In this study we found that follicle to monolayer
conversion is associated with an increase in cellular
phosphotyrosine. This was particularly evident at nascent
focal adhesions (cell-substrate adhesive junctions) and later
at cell-cell junctions. Focal adhesion assembly was
accompanied by reorganization of the actin cytoskeleton, with
the appearance of prominent stress fibers. Genistein, a potent
inhibitor of protein tyrosine kinases, inhibited the
accumulation of phosphotyrosine, focal adhesion assembly, and
follicle to monolayer conversion. We conclude that tyrosine
phosphorylation exerts an important influence on thyroid
epithelial organization in culture, at least partly mediated
through regulation of focal adhesion assembly.
An extract of soy flour influences serum
cholesterol and thyroid hormones in rats and hamsters
Balmir F.; Staack R.; Jeffrey E.; Jimenez M.D.B.; Wang L.;
Potter S.M.
S.M. Potter, Division of Nutritional Sciences, Institute of
Environmental Sciences, University of Illinois, Urbana, IL
61801 USA
Journal of Nutrition (USA), 1996, 126/12
(3046-3053)
The effects of an ethanol-acetone extract from soy flour on
serum lipids and thyroid hormones were studied in rats and
hamsters. In Study 1, male Sprague-Dawley rats were fed diets
containing protein from ethanol- acetone extracted isolated
soy protein (ISP-), nonextracted ISP (ISP), casein (casein-),
or casein to which 0.36 mg ethanol-acetone extract/g protein
was added (casein+). Rats fed either ISP-containing diet had
lower serum total cholesterol concentrations compared with
those fed either casein diet (P < 0.05). Lower serum
LDL-cholesterol concentrations were present in rats fed either
ISP-containing diet and in those fed casein+ compared with
those fed casein- (P < 0.05). Adding the extract to casein
(casein+) produced higher serum thyroxine concentration and
free thyroxine indices compared with all other groups (P <
0.05). In Study 2, male Golden Syrian hamsters were fed
experimental diets containing protein from ISP, ISP with added
ethanol-acetone extract (0.36 mg extract/g protein; ISP+),
casein-, casein+ (0.36 mg extract/g protein), or casein with
twice the level of extract (0.72 mg/g protein; casein++).
Lower serum total cholesterol and LDL (LDL + VLDL + IDL)
cholesterol concentrations were observed in hamsters fed ISP,
ISP+ or casein+ compared with those fed casein (P < 0.05).
Addition of the extract at higher levels to casein (casein++)
did not lower serum lipids relative to those fed casein-.
Serum thyroxine concentration and the free thyroxine index
were greater in both ISP groups as well as in hamsters fed
casein++ compared with those fed casein or casein+ (P <
0.05). In conclusion, both studies show that protein from
soybeans decreases serum total and LDL cholesterol while the
effects on thyroxine are different in rats and hamsters. It is
also apparent that the ethanol-acetone extract of soy flour
produces changes in serum cholesterol, particularly in the LDL
fraction in both species.
Identification of hormonogenic tyrosines in
fragment 1218-1591 of bovine thyroglobulin by mass
spectrometry. Hormonogenic acceptor Tyr-1291 and donor
Tyr-1375
Gentile F.; Ferranti P.; Mamone G.; Malorni A.; Salvatore
G.
Italy
Journal of Biological Chemistry (USA), 1997, 272/1
(639-646)
A fragment of bovine thyroglobulin encompas18-1591 was
prepared by limited proteolysis with thermolysin and
continuous-elution polyacrylamide gel electrophoresis in SDS.
The reduced and carboxymethylated peptide was digested with
endoproteinase Asp-N and fractionated by reverse- phase high
performance liquid chromatography. The fractions were analyzed
by electrospray and fast atom bombardment mass spectrometry in
combination with Edman degradation. The post-translational
modifications of all seven tyrosyl residues of the fragment
were characterized at an unprecedented level of definition.
The analysis revealed the formation of: 1) monoiodotyrosine
from tyrosine 1234; 2) monoiodotyrosine, diiodotyrosine,
triiodothyronine (T3), and tetraiodothyronine (thyroxine, T4)
from tyrosine 1291; and 3) monoiodotyrosine, diiodotyrosine,
and dehydroalanine from tyrosine 1375. Iodothyronine formation
from tyrosine 1291 accounted for 10% of total T4 of
thyroglobulin (0.30 mol of T4/mol of 660-kDa thyroglobulin),
and 8% of total T3 (0.08 mol of T3/mol of thyroglobulin). This
is the first documentation of the hormonogenic nature of
tyrosine 1291 of bovine thyroglobulin, as thyroxine formation
at a corresponding site was so far reported only in rabbit,
guinea pig, and turtle thyroglobulin. This is also the first
direct identification of tyrosine 1375 of bovine thyroglobulin
as a donor residue. It is suggested that tyrosyl residues 1291
and 1375 may support together the function of an independent
hormonogenic domain in the mid-portion of the polypeptide
chain of thyroglobulin.
Selectivity in tyrosyl iodination sites in human
thyroglobulin
Xiao S.; Dorris M.L.; Rawitch A.B.; Taurog A.
Department of Pharmacology, U. T. Southwestern Medical
Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9041
USA
Archives of Biochemistry and Biophysics (USA), 1996, 334/2
(284-294)
Previous studies indicate that when low iodine
thyroglobulin (Tg) is iodinated enzymatically with thyroid
peroxidase (TPO), the tyrosyl residues that are used for the
formation of thyroid hormone (hormonogenic sites) are selected
for early iodination. The aim of the present study was to
assess the relative importance of the substrate (Tg) and the
enzyme (TPO) in the selection of the early tyrosyl sites that
undergo iodination. For this purpose, low iodine human Tg (2.0
atoms I per 660,000 dimer) was iodinated chemically with 125I3
and enzymatically with TPO + 125I to a matched low level of
iodination (similar8 added I atoms per molecule). After
reduction and alkylation, the two Tg preparations were
digested with trypsin, and the tryptic digests were separated
by reverse-phase HPLC into 10 125I- containing pools. Each
pool was further fractionated by HPLC to provide purified
125I-peptides suitable for sequence analysis. From the
sequence information and the known amino acid sequence of Tg,
it was possible to define the location of the iodinated
tyrosyl residues. Surprisingly, almost identical results were
obtained with chemically and enzymatically iodinated Tg. Not
only were the 125I-peptide maps very similar, but all of the
recovered 125I in the purified peptides from both samples was
located in only three different tyrosyl sites, 5, 2553, and
2520. Tyr 5 and Tyr 2553 are well-established sites of
thyroxine formation, while Tyr 2520 has previously been
proposed by us to be a donor site. Our observation that the
same hormonogenic tyrosyl sites are iodinated by chemical as
well as enzymatic iodination indicates that preferential
iodination of hormonogenic sites is dependent primarily on the
native structure of Tg. TPO plays a minor role, if any, in the
selection of early tyrosyl iodination sites in Tg. Consistent
with this conclusion was our finding that chemical iodination,
as well as enzymatic iodination, led to formation of uniformly
iodinated Tg, as determined by isopycnic centrifugation in
rubidium chloride. However, we observed a slightly higher
diiodotyrosine (DIT) content and a correspondingly lower
monoiodotyrosine content in enzym iodinated Tg, compared to
matched chemically iodinated Tg. This was not observed with
two other proteins, bovine serum albumin and trypsinogen, or
with free tyrosine, as substrates for iodination. The same
preferential formation of DIT in Tg was, however, observed
when lactoperoxidase was substituted for TPO. Preferential
formation of DIT, therefore, appears to involve interaction
between Tg and the peroxidase.
Soy protein concentrate and isolated soy protein
similarly lower blood serum cholesterol but differently affect
thyroid hormones in hamsters
Potter ez M.D.
463 Bevier Hall, 905 S. Goodwin Ave., Urbana, IL 61801
USA
Journal of Nutrition (USA), 1996, 126/8
(2007-2011)
There is a wide variation in the hypocholesterolemic
response to ingestion of soy protein in humans. One possible
explanation is that the different soy protein preparations
used contain different spectra of biologically active
components. This could affect a number of indices including
thyroid hormone status. An increased level of thyroxine has
been proposed as an underlying mechanism of the
hypocholesterolemic effect of soy protein. The objective of
this study was to determine if serum cholesterol and thyroid
hormone concentrations differed because of feeding soy protein
from different sources. Twenty-nine male weanling golden
Syrian hamsters were fed rations containing 25 g/100 g protein
from either isolated soy protein (ISP), soy protein
concentrate (SPC) or casein for 35 d. Serum total cholesterol
concentrations were lower in hamsters fed ISP and SPC compared
with those fed casein (P < 0.05). No differences in
cholesterol concentrations were observed in lipoprotein
fractions. Serum thyroxine and free thyroxine were greater
only in hamsters fed ISP than in those fed casein (P
<0.05), whereas triiodothyronine concentrations were higher
in casein-fed than in SPC-fed hamsters (P < 0.05). Results
indicate that protein from ISP and SPC are both effective in
lowering blood cholesterol concentrations, whereas only ISP
increases thyroxine concentrations. Therefore, it appears
unlikely that modulation of thyroid hormone status is
responsible for the cholesterol-lowering effect of soy
protein.
Involvement of tyrosine phosphorylation in the
regulation of 5'- deiodinases in FRTL-5 rat thyroid cells and
rat astrocytes
Mori K.; Stone S.; Braverman L.E.; DeVito W.J.
Division of Endocrinology, Massachusetts Univ. Medical
Center, 55 Lake Avenue North, Worcester, MA 01655 USA
Endocrinology (USA), 1996, 137/4 (1313-1318)
Recent studies suggest that protein tyrosine
phosphorylation may play a role in the regulation of thyroid
growth and function. In the present study, we used genistein,
a specific inhibitor of tyrosine phosphorylation, to determine
if tyrosine phosphorylation is involved in the regulation of
type 1 5'-deiodinase (5'D-I) expression in FRTL-5 cells and
type II 5'-deiodinase (5'D-II) in rat astrocytes. Incubation
of FRTL-5 cells with genistein (100 microM) for 3 days had no
effect on cell viability as assessed by trypan blue exclusion.
In TSH-deprived cells, incubation of FRTL-5 cells with
genistein (100 microM) resulted in a modest, but not
significant, decrease in 5'D-I activity. Incubation of FRTL-5
cells with TSH (100 microU/ml), Bu2cAMP (0.5 mM) or forskolin
(1 microM) resulted in marked increases in 5'D-I activity. In
the presence of genistein (106 microM), however, the TSH,
Bu2cAMP and forskolin- induced increases in 5'D-I activity
were completely inhibited. In Bu2cAMP- stimulated FRTL-5
cells, incubation with genistein (1, 10, and 100 microM)
resulted in a dose-dependent decrease in 5'D-I activity, with
100 microM genistein completely blocking the Bu2cAMP-induced
increase in 5'D-I activity. Similarly, we found that in FRTL-5
cells, genistein(100 microM) completely blocked the
Bu2cAMP-induced increase in 5'D-I messenger RNA (mRNA) levels,
DNA synthesis as assessed by (3H)thymidine incorporation, and
the T3- induced increase in 5'D-I activity. To determine if
addition of genistein to FRTL-5 cells resulted in a general
inhibition of Bu2cAMP-induce-induced increase in c-fosmRNA
levels. Bu2cAMP-induced c-fos mRNA levels were not affected by
the treatment of cells with genistein (100 microM). We then
examined the effect of genistein on the Bu2cAMP and
hydrocortisone-induced 5'D-II activity in cultured rat
astrocytes. Genistein (100 microM) had no effect on cell
viability as assessed by trypan blue exclusion. In serum
deprived astrocytes, addition of Bu2cAMP (1 mM) and
hydrocortisone (100 nM) resulted in a 110-fold increase in
5'D-II activity. Addition of genistein (100 microM) to
stimulated astrocytes completely blocked the Bu2cAMP and
hydrocortisone-induced increase in 5'D-II activity. The
present data suggest that tyrosine
phosphorylation-dephosphorylation may play animportant role in
the regulation of thyroid hormone deiodination and action in
the thyroid and brain.
Characterization of a melanosomal transport system
in murine melanocytes mediating entry of the melanogenic
substrate tyrosine
Potterf S.B.; Muller J.; Bernardini I.; Tietze F.; Kobayashi
T.; Hearing V.J.; Gahl W.A.
Heritable Disorders Branch, Sec. on Human Biochemical
Genetics, NICHD, 10 Center Dr., Bethesda, MD 20892-1830
USA
Journal of Biological Chemistry (USA), 1996, 271/8
(4002-4008)
In this study, we identify a transport system for tyrosine,
the initial precursor of melanin synthesis, in the melanosomes
of murine melanocytes. Melanosomes preloaded with tyrosine
demonstrated countertransport of 10 microM (3H)tyrosine,
indicating carrier-mediated transport. Melanosomal tyrosine
transport was saturable, wit h an apparent K(m) for tyrosine
transport of 54 microM and a maximal velocity of 5 pmol of
tyrosine/unit of hexosaminidase/min. Transport was
temperature-dependent (E(a) = 7.5 kcal/mol) and showed
stereospecificity for the L-isomer of tyrosine. Aromatic,
neutral hydrophobic compounds (such as tryptophan and
phenylalanine), as well as the small, bulky neutral amino
acids (such as leucine, isoleucine, and methionine) competed
for tyrosine transport. Tyrosine transport was inhibited by
the classical system L
analogue,2-aminobicyclo(2.2.1)heptane-2-carboxylic acid and by
monoiodotyrosine, but not by cystine, lysine, glutamic acid,
or 2- (methylamino)isobutyric acid. Tyrosine transport showed
no dependence on Na+ or B+, and did not require an acidic
environment or the availability of free thiols. These results
demonstrate the existence of a neutral amino acid carrier in
murine melanocyte melanosomes which resembles the rat thyroid
FRTL-5 lysosomal system h. This transport system is critical
to the function of the melanosome since tyrosine is the
essential substrate required for the synthesis of the pigment
melanin.
Influence of the thyroid hormone status on tyrosine
hydroxylase in central and peripheral catecholaminergic
structures
Claustre J.; Balende C.; Pujol J.F.
INSERM U 45, Hopital Edouard Herriot, 69437 Lyon Cedex 03
France
Neurochemistry International (United Kingdom), 1996, 28/3
(277-281)
We investigated the effect of hyper- and hypothyroidism on
tyrosine hydroxylase protein concentration in the locus
coeruleus (divided into anterior and posterior parts), the
substantia nigra and the adrenals of adult rats. Rats were
made hypothyroid with propylthiouracile (PTU, 0.02% in
drinking water for 21 days) or hyperthyroid by thyroxine
injection (100 or 250 pg/kg/day), for 3 or 17 days. PTU
treatment resulted in a statistically significant decrease of
tyrosine hydroxylase in the anterior locus coeruleus (-13%)
and the adrenals (-14%). After thyroxine treatment, in the
anterior locus coeruleus, tyrosine hydroxylase was
significantly higher (2 way ANOVA) after the 3 day treatment
than after the 17 day treatment: tyrosine hydroxylase showed a
trend to increase after the 3 day treatment (+20% with the 250
microg/kg dose) and to decrease after the 17 day treatment
(-15% with the 250 microg/kg dose). In the adrenals, tyrosine
hydroxylase was increased by the 3 day treatment (+42% after
the 250 microg/kg dose), but this increase was not observed
after 17 days of treatment. Tyrosine hydroxylase was not
altered in the posterior locus coeruleus and the substantia
nigra, whatever the treatment. Together, our results support
the hypothesis that in the anterior locus coeruleus and in the
adrenals tyrosine hydroxylase level is positively modulated by
thyroid hormones. After long-term treatment (17 days) this
effect is not observed.
Soy protein, thyroid regulation and cholesterol
metabolism
Forsythe W.A. III
School of Home Economics, University of Southern Mississippi,
Hattiesburg, MS 39406 USA
Journal of Nutrition (USA), 1995, 125/3 Suppl.
(619S-623S)
The effects of dietary protein on plasma cholesterol
concentrations are well documented: animal proteins (casein)
are hypercholesterolemic compared with plant proteins (soy
protein). Although this effect of protein source on plasma
cholesterol has been shown in many species, the mechanism is
not completely understood. This paper reviews the relationship
between dietary protein source and plasma thyroxine
concentration. The basic premise is that feeding soy protein
lowers plasma cholesterol concentration by causing an increase
in plasma thyroxine concentrations. The metabolic changes
involving cholesterol that occur when soy protein is fed are
discussed. These changes are consistent with changes induced
by elevating thyroxine. Data are presented from animal studies
showing that feeding soy protein to laboratory animals
consistently elevates plasma thyroxine concentrations.
Furthermore, this elevation in plasma thyroxine concentrations
precedes the change in plasma cholesterol concentrations: a
necessary requirement for hypothesizing a causative effect.
Possible mechanisms as to how a dietary protein source affects
plasma thyroxine are also presented.
Comparative pharmacology of the thyroid
hormones
Sypniewski E.
Department of Pharmacy, Medical College of Virginia, Virginia
Commonwealth University, Box 553, MCV Station, Richmond, VA
23298 US
Ann. Thorac. Surg. (USA), 1993, 56/1 Suppl.
(S2-S8)
The thyroid hormones tetraiodothyronine and
triiodothyronine (T3) are involved in a variety of biologic
mechanisms. Thyroid hormones regulate protein, lipid, and
carbohydrate anabolism and improve oxygen consumption in
almost all body tissues. Thyroid hormone is formed by coupling
of iodinated tyrosine molecules in the thyroid gland.
Tetraiodothyronine is converted to T3, the active thyroid
hormone. Drugs, disease states that induce severe physiologic
stress, and surgical conditions (eg, cardiopulmonary bypass)
can alter the levels of circulating active hormone by
interfering with the peripheral conversion of
tetraiodothyronine to T3/ This low T3 ('euthyroid sick
syndrome') state is manifested by low circulating levels of T3
and hemodynamic abnormalities. Active thyroid hormone
replacement with T3, because of its pharmacologic actions, may
be an ideal therapy in these conditions.
Primary hypothyroidism in an adult patient with
protein-calorie malnutrition: A study of its mechanism and the
effect of amino acid deficiency
Tahara Y.; Hirota M.; Shima K.; Kozu S.; Ikegami H.; Tanaka
A.; Kumahara Y.; Amino N.; Hayashizaki S.; Miyai K.
Department of Medicine and Geriatrics, Osaka University
Medical School, Osaka 553 Japan
Metab. Clin. Exp. (USA), 1988, 37/1 (9-14)
A man with diabetes mellitus, chronic hepatitis, chronic
pancreatitis, and blind loop syndrome but without any previous
thyroid disease developed three episodes of transient primary
hypothyroidism associated with protein-calorie malnutrition
(PCM). Clinical examinations sugested that this primary
hypothyroidism was not caused by chronic thyroiditis, iodine
deficiency, or iodine excess. Since the three times
association of primary hypothyroidism with PCM suggested the
possibility that the primary hypothyroidism was caused by PCM,
we have tried to clarify its mechanism. For this purpose we
have investigated the change of thyroid functions during
protein-calorie repletion and the effect of amino acid
deficiency. Total parenteral nutrition with full
supplementation of amino acids resulted in a rapid increase in
serum thyroxine (T4), triiodothyronine (T3), free T4, and
reverse T3, and subsequently, a rapid decrease in TSH in
several days after the nutrition was begun. When amino acid
solution was changed to that depleted of phenylalanine and
tyrosine after the restoration of thyroid functions, serum T4
and T3 showed a gradual decrease, but serum free T4 and TSH
remained within normal range. However, resupplementation of
phenylalanine and tyrosine after 8 weeks of depletion gave a
rapid increase in serum T4, T3, free T4, and reverse T3. These
results suggested that the primary hypothyroidism was caused
by an impaired T4 production and that the deficiency of amino
acids in PCM partly contributed to the impairment of T4
production.
Preferential formation of triiodothyronine residues
in newly synthesized (14C)tyrosine-labeled thyroglobulin
molecules in follicles reconstructed in a suspension culture
of hog thyroid cells
Sho K.; Hayashi H.; Ohmiya Y.; Kondo Y.
Department of Physical Biochemistry, Institute of
Endocrinology, Gunma University, Maebashi 371 Japan
Mol. Cell. Endocrinol. (Ireland), 1988, 59/1-2
(117-124)
Early processes of thyroid hormone (T4 and T3) synthesis in
thyroglobulin molecules were studied using follicles
reconstructed in a primary culture of hog thyroid cells under
the influence of TSH. When the reconstructed follicles were
incubated with 14C-tyrosine, thyroglobulin containing the
labeled tyrosine was newly synthesized and in the presence of
iodide, some of the labeled tyrosine residues were iodinated
and coupled to produce labeled iodothyronines, T4 and T3.
Coupling efficiency, especially the efficiency of T3
production, was much higher than that obtained from the
average iodoamino acid composition of mature thyroglobulin
from the gland, indicating a preferential iodination of
hormonogenic tyrosines and synthesis of T3. The total
production of T3 was higher than T4 under the present
conditions. However, free labeled T4 released into the medium
was more than T3 after 16 h incubation of the labeled
follicles with non-labeled tyrosine, suggesting the
preferential liberation of T4 from the labeled peptide and/or
release from the cells.
Importance of the content and localization of
tyrosine residues for thyroxine formation within the
N-terminal part of human thyroglobulin den
Hartog M.T.; Sijmons C.C.; Bakker O.; Ris-Stalpers C.; De
Vijlder J.J.M.
Academic Medical Center, University of Amsterdam, Children's
Hospital, PO Box 22700, 1100 DE Amsterdam Netherland
European Journal of Endocrinology (Norway), 1995, 132/5
(611-617)
Thyroxine (T4) is formed by coupling of iodinated tyrosine
residues within thyroglobulin (TG). In mature TG, some
iodinated tyrosine residues are involved preferentially in T4
formation. In order to investigate the specific role of
various tyrosine residues in T4 formation, N-terminal TG
fragments with mutated tyrosine residues were constructed. An
N-terminal TG fragment 198 amino acids in size and containing
seven tyrosine residues at amino acid positions 5, 29, 89, 97,
107, 130 and 192 was expressed in a baculovirus system. Using
site-directed mutagenesis, eight mutant TG fragments were
constructed in which different tyrosine residues were replaced
by phenylalanine. In the first four TG mutants, one single
tyrosine residue (5, 89, 97 or 130) was mutated. In the mutant
Y(5,89,97,130)F all of these four tyrosine residues were
replaced. The sixth mutant Y(29,89,107,130,192)F contained
only tyrosine residues 5 and 97 and the seventh
(Y(29,89,97,192)F) contained only tyrosine residues 5,107 and
130. A TG fragment (Y(5,29,89,97,107,130,192)F) in which all
tyrosine residues were replaced by phenylalanine was used as a
negative control. After in vitro iodination with
lactoperoxidase, specific T4 formation was established in the
non-mutated wild-type N-terminal TG fragment. In general the
T4 formation in the mutant TG constructs decreased when the
total number of tyrosine residues in the 198 amino acid
fragment decreased, except fragment Y(29,89,97,192) containing
three tyrosine residues, two of them being 5 and 130. Although
the rate of T4 formation in this mutated N-terminal TG
fragment was lower, the ultimate T4 generation was the same as
in the wildtype fragment. This indicates that a preferential
involvement of tyrosines 5 and 130 in thyroid hormonogenesis
may exist.
Melatonin and the endocrine role of the pineal
organ
Cardinali D.P
ILAFIR, Univ. Salvador, San Miguel Argentina
Curr.Topics Exp.Endocrin. (USA), 1974, Vol. 2
(107-128)
Fourteen years have elapsed since the discovery of the
pineal hormone melatonin; since then, interest in the
physiology of the pineal has grown steadily, as has the
knowledge of the contribution of the pineal to the economy of
the body. Sufficient information is now available to encourage
acceptance of the 'melatonin hypothesis of pineal function',
put forth in 1965 by Wurtman and Exelrod. This hypothesis
holds that the mammalian pineal synthesized and secretes
melatonin at a rate inversely dependent on environmental
lighting, and receives signals concerning the lighting milieu
via a complex pathway involving the retinas the brain, and the
sympathetic neurons to and from the superior cervical ganglia.
Melatonin ultimately enters the general circulation, either by
direct secretion from the pinealocytes or indirectly via the
CSF. Melatonin acts on the brain, and perhaps directly, to
depress the rate of gonadal maturation, and to interfere with
subsequent gonadal function and cyclicity; it may also modify
the functions of the thyroid and the adrenal cortex, sice
melatonin ijnections haven been shown to inhibit thyroid
hormone secretion rate and the secretion of adrenal steroids.
It seems likely that the pineal participates, through the
secretion of melatonin, in the control of certain
neuroendocrine and neurophysiological rhythms; it may also
mediate some of the effects of light on gonadal maturation,
the ovulatory cycle, and the secretion of pituitary hormones.
This is a good review article with some 200 references.
Brief report: Circadian melatonin,
thyroid-stimulating hormone, prolactin, and cortisol levels in
serum of young adults with autism
Nir I.; Meir D.; Zilber N.; Knobler H.; Hadjez J.; Lerner
Y.
Department of Pharmacology, Hebrew Univ.-Hadassah Medical
School, P.O.Box 12065, Jerusalem 91010 Israel
Israel Journal of Autism and Developmental Disorders (USA),
1995, 25/6 (641-654)
An abnormal circadian pattern of melatonin was found in a
group of young adults with an extreme autism syndrome.
Although not out of phase, the serum melatonin levels differed
from normal in amplitude and mesor. Marginal changes in
diurnal rhythms of serum TSH and possibly prolactin were also
recorded. Subjects with seizures tended to have an abnormal
pattern of melatonin correlated with EEG changes. In others, a
parallel was evidenced between thyroid function and impairment
in verbal communication. There appears to be a tendency for
various types of neuroendocrinological abnormalities in
autistics, and melatonin, as well as possibly TSH and perhaps
prolactin, could serve as biochemical variables of the
biological parameters of the disease.
Effects of melatonin and thyroxine replacement on
thyrotropin, luteinizing hormone, and prolactin in male
hypothyroid hamsters
Vriend J.
Department of Anatomy, University of Manitoba School of
Medicine Winnipeg, Man. R3E 0W3 Canada
Endocrinology (USA), 1985, 117/6 (2402-2407)
The effects of daily evening melatonin injections on plasma
and pituitary levels of TSH, LH, and PRL in hypothyroid
hamsters maintained under a 14-h light, 10-h dark photoperiod
were investigated. Circulating levels of thyroid hormones were
monitored, and testicular weights were recorded.
Thiourea-induced increases in serum and pituitary TSH were
significantly reduced by melatonin injections. Control
hamsters, not receiving thiourea, responded to daily evening
melatonin injections with a decrease in serum Tsub 4. Serum
Tsub 3 levels were decreased by thiourea and increased by Tsub
4 replacement. The pituitary PRL content was significantly
reduced below control values in hamsters receiving melatonin
injections; the sensitivity to melatonin was inhibited by
thiourea and restored by Tsub 4 replacement. Tsub 4
replacement injections were associated with a significant
decrease in serum PRL and a significant increase in serum LH.
Melatonin-induced testicular involution was attenuated by
thiourea administration; this attenuation was reversed by Tsub
4 replacement. Similarly, a melatonin-induced decrease in
serum LH was prevented by thiourea administration and restored
by Tsub 4 replacement. The data suggest that melatonin
injections increase the sensitivity of the pituitary to Tsub
4/Tsub 3 feedback inhibition of TSH. Furthermore, these data
show that thyroid status may influence melatonin-induced
changes in release of PRL and LH from the hamster pituitary.
The data showing an interaction of thyroid hormones in the
control of testicular size are interpreted as evidence that
thyroid hormones play a major role in the mechanism regulating
gonadal cycles in the hamster.
Influence of phytogenic substances with
thyreostatic effects in combination with iodine on the thyroid
hormones and somatomedin level in pigs
Jahreis G.; Hesse V.; Plenert W.; et al.
Department of Pediatric Endocrinology, Children Hospital,
Friedrich Schiller University, DDR-6900 Jena Germany,
East
Exp. Clin. Endocrinol. (Germany, East), 1985, 85/2
(183-190)
Growing pigs were given 8% rape seed meal (RSM), which was
offered without or with different iodine-supplements and
further trace elements. RSM without I-supplementation reduced
food intake and weight gains by more than 50%, thyroid weight
increased by the factor 6, Tsub 4 declined below the
detectable limit, Tsub 3 by two thirds and somatomedin
activity by 50% compared to the control group (soy bean meal).
In spite of supplementation with iodine and further trace
elements the Tsub 3-level reached the level of the control
group in no variant due to nutrient deficiency (reduced food
intake) and the conversion-impeding effect of goitrogenic
substances. The same is true for Sm-activity and weight gains,
whereas the Tsub 4-level increased even above the level of
control animals due to I-supplementation. There are
significant correlations (correlation coefficients 0.77 and
0.64 resp.; p < 0.001) between food intake and Tsub
3-concentration resp. and Sm-activity. This study demonstrates
that the reduced growth in case of the intake of phytogenic
substances with thyreostatic effects is directed by the
diminished food consumption and the peripheral hypothyroid
situation via decreased Sm-synthesis. The high content of
thyreostatic substances in tissues of rape seed fed animals is
a potential danger for the human consumer.
|