Notes of pathophysiology of thyroid and thermoregulation.
Thyroid: physiology, thyroid hormones production and function; hypothyroidism, classification, diagnosis, clinical presentation; hyperthyroidism, classification, diagnosis, clinical presentation; goitre, pathogenesis and types.
Thermoregul...
THYROID AND THERMOREGULATION
THYROID
PHYSIOLOGY AND THYROID HORMONE FUNCTIONS
THYROID STRUCTURE AND HORMONE PRODUCTION
The thyroid gland is an endocrine gland localised at the base of the neck, and the basic anatomical
structure is the thyroid follicle. The follicles are spheric structures made of a single layer of thyrocytes,
which surrounds the internal space that is filled with colloid.
The colloid contains thyroglobulin (TG), the precursor of the
thyroid hormones, which are the triiodothyronine (T3) and
tetraiodothyronine, or thyroxine (T4). These are lipophilic
hormones that derive from the iodinated tyrosine. Since
they are not water-soluble, they should be transported in
the blood, and this activity is performed by the thyroid-
binding globulin (TBG, 70%), transthyretin (TTR, 20%), and
albumin (10%). The free concentration in the blood is less
than 1%. The main active form is the T3; however, most of
the thyroid hormone that is produced by the thyroid is the
T4; it is converted then in the peripheral tissues into T3.
The thyroid gland releases T3 and T4 upon induction of the
thyroid-stimulating hormone (TSH) produced by the
thyrotropic cells of the
adenohypophysis. The
TSH is in turn released
upon stimulation of the thyrotropin-releasing hormone (TRH)
released by the hypothalamus. This is the hypothalamus-
hypophysis-thyroid axis. Together with this steady state control,
there is a negative feedback mechanism that is provided by
thyroid hormones; according to their levels, TSH can be released
in greater or lower amounts. The higher their levels, the lower the
TSH production.
The TSH is made of an - and a -subunit, and the -subunit is in
common with other hormones of the adenohypophysis, which are
LH and PRL.
TSH ACTION
The thyroid hormones are maintained in the thyroglobulin within the colloid. When they are required,
the thyroglobulin is degraded (proteolysis), allowing the release of them. The TSH has multiple
functions in the thyrocytes, which are:
• Stimulation of the biosynthesis
of thyroid hormones.
• Stimulation of iodination of the
tyrosine with promotion of
iodine active transport (Na+/I+
symporter).
• Promotion of the degradation
of the colloid.
• Release of T3 and T4 (ratio
1:10).
The TSH acts in a 7-TM receptor coupled with two G-proteins (Gq and Gs), and through this interaction
it promotes all the biochemical activities of the thyroid, with the changes in the polarity (activity from
, apical to basal membrane). Moreover, the TSH induces the proliferation of the thyroid gland, which
results in hypertrophy and hyperplasia of it.
The T4 is the major hormone to be produced by the thyroid (80%-90%), while the T3 is mainly
produced from T4 in the periphery via deiodination. If the T4 is deiodinated in the internal ring, the
reverse T3 (rT3) is produced, which is the inactive form the hormone.
THYROID HORMONE FUNCTIONS
The thyroid hormones are lipophilic hormones, and therefore they have nuclear receptors, which is
the thyroid nuclear receptor. The signalling pathway that is mediated by them is longer in being
developed but long-lasting, since it is
related to changes in gene transcription.
Among the main functions of the thyroid
hormone, the main one is to increase the
basal metabolism, which is the baseline
metabolism require to produce energy
for the body in resting conditions. The
increase in the basal metabolism is
mainly achieved by increasing the heat
production.
When an individual that used to live in
warm environments moves in a cold
environment, the first action that the
body does is to shiver and retain more
heat. Then, adaptive thermogenesis is
activated, and it induces a less functionality of mitochondria, which instead of producing ATP creates
heat via uncoupling proteins (UCPs). This allows to produce more heat, which counteract the lower T
encountered. In this case, the oxidation is not used to produce energy (ATP); the system is uncoupled.
The thyroid hormones stimulate the synthesis of UCPs to allow an increase production of heat.
Together with this, they induce several other changes, which are:
• Synthesis of respiratory complex proteins: it is required to allow more heat production, as
well as maintaining some degree of ATP synthesis.
• Production of -adrenergic receptors: they promote the chronotropic and inotropic effects
in the heart.
• Increased respiratory rate.
• Increase trophism of tissues: examples are erythrocytes, and skeletal muscles.
Moreover, it was seen that the thyroid hormones may act also in a non-genomic way. These are short-
term mechanisms directly performed by thyroid hormones. Examples are regulation of mitochondrial
proteins, trophic adjustment and osteocyte proliferation, and Na+/K+ ATPase regulation.
BAT AND OTHER TISSUES
The thyroid hormones are regulators of the metabolism, and they stimulate the increase in the basal
metabolic rate resulting in increased heat production. The main tissue involved in thermoregulation is
the brown adipose tissue (BAT), but it is present in
newborns and in hibernated animals. In adults the
thermogenesis is mainly regulated by skeletal
muscles.
The thyroid hormones also control the general
metabolism of the organism. It regulates the
metabolism of the liver, WAT, BAT, pancreas, and
skeletal muscles.
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