Transcript gh the growth hormone

Growth Hormone
Somatotropin effects in children and adolescents:
Stimulation of protein synthesis
Inhibition of protein breakdown
Stimulation of rate of increase of cell size and
Extension of long bones (arms and legs)
Adult pituitary produces more GH than any of its other hormones.
General metabolic effect in adults:
Decreases glucose uptake by muscle. This increases plasma
glucose levels and forces muscles to burn fat instead of glucose.
This is sometimes called the fat-mobilizing effect of GH.
Growth Promotion by Growth Hormone
Tissue growth is primarily the result of effects on protein synthesis
and breakdown, and by stimulation of rate of uptake of amino
acids. All of this causes increased amounts of protein, which causes
increased cell size and cell number.
The observable effects of GH are due to peptides called
somatomedins, whose secretion is stimulated by GH (it actually is a
tropic hormone, but there’s no feedback inhibition by
somatomedins). Many tissues produce somatomedins, but liver is
biggest source.
Extension of long bones is most rapid in adolescents. The growing
region is the epiphyseal plate. As it grows, the bone lengthens. It
ossifies as the end of adolescence, which prevents it from growing
longer. That’s why growth in height ends at the end of
adolescence.
Growth Hormone Deficiency
GH deficiencies can result from pituitary or hypothalamic
dysfunction.
In adults: muscle mass (hence, strength) is reduced, bone density is
reduced. Not very obvious symptoms.
In children: Results in dwarfism (adult averages about 4’0”). Poor
muscle development, excess subcutaneous fat. Typically, arms and
legs are short in proportion to trunk, head is disproportionately
large, bowed legs. Intellectual development is normal.
Hypersecretion of Growth Hormone
Usually the result of a GH secreting tumor (hence, no feedback
control by hypothalamus).
In children: Causes abnormal height (up to 8’0”; gigantism), body
proportions remain normal until end of adolescence.
Pituitary giants can’t grow taller after long bone epiphyseal plates
ossify, but short bones continue to thicken. This is obvious in face,
feet and hands. Condition (acromegaly) can develop when a GH
secreting tumor arises in an adult (who remains at normal height) or
when a GH secreting tumor that arose in childhood continues to
secrete after adolescence.
There are other endocrine influences on body size; we’ll get to them
later.
Thyroid Gland
Two lobes connected by isthmus, just below larynx.
Internal Anatomy of the Thyroid
“Colloid” is archaic term for large molecules. In thyroid, it’s a
solution with lots of thyroglobulin, a protein with large amounts of
tyrosine in it.
“Thyroid Hormone” is Two Hormones
Thyroxine (T4) and triiodothyronine (T3) are tyrosine derivatives,
referred to as thyroid hormone. T4 contains 4 atoms of iodine, T3
contains 3 atoms of iodine. Major effect is to increase metabolic
rate (burning of fuels with oxygen).
Thyroid also secretes calcitonin; we’ll cover it in the context of
control of plasma calcium levels.
Synthesis and Secretion
Follicle cells actively absorb tyrosine and iodide from the circulation.
They use some of the tyrosine in the synthesis of thyroglobulin,
which they secrete into the colloid by exocytosis.
Since follicle cell iodide concentration becomes high, iodide diffuses
into colloid.
Tyrosines in protein react spontaneously with iodide. Some wind up
with one iodine atom attached (monoiodotyrosine), some with two
(diiodotyrosine).
Iodinated tyrosines in thyroglobin react with each other.
Diiodotyrosine is highly reactive, so most of what’s formed is pairs
of diiodotyrosine. That’s tetraiodothyronine. There is also some
pairing of monoiodotyrosine and diiodotyrosine. That’s
triiodothyronine. So, still in the colloid, thyroglobulin turns into
thyroglobulin with derivatized tyrosines.
Secretion
Follicular cells endocytose some of the colloid; lysosomes fuse with
the endocytosed vesicles. This partially digests thyroglobulin; T3
and T4 are among the digestion products.
T3 and T4 are fat-soluble, so they diffuse out of the follicular cells
as they are released from thyroglobulin.
More than 9x as much T4 is secreted as T3. But T3 is about 5x as
potent as T4. Also liver and kidneys each have an enzyme that can
remove one iodine atom from T4, converting it into T3. Thus, even
though most of what follicular cells secrete is T4, nearly all the
responses are effects of T3.
Transport in the Circulation
Most T3 (about 65%) and about 50% of the T4 circulates while
bound to thyroxine binding protein. More than 99% of the rest is
bound to other plasma proteins.
These bindings are reversible, so as T3 and T4 are removed from
the plasma, more is released into it from the bound reservoir.
Responses to Thyroid Hormone
Best known effect is stimulation of metabolic rate in nearly every
kind of cell. Since oxidative metabolism generates heat, this is
called the calorigenic effect.
Thyroid hormone was used to promote weight loss for awhile
(because of the calorigenic effect), but has some nasty side effects
(we’ll get to them) that ended that.
Effects of high levels of thyroid hormone are catabolic (promote
burning of protein, fat and glycogen), but protein synthesis and
glycogen synthesis won’t happen in total absence of thyroid
hormone. This is called a permissive effect – thyroid hormone
doesn’t promote protein synthesis, but it permits it to occur.
Hyperthyroidism results in depletion of fat, glycogen and protein.
This, in turn, results in muscle weakness.
Thyroid hormone also causes increased numbers of receptors for
catecholamines (sympathetic transmitters). This makes the person
more sensitive to sympathetic stimulation, and is called the
sympathomimetic effect. Thus, thyroid hormone increases heart
rate, stroke volume, arterial pressure, peripheral resistance.
Growth hormone effects on growth require that some thyroid
hormone is present. Therefore, hypothyroidism in children results
in depressed growth.
Thyroid hormone is also essential to development of CNS in
children and to normal CNS function in adults.
Control of Thyroid Secretion
Major regulator is TSH. Nearly all follicle cell activities
are stimulated by TSH. Therefore, hypersecretion of TSH
causes thyroid hypertrophy; hyposecretion causes
thyroid atrophy.
Thyroid hormone exerts negative feedback inhibition of
TSH secretion, which is how thyroid hormone levels are
regulated in short term.
Hypothalamic TRH determines the set point for the
TSH/thyroid hormone negative feedback loop, controlling
thyroid hormone levels over the long term. There are
also neural influences via the hyopthalamus.
Hypothyroidism
Can result from:
Follicle cell defect in T3 and T4 synthesis/secretion
Hypothalamic defect in TRH synthesis/secretion
Anterior lobe of pituitary defect in TSH synthesis/secretion
Dietary iodine deficiency – very rare in USA because salt is
iodized; very rare with significant seafood in the diet
Symptoms:
Low BMR -> weight gain, poor cold tolerance
Loss of sympathomimetic effect -> fatigue, low cardiac output,
mental sluggishness
Prominent edema in skin (myxedema in adults). Cause unknown
Cretinism if newborn is hypothyroid and untreated for the first
few months. Growth and CNS development are suppressed,
cretins (unlike pituitary dwarfs) are profoundly retarded.
Hyperthyroidism
Usually results from production of an antibody that interacts with
TSH receptor (Grave’s Disease). Effects mimic those of TSH.
Symptoms:
Elevated BMR -> loss of weight and reduced muscle mass
( ->muscle weakness)
Elevated sympathomimetic effect -> elevated heart rate,
hypertension
Nervous system activation -> irritability, anxiety, reduced
emotional control
Exophthalmos (only in Grave’s disease). Fluid accumulates
behind eyeballs. Doesn’t occur in other forms of
hyperthyroidism.
Goiter
Goiter = enlarged thyroid. Obviously, indicates thyroid problem.
Goiter can occur in some kinds of hyperthyroidism AND in some
kinds of hypothyroidism.
Any hyperstimulation of thyroid gland -> goiter
Hypersecretion of TSH or of TRH -> goiter in hyperthyroidism
Iodine deficiency (can’t make thyroid hormone, so there’s no
negative feedback inhibition of TSH secretion) -> goiter in
hypothyroidism.
Thyroid hormone secreting tumor doesn’t result in goiter.