1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. Thyroid Gland Two lobes connected by isthmus, just below larynx.

7. 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.

8. “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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.