section 3 thyroid gland. i. biological actions of thyroid hormones t 3 and t 4 bind with nuclear...

Section 3 Thyroid Gland

I. Biological Actions of Thyroid Hormones

T3 and T4 bind with nuclear receptor, activate and initiate genetic

transcription. ---- mRNA protein synthesis in cytoplasmic

ribosomes ---- general increase in functional activity

throughout the body.

1. On Metabolism

Calorigenic action of thyroid hormones

Effect on metabolism of protein carbohydratefat

Calorigenic action

increase O2 consumption of most tissues in the body, increasing heat production and BMR.

mechanism A: Enhances Na+-K+ ATPase activity B: Causes the cell membrane of most

cells to become leaky to Na+ ions

on metabolism of protein

• Physiological level: stimulates synthesis of proteins and enzymes,

• Hyperthyroidism: catabolism of protein, leads weigh-loss and muscle weakness

• Hypothyroidism: myxedema ( 粘液性水肿） develops because of deposition of mucoprotein binding with positive ions and water molecules in the interstitial spaces while protein synthesis decreases

On carbohydrate metabolism

Increase absorption of glucose from the gastrointestinal tract

Enhance glycogenolysis, and even enhanced diabetogenic effect of glucagon, cortisol and growth hormone.

Enhancement of glucose utilization of peripheral tissues.

On fat metabolism

Fatty acids: accelerate the oxidation of free fatty

acids increase the effect of catecholamine

on decomposition of fat. decrease plasma cholesterol

concentration promote synthesis increase decomposition

2. on Growth and Development

essential for normal growth and development especially skeletal growth and

development. stimulate formation of dendrites,

axons, myelin and neuroglia. Critinism

A child without a thyroid gland growth and mental retardation.

.

HyperthyroidismHyperthyroidism

3. Effects on Nervous System

increase excitability of central nervous system sympathetic nervous

system Hyperthyroidism:

extreme nervousness, many psychoneurotic

tendencies including anxiety complexes, extreme worry, paranoia （妄想） and muscle tremor

Effects on Nervous System

HypothyroidismHypothyroidism fatigue extreme somnolence poor memory slow mentation （精神状态）

4. Other Effects on cardiovascular system

increase heart rate and stroke volume, (may through enhance calcium release from

sarcoplasmic reticulum) on gastrointestinal tract

increase the appetite and food intake by metabolic rate increased.

increase both the rate of secretion of the digestive juices and the motility of the gastrointestinal tract.

Lack of thyroid hormone can cause constipation.

II Regulation of Thyroid Hormone Secretion

Hypothalamic Pituitary Thyroid Axis

Feedback MechanismsAutoregulation Effect of Autonomic Nervous System

Hypothalamic Pituitary Thyroid Axis

TSH (throid-stimulating hormone):

Increase secretion of T4 and T3

Stimulate thyroid gland to growth, increasing size and number of thyroid cells

Hypothalamic Pituitary Thyroid Axis

TRH （ thyrotropin-releasing hormone) causes the anterior

pituitary to produce and release of TSH.

Cold and various emotional reactions can increase TRH secretion through nervous system

Feedback Mechanisms of Thyroid Hormones

T3 and T4 inhibitory protein in anterior pituitary reduces production and secretion of

TSH decrease response of pituitary to TRH

Negative feedback

(Inhibitory Protein)

In the absence of sufficient dietary iodide the thyroid cannot produce adequate amounts of T4 and T3.

causes abnormally high level of the TSH secretion, which in turn stimulate the abnormal growth of the thyroid (a goiter).

Autoregulation of Thyroid Hormone Secretion

thyroid gland adapt itself function to iodide uptake, When iodine is insufficient, the thyroid

gland increases formation of hormones large doses of iodide act directly on the

thyroid gland to produce a mild and transit inhibition of hormone synthesis.

In patients with hyperthyroidism iodides cause the vascularity of hyperplastic gland to

decrease (Wolff-Chaikoff effect) making iodide treatment considerable in preparing patients for

surgery.

Effect of Autonomic Nervous System on Thyroid Activity

The thyroid gland is innervated by both sympathetic nerve and parasympathetic nerve. sympathetic nerve increases

formation of thyroid hormones cholinergic fibers (vagus nerve) inhibits

secretion of thyroid hormone

Section 4 Adrenal Gland

I. Adrenal Cortical Hormones

The mineralocorticoids are secreted by zona glomerulosa

regulates the concentration of the extracellular fluid.

Aldosterone is the principal mineralocorticoid.

The glucocorticoids are secreted by both zona fasciculata and zona reticularis,

exhibiting an important effect on increasing blood glucose concentration

Cortisol is the principal glucocorticoid

Small amounts of sex hormones are secreted by the zona reticularis.

1. Biological Effects of Adrenocortical Hormones

CBD, corticosteroid-binding globulin; GR, glucocorticoid receptor

(1)On metabolism

1) On carbohydrate metabolism.

A, Stimulation of gluconeogenesis by the liver cell

----activates DNA transcription in the liver cell nuclei and increase the synthesis of enzymes required for gluconeogenesis.

----causes mobilization of amino acids from extrahepatic tissues, mainly from muscle.

Result: a marked increase in glycogen storage in the liver cells.

B, Reduction of glucose utilization by the cells.

by inhibition of response of cells to insulin.

Elevate blood glucose concentration

2) On protein metabolism

A. mobilizes amino acids from the nonhepatic tissues and diminishes the tissue stores of protein.

B. decreases protein synthesis and increases catabolism of protein in many extrahepatic tissues

especially in muscle and lymphoid tissue

In the presence of great excesses of cortisol, the muscles become weak and the immunity functions of lymphoid tissue decrease.

3) On fat metabolism

A. Promote mobilization of fatty acids from adipose tissue and increases the concentration of free acids in the plasma

B. Increases oxidation of fatty acids in the liver cells for energy.

Cushing’s Syndrome

People with excess cortisol secretion

develop a peculiar type of obesity

excess deposition of fat in the chest and head regions of the body

a buffalo-like torso and a rounded “moon-face”.

Cushing’s Syndrome

striae

“moon face”

4) Effects on water and electrolytes

slight enhancement of sodium reabsorption and potassium excretion by distal tubules and colleting ducts in kidney.

increases the rate of renal blood flow and then glomerular filtration rates, facilitating water excretion

In patients with adrenal insufficiency, excretion of water is so slow that there is a danger of water intoxication and only glococorticoids can repair this deficit.

(2) On blood cells

increase the production of red cells and platelets by stimulating bone marrow.

decrease the number of lymphocytes and eosinocytes ( 嗜酸性粒细胞）

causes atrophy of the all lymphoid tissues and promotion of destruction of lymphocytes and eosinocytes.

(3) On cardiovascular system

necessary for maintenance of normal blood pressure.

1) Cause permissive action, enhancing the response of vascular muscle to catecholamines.

2) Inhibit synthesis of prostaglandins that have vasodilator effect.

3) Reduces the permeability of capillaries, which is useful to maintenance of blood volume.

(4) Effect on stress.

Almost any type of stress cause increase in ACTH secretion, and consequent cortisol secretion.

essential for survival.

(5) Other effects.

increase in production of HCl and pepsin,

promotion of synthesis of fetal surfactant.

pharmacological effects including anti-inflammatory, antiallergic and antishock effect.

2. Regulation of Secretion of Adrenocortical HormoneHypothalamus –

Anterior Pituitary – Adrenocortical Axis

(1)Action of ACTH (adrenocorticotropin hormone)

control of cortisol secretion

ACTH causes

formation of adrenocortical

adrenocortical secretion.

hypertrophy and proliferation of the adrenocorticol cells.

(2) CRH (corticotropin releasing hormone)

A, Action of CRH

promote synthesis and release of ACTH

B, Regulation of CRH secretion

Fluctuations in plasma ACTH and glucotorticoids throughout the day in a normal girl (age 16).

The circadian rhythm is driven by impulses from the supra-chiasmatic nuclei

11-OHCS (11-hydroxycorticosteroids, １１－羟皮质类醇 )

(3) Feedback mechanism

Cortisol has direct negative feedbacks on the hypothalamus to decrease formation of CRH

High circulating levels of cortisol inhibit secretion and formation of ACTH, decreasing response of anterior pituitary gland to CRH.

High levels of ACTH also inhibit CRH secretion by a negative feedback mechanism.

These feedbacks help regulate the plasma concentration of cortisol toward a normal control level.

Clinical treatment of cortisol (large does and long time) always cause the atrophy of the adrenal gland.