Chapter 11, ENDOCRINE SYSTEM. Section 1 Introduction I. Organization of Endocrine System The functions of the body are regulated by the nervous and the endocrine system. The endocrine system consists of endocrine glands and cells that secrete hormones in various tissues.
I. Organization of Endocrine System
The functions of the body are regulated by the nervous and the endocrine system.
The endocrine system consists of endocrine glands and cells that secrete hormones in various tissues.
Endocrine glands: Glands that do not use ducts to convey the secretion to a neighboring target, they are also called ductless glands.
The secretions, known hormones, circulate all over the body in the blood but may produce effects only in selected sites.
The target organ(s) may or may not be near the site of production of the hormone.
--is secreted into the internal body fluids by one specialized cell or a group of cells and
--has a physiological control effect on other cells of the body.
1, Endocrine, or telecrine: glands or specialized cells release hormones into the circulating blood that influence the function of cells at another location in the body.
2, Neuroendocrine: neurons secrete substances (neurohormones) that reach the circulating blood and influence the function of cells at another location of the body.
3. Paracrine, in which cells secret substances that diffuse into the extracellular fluid and affect neighboring cells.
2. Steroids secreted by the adrenal cortex (cortisol and aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone)
3. Derivatives of the amino acid tyrosine, secreted by the thyroid (thyroxine and triiodothyronine) and the adrenal medullae (epinephrine and norepinephrine)
The special feature of the the target cells is the presence of receptors which can “attract” and interact with the hormone.
The receptors may be present either on the plasma membrane, or in the cytoplasm, or in the nucleus.
These receptor molecules are protein in nature and may contain carbohydrate or phospholipid moieties.
The role of the hormones is to transit the regulatory signals from the control (endocrine) system to the target cells (organs or glands).
It could enhance or inhibit some function of the target.
Low plasma concentration (nmol – pmol/L) great regulatory function
Signal amplification during the transmembrane and intracellular transmission
(1) Synergistic effects. When two or more hormones work together to produce particular result their effect are said to be synergistic.
These effects may be additive or complementary.
Additive: Same effect of the hormones on one target organ, for example, epinephrine and norepinephrine on the heart rate
Complementary: Work on different stages of a physiological procedure, for example, FSH (initiation) and testosterone (maintenance) on spermatogenesis
(2) Permissive effect. A hormone is said to have a permissive effect on the action of a second hormone when it enhances the responsiveness of a target organ to the second hormone or when it increases the activity of the second hormone.
Estrogen – Expression of progesterone receptors on uterus – progesterone effect on the uterus.
Glucocorticoids – effects of catecholamines on cardiovascular system
(3) Antagonist Effects. In some situations the actions of one hormone antagonize the effects of another.
Lactation during pregnancy is prevented because the high concentration of estrogen in the blood inhibits the milk secretion and action of prolactin.
The first step of a hormone’s action is to bind to specific receptors at the target cell.
Locations for the different types of hormones:
1) On the surface of the cell membrane.
protein, peptide, and catecholamine hormones
2) In the cell cytoplasm.
3) In the cell nucleus.
thyroid hormones (T3 and T4)
1.Second Messenger Mechanisms for Mediating Intracellular Hormonal Functions
Hydrophilic hormones (proteins, peptides and catecholamine)
--bind the receptors on the membrane,
--activate some enzyme on the membrane,
-- regulate the concentration of some messengers (second messengers) in the cytoplasm. .
There are at least three kinds of second messengers: cAMP, Calcium ions and products of membrane phospholipid metabolism.
Anatomical and Functional Connection Between the Hypothalamus and Pituitary
Anterior pituitary, also known as the adenohypophysis,
Important peptide hormones that secreted by the anterior pituitary and the targets:
ACTH, Adrenocorticotropin hormone
FSH, Follicle-stimulating hormone
LH, Luteinizing hormone
MSH, Melanophore-stimulating hormone
GH, Growth Hormone;
Two important peptide hormones that secreted by the posterior pituitary,
Neurons in the hypothalamus secreted releasing hormones into the blood vessels of the hypothalamo-hypophyseal portal system.
These releasing hormones regulate the anterior pituitary to secrete its hormones in the general circulation.
3. Hormones Secreted by the Hypothalamus and Their Effects on Anterior Pituitary
Corticotropin-releasing hormone (CRH) – Stimulates secretion of ACTH (adrenocorticotropic hormone)
Gonadotropin-releasing hormone (GnRH) Stimulates secretion of FSH (follicle-stimulating hormone) and LH (luteinizing hormone)
Thyrotropin-releasing hormone (TRH)-stimulates secretion of TSH (thyroid-stimulation hormone)
Melanocyte-stimulating hormone release inhibiting factor (MIF)-inhibits secretion of MSH (Melanocyte-stimulating hormone)
Melanocyte-stimulating hormone releasing factor (MRF)-stimulate secretion of MSH
Growth hormone release inhibiting hormone (GHRIH) or Somatostatin (SS) – inhibits secretion of growth hormone
Growth hormone-releasing hormone (GHRH)– stimulates growth hormone secretion
Prolactin-inhibiting factor (PIF)- inhibits prolactin secretion
Prolactin-releasing factor (PRF)-stimulates prolactin section
vasopressin and oxytocin
produced in neuron cell bodies within the supraoptic and paraventricular nuclei of the hypothalamus
transported to the posterior pituitary by nerve fibers of the hypothalamo-hypophyseal tract.
II. Physiological Function of Hormones Secreted From Anterior and Posterior Pituitary
skeletal muscle, heart, skin, connective tissue, liver, kidney, pancreas, intestines, adrenals and parathyroids.
Hypersecretion of GH leads to cause gigantismin children and acromegaly in adult.
Hyposection of GH results in dwarfism during childhood.
Both monkeys were the same size and weight 2 years previously, when the one on the left was hypophysectomized.
Effect of growth hormone treatment for 4 days on the proximal tibial epiphysis of the hypophysectiomized rat.
Note that increased width of the unstained cartilage plate in the tibia of the right, compared with the control in the left.
that is , after the epiphyses of the lone bones have fused with shafts
– the person cannot grow taller,
but the soft tissue can continue to grow and the bones can grow in thickness.
This condition is known as acromegaly.
GH somatomedins (SM) （also called insulin-like growth factor, IGF) in the liver growth of bone and other peripheral tissues.
A, On Protein metabolism
Enhance amino acid transport to the interior of the cells and increase RNA translation and nuclear transcription of DNA to form mRNA, and so increase rate of protein synthesis.
GH also reduces the breakdown of cell proteins by decreasing catabolism of protein.
Cause release of fatty acids from adipose tissue and then increasing the concentration of fatty acids.
Therefore, utilization of fat is used for providing energy in preference to both carbohydrates and proteins.
Decreases cellular uptake of glucose and glucose utilization,
leads to increase of the blood glucose concentration.
The plasma concentration of GH changes with age. 5 – 20 years old, 6ng/ml; 20 – 40 years old, 3ng/ml; 40 –70 years old, 1.6ng/ml.
The change of GH concentration within one day.
+ increase the secretion; - inhibit the secretion
A, Starvation, especially with severe protein deficiency
B, Hypoglycemia or low concentration of fatty acids in the blood
Immediately after thebaby is born, the sudden loss of estrogen and progesterone secreted by the placenta allows the lactogenic effect of PRL to assume its nature milk promoting role, initiating milk secretion.
After birth of the baby, the level of PRL secretion returns to the normal level before pregnancy but each time the mother nurses her baby causes a 10 to 20 fold surge in PRL secretion that lasts for about 1 hour. Lactation is maintained for nursing period.
In women, PRL combined with PRL receptors in granulosa cells stimulates production of LH receptors. Through LH receptors, LH promotes ovulation and then formation of corpus luteum. (permissive effect)
In male, PRL promotes growth of prostate glands and seminal vesicle, enhancing the effect of LH on the interstitial cells producing testosterone.
1) Hypothalamic hormones and feedback mechanism
Hypothalamus: PIF PRF
Anterior pituitary: Prolactin
+ increase the secretion; - inhibit the secretion
Sucking, tactile stimulation
Afferent nerve (somatic nerve)
Centers including spinal cord and hypothalamus
Myoepithelial cells contraction of mammary glands
Milk production increase
Cells in neurohypophysis do not synthesize hormones but act simply as supporting structure for nerve fibers.
Vasopressin (VP), also called ADH, and oxytocin (OXT) are initially synthesized in the cell bodies of the supraoptic and paraventricuar nuclei of hypothalamus
and are transported down to the nerve endings in the neurohypophysis by hypothalamic hypophyseal tract.
When nerve impulses are transmitted downward along the fibers from nuclei, the hormone is immediately released from secretary granules in the nerve endings by exocytosis and is absorbed into adjacent capillaries.
OXT powerful stimulate the smooth muscle contraction, especially that towards the end of gestation.
It is believed that OXT is at least partially responsible for causing birth of the baby
composed of large numbers of closed follicles filled with colloid and lined with a layer of cuboidal epithelioid cells.
The thyroid hormones are synthesized and secreted by the epithelioid cells but stored in colloid.
Within the colloid, enzymes modify the structure of MIT and DIT and couple them together.
When two DIT molecules are coupled together, a molecule of tetraiodothyronine, T4, or thyroxine, is produced.
The combination of one MIT with one DIT forms triiodythyronine, T3.
DIT + DIT = THYROXINE (T4)
3, 5, 3’, 5’-TETRAIODOTHYRONINE
MIT + DIT = TRIIODOTHYRONINE (T3)
3, 5, 3’-TRIIODOTHYRONINE
Note that within the colloid T4 and T3 are still attached to thyroglobulin.
Upon stimulation by TSH,
the cells of the follicle take up a small volume of colloid by pinocytosis,
hydrolyze the T3 and T4 from the thyroglobulin, and
secrete the free hormones into the blood.
T3 and T4 (Almost all is deiodinated by one iodide ion, forming T3) bind with nuclear receptor,
activate and initiate genetic transcription. ---- mRNA
protein synthesis in cytoplasmic ribosomes ----
general increase in functional activity throughout the body.
In patient with hyperthyroidism, catabolism of protein increases, especially muscular protein, which leads weigh-loss and muscle weakness.
In patients with hypothyroidism, myxedema develops because of deposition of mucoprotein binding with positive ions and water molecules in the interstitial spaces while protein synthesis decreases.
A: Increase absorption of glucose from the gastrointestinal tract
E: Enhance glycogenolysis, and even enhanced diabetogenic effect of glucagon, cortisol and growth hormone.
C: Enhancement of glucose utilization of peripheral tissues.
Thyroid hormones accelerate the oxidation of free fatty acids by cells and increase the effect of catecholamine on decomposition of fat.
Thyroid hormones not only promote synthesis of cholesterol but also increase decomposition of cholesterol by liver cells.
The net effect of T3 and T4 is to decrease plasma cholesterol concentration because the rate of synthesis is less than that of decomposition.
Thyroid hormone is essential for normal growth and development especially skeletal growth and development.
Thyroid hormones stimulate formation of dendrites, axons, myelin and neuroglia.
A child without a thyroid gland will suffer from critinism, which is characterized by growth and mental retardation.
Without specific thyroid therapy within three months after birth, the child with cretinism will remain mentally deficient throughout life.
Thyroid hormones increase excitability of central nervous system.
In hyperthyroidism, the patient is likely to have extreme nervousness, many psychoneurotic tendencies including anxiety complexes, extreme worry andparanoia, and muscle tremor.
In addition, thyroid hormones can also stimulate the sympathetic nervous system.
The hypothyroid individual is to have fatigue, extreme somnolence, poor memory and slow mentation.
Thyroid hormones increase the appetite and food intake by metabolic rate increased.
Thyroid hormones increase both the rate of secretion of the digestive juices and the motility of the gastrointestinal tract.
Lack of thyroid hormone can cause constipation.
1. Hypothalamic Pituitary Thyroid Axis
through enhancement of ioidide trapping, ioidination of tyrosine and coupling to form hormones
3) Stimulate thyroid gland to growth, increasing size and number of thyroid cells
(2) TRH secreted by hypothalamus causes the anterior pituitary to produce and release of TSH.
Cold and various emotional reactions can increase TRH secretion through nervous system and then
indirectly affect the secretion of TSH and thyroid hormones.
T3 and T4inhibitory proteinin anterior pituitary
reduces production and secretion of TSH,
decrease response of pituitary to TRH.
Because of the negative mechanism, the concentration of free thyroid hormone in the blood can be maintained within a normal range.
In the absence of sufficient dietary iodide the thyroid cannot produce adequate amounts of T4 and T3.
The resulting lack of negative feedback inhibition causes abnormally high level of the TSH secretion, which in turn stimulate the abnormal growth of the thyroid (a goiter).
Without control of TSH, the thyroid gland can adapt itself function to iodide uptake, which is the autoregulation of thyroid gland.
In normal individuals, large doses of iodide act directly on the thyroid gland to produce a mild and transit inhibition of hormone synthesis.
When iodine is insufficient, the thyroid gland increases formation of hormones.
iodides cause colloid to accumulate and the vascularity of hyperplastic gland to decrease,
making iodide treatment considerable in preparing patients for surgery.
The thyroid gland is innervated by both sympathetic nerve and parasympathetic nerve.
Electrical stimulation of sympathetic nerve increases formation of thyroid hormones
while stimulation of cholinergic fibers (vagus nerve) inhibits secretion of thyroid hormone.
The adrenal cortex secrete steroid hormones, which participate in the regulation of mineral balance, energy balance and reproductive function.
Divided into three regions:
- secretes aldosterone
- secretes glucocorticoids
- secretes androgens
C = O
Hormones of the Adrenal Cortex
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.
Cortisol decrease the rate of glucose utilization by the cells everywhere in the body because of inhibition of response of cells to insulin.
C, Elevate blood glucose concentration
A. Cortisol mobilizes amino acids from the nonhepatic tissues and diminishes the tissue stores of protein.
B. Cortisol decreases protein synthesis in body cells except those of the liver and increases catabolism of protein in many extrahepatic tissues especially in muscle and lymphoid tissue.
C. In the presence of great excesses of cortisol, the muscles become weak and the immunity functions of lymphoid tissue decrease.
A. Cortisol promote mobilization of fatty acids from adipose tissue which increases the concentration of free acids in the plasma
B. Increases oxidationof fatty acids in the liver cells for energy.
Many people with excess cortisol secretion develop a peculiar type of obesity, with excess deposition of fat in the chest and head regions of the body, giving a buffalo-like torso and a rounded face, a “moon-face”.
Cortisol has a slight effect on enhancement of sodium reabsorption and potassium excretion by distal tubules and colleting ducts in kidney.
It 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.
Cortisol increase the production of red cells and platelets by stimulating bone marrow.
Cortisol decrease the number of lymphocytes and eosinocytes because it causes atrophy of the all lymphoid tissues and promotion of destruction of lymphocytes and eosinocytes.
Almost any type of stress, whether physical or neurogenic, will cause increase in ACTH secretion, and consequent cortisol secretion. This increase is essential for survival.
Glucocorticoids also have many other effects such as:
increase in production of HCl and pepsin,
promotion of synthesis of fetal surfactant.
Glucocorticoids have pharmacological effects including anti-inflammatory, antiallergic and antishock effect.
Hypothalamus – Anterior Pituitary – Adrenocortical Axis
(1) Action of ACTH: Cortisol secretion is almost entirely controlled by ACTH (adrenocorticotropin hormone)
ACTH causes formation of adrenocortical hormones by increasing cAMP as a second messenger and activates steps for controlling adrenocortical secretion.
Long-term stimulation of the adrenal cortex by ACTH not only increases secretory activity but also causes hypertrophy and proliferation of the adrenocorticol cells, especially in the zona fasciculata and zona reticularis, where cortisol and androgens are secreted.
A, Action of CRH
The action of CRH is to promote synthesis and release of ACTH in the cells of anterior pituitary gland.
B, Regulation of CRH secretion
CRH is secreted in irregular bursts throughout the day and plasma ACTH and cortisol tends to rise and fall in response to these bursts.
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
Any type of stress can lead to enhance secretion of CRH through afferent nerve pathways on hypothalamus.
Consequently, ACTH secretion increases and cortisol concentration becomes very high in the blood.
CRH secretion is inhibited by cortisol via a 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. Please describe the mechanism.