Endocrine system
Types of hormone:
Affect many different types of cells e.g. GH and Thyroxine Affect only specific target cells e.g. ACTH and estrogen
Endocrine glands and hormones
The hypothalamus has both neural functions and releases hormones
Other tissues and organs that produce hormones: adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart
Hormones can exert their effects at distance from their site of production
Neurohormone
Hormone: Affect metabolism of target organs.
◦ Help regulate total body metabolism, growth, and reproduction.
Neurohormone: Specialized neurons that secrete chemicals into the blood rather than synaptic cleft.
◦ Chemical secreted is called neurohormone.
Body function regulation
The multiple hormone systems play a key role in regulating almost all body functions:
◦ Metabolism
◦ Growth and development
◦ Water and electrolyte balance ◦ Reproduction
◦ Behavior
Released into and carried via bloodstream to target tissues
Target cells
Target cells refer to cells that contain specific receptors (binding sites) for a particular hormone.
Classes of hormone
There are three general classes of hormone:
◦ 1. Proteins and polypeptides (peptide hormones), including hormones secreted by the anterior and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others.
◦ 2. Steroids secreted by the adrenal cortex (cortisol and aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone). Steroid hormones are derived from cholesterol.
◦ 3. Amines (derivatives of the amino acid tyrosine), secreted by the thyroid (thyroxine and triiodothyronine), the adrenal medulla (epinephrine and norepinephrine) and the hypothalamus (dopamine).
Peptide hormones
They can dissolve in water (plasma)
Amine hormones
Derived from the amino acid tyrosine
Include:
◦ Thyroid hormones
◦ Epinephrine and norepinephrine (produced by the adrenal medulla) ◦ Dopamine (produced by the hypothalamus)
Hormone transport in the blood
Most hormones are transported simply dissolved in plasma
Poorly soluble hormones (e.g. steroid hormones and thyroid hormones) circulate bound to plasma proteins
◦ Small concentrations will still be dissolved in plasma
◦ Dissolved hormone + binding protein = total hormone concentration
◦ Only dissolved hormone diffuses out of capillary so is biologically important
Hormone clearance
Once a hormone has acted on the target tissue, blood hormone concentrations should return to normal
◦ Prevent excessive / harmful effects of prolonged exposure
Two factors control the concentration of a hormone in the blood: ◦ The rate of its secretion by endocrine gland
◦ The rate of its removal (metabolic clearance) by liver and kidneys
Hormones are cleared by:
◦ Metabolic destruction by tissues ◦ Excretion by the liver into bile
◦ Excretion by the kidney into urine
Clearance of protein-bound hormones is slower than clearance of peptide hormones
Hormones: mechanism of action (non-
steroid)
Mechanism of action :
- Hormone-receptor interaction (first messenger)
- Enzyme activation
- Release of the second messenger
Effects on cellular function
Hormones: mechanism of action (steroid)
Mechanism of action:
- Steroid hormones pass through the cytoplasm and
- enter nucleus
- where they bind with a receptor (lock-and-key model)
Hormone receptors
Receptors:
◦ Hormonal receptors are large proteins
◦ 2000-100,000 receptors/cell
◦ Receptors are highly specific for a single hormone
Receptor’s Location:
◦ On the surface of cell membrane ◦ Peptides and catecholamines
◦ In the cell cytoplasm ◦ Steroids
◦ In the cell nucleus
◦ Thyroid hormones
Control of hormone release
Blood levels of hormones are controlled by feedback mechanisms :
◦ Negative feedback
◦ Originalstimulusreversed
◦ Most feedback systems in the body are negative
◦ Used for conditions that need frequent adjustment
◦ Positive feedback
◦ Originalstimulusintensified
◦ Seenduringnormalchildbirth
Negative feedback
• The secretion of most hormones is regulated by negative feedback mechanisms that tend to reverse any deviations from normal.
• In this example, an increase in blood glucose triggers secretion of insulin. Because insulin promotes glucose uptake by cells, the blood glucose level is restored to its lower, normal level.
Prostaglandins
Prostaglandins (PGs) are powerful substances found in a wide variety of body tissues
Often produced in a tissue and diffuse only a short distance to act on cells in that tissue
Several classes of PGs include prostaglandin A (PGA), prostaglandin E (PGE), and prostaglandin F (PGF)
Influence many body functions, including respiration, blood pressure, gastrointestinal secretions, and reproduction
The Pituitary Gland
Located in the diencephalon, and linked to the hypothalamus
Two-lobed organ that secretes important hormones
◦ Adenohypophysis – anterior lobe, made up of glandular tissue
◦ Synthesizes and secretes a number of hormones
◦ Neurohypophysis – posterior lobe (neural tissue) ◦ Receives, stores, and releases hormones from the hypothalamus
Anterior Pituitary Hormones
The six hormones of the anterior pituitary:
- Growth hormone (GH)
- Prolactin (PRL)
- Thyroid-stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
- Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Anterior pituitary hormones
Trophic effects:
◦ High blood hormone causes target organ to hypertrophy ◦ Low blood hormone causes target organ to atrophy
Functions of major hormones
◦ TSH
◦ Stimulates growth of the thyroid gland; also stimulates it to secrete thyroid hormone
◦ ACTH
◦ Stimulates growth of the adrenal cortex and stimulates it to secrete glucocorticoids (mainly
cortisol)
◦ FSH
◦ Initiates growth of ovarian follicles each month in the ovary and stimulates one or more
follicles to develop to the stage of maturity and ovulation
◦ Stimulates estrogen secretion by developing follicles
◦ Stimulates sperm production in the male
LH
◦ Acts with FSH to stimulate estrogen secretion and follicle growth to maturity
◦ Causes ovulation
◦ Causes luteinization of the ruptured follicle and stimulates progesterone secretion by corpus luteum ◦ Causes interstitial cells in the testes to secrete testosterone in the male
◦ GH
◦ Stimulates growth by accelerating protein anabolism
◦ Accelerates fat catabolism and slows glucose catabolism
◦ By slowing glucose catabolism, tends to increase blood glucose to higher than normal level (hyperglycemia)
◦ PRL
◦ Stimulates breast development during pregnancy and secretion of milk after the delivery of the baby
Hypothalamic Control of the Anterior
Pituitary
• Hormonal control rather than neural
• Hypothalamus neurons synthesize releasing
and inhibiting hormones
• Hormones are transported to axon endings of median eminence
• Hormones secreted into the hypothalamo- hypophyseal portal system regulate the secretions of the anterior pituitary
There is no direct neural contact with the hypothalamus
There is a vascular connection, the hypothalmic-hypophyseal portal system
Hypothalamic Control of Posterior
Pituitary
• Hypothalamus neuron cell bodies produce: • ADH: supraoptic nuclei
• Oxytocin:paraventricularnuclei
• Transported along the hypothalamo-hypophyseal tract
• Stored in posterior pituitary
• Release controlled by neuroendocrine reflexes
Posterior pituitary gland
Does not synthesize hormones ◦ ADH also known as Vasopressin ◦ Oxytocin
Consists of axon terminals of hypothalamic neurons
Hormones are synthesized in the neuron cell bodies in the hypothalamus and packed in secretory vesicles with neurophysin (carrier protein)
Hypothalamic control of pituitary
secretions
The posterior lobe is a down-growth of hypothalamic neural tissue
◦ Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract)
Secretions of the posterior pituitary are controlled by nervous signals from hypothalamus
Antidiuretic Hormone (ADH)
Also known as vasopressin
Synthesized in the cell bodies of hypothalamic neurons (supraoptic nucleus) ADH is stored in the posterior pituitary
Decreases urine production
◦ Causes kidneys to return more water to the blood; therefore reduces urine volume
ADH receptors
2 types of receptors for ADH: ◦V1
◦ V1 receptors mediate vasoconstriction ◦V2
◦ V2 receptors are located in the principle cells in distal convoluted tubule and collecting ducts in the kidneys
ADH mechanism of action: Antidiuresis
ADH binds to V2 receptors on the principle cells of the distal convoluted tubules and collecting ducts
Via adenylate cyclase/cAMP induces production of specific proteins into the luminal membrane and enhances permeability of cell to water
Increased membrane permeability to water permits back diffusion of free water, resulting in increased urine osmolality (concentrates urine)
Control of ADH release
Osmotic pressure:
Blood volume:
◦ Baroreceptor in carotid artery and aortic arch, and Stretch receptors in left atrium ◦ blood pressure ADH secretion
◦ blood pressure ADH secretion
Oxytocin
Synthesized in the cell bodies of hypothalamic neurons (paraventricular nucleus)
Stored in the posterior pituitary
Hypothalamus
• Actual production of ADH and oxytocin occurs in the hypothalamus
• After production in the hypothalamus, hormones pass along axons into the
pituitary gland
• The secretion and release of posterior pituitary hormones is controlled by nervous stimulation
• The hypothalamus controls many body functions related to homeostasis (temperature, appetite, and thirst)
Thyroid gland
Normally weighing 15 to 20 grams in adults
Thyroids hormones profoundly increase the metabolic rate of the body.
Complete lack of thyroid secretion usually causes the basal metabolic rate to fall 40 to 50 percent below normal, and extreme excesses of thyroid secretion can increase the basal metabolic rate to 60 to 100 percent above normal.
Calcitonin (CT)
◦ Decreases the blood calcium concentration by inhibiting breakdown of bone, which would release calcium into the blood
Thyroid tissue
The thyroid tissue is made up of two types of cells: follicular cells and parafollicular cells.
Most of the thyroid tissue consists of the follicular cells, which secrete the iodine-containing thyroid hormones.
The parafollicular cells (also called C cells) secrete the hormone calcitonin
Thyroxine
Iodine is required for formation of Thyroxine
To form normal quantities of thyroxine, about 50 milligrams of ingested iodine in
the form of iodides are required each year, or about 1 mg/week.
To prevent iodine deficiency, common table salt is iodized with about 1 part sodium iodide to every 100,000 parts sodium chloride.
Disease of thyroid gland
Hyperthyroidism = overactive thyroid Hypothyroidism = underactive thyroid
Parathyroid Glands
Parathyroid glands are small lumps of glandular epithelium
There are usually four parathyroid glands, and they are found on the posterior surfaces of the thyroid gland.
Parathyroid hormone (PTH)
◦ Increases blood calcium concentration by increasing the breakdown of bone with the release of calcium into the blood
Action of PTH on bone
• •
•
•
PTH causes resorption of bone. (osteoclastic activity)
This causes mobilization of Ca++ from the bone or demineralization.
Hence it increases serum Ca++ levels
Adrenal Glands
Located on the superior surface of each kidney
Adrenal cortex
◦ Outer region is glandular
Adrenal medulla
◦ Inner region and is secretory nervous tissues ◦ Adrenal medulla (20%)
◦ Adrenal cortex (80%)
Adrenal Cortex
Synthesizes and secretes steroid hormones called corticosteroids (Adrenocorticoids).
Different Corticosteroids are produced in each of the three layers: ◦ Zona glomerulosa – Mineralocorticoids (Aldosterone)
◦ Zona fasciculata – Glucocorticoids (hydroCortisol)
◦ Zona reticularis – Androgens (Small amounts of male hormones (androgens) secreted by adrenal cortex of both sexes)
Mineralocorticoids (MCs)
Aldosterone – is the most important mineralocorticoid hormone
◦ Maintains Na+ balance by reducing excretion of Na+ from the body
◦ Stimulates reabsorption of Na+ by the distal tubule and collecting duct
in kidneys
◦ Stimulates the active secretion of potassium from the tubular cell into the urine.
◦ It also stimulates sodium & potassium transport in sweat glands, salivary glands, & intestinal epithelial cells.
Regulation of Aldosterone secretion
Aldosterone secretion is stimulated by:
Decreasing blood volume or pressure (renin-angeotensin system) is the major stimulant
Rising blood levels of K+ Low blood Na+
ACTH
Glucocorticoids (Cortisol)
- Help the body resist stress by:
◦ Glucocorticoids are essential for life, without them the person will die
◦ Without Glucocorticoids, the body cannot cope with even mild stressors
Cortisol promotes:
Lipolysis Gluconeogenesis (formation of glucose from noncarbohydrates). Rises in blood glucose, fatty acids, and amino acids. Mobilization of amino acids from proteins
Glucocorticoids (Cortisol)
• •
• • •
Maintain normal renal function
Blood pressure regulation & cardiovascular function: Sensitizes arterioles to catecholamines (Permissive effect)
Suppression of immune response and anti-inflammatory effects Inhibit bone formation
Decrease REM sleep
•
Target tissues: most body tissues
Adrenal Medulla
Produces epinephrine (80%) Produces norepinephrine (20%)
They are released from chromaffin cells
Secretion of these hormones causes:
◦ Blood to be diverted to the brain, heart, and skeletal muscle
Effects of Catecholamines
1- Glycogenolysis in liver and skeletal muscle (can lead to hyperglycemia) which increases blood glucose level
2- Increase heart rate and blood pressure
3- Cause vasoconstriction of blood vessels
4- Mobilization of free fatty acids 5- Increase metabolic rate
6- Increase O2 consumption
Adrenal Medulla
◦ Secretes hormones
◦ Epinephrine (Epi), or adrenaline ◦ Norepinephrine (NR)
◦ Functions of hormones
◦ Help the body resist stress by intensifying and prolonging the effects of
sympathetic stimulation
◦ Increased epinephrine secretion is the first endocrine response to stress
Pancreas
A triangular gland, which has both exocrine and endocrine cells, located behind the stomach
◦ Strategic location
Acinar cells produce an enzyme-rich juice used for digestion
(exocrine product)
Pancreatic islets (islets of Langerhans) produce hormones involved in regulating glucose, lipids, and protein metabolism
Pancreatic Islets (Islets of Langerhans)
1-2 million islets
Beta (β) cells produce insulin (60%)
Alpha (α) cells produce glucagon (20%)
Delta (δ) cells produce somatostatin (10%) (GHIH growth hormone- inhibiting hormone)
PP cells produce pancreatic polypeptide (remainder: approx. 10%) which inhibits pancreatic exocrine secretion of enzymes and bicarbonate
Islet cells are highly vascularized (10-15% of blood flow) and innervated by parasympathetic and sympathetic neurons
Paracrine signals in the Islets
• Blood glucose concentration is tightly maintained between 70 - 110 mg/dL.
• If blood glucose concentration rises above this range, insulin is released, which stimulates body cells to remove glucose from the blood.
• If blood glucose concentration drops below this range, glucagon is released, which stimulates body cells to release glucose into the blood.
Insulin
Hormone of nutrient abundance.
Promotes entry of glucose and amino acids from extracellular fluid into cell.
Stimulates storage of fat and inhibits protein degradation.
Needed for normal growth.
A protein hormone consisting of two amino acid chains linked by disulfide bonds.
Synthesized as part of proinsulin and then excised by enzymes, releasing functional insulin (51 AA) and C- peptide.
Has a plasma half-life of 6 minutes
Glucagon secretion Stimuli for glucagon secretion ◦ low Blood glucose ◦ High Serum amino acids (arginine, alanine) ◦ Sympathetic nervous system stimulation ◦ Stress ◦ Exercise Inhibitors of glucagon secretion ◦ Somatostatin ◦ Insulin ◦ High Blood glucose
Mechanism of release: Insulin and
Glucagon
The calcium channels are different:
◦ In insulin-producing beta cells, calcium channels open in response to membrane depolarization
◦ In glucagon-producing alpha cells, the calcium channels close in response to membrane depolarization
Diabetes Mellitus
•Type 1: inadequate insulin secretion
• Pancreatic islets secrete too little insulin
• insulin-dependent diabetes mellitus
• Caused by an immune-mediated selective destruction of β cells
•Type 2: defect in insulin action (insulin resistance)
• Decrease of insulin and an abnormality of the insulin receptors • non-insulin-dependent diabetes mellitus
•Type 3: Gestational diabetes
• Associated with decreased insulin levels and/or insulin resistance
Female Sex Glands
The ovaries contain two structures that secrete hormones ◦ Ovarian follicles
◦ Corpus luteum
Effects of estrogen (feminizing hormone)
◦ Development and maturation of breasts and external genitals
◦ Development of adult female body contours
◦ Initiation of menstrual cycle
Male Sex Glands
The interstitial cells of testes secrete the male hormone testosterone
Effects of testosterone (masculinizing hormone) ◦ Maturation of external genitals
◦ Beard growth
◦ Voice changes at puberty
◦ Development of musculature and body contours typical of the male
Thymus
Name of hormone ◦ Thymosin
Function of hormone
◦ Plays an important role in the development and function of the body’s immune system
Placenta
Produces hormones
◦ Chorionic gonadotropins ◦ Estrogen
◦ Progesterone
Function of hormones
◦ Maintain the corpus luteum during pregnancy
Pineal Gland
A small gland near the roof of the third ventricle of the brain ◦ Glandular tissue predominates in children and young adults
◦ Becomes fibrous and calcified with age
Called the third eye because its influence on secretory activity is related to the amount of light entering the eyes
Secretes melatonin, which:
◦ Inhibits ovarian activity
◦ Regulates the body’s internal clock
Endocrine Functions Throughout the
Body
Many organs (e.g. the stomach, intestines, and kidney) produce endocrine hormones
◦ Stomach lining produces ghrelin, which affects appetite and metabolism
The atrial wall of the heart secretes atrial natriuretic hormone (ANH), which
stimulates sodium loss from the kidneys
Fat-storing cells secrete leptin, which controls how full or hungry one feels (Leptin decreases your appetite, while ghrelin increases it)
Endocrine Hormone Conditions
Gigantism
◦ Hypersecretion of growth hormone during the early years of life
Diabetes insipidus ◦ Hyposecretion of ADH
Goiter
◦ Low dietary take of iodine
Cretinism
◦ Hyposecretion of thyroid hormones during the formative years
Glycosuria
◦ Excess glucose is filtered out of the blood and lost in the urine