Endocrine System
The Classical Endocrine System
Pineal gland Hypothalamus / Pituitary Thyroid Parathyroid Thymus Adrenal glands Pancreas Gonads
Other Endocrine Organs
Stomach - releases gastrin from G-cells Duodenum CCK, secretin Heart ANP Kidney renin, erythropoietin Placenta - hCG
Endocrine System Function
Maintenance of homeostasis through negative feedback loops
Endocrine System Function
Communication between organ systems within the body (like nervous system)
Differs from the nervous system:
changes take longer to occur and changes persist longer as well.
Endocrine System Function
Hormones are utilized as chemical messengers Messages are received by target cells
Hormones
Recall the distinction between exocrine and endocrine glands
Exocrine: through a duct
Endocrine: into the blood
Hormones
Endocrine hormones are transmitted in the bloodstream to all parts of the body Hormones only have an effect on those cells that have a hormone receptor embedded in the cell membrane (target cells) 2 types of endocrine hormones:
steroid & non-steroid
Hormones
Steroid
-Derived from cholesterol (lipid) -Lipid soluble passes through cell membrane to directly cause a change in DNA within the nucleus (activates a gene) -Slower, longer lasting effect than non-steroid hormones Derived form cholesterol Lipid soluble, need to be transported in the bloodstream combined with a transport proteinMainly from the adrenal cortex and/or gonads Mineralocoritcoid aldosterone Glucocorticoids cortisol, cortisone
Non-steroid
-Derived from an amino acid -Hormone is 1st messenger -Membrane receptor alters protein inside the cell, which serves as the 2nd messenger to alter metabolism of the cell -Water soluble most are transported freely in the blood Cascade of reactions within the cell amplifies the signal This type of hormone causes a more rapid onset and shorter duration of the effect than steroid hormonesTypes of Non-steroid hormones Protein (polypeptide) insulin, growth ho Glycoprotein LH, TS Oligopeptide ADH, oxytocin Amine norepinephrine, epinephrine,
Sex steroids progestin, estrogen
Mechanism of hormone action
Hormones produce their effects on target tissues by binding to specific proteins called hormone receptors located in the target tissues only. Hormone receptors present on the cell membrane of the target cells are called membrane-bound receptors and the receptors present inside the target cell are called intracellular receptors, mostly nuclear receptors (present in the nucleus). Binding of a hormone to its receptor leads to the formation of a hormone-receptor complex Each receptor is specific to one hormone only and hence receptors are specific. Hormone-Receptor complex formation leads to certain biochemical changes in the target tissue. Target tissue metabolism and hence physiological functions are regulated by hormones.
Hormones
Second Messenger
ACTION OF MEMBRANE BOUND RECEPTORS Hormones which interact with membrane-bound receptors normally do not enter the target cell, but generate second messengers (e.g., cyclic AMP, IP3, Ca++ etc) which in turn regulate cellular metabolism .
ACTION OF NUCLEAR RECEPTORS Hormones which interact with intracellular receptors (e.g., steroid hormones, iodothyronines, etc.) mostly regulate gene expression orchromosome function by the interaction of hormonereceptor complex with the genome. Cumulative biochemical actions result in physiological and developmental effects .
HYPOTHALAMUS
the hypothalamus is the basal part of diencephalon, forebrain. These hormones regulate the synthesis and secretion of pituitary hormones. However, the hormones produced by hypothalamus are of two types, the releasing hormones (which stimulate secretion of pituitary hormones) and the inhibiting hormones (which inhibit secretions of pituitary hormones). For example hypothalamic hormone called Gonadotrophin releasing hormone (GnRH) stimulates the pituitary synthesis and release of gonadotrophins. On the other hand, somatostatin from the hypothalamus inhibits the release of growth hormone from the pituitary. These hormones originating in the hypothlamic neurons, pass through axons and are released from their nerve endings. These hormones reach the pituitary gland through a portal circulatory system and regulate the functions of the anterior pituitary. The posterior pituitary is under the direct neural regulation of the hypothalamus
Anterior Pituitary
The releasing hormone is secreted into a portal system
Cells in the anterior pituitary are stimulated to secrete another hormone
Posterior Pituitary
Neurons from the hypothalamus enter the posterior pituitary and stimulate cells to secrete hormones
Pituitary
Interacts with many (not all) endocrine glands as part of a feedback loop between the hypothalamus and the respective gland.
Pituitary
The pituitary serves as a link between the CNS (hypothalamus) and the rest of the endocrine system
Pituitary
The pituitary is suspended from a stalk (infundibulum) attached to the hypothalamus and enclosed within the sella turcica (sphenoid bone)
Pituitary
Actually 2 separate glands: anterior pituitary & posterior pituitary
No blood brain barrier in the hypothalamus
Anterior Pituitary
hypothalamus GHRH (releasing hormones) pituitary (tropic hormones) end organ
PRF PRL
mammary gl.
TRH TSH
thyroid
CRH
GnRH
GH
muscle,bone adipose
ACTH FSH/LH
adrenal cortex ovary & testes
Note:
1. GH is also called somatotropin
2. There are also inhibitory factors from the hypothalamus for GH and PRL
Posterior Pituitary
anti-diuretic hormone, causes kidney to retain water Oxytocin contraction of smooth muscle (uterus/childbirth & mammary gland ducts) ADH * failure of the posterior pituitary to secrete ADH results in Diabetes Insipidus (DI)if no ADH is produced the result is production of LARGE volumes of dilute urine
Growth Hormone
GHRH/somatostatin GH or somatotropin cells related to body growth Produced in the ant. Pituitary
Secretion declines gradually with age
Many more GH producing cells in ant. pituitary than any other type
Growth Hormone
Increased cell division (mitosis) & increased cell growth & differentiation The main effects are on cartilage, muscle, bone, fat Promotes protein synthesis (transcription/translation) Anti-insulin effect - elevates blood sugar
Growth Hormone
Catabolism of fat for energy instead of glucose Muscle & bone are effected indirectly through Insulin like Growth Factor (IGF-1)
increased muscle mass, bone lengthening and decreased fat tissue
Growth Hormone
Continued secretion of high levels after epiphysial plate closure is called acromegaly Bones continue to thicken even after epiphysial plate closure
Growth Hormone
Acromegaly is usually related to a pituitary tumor
Prolactin
In women
increased levels during pregnancy after delivery causes mammary glands to produce milk
In men
increases sensitivity to LH and indirectly enhances testosterone production
Thyroid Gland
TRH (hypothalamus) TSH (pituitary) Thyroid hormone (Thyroid gland)
Thyroid Gland
2 lobes, on either side of the trachea, connected by an isthmus
Microscopic anatomy Thyroid follicles, lined by secretory epithelium (follicular cells) Filled with thyroglobulin (transport protein)
Thyroid Gland
Parafollicular cells between the follicles
Thyroid Function
Secretes two hormones (both require iodine as a precursor)
Thyroxine (T4) & Triiodothyronine (T3)
Thyroid Function
(T4): 90% of all Thyroid hormone Less active Converted to T3 in the cell Most remains in the bloodstream as reservoir of thyroid hormone
Thyroid Function
(T3): 5 times more metabolically active, but only 10% of total hormone that is produced
Thyroid Function
Binds to three sites in the cell
1. Mitochondria: increased cellular respiration 2. Ribosomes: increased protein synthesis 3. Chromatin: increased transcription DNA to mRNA
Hyperthyroidism
Thyroid hormones promote cellular respiration Cellular respiration requires oxygen, therefore heart rate & respiratory rate are increased Produces heat; causes sweating Higher metabolic rate requires more calories, which is a stimulus for hunger
The most common form of hyperthyroidism (autoimmune) Signs and symptoms may include heat intolerance, appetite, weight loss, warm moist skin, nervousness, tremor, BP, tachycardia, goiter, exophthalmos
Graves Disease
Exophthalmos may be due to an autoimmune, inflammatory reaction in the soft tissue that is confined within the boney orbit
A goiter is an enlarged thyroid gland
Endemic goiter is due to lack of iodine in the diet No thyroid hormone is produced so there is no negative feedback
Endemic Goiter
The thyroid gland hypertrophies as it tries to make more thyroid hormone
Hypothyroidism
In children (cretinism) permanent mental retardation due to inadequate nervous system development In adults common cause of fatigue other symptoms are related to low BMR cold intolerance, weight gain, CNS function (mentation), BP, dry skin
Parathyroid Glands
Not linked to the hypothalamic-pituitary axis 4 small nodules of tissue in the thyroid gland
Parathyroid Glands
PTH is secreted in response to low serum Ca++ (hypocalcemia)
1. Promotes synthesis of calcitrol (active metabolite of vitamin D), which GI absorption of Ca++
2. Limits Ca++ secretion by the kidney
3. Stimulates osteoclasts to reabsorb bone
PARATHYROIDS
In humans, four parathyroid glands are present on the back side of the thyroid gland, one pair each in the two lobes of the thyroid gland The parathyroid glands secrete a peptide hormone called parathyroid hormone (PTH). The secretion of PTH is regulated by the circulating levels of calcium ions. Parathyroid hormone (PTH) increases the Ca2+ levels in the blood. PTH acts on bones and stimulates the process of bone resorption (dissolution/ demineralisation). PTH also stimulates reabsorption of Ca2+ by the renal tubules and increases Ca2+ absorption from the digested food. It is, thus, clear that PTH is a hypercalcemic hormone, i.e., it increases the blood Ca2+ levels. Along with TCT(THYROID CALCITONIN) it plays a significant role in calcium balance in the body.
PTH is opposed by the action of calcitonin
Secreted in response to elevated Ca++ (hypercalcemia) by parafollicular (C-cells) of the thyroid gland
Little effect in adults
Parathyroid Glands
Stimulates mineral deposition in bone by osteoblasts
Adrenal Glands
Each gland is actually 2 separate glands: the cortex & medulla
Adrenal Functions
Adrenal Medulla
Secretes Catecholamines
(Epinephrine & Norepinephrine)
Derived from SNS neurons (Chromaffin cells) that lack dendrites & axons
Catecholamines
Adrenaline and noradrenaline are called catecholamines which are rapidly secreted in response to stress of any kind and during emergency situations and are called emergency hormones or hormones of Fight or Flight. These hormones increase alertness, pupilary dilation, piloerection (raising of hairs), sweating etc. Both the hormones increase the heart beat, the strength of heart contraction and the rate of respiration. Catecholamines also stimulate the breakdown of glycogen resulting in an increased concentration of glucose in blood. In addition, they also stimulate the breakdown of lipids and proteins.
Adrenal Medulla
Innervated by SNS
Secretes SNS neurotransmitters mostly Epinephrine (Adrenalin) The presence of these neurotransmitters in the circulation lowers the threshold for transmission of an impulse in the SNS for about 30 min.
Epinephrine
Elevates blood sugar glucose sparing effects to preserve glucose for the CNS
glycogenolysis gluconeogenesis
Adrenal Cortex
3 layers
Adrenal Cortex
Zona mineralocorticoids Aldosterone: renal Na+ & water Glomerulosa reabsorption Zona gluccorticoids Cortisol Fasciculata Zona Reticularis sex steroids Androgen, Estrogen
Glucocorticiods
Glucocorticoids stimulate, gluconeogenesis, lipolysis and proteolysis; and inhibit cellular uptake and utilisation of amino acids. Cortisol is also involved in maintaining the cardio-vascular system as well as the kidneyfunctions. Glucocorticoids, particularly cortisol, produces anti-inflamatory reactions and suppresses the immune response. Cortisol stimulates the RBC production. Aldosterone acts mainly at the renal tubules and stimulates the reabsorption of Na+ and water and excretion of K+ and phosphate ions. Thus, aldosterone helps in the maintenance of electrolytes, body fluid volume, osmotic pressure and blood pressure. Small amounts of androgenic steroids are also secreted by the adrenal cortex which play a role in the growth of axial hair, pubic hair and facial hair during puberty
Adrenal Cortex: Z. Glomerulosa
Aldosterone Na+ retention/ K+ secretion
Water follows Sodium, so fluid volume and BP increase too
Recall that aldosterone secretion can be promoted by:
1. 2. 3. 4. ACTH Angiotensin II Low Na+ High K+
Adrenal Cortex: Z. Fasciculata
Secretes Cortisol (hydrocortisone)
Corticosterone and cortisone are two other similar hormones that are secreted Steroid medication can suppress adrenal function
Adrenal Cortex: Z. Fasciculata
Two basic effects of Cortisol:
1. Glucose sparing effects: increased glucose synthesis & protein/lipid catabolism (gluconeogenesis) 2. Anti-inflammatory effects: inhibits WBC function, decreased phagocytosis, decreased chemotaxis, decreased mast cell degranulation
Adrenal Cortex: Z. Reticularis
Sex steroids small amount of estrogens & weak androgens (DHEA), which is a precursor of testosterone Testosterone is required in men & women pubic & axillary hair, libido, apocrine sweat glands
most testosterone is produced in testes in men 50% produced by the adrenal gland in women
Hyperfunction of the Adrenal glands
Disrupts normal carbohydrate & protein metabolism (Cortisol)
characteristic lipid deposits in the face
Cushings Disease
Potential electrolyte imbalance (Aldosterone) Mood changes (Testosterone)
Ovaries
Gonads
Testes
Secrete estrogen & progesterone during the menstrual cycle FSH from the pituitary causes maturation of the follicle & egg LH causes ovulation (rupture of the follicle release of the egg)
FSH promotes spermatogenesis LH causes interstitial cells to secrete testosterone Testosterone from adrenal gland is also present in women, but at much lower levels Produces secondary sexual characteristics in men
PTH is opposed by the action of calcitonin
Secreted in response to elevated Ca++ (hypercalcemia) by parafollicular (C-cells) of the thyroid gland
Little effect in adults
Parathyroid Glands
Stimulates mineral deposition in bone by osteoblasts
Pancreas
Not linked to hypothalamic pituitary axis Both exocrine & endocrine functions
Pancreas
Endocrine hormones: insulin & glucagon secreted by cells in the islets of Langerhans
Glucagon
Alpha cells secrete glucagon
Glucagon is secreted in response to low blood sugar, causing glycogen to be converted to glucose (glycogenolysis)
Glucagon
Glucagon is a peptide hormone, and plays an important role in maintaining the normal blood glucose levels. Glucagon acts mainly on the liver cells (hepatocytes) and stimulates glycogenolysis resulting in an increased blood sugar (hyperglycemia). In addition, this hormone stimulates the process of gluconeogenesis which also contributes to hyperglycemia. Glucagon reduces the cellular glucose uptake and utilisation. Thus, glucagon is a hyperglycemic hormone.
Beta cells secrete insulin
Insulin
insulin is secreted in response to blood sugar, causes permeability of cell membranes throughout the body to glucose Except CNS...does not require insulin to take up glucose
Insulin
Insulin is a peptide hormone, which plays a major role in the regulation of glucose homeostasis . Insulin acts mainly on hepatocytes and adipocytes (cells of adipose tissue), and enhances cellular glucose uptake and utilisation. As a result, there is a rapid movement of glucose from blood to hepatocytes and adipocytes resulting in decreased blood glucose levels (hypoglycemia). Insulin also stimulates conversion of glucose to glycogen (glycogenesis) in the target cells. The glucose homeostasis in blood is thus maintained jointly by the two insulin and glucagons
Diabetes Mellitus
Elevated blood sugar
Normal fasting blood sugar is 70 100 mg/dL
100 125 mg/dL is prediabetic
Higher than 125 mg/dL is either Type I or Type II diabetes
Type I Diabetes Mellitus
A failure of beta cells to produce insulin
Also called IDDM (Insulin Dependent DM)
complete loss of insulin means that replacement is required
Usually onset is in childhood (juvenile onset)
Type I Diabetes Mellitus
Abrupt onset of symptoms
DKA (diabetic ketoacidosis)
No glucose is available to cells They utilize lipids instead This produces ketoacids (lower the pH)
Polydipsia (thirst) Polyphagia (hunger) Polyuria (osmotic diuresis)
Type I Diabetes Mellitus
The renal threshold for glucose resorption is exceeded resulting in glycosuria Poorly controlled DM is a disease of small blood vessels
diabetic nephropathy diabetic retinopathy diabetic neuropathy changes in coronary & peripheral vessels increase the risk of vascular disease
Diabetes Mellitus type II
An insensitivity of an insulin receptor in cell membranes to insulin
NIDDM (Non Insulin Dependent DM) usually does not require insulin (oral hypoglycemics) Usually onset is as an adult Onset is insidious Usually no ketoacidosis
Diabetes Mellitus
Long term monitoring of blood sugar levels (months) Hgb A1C (glycosylated hemoglobin) A type of hgb that incorporates a sugar molecule More Hgb A1C is made when blood sugar levels are high
Pineal gland
The main hormone is melatonin The precursor is a CNS neurotransmitter, serotonin
Pineal gland
Production and secretion of melatonin is stimulated by darkness Information about light levels is provided through the retina in mammals
PINEAL GLAND
The pineal gland is located on the dorsal side of forebrain. Pineal secretes a hormone called melatonin. Melatonin plays a very important role in the regulationof a 24-hour (diurnal) rhythm of our body. For example, it helps in maintaining the normal rhythms of sleep-wake cycle, body temperature. In addition, melatonin also influences metabolism, pigmentation, the menstrual cycle as well as our defense capability.
Circadian rhythm
Regulates sleep / wake cycle
Pineal gland
Undergoes involution during childhood, which may bring about the onset of puberty
Near the skin in non-mammal vertebrates
Light levels are perceived directly
Regulates seasonal behavior in other animals
Migratory patterns in birds Breeding cycles in animals with seasonal reproductive patterns
Thymus
Posterior to the sternum Larger in adolescence Regresses at puberty Secretes thymosin
THYMUS
The thymus gland is a lobular structure located on the dorsal side of the heart and the aorta. The thymus plays a major role in the development of the immune system. This gland secretes the peptide hormones called thymosins. Thymosins play a major role in the differentiation of Tlymphocytes, which provide cell-mediated immunity. thymosins also promote production of antibodies to provide humoral immunity. Thymus is degenerated in old individuals resulting in a decreased production of thymosins. As a result, the immune responses of old persons become weak.
Thymus
cortex medulla
Thymosin causes undifferentiated lymphocytes to become T cells
Blood thymus barrier in the cortex Only T cells that are self tolerant are released to the medulla and into the rest of the body
Testis
The Leydig cells or interstitial cells, which are present in the intertubular spacesproduce a group of hormones called androgens mainly testosterone. Androgens regulate the development, maturation and functions of the male accessory sex organs like epididymis, vas deferens, seminal vesicles, prostate gland, urethra etc. These hormones stimulate muscular growth, growth of facial and axillary hair, aggressiveness, low pitch of voice etc. Androgens play a major stimulatory role in the process of spermatogenesis (formation of spermatozoa). Androgens act on the central neural system and influence the male sexual behaviour (libido). These hormones produce anabolic (synthetic) effects on protein and carbohydrate metabolism.
Ovary
Females have a pair of ovaries which produce two groups of steroid hormones called estrogen and progesterone. Ovary is composed of ovarian follicles and stromal tissues. The estrogen is synthesised and secreted mainly by the growing ovarian follicles. After ovulation, the ruptured follicle is converted to a structure called corpus luteum, which secretes mainly progesterone. Estrogens produce wide ranging actions such as stimulation of growth and activities of female secondary sex organs, development of growing ovarian follicles, appearance of female secondary sex characters (e.g., high pitch of voice, etc.), mammary gland development. Estrogens also regulate female sexual behaviour. Progesterone supports pregnancy. Progesterone also acts on the mammary glands and stimulates the formation of alveoli (sac-like structures which store milk) and milk secretion.
ANF
hormones are also secreted by some tissues which are not endocrine glands. For example the atrial wall of our heart secretes a very important peptide hormone called atrial natriuretic factor (ANF),which decreases blood pressure. When blood pressure is increased, ANF is secreted which causes dilation of the blood vessels. This reduces the blood pressure.
Other hormones
The juxtaglomerular cells of kidney produce a peptide hormone called erythropoietin which stimulates erythropoiesis (formation of RBC). Endocrine cells present in different parts of the gastro-intestinal tract secrete four major peptide hormones, namely gastrin, secretin, cholecystokinin (CCK) and gastric inhibitory peptide (GIP). Gastrin acts on the gastric glands and stimulates the secretion of hydrochloric acid and pepsinogen. Secretin acts on the exocrine pancreas and stimulates secretion of water and bicarbonate ions. CCK acts on both pancreas and gall bladder and stimulates the secretion of pancreatic enzymes and bile juice, respectively. GIP inhibits gastric secretion and motility
Types of hormones
On the basis of their chemical nature, hormones can be divided into groups : (i) peptide, polypeptide, protein hormones (e.g., insulin, glucagon,pituitary hormones, hypothalamic hormones, etc.) (ii) steroids (e.g., cortisol, testosterone, estradiol and progesterone) (iii) iodothyronines (thyroid hormones) (iv) amino-acid derivatives (e.g., epinephrine).
Stress
A stressor is a stimulus to promote a response to a threatening situation
physical stress - an actual physical change post surgical hot/cold trauma malnutrition hemorrhage psychological stress originates in the cerebral cortex abstraction about a potentially harmful situation anger, grief, depression, anxiety, guilt
Stress
3 phases of the stress response 1. The alarm phase 2. Resistance phase: occurs as glycogen is consumed 3. Exhaustion phase: chronic stress occurs over a period of weeks
Stress: The Alarm Phase
An immediate response
Increased sympathetic output (fight or flight) The adrenal medulla secretes catecholamines like adrenalin (SNS neurotransmitter)
Stress: The Alarm Phase
SNS input to the kidney initiates the RAA cascade which leads to :
Increased BP to supply large skeletal muscles Increased fluid retention to compensate for potential fluid loss through sweat or hemorrhage Glycogen stores are consumed in a few hours
Stress: The Resistance Phase
Occurs as glycogen is consumed:
Hypothalamus CRH ACTH Cortisol
Stress: The Resistance Phase
Cortisol decreases glucose use peripherally (glucose sparing for the CNS) Promotes the breakdown of protein & fatty acids, which are converted to glucose in the liver (gluconeogenesis)
Stress and Blood Sugar
Both Adrenaline (alarm phase) and Cortisol (resistance phase) elevate blood sugar
Stress: The Exhaustion Phase
Chronic stress occurs over a period of weeks: Less protein is available for immune system function (gluconeogenesis)
ability to make antibodies (protein) susceptibility to infections protein available for wound healing
Paracrine Secretions
Paracrine hormones exert a local effect Eicosanoids are paracrine secretions They are produced by the Arachidonic acid pathway
Arachidonic Acid Pathway
Arachidonic acid (a fatty acid) is produced from phospholipids in the cell membrane This reaction is catalyzed by phospholipase A2
Arachidonic Acid Pathway
Arachidonic acid is then subjected to either of two metabolic pathways
1. lipoxygenase leads to the production of leukotrienes, chemical mediators of inflammation
Arachidonic Acid Pathway
2. cyclooxygenase leads to the production of prostaglandins, thromboxane, and prostacyclin
Paracrine Secretions
Thromboxane is secreted by platelets to enhance platelet aggregation Prostaglandins have many effects depending upon the specific metabolite
fever pain etc.
Paracrine Secretions
Steroid medication (e.g. cortisol/prednisone) blocks the production of arachidonic acid (phosphlipase)
*Non-steroidal anti-inflammatories (NSAIDs) like aspirin and Ibuprofen block the cyclooxygenase pathway to reduce inflammation & fever
