Download - Endocrine System 2014
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THE MIGHTY MOLECULES: The Physiology of the
Endocrine System
VIVIEN FE F. FADRILAN-CAMACHO, MD, MPH, FPAFP
Associate Professor
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OBJECTIVES
At the end of the course, the students would be able to:
To discuss the basic functions of the endocrine system
To discuss the structural and functional organization of the endocrine system
To explain the physiologic mechanisms of the endocrine system
To discuss the role of specific intrinsic and extrinsic stimuli on the normal physiology of the endocrine system
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ENDOCRINE SYSTEM
second great control system of the body
interacts with the nervous system to coordinate
and integrate the activity of body cells
Nervous sytem = via electrochemical impulses; with responses in milliseconds
Endocrine system = via hormones; responses
that occur after a lag period of seconds or
even daysonce initiated, more prolonged
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ENDOCRINE SYSTEM: FUNCTIONS
Water balance: controls solute concentration of blood
Uterine contractions and milk release
Growth, metabolism and tissue maturation
Ion regulation
Heart rate and blood pressure regulation
Blood glucose control
Immune system regulation
Reproductive functions control
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EXOCRINE VS ENDOCRINE GLAND
Exocrine gland glands with ducts; produce non-hormonal substances membrane surface e.g. sweat and salivary glands
Endocrine glands ductless glands which produce hormones vascular and lymphatic drainage
- Pituitary , thyroid, parathyroid, adrenal, pineal and thymus gland
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ENDOCRINE SYSTEM
Hypothalamus neuroendocrine organ
Organs with endocrine and exocrine products:
- pancreas
- ovaries and testes
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LOCAL CHEMICAL MESSENGERS Autocrines exert effects on the same cells that
secrete them.
- e.g. prostaglandins smooth muscle cell contraction
Paracrines act on surrounding cells
- e.g. somatostatin inhibits release of insulin release produced by other cells
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HORMONE RECEPTORS
Membrane Bound Receptors
Receptor sites on the outer surface of the cell membrane
Interact with large and water-soluble molecules
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HORMONE RECEPTORS Membrane Bound Receptor Responses
1. Receptors that directly alter membrane permeability
- opening and closing of ion channels e.g. Ach and Na+ channels in skeletal muscle membranes
2. Receptors that directly alter the activity of enzymes
- or enzyme activities through or activity of cyclic guanosine monophosphae (cGMP)
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HORMONE RECEPTORS
3. Receptors and G proteins
- activation of G proteins (complex proteins)
- inactive G protein with , , subunits
- GDP is bound to subunit
- Receptor bindingthe subunit separates from the and . GTP replaces GDP
can open or close channels
activate enzymes
affect gene exporession
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HORMONE RECEPTORS
Intracellular receptors
Located in the cytoplasm or nucleus of the cell
Interact with small, lipid intercellular signals
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HORMONES
chemical substances
secreted by cells into the extracellular fluids
regulate the metabolic function of other cells in the body
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HORMONE ACTIONS
1. Alters plasma membrane permeability or membrane potential, or both, by opening or closing ion channels
2. Stimulates synthesis of proteins or regulatory molecules such as enzymes
3. Activates or deactivates enzymes
4. Induces secretory activity
5. Stimulates mitosis
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HORMONES: CHEMICAL STRUCTURE 1. Proteins, peptides and amino acid derivatives
- Bind to membrane-bound receptors with exception to the thyroid hormones which diffuse through membranes and bind to intracellular receptors.
a. Proteins- most hormones of the anterior pituitary glands
b. Peptide hormones hormones of the posterior pituitary gland
c. Amino acid derivatives amino acids that have been chemically modified; hormones of the adrenal medulla
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HORMONES: CHEMICAL STRUCTURE 2. Lipid hormones lipid soluble
a. Steroid hormones derived from cholesterol
- hormones produced by the adrenal cortex and gonads
- diffuse across the cell membrane and bind to intracellular receptor molecules
b. Eicosanoids from arachidonic acid
- include prostaglandins, prostacyclins and leukotrienes
- boound to membrane bound receptors that are associated with G proteins
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HORMONE RESPONSES
Permissiveness - situation when one hormone cannot exert its full effects without another hormone being present e.g. thyroid hormone on reproductive system
Synergism -occurs where more than one hormone produces the same effects at the target cell and their combined effects are amplified (1+1 =2) e.g. glucagon and epinephrine
Antagonism -one hormone opposes the action of another hormone e.g. insulin and glucagon
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NEGATIVE FEEDBACK MECHANISM
ensure a proper level of hormone activity at the target tissue.
After a stimulus causes release of the hormone, products resulting from the action of the hormone tend to suppress its further release.
the hormone has a negative feedback effect to prevent oversecretion of the hormone or overactivity
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POSITIVE FEEDBACK MECHANISM
occurs when biological action of the hormone causes additional secretion of the hormone.
luteinizing hormone (LH) release as a result of the stimulatory effect of estrogen on the anterior pituitary before ovulation.
LH ovaries estrogen LH
After LH reaches an appropriate concentration
negative feedback
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HORMONE CLEARANCE
(1) metabolic destruction by the tissues
(2) binding with the tissues
(3) excretion by the liver into the bile
(4) excretion by the kidneys into the urine
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ENDOCRINE GLAND STIMULI Humoral direct response to changing blood levels
e.g. parathyroid hormone, insulin and aldosterone
Neural stimulated by nerve fibers e.g. catecholamines
Hormonal in response to hormones produced by other endocrine organs e.g. hypothalamic-pituitary axis
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Fig 19.1 Endocrine System
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HYPOTHALAMUS THE MASTER GLAND
regulates the NS and endocrine system activities by 3 different mechanisms
1) by secreting regulatory hormones that control endocrine cells in the adenohypophysis (anterior lobe) of the pituitary gland:
- Releasing hormones (RH) stimulate production of one or more hormones
- Inhibiting hormones (IH) prevent the synthesis and secretion of specific pituitary hormones
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THE MASTER GLAND
2) acts as an endocrine organ, releasing the hormones ADH and oxytocin into the circulation at the neurohypophysis (posterior lobe)
3) contains autonomic centers that have direct neural control over the endocrine cells of the suprarenal medulla sympathetic division is activated medulla hormones
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Hypothalamic Control over Endocrine Organs
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THE PITUITARY GLAND
Pea on a stalk (infundibulum)
2 lobes: the adenohypophysis (anterior lobe) and the neurohypophysis (posterior lobe)
Hypothalamus regulates secretions of anterior pituitary
Posterior pituitary is an extension of the hypothalamus
Anterior pituitary 9 major hormones that
Regulate body functions
Regulate the secretions of other endocrine glands
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Pituitary Gland Structure
Posterior pituitary (neurohypophysis): extension of the nervous system via the infundibulum Secretes neurohormones
Anterior pituitary (adenohypophysis) Consists of three areas with
indistinct boundaries: pars distalis, pars intermedia, pars tuberalis
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THE PITUITARY GLAND
Posterior lobe connected to the hypothalamus via the hypothalamic-hypophyseal tract
- paraventricular neurons oxytocin
- supraoptic neurons antidiuretic hormone (ADH)
Anterior lobe
- Hypophyseal portal system vascular connection with the hypothalamus
- where releasing and inhibitory hormones are secreted
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Hormones of Posterior Pituitary: ADH
Antidiuretic hormone (ADH). Also called vasopressin.
A. Osmoreceptors (specialized neurons of hypothalamus monitor changes in intercellular osmolality (relative concentrations of electrolytes and water). If the concentration of electrolytes increases or if the concentration of water decreases, then ADH secretion is stimulated.
B. Baroreceptors (specialized neurons found in walls of atria of heart, large veins, carotid arteries, aortic arch) sense changes in blood pressure (BP). If BP decreases, then ADH secretion is stimulated.
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Control of ADH Secretion
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Control of Oxytocin Secretion
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POMC
Propiomelanocortin (POMC)
- prohormone from the anterior pituitary
- source of ACTH, enkephalin, beta-endorphin, lipotropin
- source of melanocyte-stimulating hormone CNS neurotransmitter involved in appetite control
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Melanocyte Stimulating Hormone, Endorphins, and Lipotropins
ACTH, MSH, endorphins and lipotropins all derived from the same large precursor molecule when stimulated by CRH
MSH causes melanocytes to produce more melanin
Endorphins act as an analgesic; produced during times of stress.
Lipotropins cause adipose cells to catabolize fat
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Adrenocorticotrophic Hormone (ACTH)
CRH from hypothalamus causes release of ACTH from anterior pituitary which
Causes cortisol secretion from the adrenal cortex (a glucocorticoid from the zona fasciculata) against stress
Causes aldosterone secretion from the adrenal cortex (a mineralocorticoid from the zona glomerulosa)
Binds directly to melanocytes of the skin; causes increase in production of melanin.
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Growth Hormone (GH or somatotropin)
Stimulates uptake of amino acids; protein synthesis; growth in most tissues.
Stimulates breakdown of fats to be used as an energy source but stimulates synthesis of glycogen: glucose sparing
Promotes bone and cartilage growth
Regulates blood levels of nutrients after a meal and during periods of fasting
Stimulates glucose synthesis by liver
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Regulation of GH Secretion
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TSH (thyrotropin) and Thyroid Hormones
TRH from hypothalamus causes the release of TSH from anterior pituitary which causes secretion and storage of hormones T3 and T4 from and within the thyroid gland
T3 and T4 inhibit TRH and TSH secretion
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LH, FSH, Prolactin
Gonadotropins: glycoprotein hormones that promote growth and function of the gonads
LH and FSH
Both hormones regulate production of gametes and reproductive hormones
Testosterone in males
Estrogen and progesterone in females
GnRH from hypothalamus stimulates LH and FSH secretion
Prolactin: role in milk production
Regulation of secretion: prolactin-releasing hormone (PRH) and prolactin-inhibiting hormones (PIH)
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Thyroid Gland Highly vascular Iodine enters follicular cells
by active transport. Only gland that stores hormone.
Histology
Composed of follicles: follicular cells surrounding thyroglobulin/thyroid hormones
Parafollicular cells: between follicles
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Follicular cells secrete thyroglobulin into lumen of follicle.
- Iodine and tyrosine necessary for production of T3 and T4.
- Hormones stored here attached to the thyroglobulin then absorbed into follicular cells
- hormones disattached from thyroglobulin and released into circulation.
Parafollicular cells -secrete calcitonin which reduces [Ca2+] in body fluids when Ca levels are elevated.
Thyroid Gland
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Thyroid Hormones
Only free thyroxine and T3 can enter cells; bound-thyroxine serves as a reservoir of this hormone
33-40% of T4 converted to T3 in cells T3 more potent Bind with intracellular receptor molecules and
initiate new protein synthesis Normal growth of many tissues dependent on
presence of thyroid hormones.
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Effects of T3 and T4
1. Maintain normal rate of metabolism. 2. Increase the rate at which glucose,
fat, and protein are metabolized. 3. Increase the activity of Na+-K+ pump
which increases body temperature. 4. Can alter the number and activity of
mitochondria resulting in greater ATP synthesis and heat production.
5. Normal growth and maturation of bone, hair, teeth, c.t., and nervous tissue require thyroid hormone.
6. Both T3 and T4 play a permissive role for GH
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REGULATION OF THYROID HORMONES
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Regulation of Calcitonin Secretion
Produced by parafollicular cells
Secretion triggered by high Ca2+ concentration in blood; acts to decrease Ca2+ concentration
Primary target tissue: bone
Decreases osteoclast activity, lengthens life span of osteoblasts.
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Parathyroid Glands
Secrete PTH: target tissues are bone, kidneys and intestines.
Increases blood calcium and phosphate levels
Stimulates osteoclasts
Promotes calcium reabsorption by kidneys and PO4 excretion
Increases synthesis of vitamin D absorption of Ca and PO4 by intestines
Regulation depends on calcium levels.
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Effects of Parathyroid Hormone
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Adrenal Glands Near superior poles of
kidneys; retroperitoneal
Inner medulla; outer cortex
Medulla: Secretes epinephrine and norepinephrine
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Adrenal Glands
Cortex: three zones from superficial to deep
Zona glomerulosa
Zona fasciculata
Zona reticularis
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Hormones of Adrenal Cortex
Mineralocorticoids: Zona glomerulosa
Aldosterone - rate of sodium reabsorption by kidneys sodium blood levels
Glucocorticoids: Zona fasciculata
Cortisol - fat and protein breakdown, glucose synthesis, inflammatory response
Androgens: Zona reticularis
Weak androgens secreted then converted to testosterone by peripheral tissues. Stimulate pubic and axillary hair growth and sexual drive in females
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Adrenal Medulla neurohormones: epinephrine and norepinephrine
Combine with adrenergic membrane-bound receptors
All function through G protein mechanisms
Secretion of hormones prepares body for physical activity
Effects are short-lived; hormones rapidly metabolized
Epinephrine
blood levels of glucose
Fat breakdown in adipose tissue
Causes dilation of blood vessels in skeletal muscles and cardiac muscles.
Epinephrine and norepinephrine HR and force of contraction; cause blood vessels to constrict in skin, kidneys, GI tract, and other viscera
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REGULATION OF ADRENAL MEDULLARY SECRETIONS
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Stress and the Adrenal Gland
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PANCREAS retroperitoneal
Exocrine gland
Produces pancreatic digestive juices
Endocrine gland
Consists of pancreatic islets
Composed of
Alpha cells-secrete glucagon
Beta cells-secrete insulin
Delta cells-secrete somatostatin
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THE PANCREAS
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Its major target is the liver, where it promotes:
Glycogenolysis the breakdown of glycogen to glucose
Gluconeogenesis synthesis of glucose from lactic acid and noncarbohydrates
Release of glucose to the blood from liver cells
Glucagon
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Target tissuesliver, adipose tissue, muscle, and satiety center of hypothalamus
Lowers blood glucose levels
Enhances transport of glucose into body cells
Counters metabolic
activity that would
enhance blood
glucose levels
Insulin
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Regulation of Blood Glucose Levels
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Results from hyposecretion or hypoactivity of insulin
The three cardinal signs of DM are:
Polyuria huge urine output
Polydipsia excessive thirst
Polyphagia excessive hunger and food consumption
Hyperinsulinism excessive insulin secretion, resulting in hypoglycemia
Diabetes Mellitus (DM)
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Diabetes Mellitus (DM)
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Hormones of the Reproductive System
Male: Testes
Testosterone
Regulates production of sperm cells and development and maintenance of male reproductive organs and secondary sex characteristics
Inhibin
Inhibits FSH secretion
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Hormones of the Reproductive System Female: Ovaries
Estrogen and Progesterone
Uterine and mammary gland development and function, external genitalia structure, secondary sex characteristics, menstrual cycle
Inhibin
Inhibits FSH secretion
Relaxin
Increases flexibility of symphysis pubis
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Pineal Body In epithalamus; produces melatonin
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Thymus Gland, GI Tract, Kidneys
Thymosin-development of the immune system.
GI tract- several hormones regulate digestion and enzyme secretion
Kidneys secrete erythropoietin, which signals the production of red blood cells
Adipose tissue releases leptin, which is involved in the sensation of satiety, and stimulates increased energy expenditure
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Hormone-like Substances
Autocrines: chemical signals released by a cell and the substance affects that same cell.
Chemical mediators of inflammation which are modified fatty acids: eicosanoids such as prostaglandins, thromboxanes, prostacyclins, and leukotrienes
Paracrines: chemical signals released into intercellular fluid and affecting nearby cells.
Endorphins and enkephalins modulate sensation of pain
Several growth factors
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REFERENCES
Seely, R, Stephens, T, Tate, P. Essentials of Anatomy and Physiology. 6th ed. International Edition 2008. Mc Graw Hill Publishing
Marieb, E., Hoehn, K. Essentials of Human Anatomy and Physiology. 9th ed. Pearson Education Inc. 2011.