Endocrine System: Overview Acts with nervous system to coordinate and integrate activity of body cells Influences metabolic

ic activities via hormones transported in blood Response slower but longer lasting than nervous system Endocrinology
Study of hormones and endocrine organs

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Endocrine System: Overview Controls and integrates

Reproduction Growth and development Maintenance of electrolyte, water, and nutrient balance of blood Regulation of cellular metabolism and energy balance Mobilization of body defenses

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Endocrine System: Overview Exocrine glands

Nonhormonal substances (sweat, saliva) Have ducts to carry secretion to membrane surface

Endocrine glands
Produce hormones Lack ducts

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Endocrine System: Overview Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands Hypothalamus is Neuroendocrine organ Some have exocrine and endocrine functions
Pancreas, gonads, placenta

Other tissues and organs that produce hormones

Adipose cells, thymus, and cells in walls of small intestine, stomach, kidneys, and heart
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Figure 16.1 Location of selected endocrine organs of the body.

Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands (on dorsal aspect of thyroid gland) Thymus

Adrenal glands Pancreas

Gonads Ovary (female) Testis (male)

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Chemical Messengers Hormones: long-distance chemical signals; travel in blood or lymph Autocrines: chemicals that exert effects on same cells that secrete them Paracrines: locally acting chemicals that affect cells other than those that secrete them Autocrines and paracrines are local chemical messengers; not considered part of endocrine system
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(exclude neurohormone)

Chemistry of Hormones Two main classes

Amino acid-based hormones
Amino acid derivatives, peptides, and proteins Polar Molecules

Steroids
Synthesized from cholesterol Gonadal and adrenocortical hormones Non-Polar Molecules (except thyroid hormones)

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Mechanisms of Hormone Action Though hormones circulate systemically only cells with receptors for that hormone affected Target cells
Tissues with receptors for specific hormone

Hormones alter target cell activity

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Mechanisms of Hormone Action Hormone action on target cells may be to

Alter plasma membrane permeability Open / Close ion channels Stimulate protein synthesis Activate or deactivate enzymes Induce secretory activity Stimulate mitosis

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Mechanisms of Hormone Action Hormones act at receptors in one of two ways, depending on their chemical nature and receptor location
1. Water-soluble hormones (all amino acid based hormones except thyroid hormone)
Act on plasma membrane receptors Act via G protein second messengers Cannot enter cell

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Mechanisms of Hormone Action

2. Lipid-soluble hormones (steroid and thyroid hormones)
Act on intracellular receptors that directly activate genes Can enter cell

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Plasma Membrane Receptors and Secondmessenger Systems cAMP signaling mechanism:

1. 2. 3. 4. Hormone (first messenger) binds to receptor Receptor activates G protein G protein activates adenylate cyclase Adenylate cyclase converts ATP to cAMP (second messenger) 5. cAMP activates protein kinases that phosphorylate proteins

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Plasma Membrane Receptors and Secondmessenger Systems cAMP signaling mechanism

Activated kinases phosphorylate various proteins, activating some and inactivating others cAMP is rapidly degraded by enzyme phosphodiesterase Intracellular enzymatic cascades have huge amplification effect

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G-Protein Linked Receptor

Specifically, cAMP

Amplifying system
1st Messenger

Fig 3-15
Norris, 2007

2nd Messenger

Protein kinase
144

(+) Enzyme
amplify effects

Effect

Effect

Plasma Membrane Receptors and Secondmessenger Systems PIP2-calcium signaling mechanism

Involves G protein and membrane-bound effector phospholipase C Phospholipase C splits PIP2 into two second messengers diacylglycerol (DAG) and inositol trisphosphate (IP3)
DAG activates protein kinase; IP3 causes Ca2+ release Calcium ions act as second messenger

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Hormone 1 Hormone 1 Receptor

2nd messengers

(protein kinase C)

Other Signaling Mechanisms Cyclic guanosine monophosphate (cGMP) is second messenger for some hormones

Similar to cAMP
Map Kinase
Receptor Binding causes

Cross-Phosphorylation

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Epidermal Growth Factor = EGF

MAP Kinase pathway

Fig 3-22
Cross phosphorylate

adapter proteins

adapter proteins

Norris, 2007

Intracellular Receptors and Direct Gene Activation Steroid hormones and thyroid hormone
1. Diffuse into target cells and bind with intracellular receptors 2. Receptor-hormone complex enters nucleus; binds to specific region of DNA

Change in protein production!

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Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones.

Slide 1

Extracellular fluid

Steroid hormone

Plasma membrane

Cytoplasm Receptor protein

1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor.

Receptorhormone complex 2 The receptorhormone complex enters the nucleus.

3 The receptor- hormone complex binds a specific DNA region. 4 Binding initiates transcription of the gene to mRNA.

Nucleus

Receptor Binding region

DNA

mRNA

5 The mRNA directs protein synthesis. New protein

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 Clicker question

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Target Cell Specificity Target cells must have specific receptors to which hormone binds, for example
ACTH receptors found only on certain cells of adrenal cortex Thyroxin receptors are found on nearly all cells of body

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Target Cell Specificity Target cells must have specific receptors to which hormone binds, for example
ACTH receptors found only on certain cells of adrenal cortex Thyroxin receptors are found on nearly all cells of body

Hard to start the car, with the wrong key!

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 CLICKER QUESTION

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Target Cell Activation Target cell activation depends on three factors

Blood levels of hormone Relative number of receptors on or in target cell Affinity of binding between receptor and hormone

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Target Cell Activation Hormones influence number of their receptors

Up-regulationtarget cells form more receptors in response to low hormone levels Down-regulationtarget cells lose receptors in response to high hormone levels

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[A receptor is exposed to compound A and compound B, and compound A generates a greater response. Why might this be?] A. [A has a higher binding affinity] B. [B has a higher binding affinity] C. [[A] > [B]] D. [A and C]

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Control of Hormone Release Blood levels of hormones

Controlled by negative feedback systems Vary only within narrow, desirable range

Endocrine gland stimulated to synthesize and release hormones in response to

Humoral stimuli Neural stimuli Hormonal stimuli

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When a receptor is exposed to compound A and compound B, compound A generates a greater response. What could be the reason for this? A. Binding affinity B. Higher of [A] and [B] C. Receptor up regulation D. A and B

Humoral Stimuli Changing blood levels of ions and nutrients directly stimulate secretion of hormones Example: Ca2+ in blood
Declining blood Ca2+ concentration stimulates parathyroid glands to secrete PTH (parathyroid hormone) PTH causes Ca2+ concentrations to rise and stimulus is removed

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Figure 16.4a Three types of endocrine gland stimuli.

Slide 2

Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca2+ in blood) Thyroid gland (posterior view)

Parathyroid glands

Parathyroid glands

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Figure 16.4a Three types of endocrine gland stimuli.

Slide 3

Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca2+ in blood) Thyroid gland (posterior view)

Parathyroid glands

Parathyroid glands PTH Stimulus: Low concentration of Ca2+ in capillary blood. Response: Parathyroid glands secrete parathyroid hormone (PTH), which increases blood Ca2+.
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Neural Stimuli Nerve fibers stimulate hormone release

Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines

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Figure 16.4b Three types of endocrine gland stimuli.

Slide 2

Neural Stimulus
Hormone release caused by neural input.

CNS (spinal cord)

Preganglionic sympathetic fibers

Medulla of adrenal gland

Capillary

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Figure 16.4b Three types of endocrine gland stimuli.

Slide 3

Neural Stimulus
Hormone release caused by neural input.

CNS (spinal cord)

Preganglionic sympathetic fibers

Medulla of adrenal gland

Capillary

Stimulus: Action potentials in preganglionic sympathetic fibers to adrenal medulla. Response: Adrenal medulla cells secrete epinephrine and norepinephrine.
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Hormonal Stimuli Hormones stimulate other endocrine organs to release their hormones
Hypothalamic hormones stimulate release of most anterior pituitary hormones Anterior pituitary hormones stimulate targets to secrete still more hormones Hypothalamic-pituitary-target endocrine organ feedback loop: hormones from final target organs inhibit release of anterior pituitary hormones
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Hormonal Stimuli Example: Thyroid Hormone

Releasing Hormone

Hypothalamus

TRH

Stimulating Hormone

Anterior Pituitary

TSH

Hormone

Thyroid Gland

T3,T4

Figure 16.4c Three types of endocrine gland stimuli.

Slide 2

Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus

Anterior pituitary gland Thyroid gland

Adrenal Gonad cortex (Testis)

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Figure 16.4c Three types of endocrine gland stimuli.

Slide 3

Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus

Anterior pituitary gland Thyroid gland

Adrenal Gonad cortex (Testis)

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Figure 16.4c Three types of endocrine gland stimuli.

Slide 4

Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus

Anterior pituitary gland Thyroid gland

Adrenal Gonad cortex (Testis)

Stimulus: Hormones from hypothalamus. Response: Anterior pituitary gland secretes hormones that stimulate other endocrine glands to secrete hormones.
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Nervous System Modulation

Nervous system can override normal endocrine controls Example

Feed Forward Mechanism

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Hormones in the Blood Hormones circulate in blood either free or bound

Steroids and thyroid hormone are attached to plasma proteins All others circulate without carriers

Concentration of circulating hormone reflects

Rate of release Speed of inactivation and removal from body
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Hormones in the Blood Hormones removed from blood by

Degrading enzymes Kidneys (excretion) Liver

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Onset of Hormone Activity Some responses ~ immediate Some, especially steroid, hours to days Some must be activated in target cells

Why do steroids take so long to exert an effect?

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Duration of Hormone Activity Limited

Ranges from 10 seconds to several hours Effects may disappear as blood levels drop Some persist at low blood levels

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Interaction of Hormones at Target Cells Multiple hormones may act on same target at same time
Permissiveness: one hormone cannot exert its effects without another hormone being present Synergism: more than one hormone produces same effects on target cell amplification Antagonism: one or more hormones oppose(s) action of another hormone
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The Pituitary Gland and Hypothalamus Pituitary gland (hypophysis) has two major lobes Posterior pituitary (lobe)
(Neurohypophysis)

Neural tissue

Anterior pituitary (lobe) (adenohypophysis)

Glandular tissue

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Pituitary-hypothalamic Relationships Posterior pituitary (lobe)

Downgrowth of hypothalamic neural tissue Neural connection to hypothalamus (hypothalamic-hypophyseal tract) Nuclei of hypothalamus synthesize neurohormones oxytocin and antidiuretic hormone (ADH) Neurohormones are transported to and stored in posterior pituitary

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Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2). Slide 1

Paraventricular nucleus Hypothalamus 1 Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH).

Posterior lobe of pituitary

Optic chiasma

Infundibulum (connecting stalk) Hypothalamichypophyseal tract Axon terminals Posterior lobe of pituitary

Supraoptic nucleus Inferior hypophyseal artery

2 Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary.

3 Oxytocin and ADH are stored in axon terminals in the posterior pituitary. Oxytocin ADH 4 When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood.

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Posterior Pituitary and Hypothalamic Hormones Oxytocin and ADH

Each composed of nine amino acids Almost identical differ in two amino acids

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Oxytocin Strong stimulant of uterine contraction Released during childbirth Hormonal trigger for milk ejection Acts as neurotransmitter in brain

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ADH (Vasopressin) Inhibits or prevents urine formation Regulates water balance Targets kidney tubules reabsorb more water Release also triggered by pain, low blood pressure, and drugs Inhibited by alcohol, diuretics High concentrations vasoconstriction
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ADH Diabetes insipidus

ADH deficiency due to hypothalamus or posterior pituitary damage Must keep well-hydrated

Syndrome of inappropriate ADH secretion (SIADH)

Retention of fluid, headache, disorientation Fluid restriction; blood sodium level monitoring

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Pituitary-hypothalamic Relationships Adenohypophysis:

Originates as out-pocketing of oral mucosa Vascular connection to hypothalamus
Hypophyseal portal system

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Hypothalamus
Neurohypophysis

Portal Veins

PT

Adenohypophysis
Fig 4-3 Norris, 2007

What is a portal system?

A circulation that begins and ends in capillary beds

capillary bed (Median Eminenc

portal veins
capillary bed (adenohypophysis)

What is a portal system?

A circulation that begins and ends in capillary beds

capillary bed (ME)

portal veins
capillary bed (adenohypophysis)

What is a portal system?

A circulation that begins and ends in capillary beds

general circulation

capillary bed (ME)

portal veins
capillary bed (adenohypophysis)

Hypothalamus
Neurohypophysis

Portal Veins

PT

Adenohypophysis
Fig 4-3 Norris, 2007

Releasing Hormones
Growth hormone releasing hormone(GHRH) Growth hormone inhibiting hormone (Somatostatin) Thyrotropin Releasing hormone (TRH) Corticotropin Releasing hormone (CRH) Gonadotropin releasing hormone (GnRH) Dopamine

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Hypothalamus
Neurohypophysis

Portal Veins

PT

Adenohypophysis
Fig 4-3 Norris, 2007

Anterior Pituitary Hormones Growth hormone (GH) Thyroid-stimulating hormone (TSH) or thyrotropin Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin (PRL)

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Anterior Pituitary Hormones All are proteins All except GH activate cyclic AMP secondmessenger systems at their targets TSH, ACTH, FSH, and LH are all tropic hormones (regulate secretory action of other endocrine glands)

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Growth Hormone (GH, or Somatotropin) Produced by somatotropic cells

Targets Muscle / Bone / Fat / Liver

Directly!

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Growth Hormone (GH, or Somatotropin)

Direct actions on metabolism

Increases blood levels of fatty acids; encourages use of fatty acids for fuel; protein synthesis Decreases rate of glucose uptake and metabolism conserving glucose Glycogen breakdown and glucose release to blood (anti-insulin effect)

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Growth Hormone (GH, or Somatotropin) Mediates growth via growth-promoting proteins insulin-like growth factors (IGFs) IGFs stimulate
Uptake of nutrients DNA and proteins Formation of collagen and deposition of bone matrix

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Growth Hormone Regulation (GH) GH release chiefly regulated by hypothalamic hormones

GHRH ( + ) Somatostatin ( - )

Ghrelin (hunger hormone) also stimulates release Highly influenced by Slow wave Sleep
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Homeostatic Imbalances of Growth Hormone Hypersecretion

In children results in gigantism In adults results in acromegaly

Hyposecretion
In children results in pituitary dwarfism

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Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH).

Inhibits GHRH release Stimulates GHIH release Inhibits GH synthesis and release Growth hormone (GH) Hypothalamus secretes growth hormonereleasing hormone (GHRH), and GHIH (somatostatin)

Feedback

Anterior pituitary

Indirect actions
(growthpromoting)

Direct actions
(metabolic, anti-insulin)

Liver and other tissues

Produce Insulin-like growth factors (IGFs) Effects Effects

Skeletal

Extraskeletal

Fat metabolism

Carbohydrate metabolism Increases, stimulates Reduces, inhibits

Increased cartilage formation and skeletal growth

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Increased protein synthesis, and cell growth and proliferation

Increased fat breakdown and release

Increased blood glucose and other anti-insulin effects

Initial stimulus Physiological response Result

Figure 16.7 Disorders of pituitary growth hormone.

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Thyroid-stimulating Hormone (Thyrotropin) Produced by thyrotropes

Stimulates normal development and secretory activity of thyroid

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Figure 16.8 Regulation of thyroid hormone secretion.

Hypothalamus

TRH
Anterior pituitary

TSH Thyroid gland

Thyroid hormones Target cells
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Stimulates Inhibits

Adrenocorticotropic Hormone (Corticotropin) Secreted by corticotropic cells of anterior pituitary Stimulates adrenal cortex to release corticosteroids

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Adrenocorticotropic Hormone (Corticotropin) Secreted by corticotropic cells of anterior pituitary Stimulates adrenal cortex to release corticosteroids

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Adrenocorticotropic Hormone (Corticotropin) Regulation of ACTH release

Triggered by hypothalamic corticotropinreleasing hormone (CRH) in daily rhythm
Circadian regulation

Internal and external factors such as fever, hypoglycemia, and stressors can alter release of CRH

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Gonadotropins Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Secreted by gonadotrophs of anterior pituitary FSH stimulates gamete (egg or sperm) production LH promotes production of gonadal hormones Absent from the blood in prepubertal boys and girls
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Gonadotropins Regulation of gonadotropin release

Triggered by gonadotropin-releasing hormone (GnRH) during and after puberty Suppressed by gonadal hormones (feedback)

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Prolactin (PRL) Regulation

Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine) Secreted by Lactotropes

Lactotropes are always on

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Prolactin (PRL) Functions

Promotes continued milk production Libido Hypersecretion causes inappropriate lactation, lack of menses, infertility in females, and impotence in males
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