Endocrine System: Overview

• With nervous system, coordinates and integrates

activity of body cells

• Influences metabolic activities via hormones

transported in blood

• Response slower but longer lasting than

nervous system

• Examples of control and integration

– Reproduction

– Growth and development

– Maintenance of electrolyte, water, and nutrient

balance of blood

– Regulation of cellular metabolism and energy balance

– Mobilization of body defenses

Endocrine System: Overview

• Endocrine glands:

– pituitary, thyroid, parathyroid, adrenal, and pineal glands

• Hypothalamus is neuroendocrine organ

• Mixed glands:

– Pancreas, gonads, placenta

• Other tissues and organs that produce hormones

– Adipose cells, thymus, and cells in walls of small intestine, stomach, kidneys, and heart

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

• Testis (male)

• Ovary (female)

Chemistry of Hormones

• Two main classes

– Amino acid-based hormones

• Amino acid derivatives, peptides, and proteins

• Many are at least partially water soluble and travel

through blood without need of stabilizing ‘binding’

protein

• Often short-lived, existing for seconds or minutes

– Steroids

• Synthesized from cholesterol

• Gonadal and adrenocortical hormones

• Most are lipophilic and poorly water soluble; need

‘binding’ during blood transport

• Often long-lived, existing for minutes to hours

Mechanisms of Hormone Action

• Though hormones circulate systemically

only cells with receptors for that hormone

affected

– Target cells - must have specific receptors to

which hormone binds

– Hormones alter target cell activity• Alter plasma membrane permeability and/or membrane

potential by opening or closing ion channels

• Stimulate synthesis of enzymes or other proteins

• Activate or deactivate enzymes

• Induce secretory activity

• Stimulate mitosis

Mechanisms of Hormone Action

• Hormones act at receptors in one of two

ways, depending on their chemical nature

and receptor location

1. Plasma membrane receptors respond to

water-soluble hormones (all amino acid–

based hormones except thyroid hormone)

2. Intracellular/nuclear receptors respond to

lipid-soluble hormones (steroid and thyroid

hormones)

Plasma Membrane Receptors and Second-

messenger Systems

cAMP signaling mechanism:

1. Hormone (first messenger) binds to receptor

2. Receptor activates G protein

3. G protein activates adenylate cyclase

4. Adenylate cyclase converts ATP to cAMP (second messenger)

5. cAMP activates protein kinases that phosphorylate proteins

6. Activated kinases phosphorylate various proteins, activating

some and inactivating others

7. cAMP is rapidly degraded by enzyme phosphodiesterase

8. Intracellular enzymatic cascades have huge amplification

effect

Slide 6Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones.

Recall from Chapter 3 that

G protein signaling mechanisms

are like a molecular relay race.

Hormone

(1st messenger)

Receptor G protein Enzyme 2nd

messenger

Adenylate cyclase Extracellular fluid

G protein (Gs)

GDP

Receptor

Hormone (1st messenger)

binds receptor.

Receptor

activates G

protein (Gs).

G protein

activates

adenylate

cyclase.

Adenylate

cyclase converts

ATP to cAMP (2nd

messenger).

Inactive

protein

kinase

Triggers responses of

target cell (activates

enzymes, stimulates

cellular secretion,

opens ion channel, etc.)

Active

protein

kinase

cAMP activates

protein kinases.

Cytoplasm

cAMP

GTP

GTP

GTP

ATP

1

2 3 4

5

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

3. Prompts DNA transcription to produce mRNA

4. mRNA directs protein synthesis

5. Promote metabolic activities, or promote synthesis of structural proteins or proteins for export from cell

Slide 6Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones.

The steroid hormone

diffuses through the plasma

membrane and binds an

intracellular receptor.

1

5

The receptor-hormone complex enters the nucleus.

The receptor- hormone complex binds a specific DNA region.

Binding initiates transcription of the gene to mRNA.

The mRNA directs protein synthesis.

New protein

Nucleus

mRNA

DNA

ReceptorBinding region

Receptor-hormonecomplex

Receptor

protein

Steroidhormone Plasma

membrane

Extracellularfluid

Cytoplasm

2

3

4

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

Target Cell Activation

• Target cell activation depends on three

factors

– Blood levels of hormone

– Relative number of receptors on or in target

cell

• Up-regulation

• Down-regulation

– Affinity of binding between receptor and

hormone

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

Figure 16.4a Three types of endocrine gland stimuli. Slide 1

Humoral Stimulus

Hormone release caused by alteredlevels of certain critical ions ornutrients.

Stimulus: Low concentration of Ca2+ incapillary blood.

Parathyroidglands

Parathyroidglands

Capillary (low Ca2+

in blood)

Thyroid gland(posterior view)

PTH

Response: Parathyroid glands secreteparathyroid hormone (PTH), whichincreases blood Ca2+.

Figure 16.4b Three types of endocrine gland stimuli. Slide 3

Neural Stimulus

Hormone release caused by neural input.

Stimulus: Action potentials in preganglionicsympathetic fibers to adrenal medulla.

CNS (spinal cord)

Preganglionicsympatheticfibers

Medulla ofadrenal gland

Capillary

Response: Adrenal medulla cells secreteepinephrine and norepinephrine.

Figure 16.4c Three types of endocrine gland stimuli. Slide 1

Hormonal Stimulus

Hormone release caused by anotherhormone (a tropic hormone).

Stimulus: Hormones from hypothalamus.

Anteriorpituitarygland

Thyroidgland

Adrenalcortex

Gonad(Testis)

Hypothalamus

Response: Anterior pituitary gland secreteshormones that stimulate other endocrine glands to secrete hormones.

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

Hormones in the Blood

• Hormones removed from blood by

– Degrading enzymes

– Kidneys

• Excretion based on water solubility, size

– Liver

• Half-life—time required for hormone's blood level

to decrease by half

– Varies from fraction of minute to a week

Onset of Hormone Activity

• Some responses ~ immediate

• Some, especially steroid, hours to days

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

The Pituitary Gland and Hypothalamus

• Pituitary gland (hypophysis) has two

major lobes

– Posterior pituitary (lobe)

• Neural tissue

– Anterior pituitary (lobe)

(adenohypophysis)

• Glandular tissue

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

Slide 1

Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH).

Oxytocin and ADH are stored in axon terminals in the posterior pituitary.

When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood.

1

2

3

4OxytocinADH

Posterior lobeof pituitary

Opticchiasma

Infundibulum(connecting stalk)

Hypothalamic-hypophyseal

tract

Axon terminals

Posterior lobeof pituitary

Paraventricular nucleus

Hypothalamus

Supraopticnucleus

Inferiorhypophysealartery

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

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

Slide 1

Hypothalamic hormones travel through portal veins to the anterior pituitary where they stimulate or inhibit release of hormones made in the anterior pituitary.

In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation.

GH, TSH, ACTH,FSH, LH, PRL

Anterior lobeof pituitary

When appropriately stimulated, hypothalamic neurons secrete releasing or inhibiting hormones into the primary capillary plexus.

Hypophysealportal system

• Primary capillaryplexus

• Hypophysealportal veins

• Secondarycapillary plexus

Superiorhypophyseal

artery

Anterior lobeof pituitary

Hypothalamus Hypothalamicneurons synthesizeGHRH, GHIH, TRH,CRH, GnRH, PIH.

A portal system is two capillary plexuses (beds) connected by veins.

12

3

Posterior Pituitary and Hypothalamic

Hormones

• Oxytocin and ADH

– Each composed of nine amino acids

– Almost identical – differ in two amino acids

Oxytocin

• Strong stimulant of uterine contraction

• Released during childbirth

• Hormonal trigger for milk ejection

• Acts as neurotransmitter in brain

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

Anterior Pituitary Hormones

• Growth hormone (GH)

• Thyroid-stimulating hormone (TSH) or

thyrotropin

• Adrenocorticotropic hormone (ACTH)

• Follicle-stimulating hormone (FSH)

• Luteinizing hormone (LH)

• Prolactin (PRL)

Anterior Pituitary Hormones

• All are proteins

• All except GH activate cyclic AMP second-

messenger systems at their targets

• TSH, ACTH, FSH, and LH are all tropic

hormones (regulate secretory action of

other endocrine glands)

Growth Hormone (GH)

• GH release chiefly regulated by

hypothalamic hormones

– Growth hormone–releasing hormone (GHRH)

• Stimulates release

– Growth hormone–inhibiting hormone (GHIH)

(somatostatin)

• Inhibits release

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

Hypothalamus

secretes growth

hormone–releasing

hormone (GHRH), and

GHIH (somatostatin)Anterior

pituitary

Inhibits GHRH release

Stimulates GHIH release

Inhibits GH synthesis

and release

Feedback

Indirect actions

(growth-

promoting)

Liver and

other tissues

Insulin-like growth

factors (IGFs)

Produce

Effects

Skeletal ExtraskeletalFat

metabolism

Carbohydrate

metabolism

Direct actions

(metabolic,

anti-insulin)

Effects

Growth hormone (GH)

Increased cartilage

formation and

skeletal growth

Increased protein

synthesis, and

cell growth and

proliferation

Increased

fat breakdown

and release

Increased blood

glucose and other

anti-insulin effects

Increases, stimulates

Initial stimulus

Reduces, inhibits

Physiological response

Result

Growth Hormone (GH, or Somatotropin)

• Produced by somatotropic cells

• 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)

Growth Hormone (GH, or Somatotropin)

• Indirect actions on growth

• 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

• Major targets—bone and skeletal muscle

Thyroid-stimulating Hormone (Thyrotropin)

• Produced by thyrotropic cells of anterior pituitary

• Stimulates normal development and secretory activity of thyroid

• Release triggered by thyrotropin-releasing hormone from hypothalamus

• Inhibited by rising blood levels of thyroid hormones that act on pituitary and hypothalamus

Hypothalamus

TRH

Anterior pituitary

TSH

Thyroid gland

Thyroidhormones

Target cellsStimulates

Figure 16.8 Regulation of thyroid hormone secretion.

Inhibits

Gonadotropins

• Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

• Secreted by gonadotropic cells 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

Gonadotropins

• Regulation of gonadotropin release

– Triggered by gonadotropin-releasing hormone

(GnRH) during and after puberty

– Suppressed by gonadal hormones (feedback)

Adrenocorticotropic Hormone

(Corticotropin)

• Secreted by corticotropic cells of anterior

pituitary

• Stimulates adrenal cortex to release

corticosteroids

Adrenocorticotropic Hormone

(Corticotropin)

• Regulation of ACTH release

– Triggered by hypothalamic corticotropin-

releasing hormone (CRH) in daily rhythm

– Internal and external factors such as fever,

hypoglycemia, and stressors can alter release

of CRH

Glucocorticoids

• Keep blood glucose levels relatively

constant

• Maintain blood pressure by increasing

action of vasoconstrictors

• Cortisol (hydrocortisone)

– Only one in significant amounts in humans

• Cortisone

• Corticosterone

Glucocorticoids: Cortisol

• Released in response to ACTH, patterns of

eating and activity, and stress

• Prime metabolic effect is gluconeogenesis—

formation of glucose from fats and proteins

– Promotes rises in blood glucose, fatty acids, and

amino acids

• "Saves" glucose for brain

• Enhances vasoconstriction → rise in blood

pressure to quickly distribute nutrients to cells