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Endocrine System: Overview • With nervous system, coordinates and integrates activity of body cells • Influences metabolic activities via 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, , parathyroid, adrenal, and pineal glands • is neuroendocrine organ • Mixed glands: – , , • Other tissues and organs that produce hormones – Adipose cells, , and cells in walls of small intestine, , kidneys, and

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 • (female) • Testis (male)

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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 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 )

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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

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

Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone Receptor G protein Enzyme 2nd 1 Hormone (1st messenger) (1st messenger) messenger binds receptor.

Adenylate cyclase Extracellular fluid

G protein (Gs)

cAMP 5 cAMP activates GTP protein kinases. Receptor GTP ATP Inactive Active GDP GTP protein protein kinase kinase Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.)

Cytoplasm

2 Receptor 3 G protein 4 Adenylate activates G activates cyclase converts protein (Gs). adenylate ATP to cAMP (2nd cyclase. messenger).

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

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

Steroid Extracellular hormone Plasma fluid membrane 1 The diffuses through the plasma membrane and binds an Cytoplasm intracellular receptor. Receptor Receptor- protein hormone complex 2 The receptor- hormone complex enters the nucleus.

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

5 The mRNA directs protein synthesis. New protein

Target Cell Specificity

• Target cells must have specific receptors to which hormone binds, for example – ACTH receptors found only on certain cells of – 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

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Control of Hormone Release

• Blood levels of hormones – Controlled by negative feedback systems – Vary only within narrow, desirable range • 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 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 (PTH), which increases blood Ca2+.

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

Capillary

Stimulus: Action potentials in preganglionic sympathetic fibers to adrenal medulla. Response: Adrenal medulla cells secrete epinephrine and .

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Figure 16.4c Three types of endocrine gland stimuli. Slide 1 Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus

Anterior pituitary gland

Thyroid Adrenal gland cortex (Testis)

Stimulus: Hormones from hypothalamus. Response: gland secretes hormones 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 – • Half-life—time required for hormone's blood level to decrease by half – Varies from fraction of minute to a week

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Onset of Hormone Activity

• Some responses ~ immediate • Some, especially steroid, hours to days • Some must be activated in target cells

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 – (lobe) • Neural tissue – Anterior pituitary (lobe) (adenohypophysis) • Glandular tissue

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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 or antidiuretic hormone (ADH). Posterior lobe of pituitary Optic chiasma Supraoptic nucleus Infundibulum (connecting stalk) 2 Oxytocin and ADH are transported down the axons of Inferior the hypothalamic- hypophyseal Hypothalamic- hypophyseal tract to the posterior pituitary. hypophyseal artery tract Axon terminals 3 Oxytocin and ADH are stored in axon terminals in Posterior lobe the posterior pituitary. of pituitary Oxytocin 4 When hypothalamic neurons fire, action potentials arriving at ADH the axon terminals cause oxytocin or ADH to be released into the blood.

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

Hypothalamus Hypothalamic neurons synthesize GHRH, GHIH, TRH, Anterior lobe CRH, GnRH, PIH. of pituitary Superior hypophyseal artery 1 When appropriately stimulated, 2 Hypothalamic hormones hypothalamic neurons secrete travel through portal veins to releasing or inhibiting hormones the anterior pituitary where into the primary capillary plexus. they stimulate or inhibit release of hormones made in Hypophyseal the anterior pituitary. portal system • Primary capillary 3 In response to releasing plexus A portal hormones, the anterior • Hypophyseal system is pituitary secretes hormones two into the secondary capillary portal veins capillary plexus. This in turn empties • Secondary plexuses into the general circulation. capillary plexus (beds) connected GH, TSH, ACTH, by veins. FSH, LH, PRL Anterior lobe of pituitary

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

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ADH ()

• Inhibits or prevents urine formation • Regulates water balance • Targets tubules  reabsorb more water • Release also triggered by pain, low blood pressure, and drugs • Inhibited by alcohol, diuretics • High concentrations  vasoconstriction

Anterior Pituitary Hormones

• (GH) • Thyroid-stimulating hormone (TSH) or thyrotropin • Adrenocorticotropic hormone (ACTH) • Follicle-stimulating hormone (FSH) • (LH) • (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)

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Growth Hormone (GH)

• GH release chiefly regulated by hypothalamic hormones – Growth hormone–releasing hormone (GHRH) • Stimulates release – Growth hormone–inhibiting hormone (GHIH) () • Inhibits release

Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH). Hypothalamus secretes growth Inhibits GHRH release Feedback hormone–releasing Stimulates GHIH release Anterior hormone (GHRH), and pituitary GHIH (somatostatin) Inhibits GH synthesis and release

Growth hormone (GH)

Indirect actions Direct actions (growth- (metabolic, promoting) anti-)

Liver and other tissues

Produce

Insulin-like growth factors (IGFs)

Effects Effects

Fat Carbohydrate Skeletal Extraskeletal metabolism metabolism

Increases, stimulates Reduces, inhibits Increased protein Initial stimulus Increased cartilage Increased Increased blood synthesis, and fat breakdown glucose and other formation and cell growth and Physiological response skeletal growth and release anti-insulin effects proliferation 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)

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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 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

Figure 16.8 Regulation of thyroid hormone secretion. Hypothalamus

TRH

Anterior pituitary

TSH

Thyroid gland

Thyroid hormones Stimulates Target cells Inhibits

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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

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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 • (hydrocortisone) – Only one in significant amounts in humans • • 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

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