Chapter 16 AMP 2

Endocrine system 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

Exocrine glands

Produce nonhormonal substances (examples: sweat, saliva)

• Have ducts to carry secretion to membrane surface

Endocrine glands

Produce hormones

• Lack ducts

Hormones:

long-distance

chemical signals; travel in

blood or lymph

• Two main classes of hormones:

• Amino acid–based hormones

(water-soluble)

• Amino acid derivatives, peptides,

and proteins

• Steroids (lipid-soluble)

• Synthesized from cholesterol

Hormone feedback loop

Positive feedback

(rare) – increases the

effect

• Negative feedback

(common) – decreases

or shuts off the effect

Hormone target receptor relationships

Hormones circulate systemically, but:

• They only effect target cells

• Tissues with receptors for a specific hormone

• Hormones alter target cell activity

• E.g., mitosis rate, enzyme activity, ion channel activity

Water-soluble hormones

(all amino acid–based hormones except thyroid hormone)

• Hormone binds to receptor on plasma membrane

• Act via G protein second messengers

• Cyclic AMP (cAMP) Signaling

• Cannot enter cell

Lipid-soluble hormones

(steroid and thyroid hormones)

• Act on intracellular receptors that directly activate genes

• Can enter cell

Cyclic AMP (cAMP) signaling mechanism steps

1. Hormone (first messenger) binds to receptor

2. Receptor activates a G protein

3. G protein activates or inhibits effector enzyme adenylate cyclase

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

5. cAMP activates protein kinases that phosphorylate (add a phosphate) other

proteins

→

• Cascades have huge amplification effect

Intracellular Receptors and Direct Gene Activation

Lipid-soluble steroid hormones and thyroid hormone can

enter into target cells and bind with intracellular receptors

• Receptor-hormone complex enters nucleus

• Binds to specific region of DNA

• Initiates DNA transcription to produce mRNA

• mRNA is then translated into specific protein

Endocrine Gland Stimuli

Endocrine glands synthesize and release hormones in response to

stimuli:

• Humoral stimuli (Ions or nutrients in blood)

• Example: Ca2+ in blood

• Declining blood Ca2+ concentration stimulates parathyroid glands to

secrete PTH

• Neural stimuli (Nerve fibers)

• Example: Sympathetic nervous system fibers stimulate adrenal medulla to

secrete catecholamines

• Hormonal stimuli (hormones trigger glands to secret hormones)

• Hypothalamic–pituitary–target endocrine organ feedback loop

Target Cell Specificity

Target cells must have specific receptors to which hormone binds

• Example: ACTH receptors are found only on certain cells of adrenal cortex, but

thyroxin receptors are found on nearly all cells of body

• Target cell activation depends on three factors:

1. Blood levels of hormone

2. Relative number of receptors on/in target cell

3. Affinity (strength) of binding between receptor and hormone

• Amount of hormone can influence number of receptors for that

hormone

• Up-regulation: target cells form more receptors in response to low hormone

levels

• Down-regulation: target cells lose receptors in response to high hormone

levels

• Desensitizes the target cells to prevent them from overreacting to persistently high

levels of hormone

Half-Life, Onset, and Duration of Hormones

Hormones circulate in blood either free or bound

• Steroids and thyroid hormone are attached to plasma

proteins

• All others circulate without carriers

• Hormones can be removed from blood by:

• Degrading enzymes, kidney, and liver

• Half-life: time required for level of hormone in blood level to

decrease by half

• Varies anywhere from fraction of a minute to a week, depending

on hormone

Duration of Hormone Activity

Hormone response times:

• Immediate

• Hours to days (especially steroid)

• Inactive until they enter target cells

• The duration of response:

• Ranges from 10 seconds to several hours

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

• Example: reproductive hormones need thyroid hormone to have effect

• Synergism: more than one hormone produces same effects on target cell,

causing amplification

• Example: glucagon and epinephrine both cause liver to release glucose

• Antagonism: one or more hormones oppose(s) action of another

hormone

• Example: insulin and glucagon

The Hypothalamus

Hypothalamus is connected to pituitary gland (hypophysis) via

stalk called infundibulum

• Pituitary secretes at least eight major hormones

• It has two major lobes:

• Posterior pituitary: composed of neural tissue derived from

a downgrowth of brain

• Anterior pituitary: consists of glandular tissue derived from

oral mucosa

Pituitary

Posterior Lobe

Hormones are stored

in axon terminals in

posterior pituitary

and are released into

blood when neurons

fire

Secretes two

neurohormones:

oxytocin and ADH

Anterior Lobe

Hormones released

into hypophyseal

portal system

Hypothalamus

secretes releasing

and inhibiting

hormones to anterior

pituitary to regulate

hormone secretion

Secretes: GH, TSH,

ACTH, FSH, LH, and

PRL

Posterior Pituitary Hormones – A.A. Based

Oxytocin

• Strong stimulant of uterine contractions released during childbirth

• Also acts as hormonal trigger for milk ejection

• Both are positive feedback mechanisms

• Acts as neurotransmitter in brain

• Antidiuretic hormone (ADH)

• Hypothalamus contains osmoreceptors that monitor solute

concentrations

• If concentration too high  ADH secreted

• Targets kidney tubules to reabsorb more water to inhibit or prevent

urine formation

Anterior Pituitary Hormones – Peptides

• Thyroid-stimulating hormone (TSH) (tropic)

• Adrenocorticotropic hormone (ACTH) (tropic)

• Follicle-stimulating hormone (FSH) (tropic)

• Luteinizing hormone (LH) (tropic)

• Prolactin (PRL)

• Growth hormone (GH)

• Tropic hormones – regulate secretion of other hormones

Releasing and Inhibiting Hormones

Secreted by the hypothalamus

• Releasing hormones – stimulate

pituitary to secrete hormone

• Inhibiting hormones – inhibit pituitary

from secreting hormone

Anterior Pituitary Hormone - GH

Growth hormone (GH)

• Direct actions on metabolism

• Triggers liver to break down glycogen into glucose

• Increases blood levels of fatty acids for use as fuel

• Indirect actions on growth:

• Major targets are bone, liver, and skeletal muscle to produce insulin-like growth factors

(IGFs)

• IGF’s stimulates most cells to enlarge and divide

• Uptake nutrients needed for cell division

• Regulation of secretion

• Growth hormone–releasing hormone (GHRH) stimulates GH release

• Triggered by low blood GH or glucose, or high amino acid levels

• Growth hormone–inhibiting hormone (GHIH) (somatostatin) inhibits release

• Triggered by increase in GH and IGF levels

• Ghrelin (hunger hormone) also stimulates GH release

Anterior Pituitary Hormones - TSH

• Thyroid-stimulating

hormone

• Stimulates normal

development and

secretory activity of

thyroid

• Release triggered by

thyrotropin-releasing

hormone (TRH) from

hypothalamus

• Inhibited by rising blood

levels of thyroid

hormones that act on

both pituitary and

hypothalamus

Anterior Pituitary Hormones - ACTH

Adrenocorticotropic hormone

(ACTH)

• ACTH stimulates adrenal cortex to

release corticosteroids

• Regulation of ACTH release

• Triggered by hypothalamic

corticotropin-releasing

hormone (CRH) in daily rhythm

• Highest levels in morning

• Internal and external factors

that alter release of CRH

include fever, hypoglycemia,

and stressors

Anterior Pituitary Hormones – FSH and LH

• Gonadotropins (FSH and LH)

• Regulation of gonadotropin release

• Triggered by gonadotropin-releasing hormone (GnRH)

• Suppressed by gonadal hormones (feedback)

• Follicle-stimulating hormone (FSH)

• FSH stimulates production of gametes (egg or sperm)

• Luteinizing hormone (LH)

• LH promotes production of gonadal hormones

• In females, LH helps mature follicles of egg, triggers ovulation and release of

estrogen and progesterone

• In males, LH stimulates production of testosterone

• LH and FSH are absent in prepubertal boys and girls

Anterior Pituitary Hormones – PRL

Prolactin (PRL)

• Stimulates milk production in females

• Regulation primarily controlled by prolactin-inhibiting

hormone (PIH), which is dopamine

• Increased estrogen levels stimulate PRL

• Reason behind breast swelling and tenderness during menstrual cycle

• Suckling stimulates PRL release and promotes continued milk

production

• Positive feedback

Thyroid Gland

Butterfly-shaped gland in anterior neck on the trachea, just

inferior to larynx, that consists of:

• Isthmus: median mass connecting two lateral lobes

• Follicular cells: secrete thyroid hormone

• Colloid: fluid of follicle lumen containing thyroglobulin plus iodine and is

precursor to thyroid hormone

• Parafollicular cells: produce hormone calcitonin

Thyroid Hormone (TH)

Body’s major metabolic hormone

• Found in two forms:

• T4 (thyroxine): major form that consists of two tyrosine molecules

with four bound iodine atoms

• Must be converted to T3 at tissue level

• T3 (triiodothyronine): has two tyrosines with three iodine atoms

• TH affects virtually every cell in body

• ONLY A.A.-based hormone that can enters target cell

• Binds to intracellular receptors within nucleus to trigger transcription

• Increases basal metabolic rate and heat production

• Regulates tissue growth and development

• Maintains blood pressure

• T3 is 10 times more active than T4

• Peripheral tissues have enzyme needed to convert T4 to T3

• Enzyme removes one iodine

• TH release is regulated by negative

feedback

• Falling TH levels stimulate release of

thyroid-stimulating hormone (TSH)

• Rising TH levels provide negative

feedback inhibition on TSH

Calcitonin

• Produced by parafollicular (C) cells in response to

high Ca2+ levels

• Antagonist to parathyroid hormone (PTH)

• No known physiological role in humans at normal

physiological levels, but at higher-than-normal doses:

• Inhibits osteoclast activity and prevents release of

Ca2+ from bone matrix

• Stimulates Ca2+ uptake and incorporation into bone

matrix

Parathyroid Gland

Four to eight tiny yellow-brown glands

embedded in posterior aspect of thyroid

• Contain oxyphil cells (function not clear)

and parathyroid cells that secrete

parathyroid hormone (PTH), or

parathormone

• PTH is most important hormone in Ca2+

homeostasis

• Secreted in response to low blood levels of

Ca2+ (stimulates osteoclasts)

• Inhibited by rising levels of Ca2+

Adrenal Gland

Paired, pyramid-shaped organs atop kidneys

• Also referred to as suprarenal glands

• Structurally and functionally, it is two glands in one

• Adrenal cortex: three layers of glandular tissue that synthesize and

secrete several different hormones

• Adrenal medulla: nervous tissue that is part of sympathetic nervous

system

• This area of adrenal gland produces over 24 different hormones

collectively called corticosteroids

• Steroid hormones are not stored in cells

• Rate of release depends on rate of synthesis

• Three layers of cortical cells produce the different corticosteroids

• Zona glomerulosa—Mineralocorticoids

• Zona fasciculata—Glucocorticoids

• Zona reticularis—Gonadocorticoids

Mineralocorticoids

Regulate electrolyte concentrations (primarily Na+ and K+) in ECF

• Importance of Na+: affects ECF volume, blood volume, blood

pressure, and levels of other ions (K+, H+, HCO3- and Cl-)

• Importance of K+: sets resting membrane potential of cells

• Aldosterone: most potent mineralocorticoid

• Stimulates Na+ reabsorption by kidneys

• Results in increased blood volume and blood pressure

• Stimulates K+ elimination by kidneys

• Effects of aldosterone are short lived

Aldosterone Control

Renin-angiotensin-aldosterone mechanism

• Decreased bp  stimulates kidney to release RENIN

• Renin cleaves off part of plasma protein, angiotensinogen, that

triggers enzyme cascade, resulting in conversion to angiotensin II

• Angiotensin II is a potent stimulator of aldosterone release

• Plasma concentration of K+

• Increased K+  aldosterone release

• Decreased K+  inhibits aldosterone release

• Adrenocorticotropic hormone (ACTH)

• Can cause small increases of aldosterone during periods of stress

• Atrial natriuretic peptide (ANP)

• Secreted by heart in response to high blood pressure

• Blocks renin and aldosterone secretion to decrease blood pressure

Major Mechanisms

Controlling Aldosterone

Release

Primary Regulators:

1. Renin-angiotensin-aldosterone

mechanism

2. Plasma concentration of K+

Other regulators:

3. Adrenocorticotropic hormone

(ACTH)

4. Atrial natriuretic peptide (ANP)

Glucocorticoids

• Influence metabolism of most cells and help us resist

stressors

• Keep blood glucose levels relatively constant

• Maintain blood pressure by increasing action of

vasoconstrictors

• Glucocorticoid hormones include:

• Cortisol (hydrocortisone); only glucocorticoid in significant amounts in

humans

• Cortisone

• Corticosterone

Cortisol

• Cortisol is released in response to

ACTH

• ACTH released in response to

corticotropin-releasing hormone

(CRH)

• CRH released in response to low

cortisol levels

• Increased cortisol levels inhibit ACTH

and CRH through negative feedback

• Cortisol secretion cycles are

governed by patterns of eating and

activity

• Acute stress (infection, physical or

emotional trauma) interrupts

cortisol rhythm

Cortisol Activities

Primary function: gluconeogenesis

• Formation of glucose from fats and proteins

• Encourages cells to use fatty acids for fuel so glucose is “saved”

for brain

• Causes rise in blood pressure to quickly distribute nutrients to

cells

• Increase blood levels of glucose, fatty acids, and amino acids

Gonadocorticoids

• Weak androgens (male sex hormones) converted to

testosterone in tissue cells, some to estrogens

• Example: androstenedione and dehydroepiandrosterone (DHEA)

• May contribute to:

• Onset of puberty and appearance of secondary sex characteristics

• Sex drive in women

• Source of estrogens in postmenopausal women

Adrenal Medulla

• Medullary chromaffin cells synthesize catecholamines:

• Epinephrine (80%)

• Norepinephrine (20%)

• Effects of catecholamines:

• Vasoconstriction

• Increased heart rate

• Increased blood glucose levels

• Blood diverted to brain, heart, and skeletal muscle

Pineal Gland

• Small gland hanging from roof of third ventricle

• Pinealocytes secrete melatonin, derived from serotonin

• Melatonin may affect:

• Timing of sexual maturation and puberty

• Day/night cycles

• Physiological processes that show rhythmic variations (body

temperature, sleep, appetite)

• Production of antioxidant and detoxification molecules in cells

Pancreas

• Triangular gland located

partially behind stomach

• Has both exocrine and

endocrine cells

• Acinar cells (exocrine)

produce enzyme-rich juice

for digestion

• Pancreatic islets (islets of

Langerhans) contain

endocrine cells

• Alpha () cells produce

glucagon (hyperglycemic

hormone)

• Beta () cells produce

insulin (hypoglycemic hormone)

Pancreas - Glucagon

Extremely potent hyperglycemic agent

• Triggered by decreased blood glucose levels, rising amino acid

levels, or sympathetic nervous system

• Raises blood glucose levels by targeting liver to:

• Break down glycogen into glucose

• Glycogenolysis

• Synthesize glucose from lactic acid and other noncarbohydrates

• Gluconeogenesis

• Release glucose into blood

Pancreas – Insulin

Secreted when blood glucose

levels increase

• Synthesized as proinsulin that is

then modified

• Insulin lowers blood glucose levels

in three ways:

1. Enhances membrane transport of

glucose into fat and muscle cells

2. Inhibits breakdown of glycogen to

glucose

3. Inhibits conversion of amino acids or

fats to glucose

• Factors that influence insulin release

• Elevated blood glucose levels: primary stimulus

• Rising blood levels of amino acids and fatty acids

• Release of acetylcholine by parasympathetic nerve

fibers

• Hormones: glucagon, epinephrine, growth hormone,

thyroxine, glucocorticoids

• Somatostatin and sympathetic nervous system inhibit

insulin release

The Gonads and Placenta

• Gonads produce same steroid sex hormones as those of adrenal

cortex, just lesser amounts

• Ovaries produce estrogens and progesterone

• Estrogen

• Maturation of reproductive organs

• Appearance of secondary sexual characteristics

• With progesterone, causes breast development and cyclic changes in uterine mucosa

• Testes produce testosterone

• Initiates maturation of male reproductive organs

• Causes appearance of male secondary sexual characteristics and sex drive

• Necessary for normal sperm production

• Maintains reproductive organs in functional state

• Placenta secretes estrogens, progesterone, and human chorionic

gonadotropin (hCG)

Hormone Secretion by Other Organs

• Adipose tissue

• Adipose cells release:

• Leptin: appetite control; stimulates increased energy expenditure

• Resistin: insulin antagonist

• Adiponectin: enhances sensitivity to insulin

• Gastrointestinal tract

• Enteroendocrine cells secrete these hormones:

• Gastrin stimulates release of HCl

• Ghrelin from stomach stimulates food intake

• Secretin stimulates liver and pancreas

• Cholecystokinin (CCK) activates pancreas, gallbladder, and hepatopancreatic sphincter

• Incretins enhance insulin release and inhibit glucagon

• Skin

• Cholecalciferol precursor of vitamin D

• Calcitriol: active form of vitamin D that helps absorb calcium from intestine

Hormone Secretion by Other Organs

• Heart

• Atrial natriuretic peptide (ANP) decreases blood Na+ concentration, therefore

blood pressure and blood volume

• Kidneys

• Erythropoietin signals production of red blood cells

• Renin initiates the renin-angiotensin-aldosterone mechanism

• Skeleton

• Osteoblasts in bone secrete osteocalcin

• Prods pancreas to secrete more insulin; restricts fat storage; improves glucose handling;

reduces body fat

• Activated by insulin

• Low levels of osteocalcin are present in type 2 diabetes: perhaps increasing levels may be

new treatment

• Thymus

• Large in infants and children; shrinks with age

• Thymulin, thymopoietins, and thymosins may be involved in

normal development of T lymphocytes in immune response

• Classified as hormones but act as paracrines