Endocrine Exert influence by a second messenger. • Hormones that are lipid soluble can enter the cell membrane; thus, their receptors are located within the cell. – These hormones

7/3/02 Mr. Davenport © 1

ENDOCRINE SYSTEMEndocrine and Nervous Systems

Two Systems of Control

Hormones: chemical substances produced at one site which initiates or regulates the activity of an organ or group of cells in another part of the body.

Neurotransmitters: chemical substances which modifies or results in the transmission of nerve impulses at synapses.


Comparison of Endocrine and Nervous Systems

• Both systems rely on release of chemicals– Nervous: synaptic (mostly) and produces a rapid

response– Endocrine: circulating hormones which may last from a

few minutes to several hours• Both systems share many chemical messengers

– examples: norepinephrine (NE) and epinephrine (E)• Both systems respond primarily by negative feedback• Both systems preserve homeostasis by regulation of

activity of other cells, tissues, organs, and systems


Overview of Endocrine System

• Endocrine cells (glands) release into interstitial fluid– may influence local cells (paracrine) or if transmitted through the

blood and lymphatic systems may target at a distance

• Exocrine cells (glands) release their secretion into ducts.


HORMONE STRUCTURE• Classes of hormones

– Amino acid based• Amino acid derivatives (similar to amino acids)• Peptide hormones (dipeptide, polypeptide, proteins)

– Lipid based (steroid hormones, derived from cholesterol, and the eicosanoids, derived from a fatty acid)


AMINO ACID DERIVATIVES

• Include:– three catecholamines-

• (1) epinephrine (E), from adrenal medullae

• (2) norepineprine (NE), from adrenal medullae

• (3) and dopamine, from hypothalamus

– the thyroid hormones– and melatonin (from pineal gland)


Amino Acid Derivative -Examples

• Catecholamines are classified as biogenic amines (other biogenic amines include neurotransmitters, the indolamines, which include serotonin (from trytophan) and histamine (from histidine)


Peptide Hormones(amino acid based)

• hormones which are grouped as (1) peptides or small proteins and (2) glycoproteins

• their production follows the pattern of protein synthesis– DNA -> mRNA -> RER ->modification at ER

or Golgi to produce functional hormone


Peptide Hormone –Example

• Insulin is a short peptide hormone (other examples include glucagon, ADH, oxytocin, calcitonin, etc.)


LIPID DERIVATIVES• Include the steroids and eicosanoids• Steroids

– Lipids which have the general structure of four hydrocarbon rings.

– Hormonal steroids produced by the adrenal cortex (cortisol,mineralocorticoids) and gonads (estrogen, testosterone) are vital

– Cholesterol is steroid produced by liver and is used in cell membranes and in the manufacture of steroid hormones

General structure of steroid Cholesterol


Steroids include:• Androgens (from testes)

– Testosterone is an androgen (steroid) produced by the testes

• Estrogens (from ovaries)– Estradiol is an estrogen

(steroid) produced by the ovaries

• Corticosteroids (from adrenal cortex)

• Calcitriol (from kidney)


Eicosanoids include:• Eicosanoids are mostly

local in action– prostaglandins and

leukotrienes• Prostaglandin E2

– Prostaglandins are types of unsaturated fatty acids which effect

• Vasomotor tone• Capillary permeability• Platelet aggregation• Smooth muscle

contraction• ANS


DISTRIBUTION OF HORMONES

• Hormones are distributed mostly by circulatory system (remain functional for a few hours to a few minutes)

• Inactivated when– bound to receptors – broken down by liver or kidneys– broken down by enzymes in plasma or

interstitial fluid


HORMONE ACTIONS• Hormones alter cell activity

– either increase or decrease what the cell normally does

• Actions include changes with influence– permeability of plasma membrane– electrical state (ion channels)– protein synthesis; structural and/or regulatory molecules– enzyme activity: activates or deactivates enzymes– secretory activity– mitotic division


HORMONE FUNCTION• The activity of the target cell can be changed by

– Changes in membrane permeability can alter electrical activity of the cell; functions include -nerve conduction, release of neurotransmitter, and muscle contraction

– A new enzyme or a protein may be produced by the activation of genes

– The rate of synthesis of enzymes or proteins may be altered by changing the rate of transcription

– An existing enzyme can be turned “on” or “off” by a hormone changing the enzyme’s structure


HORMONES AND RECEPTORS

• Cells must have receptors for the binding of the hormone; or different receptors for different hormones

• Receptors are either located on the– cell membrane or– intracellular


HORMONES AND THE CELL MEMBRANE

• Hormones that are not lipid soluble can not enter the cell; thus, their receptors are located on the cell membrane. – These hormones are mostly the amino acid based

hormones and include ACTH, FSH, LH, Glucagon, PTH, TSH, Calcitonin, Catecholamines)

– Exert influence by a second messenger.• Hormones that are lipid soluble can enter the cell

membrane; thus, their receptors are located within the cell.– These hormones are mostly the steroid based hormones

and involve gene activation/inactivation, enzyme activation/inactivation, etc.


HORMONES AND MEMBRANE PROTEINS

• Hormone acts as a first messenger and results in the appearance of at least one second messenger in the cytoplasm.– Second messenger may function as enzyme

inhibitor, activator, or cofactor. Net result is a change in the metabolic reactions of the cell

• Amplification - binding of hormone may cause the release of many second messengers

• Several types of second messengers may be released in response to one hormone


Membrane Proteins

• Membrane bound proteins are a link between the first messenger and the second messenger

• Membrane proteins are activated when the first messenger (hormone) binds to its receptor and commonly results in the appearance of the second messenger.

• Common second messengers are cyclic-AMP and calcium ions


1. Hormone binds to receptor

2. Receptor binds to stimulatory protein (G protein).

3. Stimulatory protein (G protein) activates effector enzyme (adenylate cyclase)

4. Effector enzyme (adenylate cyclase) produces second messenger, cAMP.

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5. Cyclic AMP is second messenger and activates kinases which results in the activation of cellular enzymes.

Enzyme activity includes:1. increase synthesis of proteins, 2. induce secretory activity,3. open ion channels (change

electrical state/physical state)

Amplification is due to amount of cAMP produced

• Kinase: an enzyme that catalyzes the transfer of phosphate groups from a high-energy phosphate-containing molecule (as ATP) to a substrate

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Inhibition of Adenylate Cyclase

• Inhibitory G-proteins lead to reduction of cyclic AMP

• Reduction of cAMP (second messenger) results in enzymes not be activated (or inhibited)


HORMONES AND GENE ACTIVATION(INTRACELLULAR RECEPTORS)

• Steroid hormones diffuse easily across the cell membrane

• Activation (or deactivation) of genes occurs which alters transcription.


Hormones and Intracellular Receptors (con’t)

– Examples include:– Testosterone promotes production of enzymes

and structural proteins which promotes development of skeletal muscle.

– Thyroid hormones bind to mitochondria and chromatin receptors. Mitochondria binding increases rate of ATP production and chromatin receptors alters transcription of enzymes.


RELEASE OF HORMONES

• Most are controlled by negative feedback• Most endocrine glands are stimulated to

release their hormones by one of following:– humoral stimuli– neural stimuli– hormonal stimuli


Humoral Stimuli

• Humoral (fluid) stimuli include blood levels of ions, nutrients, etc.– Includes parathyroid hormone (PTH) PTH is

released in response to declining levels of ionic calcium. Increase levels of ionic calcium inhibit release of PTH.

– Other examples include insulin (blood sugar) and aldosterone (sodium ion).


Neural Stimuli

• ANS (sympathetic) stimulation of adrenal medulla to release catecholamines (epinephrine and norepinephrine)

• Also, includes oxytocin and antidiuretic hormone (ADH).


Hormonal Stimuli• Endocrine glands are the target of hormones

released by other endocrine glands.– Hypothalamus releases releasing and inhibition

hormones which influence the anterior pituitary.– Anterior pituitary releases hormones which influence

other endocrine glands, such as thyroid stimulating hormone -TSH. An example of hypothalmic-pituitary-target pathway


Hormonal Stimuli

• Neuroendocrine adjustments – can be made by the nervous system (such as

hypothalamus and sympathetic system) overriding the endocrine system.

• Hypothalamus is a “negative feedback” center concerned with emotions, biological rhythms, water balance, hunger, temperature, etc.


PITUITARY GLAND• Divided into

– anterior lobe (adenohypophysis)

• largest of two divisions and is composed mostly of glandular tissue

– posterior lobe (neurohypophysis)

• composed mostly of nerve fibers from hypothalamus

• 1 Neurons of Hypothalamus• 2 Infundibulum• 3 Anterior lobe (adenohypophysis)• 4 Posterior lobe (neurohypophysis)


Pituitary Gland• Anterior lobe (adenohypophysis) hormones

include the following:– Thyroid-stimulating hormone (TSH)– Adrenocorticotropic hormone (ACTH)– Follicle-stimulating hormone (FSH)– Luteinizing hormone (LH)– Growth hormone– Prolactin (PRL)

• Of these the first four are called tropic hormones because they directly influence the activity of other endocrine glands.


• TSH; thyroid stimulating hormone• ACTH; adrenocorticotropic hormone• FSH; follicle stimulating hormone• LH; luteinizing hormone• GH; growth hormone• PRL; prolactin

Hormones of the Anterior Pituitary Gland


Thyroid Stimulating HormoneTSH

• Targets the thyroid• Stimulates the secretion

of thyroid hormones -thyroxine and calcitonin

Thyroxine - effect is to increase glucose oxidation and promote growth and development

Calcitonin promotes utilization (storage) of calcium and calcium secretion by kidneys if blood levels are too high


Adrenocorticotropic HormoneACTH

• Targets the adrenal cortex• Stimulates the secretion of

glucocorticoids.– Glucocorticoids regulate

cell metabolism, especially that of glucose.


Follicle-stimulating HormoneFSH

• Targets the follicles of the ovaries– stimulates follicular

development

• Targets thesustentacular cells of the testes– stimulates the

increased production of sperm


Luteinizing hormoneLH

• Targets the “mature follicle” of ovary– triggers ovulation– development of corpus luteum– secretion of progesterone and

estrogen

• Targets the interstitial cells of the testes– secretion of testosterone


Growth HormoneGH

• Targets all cells of the body– promotes protein synthesis

and mobilization of lipids


Prolactin PRL

• Targets the breasts and increases production of milk


Endocrine Glands Targeted by Pituitary Hormones

• Tropic hormones of the pituitary– Thyroid-stimulating hormone (TSH) targets the

Thyroid Gland– Adrenocorticotropic hormone (ACTH) targets

the Adrenal Gland (Cortex)– Follicle-stimulating hormone (FSH) targets

both the ovaries and the testes– Luteinizing hormone (LH) targets both the

ovaries and the testes


THYROID GLAND• Located in anterior neck and

is composed mostly of folliclesand scattered cells called parafollicular cells

• Hormones include thyroxine and calcitonin:– Follicles produce thyroid

hormones (mostly thyroxine)

– Parafollicular cells produce thyroid hormonecalcitonin.


Thyroid Gland• A follicle consists of a colloid filled cavity which is

surrounded by cuboidal follicular cells– produce thyroid hormones (mostly thyroxine)– controlled by TSH (anterior pituitary)– targets most cells of the body (except brain, spleen, testes, uterus, and

itself)

– effect to increase glucose oxidation and promote growth and development

• Parafollicular cells are located among the follicles– produce thyroid hormone calcitonin– stimulus for secretion is high blood levels of ionic calcium– targets (1) osteoblasts (deposition of calcium) and (2)

kidneys (secretion in urine)


Thyroid Gland


PARATHYROID GLANDS• Two parathyroid glands located on posterior

surface of each lobe of thyroid• Endocrine cells are called chief cells• Produce parathyroid hormone (PTH)• Stimulus for secretion of PTH is decreased blood

levels of ionic calcium (hypocalcemia)• Targets

– (1) osteoclasts - remove calcium from bone – (2) kidneys - reabsorb calcium and conversion of

vitamin D to vitamin D3, calcitriol, which promotes intestinal absorption

– (3) intestine - promotes absorption of calcium


Parathyroid Glands


ADRENAL GLAND

• Located on superior border of each kidney

• Divided into adrenal cortex (2) and medulla Glomerulosa (3), fasiculata (4), reticularis (5)

• Surrounded by a capsule (1)


Adrenal Cortex

• Adrenal cortex (is divided into three major regions ) produces three major groups of hormones– Mineralocorticoids– Glucocorticoids– Gonadocorticoids


Adrenal CortexMineralocorticoids

• Mineralocorticoids - function in the electrolyte composition of body fluids.

• Aldosterone is the principal mineralocorticoid; it maintains sodium balance. Its primary role is the reabsorption of sodium from the forming urine. Along with sodium water is reabsorbed (osmotic). Thus, blood pressure and volume are maintained.

• Secretion is regulated by • (1) low blood levels of sodium, • (2) rising levels of potassium• (3) low blood pressure and/or volume.


Aldosterone


Adrenal CortexGlucocorticoids

• Glucocorticoids• regulate cell metabolism, especially that of glucose.

Release regulated by ACTH from anterior pituitary.

• Cortisol (hydrocortisone) is the principalglucocorticoid.


Adrenal CortexGlucocorticoids

• Effects - Cortisol (hydrocortisone) – Promotes gluconeogenesis (formation of glucose from

noncarbohydrate sources). – Mobilizes fatty acids from adipose and promotes their

catabolism as a primary source of energy, – Promotes the break-down of proteins to conserve available

glucose for the brain.• Downside of Glucocorticoids

– Stress triggers increase of ACTH and, thus cortisolproduction increases. Anti-inflammatory and anti-immune effects are associated with excess of cortisol.


Adrenal CortexGonadocorticoids

• Gonadocorticoids include both androgens and estrogens. Androgens (which include testosterone) are the primary gonadocorticoids.

• Hormones may be involved in outset of puberty• Androgens for females are thought to influence sex drive

and may be converted to estrogens after menopause• Hypersecretion of gonadocorticoids produces

masculinization. At a young age females produce facial hair, male pattern of hair distribution, and enlarged clitoris. Males develop early secondary sexual characteristics and an intense sex drive.


Adrenal Medulla• Consists of postganglionic neurons

of the sympathetic nervous system• Hypothalmic control releases the

hormones (neurohormones) epinephrine and norepinephrine into the blood

• Promotes the fight-or-flight response


PANCREAS• Located inferior to

stomach along posterior wall of abdomen

• Both an endocrine (1%) and exocrine organ (99%)

• Exocrine– pancreatic acini are

clusters of pancreatic cells which produce pancreatic juice, a major digestive fluid

• Endocrine– pancreatic islets

(Islets ofLangerhans)

– produce mostly insulin and glucagon


Glucagon and Insulin• Glucagon promotes hyperglycemia (it produces an increase

in blood sugar)– promotes breakdown of glycogen into glucose– promotes neoglucogenesis– promotes the release of glucose into blood

• Insulin promotes hypoglycemia (it produces a decrease in blood sugar)– promotes oxidation of glucose for energy– promotes the formation of glycogen– promotes the formation of lipids from glucose


Hyperglycemia and Hypoglycemia

• Hyperglycemia– is defined as increased blood sugar (above

normal value)– Insulin is produced to decrease blood sugar

(hypoglycemic in function)• Hypoglycemia

– is defined as decreased blood sugar (below normal value)

– Glucagon is produced to increase blood sugar (hyperglycemic in function)


TESTES - FSH and LH• LH targets the interstitial cells

which produce androgens• FSH targets the “seminiferous

tubules” which are the sites of sperm production. – house sustentacular cells and

spermatogenic cells


FSH and Spermatogenesis

• FSH targets the sustentacular cells of the seminiferous tubules which leads to an increase in spermatogenesis, the production of sperm


LH and Androgens• Interstitial cells are targeted by LH• Interstitial cells (cells of Leydig)

are responsible for the production of androgens (testosterone and

dihydrotestosterone) -– promote development of

secondary sexual characteristics– increase protein synthesis– increase sperm production


OVARY - FSH and LH• FSH targets “receptive” follicles

and promotes their development. Developing follicles produces estrogens.

• LH targets the “mature” follicle and promotes ovulation and development of corpus luteum.


FSH and Follicle Development• FSH targets “receptive” follicle (#2)• Estrogens are produced mostly by

developing follicles (#3-4) and by the corpus luteum (#6).

• Estrogens– promote development of

secondary sexual characteristics– target uterus and promote its

development• Corpus luteum (#6) develops from

ruptured follicle


LH - Ovulation and Corpus luteum

• LH– triggers ovulation– development of

corpus luteum– secretion of

progesterone and estrogen


THYMUS• Primary role is the

production of thymic hormones (thymosin) which promote the development of T cells (lymphocytes)

• Divided into small lobules which have an outer cortex and inner medulla.


T lymphocytes• T lymphocytes (T cells)

play a role in specific immunity by direct cell-to-cell interaction and the release of chemical mediators– include helper T cells,

cytotoxic T cells, suppressor T cells, memory T cells, etc.


KIDNEY

• Produces three major hormones– erythropoietin – calcitriol – renin


Kidney - Erythropoietin• Erythropoietin targets bone

marrow to increase production of RBC.

• Increased RBC production may be due to hypoxia– hemorrhagic anemias

(hemolytic or aplastic)– secondary polycythemia (high

altitude)– hemorrhage


Kidney - Calcitriol

• Calcitriol essential for absorption of calcium and phosphate by digestive tract– produced in response to PTH– dependent upon presence of vitamin D3

(cholecalciferol)– Vitamin D3 is produced by skin and supplied in

the diet.


Kidney - Renin

• Renin is released in response to decreased blood pressure and increased sympathetic (crisis) stimulation of renal nerves.

• Functions as an enzyme which converts inactive plasma protein, angiotensinogen, into cascading reactions leading to production of angiotensin (angiotensin II).


Kidney : Renin-Angiotensin Pathway• Primary purpose of the renin-angiotensin

pathway is to increase blood pressure• Angiotensin

– is a powerful constriction of vascular smooth muscle (increases peripheral resistance, and thus blood pressure)

– targets adrenal cortex to increase secretion of aldosterone. Aldosterone increases sodium ion reabsorption by the kidneys. Thus, the osmotic reabsorption of water. Blood volume increases, thus so does blood pressure.


Renin – Angiotensin Pathway


PINEAL GLAND

• Located in brain (part of diencephalon, the roof of epithalamus.

• Produces melatonin– Peak production around mid-night produces drowsiness– Lowest production around noon produces alertness

• Indirectly receives information from optic nerve• Melatonin influences hypothalamus “biological

clock” region.


Additional Hormone Producing Organs

• Heart produces atrial natriuretic peptide (ANP)– Function to decrease blood pressure, blood volume, and

sodium .• Gastrointestinal tract has enteroendocrine cells

which influence digestive tract activity• Placenta produces estrogen, progesterone, and

hCG (human chorionic gonadotropin)• Skin produces cholecalciferol (precursor to

vitamin D)

Documents

Endocrine Exert influence by a second messenger. • Hormones that are lipid soluble can enter the cell membrane; thus, their receptors are located within the cell. – These hormones