Lecture Notes: Chemical Signals & The Endocrine System

I. Hormones / Target Cells

A. Chemical Signals -- Chemoreception

1. Food, Pheromones, Hormones, Neurotransmitter
2. Earliest organisms (single celled prokaryotes)

a. mechanisms for detecting external signals for food, for sex.
b. sensory transduction:

external signal >> cell curface Receptor >> internal signal

3. Multicellular organisms...

a. elaborate mechanisms for detecting and responding to sigals
b. external signal detection (organismic)
c. "internal" signal detection

- internal is "external" to individual cells, tissues, organs, etc.

4. Evolutionary origins of hormones / pheromones...

a. Cells / organisms leak out specialized metabolites.
b. other cells "pick up" / detect metabolites >>> "respond"
c. Evolutionary Selection
d. e.g. fish pheromones are steroid sex hormones / hormone metabolites

- males opportunistically monitor for presence of hormones in water

- male physiology and behavior responds...

B. Coordination requires communication: chemoreception

1. chemoreception very old - prokaryotes monitoring environment
2. organisms detect their own metabolites
3. system evolves towards specialization

C. hormon - "excite": "A chemical secreted by cells in one part

of the body that is transported in the bloodstream to other parts
of the body, where it affects particular target cells."

- example: hypothalamus, pituitary

D. History:

1. Darwin and Plants (review plant hormone lectures)

a. late 1800s
b. observations of factors influencing phototaxis

2. Insect hormones

a. 1930s
b. factors in blood influencing development

II. Hormone Action: triggered synthesis and/or release - target stimulation - clearance

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A. Hormones come from secretory cells

1. endocrine glands

a. loosely associated secretory cells intermingling with capillaries
b. hormone secreted, diffuses to capillary, travels blood to target
c. chemically stimulated

2. neurohemal organ

a. neurosecretory cells - neurons
b. terminate at capillary (instead of another neuron)
c. neuronally stimulated (stimulated by other neurons)

B. Hormones: chemical diversity -

1. peptides (gene products)

generally small.. few to 30 amino acids (Eckert p.296)
some proteins (200 amino acids or more; e.g. insulin, GH, TSH)

2. modified amino acids

epinephrine (adrenaline), norepinephrine (noradrenaline)
thyroid hormone (thyroxine - tyrosine dimer)

3. steroids - cholesterol-like

progesterone, estrogen, testosterone, aldosterone

4. modified fatty acids

prostaglandins

C. Synthesis and release - triggered

1. Secretory Cells

a. synthesize and release chemicals
b. hydrophilic chemicals - vesicle storage and release
c. lipophilic chemicals - move through membranes / binding proteins

2. Gland and Cell Types

a. Exocrine Glands

- secretion into lumen
- duct allows release to outside of body (e.g. skin / digestive tract)

b. Endocrine Glands

- cells in close association with capillaries
- secretion into interstitial space
- diffusion into blood - transport to target

c. Neurosecretory Cells

- neurons / endings near capillaries - release into blood
- release site
- synthesis in cell body (esp. peptides)- axonal transport to terminals

3. Mechanism of release

a. steroids:

- lipid soluble - readily enter cells
- stimulus leads to biosynthesis
- synthesized steroid leaks out
- storage in fat tissues
- transport in blood assisted by carrier proteins (serum albumin)


b. hormones that are NOT steroids or lipids

- synthesized, packaged into vesicles via golgi
- vesicles migrate to and collect at release site
- activated release
- exocytosis to dump contents
- typically Ca++ sensitive; regulate Ca++ / regulate release


4. Simulation - regulation of release - triggered release

a. "sensory" input
b. hormonal regulation
c. neural regulation


D. Target activation - Signal Transduction

1. Concept of Target Cells : Target Specific Receptors

a. since hormone enters blood every cell is exposed
b. only specific "target" cells respond
c. only "target" cells contain receptors to recognize hormone

2. Cell Surface Receptors - Second Messenger Systems

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a. Lipophobic Hormones : no crossing of membrane
b. Membrane Bound Receptor Proteins

- external binding site highly specific to given hormone structure
- like a switch - external activation leads to internal activation

c. Second messengers

- "Second messenger" is an historic term

-- stimulate a cell with a hormone
-- observe the production of an intracellular chemical
-- the intracellular chemical became known as 2nd Messenger
-- excitement because only a few identified

2nd Messenger chemicals but huge number of
cellular responses throughout the body

-- 2nd Messengers include cAMP, cGMP, Ca++, NO, CO
-- specific enzymes are activated to produce 2nd Messengers

d. G-proteins

- more recently, G-proteins were discovered
- act as intermediate messenger between many receptors

and their 2nd Messenger Enzymes

- H+R > activated G-protein >>> 2nd Messenger >>>>> Response
-"G-Protein Coupled Receptors"

e. Second Messenger activated cellular response

- activation of Protein Kinase leads to modification

by phosphorylation

- release of Ca++ into cytoplasm leads to many possible reactions

f. Detail Example 1. cAMP pathway

- Receptor >>> G-protein >>> adenylate cyclase [ATP >> cAMP]
- cAMP >>> protein kinase (PKA) >>> phosphorylation >>> activation
- PKA targets may be cytosolic proteins (biochem. regulation) or transcription factors (i.e. gene expression)

g. Detail Example 2. IP3 and Calcium

- Receptor >>> G-protein >>> phospholipase C (PIP >> IP3 + DAG)
- IP3 >>> Ca++ channels >>> [Ca++] increases
- Ca can activate many proteins by binding to them
- Protein Kinase C >>> phosphorylation >>> activation

h. others Examples, all hormone receptor mediated, could include...

cGMP, NO, CO

i. SIGNAL AMPLIFICATION

- One hormone molecule generates many 2nd Messenger molecules
- Each 2nd Messenger activated multiple targets
- Each target may be an activator, hitting many targets

-- i.e. Protein Kinases

3. Intracellular Receptors - Steroids

a. Steroids are Membrane soluble

- kept in solution by binding/carrier proteins

b. Nuclear binding proteins = receptors

- DNA regulation: H + R > HR > DNA binding > enhance transcription
- Steroid hormone receptors are homodimers in mammals (vertebrates?) and heterodimers in insects.
- Further regulation through interaction between HR and co-activator and co-supressor proteins.


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4. Responses:


a. hormones release hormones
b. alter existing proteins: physiological change / metabolic change

- ^ BP > aldosterone > ^ NaCl reabsorption distal tubule

c. make new proteins - gene expression


E. Inactivation: Metabolic Conversion

III. Endocrine Systems

A. Hypothalamus / Pituitary: Master Gland

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1. Organization

a. Neurosecretory Cells
b. Hypothalamus towards base of brain, in front of brain stem
c. Pituitary protrudes down, below hypothalamus

- posterior pituitary

-- receives two kinds of NS cell from Hypothalamus
-- Antidiuretic Hormone (ADH, vasopresin)
-- Oxytocin

- anterior pituitary

-- true endocrine tissue
-- 7 major hormones
-- stimulated by hypothalamic hormones

d. portal vessel

- artery arrives at hypothalamus, splits
- one branch passes neurohemal organ in hypothalamus

picks up NS hormones if secreted
goes directly to anterior pituitary
stimulates targets in AP, picks up AP hormones

- other branch goes to posterior pituitary

-- delivers hormones
-- picks up ADH or Oxytocin if released

2. Hormones

a. Posterior Pituitary

- ADH (peptide)

-- drop in blood osmolarity releases ADH
-- acts on kidney: distal tubule, collecting duct

--- increases water reabsorption / NaCl reuptake

- Oxytocin (peptide)

-- acts on smooth muscle
-- milk release from mammary glands
-- uterine contractions
-- recent study in transgenic mice without oxytocin

--- mice were pretty much normal (no nursing)

b. Anterior Pituitary

- Growth Hormone (GH) (peptide)

-- regulates body growth
-- increases protein synthesis, fat use, carb. storage
-- stimulates bone growth

- Prolactin (PL) (peptide)

-- stimulates development of mammary glands during preg.
-- stimulated by nursing - stimulates milk production

- Follicle-stimulating Hormone (FSH) (peptide)

-- stimulate production of sperm, testosterone
-- stimulate production of egg, estrogen, progesterone

- Luteinizing Hormone (LH) (peptide)

-- stimulate production of sperm, testosterone
-- stimulate production of egg, estrogen, progesterone

- Thyroid-stimulating hormone (TSH) (peptide)

-- stimulates thyroid gland

- Adrenocorticotropic hormone (ACTH) (peptide)

-- stimulates adrenyl gland

- Melanocyte stimulating hormone (MSH) (peptide)

-- stimulate pigment cells, not clear in humans

- Endorphins (peptides)

- natural opiates

c. Hypothalamic Hormones: releasing factors

- LHRH, TSHRH, etc.
- stimulatory, inhibitory


B. Thyroid, Parathyroid

1. glands in neck
2. Thyroid Gland

a. thyroxin

- double tyrosine with 4 iodines
- regulates metabolic rate, dev. and growth of nervous system
- stimulated by TSH from pituitary which is in turn regulated

by thyroxin in the blood
-- cold stress >> TSHRH >> (+)TSH >> (+)thyroxine >> (-)TSH
-- thyroxine action increases metabolic heat reducing cold stress


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TSHRH = "Thyroid Stimulating Hormone Releasing Hormone"
TSH = "Thyroid Stimulating Hormone"
TH = "Thyroid Hormone"
b. calcitonin (peptide)

- peptide (first identified alternatively spliced gene product)
- Calcium regulation

-- calcium absorption and release by bones

3. Parathyroid

a. parathormone (peptide)

regulates blood calcium

-- calcium absorption and release by bones
-- up-regulates during lactation - supply calcium needs


C. Pancreas

1. Exocrine - digestive enzymes
2. Endocrine - Islet cells

a. Insulin (peptide - ca. 50 amino acids)

increase in blood glucose >> insulin >> induce glucose uptake
glucose burned or stored (glycogen), lowering blood glucose

b. Glucagon (peptide)

decrease in blood glucose >> glucagon >>
activates enzyme converting glycogen to glucose
for energy metabolism

c. Diabetes mellitus

- inability to regulate glucose levels via insulin

(no functional insulin)


D. Gonads: Androgens - steroids

1. Estrogen
2. Progesterone
3. Testosterone


E. Adrenal Glands

1. Adrenal Medulla

a. epinephrine & norepinephrine (modified amino acid)

- adrenaline, noradrenaline
- fright or flight
- increase heart rate, resp. rate, blood glucose
- direct blood towards brain, away from gut
- neural activation

2. Adrenal Cortex

a. glucocorticoids (steroids)

- regulate glucose metabolism
- stimulated by ACTH (pituitary)
- stress >> ACTHRH >> ACTH >> Glucocorticoids

-- increase blood glucose

b. aldosterone (steroid)

- drop in blood sodium >> aldosterone >>

Na reabsorption in kidney increased

c. testosterone (less than testes)


F. Prostaglandins

1. produced in many cells
2. modified fatty acids - from membrane phospholipids
3. diverse forms

- blood clotting, uterine contractions
- inflammation
- lung expansion

4. egg laying in crickets!


G. Miscellaneous

1. Pineal Gland - melatonin (modified amino acid) - circadian regulation
2. Thymus- thymosin - stimulates dev. of T-Cells
3. Kidney - Erythropoietin, renin (antgiotensin regulator)
4. Heart - Atrial Natriuretic peptide (ANP)

- increase blood volume >> ANP release >> inhibit ADH and aldosterone

5. Stomach - gastrin, secretin, cholecystokinin

Lecture Outline: The Endocrine System I Chapter 35, 10/25/96

I. Hormones / Target Cells

A. Chemical Signals -- Chemoreception
B. Coordination requires communication: chemoreception
C. "hormon" - "excite": "A chemical secreted by cells in one part of the body that is transported
in the bloodstream to other parts of the body, where it affects particular target cells."

D. History: Plants and Bugs

II. Hormone Action: triggered synthesis and/or release - target stimulation - clearance

A. Hormones come from secretory cells

1. endocrine glands
2. neurohemal organ

B. Hormones: peptides; modified amino acids; steroids; modified fatty acids
C. Synthesis and release - triggered

1. Secretory Cells
2. Gland and Cell Types

a. Exocrine Glands
b. Endocrine Glands
c. Neurosecretory Cells

3. Mechanism of release

a. hormones that are not steroids or lipids
b. steroids:

4. Simulation - regulation of release - triggered release

D. Target activation - Signal Transduction

1. Concept of Target Cells : Target Specific Receptors
2. Cell Surface Receptors - Second Messenger Systems

a. Lipophobic Hormones : no crossing of membrane
b. Membrane Bound Receptor Proteins
c. Second messengers
d. G-proteins
e. Second Messenger activates cellular response
f. Detail Example 1. cAMP pathway
g. Detail Example 2. IP3 and Calcium
h. others Examples, all hormone receptor mediated, could include...
i. SIGNAL AMPLIFICATION

3. Intracellular Receptors - Steroids

a. Steroids are Membrane soluble
b. Nuclear binding proteins = receptors

4. Responses:

a. hormones release hormones
b. alter existing proteins:
c. make new proteins

E. Inactivation: Metabolic Conversion

III. Endocrine Systems

A. Hypothalamus / Pituitary: Master Gland

1. Organization
2. Hormones (peptides)

a. Posterior Pituitary, ADH, oxytocin
b. Anterior Pituitary: GH, PL, FSH, LH, TSH, ACTH, MSH, Endorphins
c. Hypothalamic Hormones: releasing factors

B. Thyroid; Parathyroid: thyroxin, calcitonin; parathormone
C. Pancreas: Islet cells - Insulin, Glucagon
D. Gonads: Androgens (steroids) Estrogen; Progesterone; Testosterone
E. Adrenal Glands

1. Adrenal Medulla: epinepherine & norepinepherine
2. Adrenal Cortex: glucocorticoids; aldosterone; testosterone

F. Prostaglandins
G. Miscellaneous

Pineal Gland -melatonin; Thymus - thymosin; Kidney - Erythropoietin, renin
Heart - Atrial Natriuretic peptide; Stomach - gastrin, secretin, cholecystokinin

Vocabulary