1

INTRODUCTION TO ENDOCRINOLOGY
Chemical Messenger Systems:
Coordinate multiple activities of cells, tissues and organs of the body
Neurotransmitters: released by axon terminals of neurons into the synaptic junctions
o act locally to control nerve cell functions
Endocrine hormones: released by glands or specialized cells into the circulating blood
o Influence the function of cells at another location in the body
o Carried by circulatory system to cells throughout the body
Hormones that affect specific target tissue
ACTH- specifically stimulates the adrenal cortes to secrete
adrenocortical hormones
Ovarian hormones-specific effects on the female sex organs as well
as on secondary sexual characteristics of the female body
Hormones that affect many different types of cells of the body
Growth hormone- causes growth in most parts of the body
Thyroxine- increases the rate of many chemical reactions in almost
all the body cells
Neuroendocrine hormones: secreted by neurons into the circulating blood
o Influence the function of cells at another location in the body
o Neuroendocrine cells located in the hypothalamus have axons that terminate in
the posterior pituitary and median eminence
ADH, Oxytocin, hypophysiotropic hormones (control secretion of anterior
pituitary hormones)
Paracrines: secreted by cells into the extracellular fluid and affect neighboring cells of a
different type
Autocrines: secreted by cells into the extracellular fluid and affect the function of the
same cells that produced them by binding to cell surface receptors
Cytokines: peptides secreted by cells into the extracellular fluid and can function as
autocrines, paracrines or endocrine hormones
o Examples: interleukins and other lymphokines that are secreted by helper cells
and act on other cells of the immune system
Cytokine hormones (Leptin) Produced by adipocytes- AKA Adipokines
Functions of Multiple hormone systems:
o Metabolism: without thyroxine and triiodothyronine- almost all chemical
reactions become sluggish
Without insulin the bodys cells could use little of the food carbohydrates
for energy
o Growth and Development: without growth hormone- dwarfism
o Water and electrolyte balance
o Reproduction : without sex hormones, sexual development and sexual functions
would be absent
3 General Classes of hormones
Proteins and polypeptides: includes hormones secreted by the anterior and posterior
pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (PTH)
o Stored in secretory vesicles until needed
o Most hormones belong to this general class
o Varied size: small peptides as few as 3 amino acids- TRH; proteins with almost 200
amino acids (GH and Prolactin)
o Polypeptides with 100 or more Amino acids are called proteins, and those with less
are called peptides
2
INTRODUCTION TO ENDOCRINOLOGY
o Water soluble which allows them to enter circulatory system easily for transport to
their target tissues
o Synthesized in the rough end of the ER of the different endocrine cells then
transferred to GA for packaging into secretory vesicles
Enzymes in vesicles cleave the prohormones into smaller, biologically active
hormones
Vesicles are stored within the cytoplasm and many are bound to the cell
membrane until their secretion is needed
Secretion of hormones occur by exocytosis
Stimulus for exocytosis is an increase in cytosolic calcium concentration
caused by depolarization of plasma membrane
Stimulus for exocytosis may also come from stimulation of endocrine cell
surface receptor that causes an increase in cAMP and subsequent activation
of protein kinases that initiate the secretion of the hormone
Steroids: secreted by adrenal cortex (Cortisol and aldosterone),the ovaries (estrogen and
progesterone), testes (testosterone) and placenta (estrogen and progesterone)
o Usually synthesized from cholesterol and are not stored
o Similar chemical structure with cholesterol
o Lipid soluble- simply diffuse across the cell membrane once synthesized and enter
the interstitial fluid and then to the blood
o There is very little hormone storage in steroid producing endocrine cells
Large stores of cholesterol esters in cytoplasm vacuoles can be rapidly
mobilized for steroid synthesis after a stimulus
Cholesterol may also be produced in steroid producing cells
Derivatives of amino acids tyrosine: secreted by thyroid gland (T4, T3) and the adrenal
medullae (epinephrine and norepinephrine)
o 2 groups of hormones derived from tyrosine
Thyroid hormones:
Formed from actions of enzymes in the cytoplasmic compartments of
glandular cells
Thyroid hormones are synthesized and stored in the thyroid gland and
incorporated into macromolecules of the protein thyroglobulin, which is
stored In large follicles within the thyroid gland
Hormone secretion occurs when the amines are split from
thyroglobulin and the free hormones are then released into the blood
stream
Thyroxin-binding globulin (TBG) are plasma proteins that bind the
thyroid hormones in the blood
o TBG slowly releases the hormones to the target tissues
Adrenal Medullary hormones:
Epinephrine and norepinephrine are formed in the adrenal medulla
Normally there are four times more epinephrine than norepinephrine
Catecholamines are taken up into preformed vesicles and stored until
secreted by exocytosis
Once catecholamines enter circulation they can exist the plasma in
free form or in conjugation with other substances.

Hormone Secretion, Transport and Clearance from the Blood

Onset of Hormone Secretion and Duration of action
3
INTRODUCTION TO ENDOCRINOLOGY
o Every hormone has its characteristic onset and duration of action- tailored to
perform its specific control function
Norepinephrine and Epinephrine: secreted within seconds after stimulation
Develop full action within another few seconds to minutes
Thyroxine, Growth Hormone: require months for full effect
Aldosterone 45 minutes up to several hours even days

Feedback Control of Hormone Secretion:

Negative feedback: prevents overactivity
o Ensures proper level of hormone activity at the target tissue
o Control variable is the degree of activity of target tissue (not rate of secretion)
Positive feedback:
o Biological action of a hormone causes additional secretion of the hormone
LH surge- occurs as a result stimulatory effect of estrogen on the anterior
pituitary before ovulation. Secreted LH then acts on the ovaries to stimulate
additional secretion of estrogen which in turn causes more secretion of LH
until it reaches an appropriate concentration, and typical negative feedback
control of hormone secretion is then exerted
Cyclical variations:
o Superimposed on negative and positive feedback control are periodic variations in
hormone release that are influenced by:
Seasonal changes
Various stages of development and aging
Diurnal cycle
Sleep
GH is markedly increased during early period of sleep but is reduced in
the later stages of sleep

Transport of Hormones in the blood:

Water soluble hormones (Peptides and Catecholamines)
o Dissolved in plasma and transported from their sites of synthesis to target tissues
where they diffuse out of capillaries, into the interstitial fluid and ultimately to
target cells
Steroid and Thyroid hormones:
o Bound to plasma proteins as they circulate in blood
o Less than 10% of steroid or thyroid hormones (99% bound) in the plasma exist free
in solution
o Protein bound hormones cannot easily diffuse across the capillaries and gain access
to target cells therefore are biologically inactive until they dissociate from plasma
proteins
Protein bound hormones serve as reservoirs and as long as bound, retards
their metabolic clearance form plasma

Clearance of Hormones from Plasma:

2 factors that affect concentration of hormone in the blood
o Rate of hormone secretion in the blood
o Rate of hormone removal from the blood/ Metabolic clearance rate (ml of plasma
cleared of the hormone/minute)
Clearance
4
INTRODUCTION TO ENDOCRINOLOGY
o Metabolic destruction
o Binding with tissues
o Excretion by liver into the bile
o Excretion by the kidneys into urine
o Peptide hormones and catecholamines being water soluble circulate freely in the
blood
Usually degraded by enzymes in the blood and tissues
Rapidly excreted by the kidneys and liver therefore remain in the blood only
for a short time
Angiotensin II half life is less than a minute
o Hormones bound to plasma proteins are cleared at a much slower rate
May remain in circulation for several hours to days
Adrenal steroids half life- 20-100 minutes
Thyroid hormone half life- 1-6 days

MECHANISMS OF ACTION OF HORMONES:

Hormone Receptors and their Activation:
Binding with specific receptors: 1st step of hormone action
o Cells that lack receptors for the hormones do not respond
Receptor sites:
o On the target cell membrane: specific mostly for the protein, peptide and
catecholamine hormones
o Cytoplasm: primary receptor for the different steroid hormones
o Nucleus: for thyroid hormones believed to be directly associated with one or
more of the chromosomes
Receptor hormone interaction results in a cascade of reactions in the cell, with each
stage becoming more powerfully activated so that even small concentrations of the
hormone can have a large effect
Receptors: large proteins numbering 2,000 to 100,000 in each cell
o Specific for a single hormone

Regulation of the Number and Sensitivity of Hormone Receptors:

Number of receptors in a target cell do not remain constant on a day to day or even on a
minute to minute basis
o Inactivated or destroyed during the course of their function
o Reactivated or new ones are manufactured by the protein manufacturing
mechanism of the cell
Down regulation (decreased target tissue responsiveness) of receptors occur as a result of:
o Inactivation of some receptor molecules
o Inactivation of some intracellular protein signaling molecules
o Temporary sequestration of the receptor to the inside of the cell
o Destruction of receptors by lysosomes after being internalized
o Decreased production of receptors
Up regulation- target tissue becomes progressively more sensitive to the stimulating
effects of the hormone
o Stimulating hormone induces a greater than normal formation of receptor or
intracellular signaling molecules by the protein manufacturing machinery of the
target cell
5
INTRODUCTION TO ENDOCRINOLOGY

Intracellular Signaling after Hormone Receptor Activation:

Ion Channel- Linked Receptors
Neurotransmitter substances combine with receptors in the postsynaptic membrane
Opening or closing of ion channels of one or more ioins
o Na, K, Ca etc..
o Altered movement of ions causes subsequent effects on postsynaptic cells
Some hormones directly affect the ion channels directly through ion channel
receptors
Most hormones open or close ion channels indirectly by coupling with:
G protein-linked receptors
Enzyme linked receptors
G protein linked Hormone receptors
o When the ligand binds to the extracellular part of the receptor, a conformational
change occurs in the receptor that that activates the G proteins that results in
intracellular signals leading to one of the following:
Open or close cell membrane ion channels
Change the activity of an enzyme in the cytoplasm of the cell
o G proteins (heterotrimeric GTP-binding proteins) are cell membrane proteins with 7
transmembrane segments that loop in and out of the cell membrane, it has a
cytoplasmic tail that is coupled with a trimeric G protein subunit, the , and
Bind guanosine diphosphate (GDP) on the subunits of G protiens
Receptor activation
Conformational change that causes GDP bound trimeric G protein to
associate with the cytoplasmic part of the receptor
GDP is exchanged for GTP. The displacement of GDP causes the subunit to
dissociate from the trimeric complex
subunit associates with other intracellular signaling proteins which in turn
alter the activity of ion channels or intracellular enzymes (adenylyl cyclase or
phospholipase C) that alter cell function
Signaling is rapidly terminated when the hormone is removed
subunit inactivates by converting GTP to GDP and recombining with
and subunits to form the inactive membrane bound trimeric G
protein
* G proteins may be inhibitory (Gi) or stimulatory (Gs)
Enzyme linked Hormone Receptors
o Receptors that when activated function directly as enzymes or are closely
associated with enzymes that they activate
o Hormone binding site is outside the cell membrane and their catalytic or enzyme
binding site on the inside
Hormone binds with extracellular site
6
INTRODUCTION TO ENDOCRINOLOGY
Enzyme immediately in the cell membrane is activated ( or occasionally
inactivated)
Intracellular Hormone receptors and Activation of Genes:
o Lipid soluble hormones: Adrenal and gonadal steroid hormones, thyroid hormones,
retinoid hormones, and vitamin D bind with protein receptors inside the cell, not on
the cell membrane
o Lipid soluble hormones readily cross the cell membrane and interact with receptors
in the cytoplasm or nucleus
Activated hormone receptor complex binds with specific regulatory sequence
(promoter) of the DNA called the hormone response element
Activate or repress transcription of specific genes and formation of mRNA
Minutes to hours or even days after the hormone entered the cell, newly
formed proteins appear in the cell to alter cellular function

Secondary messenger Mechanisms

Adenylyl Cyclase- Camp Second Messenger System
Hormone bound to receptor that couples receptor to a G protein
G protein stimulates adenylyl cyclase, a membrane bound enzyme
Adenylyl cyclase catalyzes the conversion of cytoplasmic ATP in cAMP
c AMP ACTIVATES cAMP dependent protein kinase which phosphorylates
specific proteins (cascade of enzymes) in the cell, triggering biochemical
reactions that lead to a cellular response to the hormone
o Gs promotes formation of adenylyl cyclase
o Gi inhibits formation of adenylyl cyclase
o Hormones that use adenylyl cyclase-cAMP: ACTH, Angiotensin II, Calcitonin,
Catecholamines, CRH, FSH, Glucagon, HCG, LH, PTH, Secrtin, Somatostatin, TSH,
Vasopressin
Cell membrane Phospholipid Second messenger system
o Hormones activate transmembrane receptors that activate the enzyme
phospholipase C
o Phospholipase C catalyzes the breakdown of some phospholipids in the cell
membrane, especially phosphatidylinositol biphosphate (PIP2) into inositol
triphosphate (IP3) and diacylglycerol (DAG)
o IP3 mobilizes calcium ions from mitochondria and ER, Ca ions have their own
second messenger effect such as smooth muscle contraction and changes in cell
secretion
o DAG activates protein kinase C (PKC) which phosphorylates a large number of
proteins leading to cell response
Lipid portion of DAG, arachidonic acid is the precursor for prostaglandins and
other local hormones that has multiple effects in tissues throughout the body
Calcium-Calmodulin Second Messenger System:
o Messenger system that operates in response to the entry of calcium into the cells
o Calcium entry may be initiated by:
Changes in membrane potential that open calcium channels
Hormone interacting with membrane receptors that open calcium channels
o Cacium ions as they enter the cell bind with calmodulin (has 4 calcium sites)
o When 3-4 sites are bound with calcium- it changes shape to initiate multiple effects
Activation or inhibition of calmodulin dependent protein kinases- cellular
response to the hormone
7
INTRODUCTION TO ENDOCRINOLOGY
Ex. Myosin kinase acts directly on myosin of smooth muscles to cause
contraction

Hormones that Act Mainly on the Genetic Machinery of the Cell

Steroid hormones- synthesis of protein in target cells
o Enzymes
o Transport proteins
o Structural proteins
Steroid hormone diffuses across cell membrane to bind with a specific receptor protein
Complex diffuses into or transported into nucleus
Complex binds at specific points on DNA strand of chromosomes to activate
transcription
mRNA diffuses into cytoplasm to promote translation