CLINICAL CHEMISTRY 3

MIDTERMS
Introduction to Hormones
Hypothalamus, Hypophysis
Thyroid Gland
Parathyroid Gland
Pancreas
FINALS
Adrenal Glands
Female Reproductive System
Male Reproductive System
Miscellaneous Hormones
Toxicology
 ENDOCRINOLOGY
The study of hormones, the endocrine
system, and their role in the physiology of
the body.

- Clinical chemistry 3 deals with the

diseases associated with the hormones.
 HORMONES
A chemical released from living cells
that travels through the blood to
target tissues to have a biological
effect
Secreted in very small amounts
Target cells have specific receptors
Regulates cell reactions by affecting gene
expression (often gene transcription
factors)
 CONCEPTS IN ENDOCRINOLOGY

ENDOCRINE GLANDS secretes its products into

the interstitial fluid and the blood.

A HORMONE is a chemical messenger that travel

through the bloodstream to TARGET CELLS

TARGET CELLS are those cells with specific

receptors to hormones, therefore, reacts to the
presence of such substances.
 TARGET CELLS
Body cells that contain receptors for specific
hormones

Note: only cells with specific receptor will

react with a specific receptor. The reaction
is specific and concentration dependent
CONCEPT OF TARGET CELLS
 2 Types of Glands:

1. Endocrine glands

2. Exocrine glands

9
EXOCRINE AND ENDOCRINE
 EXOCRINE GLANDS

Glands with ducts. Their products pass out of the

cell and away from the gland by means of ducts
into a luminal area such as oral cavity and
intestine.

Examples: Amylase, lipase and trypsin from the

pancreas
 ENDOCRINE GLANDS

Ductless glands interspersed with many blood

capillaries. Their products are released from the
cell, passed directly into the circulation and are
carried by the blood to body tissues

The bodys slow chemical communication system

MANNERS OF SECRETIONS
Autocrine
Paracrine
Juxtacrine
Ectocrine
Intracrine
Endocrine
AUTOCRINE
Interaction
between secreted
chemical
messenger with a
receptor on the
cell that
synthesized it
PARACRINE
Interaction of a
secreted
chemical
messenger with
receptors on
other cells
REVIEW
Endocrine: Chemical messenger produced by a
ductless gland or tissue and carried in the blood to a
target organ where it effects a change in cellular
activity.

Effector Target
Cell 1 Cell 2

Capillary
 MANNER OF SECRETIONS
1)Paracrine - released from effector cell (E) interact
with a different target cell (T)

E T

2) Autocrine - secreted by E interact with original E

cell or similar cell types.

(Figure 9-1)
MANNER OF SECRETIONS
3) Juxtacrine -expressed on surface of effector cell
and interacts with target cell via direct cell-cell
contact

E T
4) Intracrine Secretes own hormone within an
intercellular to bind to a receptor.
TYPES OF ENDOCRINE ACTIONS
5) Ectocrine (Pheromones)
One organism releases a subtance that causes
a response in another organism
 PRINCIPAL FUNCTIONS OF THE
ENDOCRINE SYSTEM

Maintenance of the internal environment

in the body (maintaining the optimum
biochemical environment)

Glucose
Calcium
Sodium
 PRINCIPAL FUNCTIONS OF THE
ENDOCRINE SYSTEM

Integration and regulation of growth and

development
1.
2.

Control, maintenance and instigation of sexual

reproduction, including gametogenesis, coitus,
fertilization, fetal growth and development
and nourishment of the newborn
NERVOUS SYSTEM VS
ENDOCRINE SYSTEM
A Comparison
NERVOUS SYSTEM

The nervous system exerts

point-to-point control through
nerves, similar to sending
messages by conventional
telephone. Nervous control is
electrical in nature and fast.
 HORMONES TRAVEL VIA THE
BLOODSTREAM TO TARGET CELLS

The endocrine system broadcasts

its hormonal messages to
essentially all cells by secretion into
blood and extracellular fluid.
Like a radio broadcast, it requires
a receiver to get the message - in
the case of endocrine messages,
cells must bear a receptor for the
hormone being broadcast in order
to respond.
 A CELL IS A TARGET BECAUSE IT HAS A
SPECIFIC RECEPTOR FOR THE HORMONE

Most hormones circulate in the blood, coming into

contact with essentially all cells. However, a given
hormone usually affects only a limited number of
cells, which are called target cells. A target cell
responds to a hormone because it bears receptors
for the hormone.
MAJOR ENDOCRINE GLANDS
CONCEPTS TO REMEMBER!!
CELL MEMBRANE are BILIPID-LAYER
(HYDROPHOBIC)
BLOOD is more than 90% water
Any water-soluble substance cannot enter but a
hydrophobic substance can easily enter a cell.
Hydrophobic substances require transport proteins.

Example: Glucose (water soluble) cannot easily enter

the cells. It requires channel for it enter. On the
other hand, cholesterol (hydrophobic) can easily
diffuse into the cell.
 Types of Hormones

PEPTIDE (at least 3 amino acids)

Water soluble; No need for transport proteins
Most abundant
Stored in vesicles
Cell surface receptors
Activation of messenger enzymes
STEROIDS Derived from Cholesterol
Water insoluble (hydrophobic)
Requires transport proteins; LONGER HALF-LIFE
Intracellular receptors
Protein synthesis
Derived from tyrosine amino acid
AMINES
T3/T4, Norepinephrine, Epinephrine
T3/T4 behaves like steroid hormones
Norepinephrine, Epinephrine behave like protein hormones
Cell surface or Intracellular receptors
Polypeptides
Insulin FSH Oxytocin
glucagon LH thyrotropin
somatotropin vasopressin ACTH

Steroids Aldosterone Estrogen

Cortisol Testosterone
Progesterone

Amino acid derivatives

T3 and T4 Epinephrine
Norepinephrine
 Peptide Hormones

synthesized in ribosomes, water soluble,

stored in vesicles, fast acting, short half-life
Rule: All peptide hormones are synthesized as
inactive pre-pro precursors

Rule: A signal peptide must be cleaved off to

activate the mature form of the hormone
 Signal

Amplification

Reception, Transduction Internal regulator

Second messengers

Tissue Specific, kinase

specific effectors

Cellular response
 Steroid Hormones

made from cholesterol

lipophilic/hydrophobic, not stored in vesicles

requires specific protein carrier molecules

slow acting - genomic actions

STEROIDS

Cholesterol C27

Pregnenolone C21

Androgens C19
Glucocorticoids C21
Mineralocorticoids C21
Estrogens C18
(Figure 9-39)
STEROID HORMONE SYNTHESIS
All steroid hormones are derived from
cholesterol. A series of enzymatic steps in
the mitochondria and ER of steroidogenic
tissues convert cholesterol into all of the
other steroid hormones and intermediates.
The rate-limiting step in this process is the
transport of free cholesterol from the
cytoplasm into mitochondria. This step is
carried out by the Steroidogenic Acute
Regulatory Protein (StAR)
STEROID HORMONE SYNTHESIS
The cholesterol precursor comes from
cholesterol synthesized within the cell from
acetate, from cholesteryl ester stores in
intracellular lipid droplets or from uptake of
cholesterol-containing low density
lipoproteins.
Lipoproteins taken up from plasma are most
important when steroidogenic cells are
chronically stimulated.
STEROID HORMONE RECEPTORS
 Amine Hormones

Derivatives of single amino acid residues, primarily

TYROSINE

can behave either like peptides or steroids

the cathecolamines behave like protein hormones

because they circulate unbound to protein and have a
short half-life and a similar mechanism of action.

the thyroid hormones have a long-life, circulate bound

to a carrier protein, and have a mechanism of action
similar to steroids.
Rule: All hormones interact with target cells by
first binding to specific receptors located either
on the plasma membrane or as a cytosolic
protein

Rule: The receptor for hormones must be linked

to a component that is able to respond to the
binding of hormone with its receptor
 Control of Hormone Release

SUBSTRATE CONTROL
- Glucose regulating insulin release
- Calcium regulating parathyroid hormone
- Sodium regulating aldosterone and ANP
NERVOUS CONTROL

- Posterior pituitary hormones and adrenal medulla

TROPHIC HORMONES

- Released by the anterior pituitary and stimulates

other glands
TSH Thyroid gland T3 and T4
GH Liver Insulin-like Growth factor
FEEDBACK CONTROL OF INSULIN BY GLUCOSE
CONCENTRATIONS
 Feedback Mechanisms Regulating Hormone Release

Homeostatic negative feedback

The final hormone produced regulates its own secretion by inhibiting the
secretion of one or more of the precursor hormones.

stimulus release

sensor
 Feedback Mechanisms Regulating Hormone Release

non-homeostatic positive feedback

The final hormone produced actually enhances or induces the

initial hormone and causes its own production to be increased.

Example oxytocin release during labour

loops can simple or complex

 Feedback Loops
Rule: Hormones elicit their own shut off mechanism
Hypothalamus

Anterior
Pituitary
Corticotropin
Adrenal
releasing factor
+ Cortex

-Corticotropin/ACTH

Cortisol
 Disorders of the Endocrine System

Primary
Dysfunction may be caused by a defect in the target gland itself.

Secondary
Dysfunction may be caused by a defect in the pituitary gland, which releases
hormone to stimulate the target gland to secrete its hormone.

Tertiary
Dysfunction may be caused by a defect in the hypothalamus, which produces
releasing factors, which in turn stimulate the pituitary to secrete its hormone.
 Disorders of the Endocrine System

Primary
Dysfunction may be caused by a defect in the target gland itself.

Secondary
Dysfunction may be caused by a defect in the pituitary gland, which releases
hormone to stimulate the target gland to secrete its hormone.

Tertiary
Dysfunction may be caused by a defect in the hypothalamus, which produces
releasing factors, which in turn stimulate the pituitary to secrete its hormone.
 HORMONES

A chemical released from living cells

that travels through the blood to
target tissues to have a biological
effect
Secreted in very small amounts
Target cells have specific receptors
Regulates cell reactions by affecting gene
expression (often gene transcription
factors)
Gland tissue Hormones Major factors Chemical
structure
Hypothalamus - Thyrotropin releasing - Stimulates secretion of TSH - Peptide
hormone TRH and Prolactin
- Corticotrophin-releasing - Peptide
hormone CRH - Causes release of ACTH.
- Growth hormone - - Causes release of growth Peptide
releasing hormone hormone .
(GHRH).
- Growth hormone - Peptide
-Inhibits release of growth
inhibitory hormone hormone .
(GHIH).
- Gonadotropin-releasing
hormone (GnRH). - Causes release of LH and FSH
- Peptide
- Dopamine or Prolactin-
- Inhabits release of Prolactin - Amine
inhibiting factor (PIF).
Posterior
pituitary - Increase water reabsorption by
-Antidiuretic hormone
(ADH) the kidneys and causes - Peptide
vasoconstriction and increased
blood pressure .
- Stimulates milk ejection from - Peptide
- Oxytocin breasts & uterine contractions
Anterior pituitary - Stimulates protein - Peptide
- Growth hormone synthesis and overall
growth of most cells
and tissues
- Stimulates protein
-
- Thyroid stimulating synthesis and secretion - Peptide
hormone (TSH). of thyroid hormones
(T3,T4)
- Adenocorticotropic - Stimulates protein - Peptide
hormone (ACTH). synthesis and secretion
of adrenocortical
hormones.
- Promotes
development of the - Peptide
- Prolactin
female breasts and
secretion of milk
- Causes growth of
- Follicle-stimulating follicles in the ovaries - Peptide
(FSH) and sperm maturation
in sertoli cells of testes
- Luteinizing hormone - Stimulates testosterone
synthesis in leydig cells of - Peptide
(LH).
testes , stimulates
ovulation , formation of
corpus luteum , estrogen
and progesterone
synthesis in ovaries
Thyroid - Thyroxin T4 - Increases the rates of chemical reactions in - Amine
and most cells ,thus increasing the body metabolic
triiodothyronine rate
T3.
-
Promotes deposition of calcium in the bones and Peptide
- Calcitonin decreases extracellular fluid calcium in the bones
and decrease extracellular fluid calcium ion
concentration
Adrenal - Has multiple metabolic functions for controlling
cortex - cortisol - Steroid
metabolism of proteins ,carbohydrates, and fats,
also has anti inflammatory effects .
- Aldosterone
- Increase renal sodium reabsorption ,potassium
Adrenal secretion ,and hydrogen ion secretion - Steroid
medulla Norepinephrine Same effect as sympathetic stimulation - Amine
,epinephrine

pancreas - Insulin - Promoted glucose entry in many cells and in -Peptide

this way controls carbohydrate metabolism
- Glucagon - Increases synthesis and release of glucose from -Peptide
the liver into the body fluids
Parathyroid - Parathyroid - Controls serum calcium ion concentration by
hormones (PTH) increasing calcium absorption by gut and kidneys -Peptide
and releasing calcium from bones .
Testes - Testosterone - Promotes development of male reproductive -Steroid
system and male secondary sexual
characteristics.
Ovaries -Progesterone - Stimulates secretion uterine milk by the - Steroid
uterine endometrial glands and promotes
development of secretory apparatus of breasts .
- Estrogens
- Promote growth and development of female
reproductive system ,female breasts ,and - Steroid
female secondary sexual characteristic s

Placenta - Human chorionic - Promotes growth of corpus luteum and Peptide

Gonadotropin (HCG) secretion of estrogens and progesterone by
- human corpus luteum .
somatomammotropin - Probably helps promote development of some - Peptide
- Estrogen fetal tissues as the mothers breasts
- Steroid
- Progesterone - Steroid
-Renin - Catalyzes conversion of angiotensinogen to
Kidney angiotensin-1(acts as an enzyme(
- Increases intestinal absorption of calcium and - Peptide
- 1,25-
dihydroxycholecalciferol bone mineralization.
- Increase erythrocyte production - steroid

- Erythropoietin