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TitleBIOCHEM-Molecular Endocrinology 1
TagsAdrenal Gland Luteinizing Hormone Hormone Cortisol Menstrual Cycle
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BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1 Page 1


 

 

 

 

 

 



Biomedical Importance of Hormones

 Survival of multicellular organism

 Intercellular communication (for survival)

 Nervous system and endocrine system (as a whole)



Hormones

 They coordinate metabolism in the body

 They are substances that carry information from
sensor cells, which senses changes in the
environment (electrolyte iimbalance, anoxia or
hypoxia or low blood sugar level) to target cells,
which respond to these changes

o Biochemical and physiological way of
defining a hormone



Hormones

 Can be categorized by the site of synthesis:

1. Endocrine hormones – are synthesized by
endocrine glands and transported by the blood
to their target cells.

- Production of hormone is faraway
from the target

2. Paracrine hormones - are synthesized near
their targets of action (ex. intestine)

3. Autocrine hormones – affect the cells that
synthesize them



Hormones are also categorized by Chemical Structure:

1. Proteins or peptides – ex: insulin, glucagon;
synthesized as larger precursors that undergo
processing and secretion.

2. Amino Acid derivatives – cathecolamines and
thyroid hormones

Ex: Triiodothyronine, T3, T4, Epinephrine,
Norepinephrine, Levothyroxine, Thyroxine

*tyrosine – very important amino acids

*TSH is not a thyroid hormone but a pituitary
hormone!

3. Fatty acid derivatives – eicosanoids
(ex.prostaglandins)

4. Cholesterol derivatives – steroids

5. Gases – nitric oxide (not a hormone in the strict
sense of the word but it can act on target cells)

*In the endothelial Nitric oxide synthase (ENOS)



Hormone Receptors

 Hormones are present at very low concentrations
in the ECF (compared to other proteins in ECF)

*they have to be low since hormones causes
significant changes when not controlled or plenty;
in signalling pathway, one hormone can amplify
millions and millions of response

 High degree of discrimination is provided by cell-
associated recognition molecules -> RECEPTORS

*receptor – protein; recogniton molecule

 Hormones initiate their biologic effects by binding
to the receptors

 A target cell is defined by its ability to the
selectively bind a given hormone to its cognate
receptors

*Hormone receptors are selective and specific. Each of the
cells will have its own receptors or binding sites of
hormones. Low amount of hormone in the ECF will bind
right away to the receptor and initiate the biologic effect.
There is an amplification of signals in the binding of
hormone and receptor.



Classification of hormones by mechanism of action

1. Hormones that bind to intracellular receptors

 Androgens

 Cacitriol (1,25(OH)2-D3)

 Estrogens

 Glucocorticoids

 Mineralocorticoids

 Progestins

 Retinoic Acid

 Thyroid Hormones (T3 and T4)

*PETCAT – Progesterone, Estrogen, Testosterone, Cortisol,
Aldosterol, Thyroid Hormones (mnemonic)

2. Hormones that bind to cell surface receptors

A. The second messenger is cAMP

 a2 -adrenergic catecholamines

 B – Adrenergic catecholamines

 Adrenocorticotropic hormone (ACTH)

 Antidiuretic Hormne (ADH)

 Calcitonin

 Chorionic gonadotropin, Human (hCG)

 Corticotropin-releasing Hormone

 FSH

 Glucagon

SUBJECT: BIOCHEMISTRY

TOPIC: MOLECULAR ENDOCRINOLOGY 1

LECTURER: DRA. UY

DATE: JANUARY 2011

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BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1 Page 2


Lipotropin (LPH)

LH

Melanocyte-stimulating hormone (MSH)

Parathyroid Hormone (PTH)

Somatostatin

Thyroid-stimulating hormone (TSH)

B. The second messenger is cGMP

Atrial Natriuretic Factor

Nitric Oxide

C. The second messenger is calcium or
phosphatidylinositol (or both)

Acetylcholine (muscarinic)

a1 – Adrenergic catecholamines

Angiotensin II

Antidiuretic Hormone (vasopressin)

Cholecystokinin

Gastrin

Gonadotropin Releasing Hormone

Oxytocin

Platelet-derived growth factor (PDGF)

Substance P

Thyrotropin-releasing hormone (TRH)

D. The second messenger is a kinase or
phosphatase cascade

Adiponectin

Chrionic somatomammotropin

Epidermal growth factor

Erythropoietin

Fibroblast growth factor (FGF)

Growth Hormone (GH)

Insulin

Insulin-like growth factors I and II

Leptin

Nerve growth factor (NGF)

Platelet-derived growth factor

Prolactin



General Feature of Hormone Classes

GROUP 1 GROUP 2

Types Steroid,
iodothyronines,
calcitriol,
retinoids

Polypeptides,
proteins,
glycoproteins,
catecholamines

Solubility Lipophilic/
Hydrophobic

Hydrophilic/
Liphophobic

Transport
Proteins

Yes No

Plasma Half-Life Long (hrs- days) Short (min.)

Receptor Intracellular Plasma
Membrane

Mediator Receptor- cAMP,cGMP,

Hormone
Complex

Ca2+,
metabolites of
complex
phosphoinositols,
kinase cascades





Diversity of Endocrine System

Hormones are synthesized in a variety of cellular
arrangements

Discrete Organs – Thyroid, Pituitary and Adrenals

*what they are is what they secrete

Organs perform 2 distinct but closely related funtions:

Ovaries – mature oocytes and estradiol and
progesterone

Testes – mature spermatozoa and testosterone

*this testosterone is weak compared to DHT
(dihydrotestosterone

Specialicez cell within other organs:

Small intestine – glucagon like peptide (targets for
new medication in diabetes)

Thyroid – calcitonin (action is in bones and
parathyroid)

Kidney – Angiotensin II (control of blood pressure;
target for all Angiotensin II blockers)

*kidneys also produces eryhtopoietin



Parenchymal Cells of more than one organ:

Skin, liver, kidney – calcitriol (vitamin B3)



Hormones are chemically diverse

They are synthesizied from a wide variety of
chemical building blocks:

o Cholesterol Derivatives (all ssteroid hormones
came here)

 17B – estradiol

 Testosterone

 Cortisol

 Progesterone

 1,25 (OH)2 – D3

*common to them is the cyclopentanoperhydropenantrene
ring

o Tyrosine

 T3 and T4

 Norepinephrine

 Epinephrine

o Iodine – very important building bloackof
Thyroxine or the thyroid hormone

o Polypeptides

 TRH

 ACTH

o Glycoproteins (TSH, FSH, LH)

 Common a subunits

 Unique b subunits

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Pro-opiomelanocortin (POMC) Peptide Family

 consists of peptides that act as hormones (ACTH,
LPH, MSH) & others that may serve as
neurotransmitters or neuromodulators (endorphins)

 Products of POMC cleavage:
o ACTH

 a-MSH
 CLIP (corticotropin-like

intermediate lobe peptide)
o B-LPH (lipotropin)

 y-LPH
 B-endorphin
 B-MSH
 y-Endorphin
 a-Endorphin





Diversity in the Storage of Hormones

Hormone Supply Store Cell

Steroid and 1,25 (OH)2-D3 None

Catecholamines and PTH Hours

Insulin Days

T3 and T4 Weeks

*no patient will suffer from hypo or hyperthyroidism
immediately. Hyperthyroidism is a suttle disease. It can
occur years after you have thyroidectomy.

*Type I diabetic patients can survive without insulin for 4-5
days and until day become coma.

*Catecholamines and PTH stores for hours that’s why you
can have an adrenaline rush for hours and feel week after.

Comparison of Receptors with Transport Proteins

Feature Receptors Transport Protein

Concentration Very Low
(thousands/cell)

Very High
(billions/uL)

Binding affinity High (pmol –
nmol/L range)

Low (umol/L
range)

Binding
Specificity

Very High Low

Saturability Yes No

Reversibility Yes Yes

Signal
Transduction

Yes No





Actions of Specific Hormones



HYPOTHALAMIC HORMONES

•VASOPRESSIN and OXYTOCIN

•OTHER HORMONES that regulate the synthesis and
release of hormones from the anterior pituitary



HORMONES OF THE ANTERIOR PITUITARY

•PROLACTINOMA

- the most common tumor of the pituitary

- double vision, amenorrhea, and galactorrhea

•Hyperprolactinona

- can result from drugs that inhibit dopamine
action: antipsychotic drugs (Thorazine)

*Galactorrhea – letting down of milk; spontaneous flow of
mlik



•GROWTH HORMONE (GH):

- Stimulates release of insulin-like growth factors
(somatomedin)

- Antagonizes the effects of insulin on
carbohydrates and fat metabolism

- its release is inhibited by somatostatin



•THYROID - STIMULATING HORMONE

- Stimulates the release of T3 and T4 from the
thyroid gland.

- released from anterior pituitary through the signal
of the TSHRH from hypothalamus

- used to screen patients for thyroid disease.

- elevated levels suggest hypothyroidism (negative
feedback)

- low levels suggest hyperthyroidism (negative
feedback)

*If patient has hyperthyroidism, the feedback mechanism
signals the anterior pituitary to decrease the release TSH.
The same can be said to those hypothyroidism.



•LH and FSH:

- stimulates the GONADS to release hormones that are
involved in reproduction

- their release is stimulated by GnRH and inhibited
by GnIH from the hypothalamus



•Protein product of the PRO-OPIOMELANOCORTIN gene

- produced in response to CRH from the
hypothalamus

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- cleaved to generate a number of peptides:

1. ACTH – cortisol ; has permissive effect on production of
aldosterone

2. Lipotropin (LPH)- cleaved to form MSH and endorphins

*If you have a pituitary problem that involves this, there will
be a darkening of the skin.

THYROID HORMONE

•T3 is more active than T4

•Most T3 is produced by deiodination of T4

•During starvation,T4 is converted to reversed T3 (RT3),
which is not active

•Binds to nuclear receptors and regulates the expression
of many genes.

•Needed for growth, development, and maintenance of
almost all tissues

•Stimulates oxidative metabolism and causes basal
metabolic rate to increase



•HYPOTHYROIDISM

- Generation of ATP id reduced, causing a sense of
weakness, fatigue, and hypokinesis

-the reduced BMR is assoc with decreased heat
production, causing cold intolerance and decreased
sweating.

- Less demand for delivery of fuels and oxygen to
peripheral tissues hence circulation is slowed, decreased
heart rate and BP



•HYPERTHYROIDISM

-BMR is increased because the rate of oxidation of
fuels by muscles and other tissues is increased.

- increased heat production: heat intolerance and
increased sweating

-elevated tone of sympathetics: inc HR and BP

- Weight loss is severe because of excessive rate of
fuel oxidation



HORMONES that STIMULATE GROWTH

•INSULIN and GH

•GH antagonizes many of the metabolic actions of INSULIN,
stimulating gluconeogenesis and promoting lipolysis.

•Alternative fuels are therefore made available so that
muscle protein can be preserved



•GIGANTISM

- Caused by excessive secretion of GH as a result
of a benign tumor of the ant pituitary gland and the
hypersecretion begins before closures of the growth
centers in the long bones

•ACROMEGALY

- if hypersecretion begins after the growth centers
have closed



HORMONES THAT MEDIATE THE RESPONSE TO STRESS

•GLUCOCORTICOIDS

- Cortisol and Epinephrine act in concert to supply
fuels to the blood so that energy can be produced to
combat stressful situations

- Anti-inflammatory effects: induce synthesis of
lipocortin which inhibits phospholipase A2, rate limiting
enzyme of protaglandin synthesis .

- Suppress the immuned response by causing lysis
of lymphocytes

- Influence metabolism by causing movement of
fuels from peripheral tissues to the liver

- Promotes gluconeogenesis by inducing synthesis
of PEPCK



HYPERCORTISOLEMIA

•likelihood of infection

•Glucose CNS effects: hyperirritability or depression

•BONES : osteoporosis

•Muscle : loss of protein leading to weakness

•Thinning of dermal and epidermal structures: striae

•Increased vascular fragility : easy bruising

•Increased intolerance or overt diabetes

•Central obesity: buffalo hump and moon facies



•CUSHING SYNDROME

- If caused by excessive production of cortisol by an
adrenal tumor or by intake of exogenous glucocorticoids



•CUSHING DISEASE

- hypercortisolemia caused by excessive secretion
of ACTH by a pituitary tumor



•EPINEPHRINE

- Increases blood glucose by stimulating liver
glycogenolysis

- Stimulates lipolysis in adipose tissue and
glycogen degredation in muscle

- Makes fuels available for “fight or flight”



HORMONES that REGULATE SALT and WATER BALANCE

•ALDOSTERONE

-causes the production of proteins in cells of the
distal tubule and the collecting ducts of the kidney:

1. Permease is produced that allows
sodium to enter cells from the lumen

2. Citrate synthase is induced ( inc TCA
hence ATP production)

3. Na-K ATPase pump is induced

- K and H ions are lost; Na is retained; water is
resorbed; blood volume and pressure are increased



•PRIMARY HYPERALDOSTERONISM

- Conn Syndrome

- aldosterone-secreting tumor of adrenal gland

- sodium retention and potassium secretion with
resultant hypertension and hypokalemia

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