HORMONE
SITI ANNISA DEVI TRUSDA
OVERVIEW
• DEFINITION
• CLASSIFICATION
• REGULATION OF SECRETION
• TRANSPORT to target cells
• RECEPTORS
• HORMONE MEASUREMENTS
Definition of Hormones
HORMONE ACTIONS
Thyroid hormones
and insect-molting
hormone (ecdysone)
also act through
nuclear receptors.
Binds to
transmembrane
protein that uses
ATP to move it into
the cell.
Lipophilic hormone → intracellular receptor :
cytoplasmic rec.: glucocorticoid, mineralocorticoid
nucleic rec. : thyroid H, estrogen, vit.D progesterone,
androgen
Hydrophilic hormone → membrane receptor (3 types) :
type I : enzyme (tyrosine kinase) activity (insulin, growth
factors)
type II : ion channels Na+, K+, Cl- (neurotransmitters)
type III: via G-proteins
Depend on the type of G-protein :
1. α- subunit of G-protein - activates adenylate cyclase (Gs)
producing c-AMP →
intracellular c-AMP ↑
inhibits adenylate cyclase (Gi) → intracellular c-AMP↓
2. α- subunit of G-protein stimulates c-GMP phosphodiesterase → c-
GMP ↓
3. α- subunit of G-protein binds to ion channel (K+ / Ca2+ channel)
→ opening of the channel
4. α- subunit of G-protein activates phospholipase C which then
hydrolyzes phosphatidyl inositol biphosphat (PIP2) producing
inositol triphosphat (IP3) + diacylglycerol (DAG)IP3 moves to
endoplasmic reticulum, stimulates release of Ca2+ from the
stores. DAG activates protein kinase C, which will phosphorylates
proteins, altering its activities
TRANSPORT OF HORMONES IN BLOOD
• Protein hormones water-soluble and readily
transported by the circulatory system.
• Steroid and thyroid insoluble in water
need carrierTBG, sex hormone–binding
globulin (SHBG), and corticosteroid-binding
globulin (CBG),as well as to albumin.
REGULATION OF SECRETION
CNS
+ Precursors
+ R
+
Hypothalamus
Liberin + H H Statin
+
Precursors
+
Pituitary + R
Tropin Negative
H feed-
back
Peripheral Precursors
+
gland +
Glandular
hormone
Target
cell
Response
External stimuli
Hypothalamic hormones
(releasing factors)
Ultimate Many Muscles, Reproductive Liver, Mammary Smooth Arteriole Liver, Liver,
targets tissues liver organs bone glands muscle, s muscles muscles,
mammary heart
glands
General features of signal
Group I Group II
Steroids, iodothyronines, Polipeptides, proteins,
Type
calcitriol, retinoids glycoproteins, catecholamines
Solubility Lipophilic Hydrophilic
Transport proteins Yes No
Plasma half life Long (hours to days) Short (minutes)
Receptor Intracellular Plasma membrane
cAMP, cGMP, Ca2+, DAG, IP3,
Mediator Receptor-hormone complex
kinase-cascades
HORMONE MEASUREMENT
Endocrine function can be assessed by
• measuring levels of basal circulating hormone,
• evoked or suppressed hormone
• evoked or suppressed hormone-binding proteins.
• Alternatively, peripheral hormone receptor function can be assessed
Condition of measurement
• Fasting: thyroid hormone, prolactin, and IGF-I levels can be accurately
assessed in fasting morning serum samples.
• when hormone secretion is clearly episodic, timed samples may be
required over a defined time course to reflect hormone bioavailability.
• early morning and late evening cortisol measurements are most
appropriate. Although 24-hour sampling for GH measurements,with
samples collected every 2,10, or 20 minutes, are expensive and
cumbersome, they may yield valuable diagnostic information. Random
sampling may also reflect secretion peaks or nadirs, thus confounding
adequate interpretation of results.
• In general, confirmation of failed glandular function is
made by attempting to evoke hormone secretion by
recognized stimuli.
• Injection of trophic hormones, including TSH and
ACTH, evokes specific target gland hormone secretion.
Pharmacologic stimuli, for example metoclopromide
for induction of prolactin secretion,may also be useful
tests of hormone reserve.
• In contrast, hormone hypersecretion can be diagnosed
by suppressing glandular function. Thus, failure to
appropriately suppress GH levels after a standardized
glucose load implies inappropriate GH hypersecretion.
• Radioimmunoassays utilize highly specific
antibodies unique to the hormone,or a hormone
fragment, to quantify hormone levels.
• Enzyme-linked immunoabsorbent assays (ELISA)
employ enzymes instead of radioactive hormone
markers, and enzyme activity is reflective of
hormone concentration.
• This sensitive technique has allowed
ultrasensitive measurements of physiologic
hormone concentrations. Hormone-specific
receptors may be employed in place of the
antibody in a radioreceptor assay.
ENDOCRINE DISEASES
Endocrine diseases fall into four broad
categories:
(1) hormone overproduction
(2) hormone underproduction
(3) altered tissue responses to hormones; and
(4) tumors of endocrine glands.