Biokimia Hormon

dr. Evi Kurniawaty, M.Sc

Bagian Biokimia Fakultas Kedokteran
Unila
Endocrine system maintains
homeostasis
The concept that hormones acting on
distant target cells to maintain the
stability of the internal milieu was a
major advance in physiological
understanding.
The secretion of the hormone was
evoked by a change in the milieu
and the resulting action on the target
cell restored the milieu to normal.
The desired return to the status quo
results in the maintenance of
homeostasis
Sensing and signaling
Endocrine “glands”
synthesize and
store hormones.
These glands
have a sensing
and signaling
system which
regulate the
duration and
magnitude of
hormone release
via feedback from
the target cell.
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 is has a
specific receptor for the hormone

 Most hormones circulate

in 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.
Mechanism of hormone action
RECEPTOR
 The actions of hormone are
mediated by binding of the hormone
to receptor molecules.
 Hormones are allosteric effectors
that alter the conformation of the
receptors to which they bind.
 The receptors are cellular proteins
that have bifunctional properties of
both recognition and signal activation.
 RECEPTOR

1. Nuclear receptors
2. Cell surface receptors
Nuclear receptors
 Superfamily - Steroid
hormone,
Vitamin D, thyroid hormone,
retinoids
 Nuclear receptors are ligand-
regulated transcription factors
that control gene expression by
binding to target genes usually
in the region near their
promoters.
Nuclear receptors

 Nuclear receptor superfamily

have generally similar structures
and functions, but there are
subclasses that differ in the
details of their actions -
especially in their interaction
with other proteins - and
function in the unliganded state.
 RECEPTOR
2. Cell surface receptors
a)Seven-transmembrane domain
b)Single-transmembrane domain
Growth factor receptor
Cytokine receptor
Guanyl cyclase-linked receptors
Principal functions of the
endocrine system
 Maintenance of the internal
environment in the body (maintaining
the optimum biochemical
environment).
 Integration and regulation of growth
and development.
 Control, maintenance and instigation
of sexual reproduction, including
gametogenesis, coitus, fertilization,
fetal growth and development and
nourishment of the newborn.
Response vs. distance
traveled
Endocrine action: the
hormone is distributed
in blood and binds to
distant target cells.
Paracrine action: the
hormone acts locally
by diffusing from its
source to target cells
in the neighborhood.
Autocrine action: the
hormone acts on the
same cell that
produced it.
Types of hormones

 Hormones are categorized into

four structural groups, with
members of each group having
many properties in common:
 Peptides and proteins
 Amino acid derivatives
 Steroids
 Fatty acid derivatives - Eicosanoids
Peptide/protein hormones

 Range from 3 amino acids to

hundreds of amino acids in size.
 Often produced as larger molecular
weight precursors that are
proteolytically cleaved to the active
form of the hormone.
 Peptide/protein hormones are water
soluble.
 Comprise the largest number of
hormones– perhaps in thousands
Peptide/protein hormones
 Are encoded by a specific gene which is
transcribed into mRNA and translated into
a protein precursor called a preprohormone
 Preprohormones are often post-
translationally modified in the ER to contain
carbohydrates (glycosylation)
 Preprohormones contain signal peptides
(hydrophobic amino acids) which targets
them to the golgi where signal sequence is
removed to form prohormone
 Prohormone is processed into active
hormone and packaged into secretory
vessicles
Peptide/protein hormones

 Secretory vesicles move to plasma

membrane where they await a
signal. Then they are exocytosed
and secreted into blood stream
 In some cases the prohormone is
secreted and converted in the
extracellular fluid into the active
hormone: an example is angiotensin
is secreted by liver and converted
into active form by enzymes
secreted by kidney and lung
Peptide/protein hormone
synthesis
Disorders of the endocrine
system

 Excess of hormone
 Deficiency of hormone
 Resistance to hormone
 Administration of
exogenous hormone or
medication
Approach to the patient with
endocrine disease

 History & physical

•Function diagnosis examination

 Laboratory studies
•Pathology diagnosis  Screening for endocrine
diseases
•Etiology adiagnosis
History & physical
examination
 Amenorrhea or  Lipido change
oligomenorrhea  Polynuria
 Anemia  Skin changes
 Anorexia  Weakness and
 Conspitation fatigue
 Depression  Weight gain
 hair change  Weight loss
 Hypothermia  Nervousness
 Diarrhea
Laboratory studies

 Measure the level of hormone

total vs. free
Plasma vs. urine

 The effect of hormone

 The sequelae of the process
Screening is important for
some endocrine diseases

 Hypertension
 Hypothyroidism
 Diabetes
Approach to the patient with
endocrine disease
 History & physical
examination
•Function diagnosis  Laboratory studies

•Pathology diagnosis  Screening for endocrine

diseases
•Etiology adiagnosis  immunologic examination

 genetic examination

 Chemical examination
Cushing’s Syndrome

 Increased cortisol
 Cushing’s disease (pituitary) - inc
ACTH
 Adrenal (hyper/neoplasia) - dec
ACTH
 Ectopic ACTH production - inc
ACTH
 Iatrogenic – inc ACTH
Cushing’s Syndrome
Cushing’s Syndrome
 CUSHINGS BAD MD
 Cataracts
 Up all night
 Suppression of HPA axis
 HTN / Hump
 Infections
 Necrosis
 Gain weight
 Straie
 Bone loss
 Acne
 Diabetes
 Myopathy / moon facies
 Depression
Addison’s Disease

 Atrophy of the adrenal gland

causing a decrease in
aldosterone and cortisol
 Hyponatremia – No Aldosterone!!
 Hyperpigmentation- Increased
ACTH but nowhere to go  MSH
from POMC
Tumors of the Adrenal Medulla

 Pheochromocytoma
 Most common tumor of the adrenal
medulla in adults (P = Parents)
 From chromoffin cells  what do these
normally secrete?
 Epinephrine and Norepinephrine!!!!! Duh!
 What would you do about it?
 Give something to block the sympathetic
receptors – most likely is the non-selective
alpha blocker  phenoxybenzamine
Tumors of the Adrenal Medulla

 Neuroblastoma
 Most common adrenal medulla
tumor in kids
 Amplification of N-myc
 (c-myc = Burkitt’s and L-myc = Lung)

Blast = immature so think of kids