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BIOCHEM-Molecular Endocrinology 1
BIOCHEM-Molecular Endocrinology 1
SUBJECT: BIOCHEMISTRY
TOPIC: MOLECULAR ENDOCRINOLOGY 1
LECTURER: DRA. UY
DATE: JANUARY 2011
Hormone Receptors
Biomedical Importance of Hormones Hormones are present at very low concentrations
Survival of multicellular organism in the ECF (compared to other proteins in ECF)
*they have to be low since hormones causes
Intercellular communication (for survival)
significant changes when not controlled or plenty;
Nervous system and endocrine system (as a whole) in signalling pathway, one hormone can amplify
millions and millions of response
Fibroblast growth factor (FGF) They are synthesizied from a wide variety of
chemical building blocks:
Growth Hormone (GH)
o Cholesterol Derivatives (all ssteroid hormones
Insulin came here)
Insulin-like growth factors I and II 17B – estradiol
Leptin Testosterone
Nerve growth factor (NGF) Cortisol
Platelet-derived growth factor Progesterone
Prolactin 1,25 (OH)2 – D3
*common to them is the cyclopentanoperhydropenantrene
ring
General Feature of Hormone Classes
o Tyrosine
GROUP 1 GROUP 2
T3 and T4
Types Steroid, Polypeptides,
iodothyronines, proteins, Norepinephrine
calcitriol, glycoproteins, Epinephrine
retinoids catecholamines
o Iodine – very important building bloackof
Solubility Lipophilic/ Hydrophilic/ Thyroxine or the thyroid hormone
Hydrophobic Liphophobic
o Polypeptides
Transport Yes No TRH
Proteins
ACTH
Plasma Half-Life Long (hrs- days) Short (min.)
o Glycoproteins (TSH, FSH, LH)
Receptor Intracellular Plasma
Membrane Common a subunits
Mediator Receptor- cAMP,cGMP, Unique b subunits
Biosynthesis of Estrogen
- not made in extramedullary tissue *Dopa carboxylase – forms dopamine from Dopa
*Dopamine b-hydroxylase – forms Norepinephrine from
dopamine.
*PNMT (phenylethanolamine-N-methytransferase – forms
epinephrine from norepinephrine.
*Catecholamines cannot cross the blood, brain barrier;
hence in the brain they must be synthesized locally.
*Parkinson’s disease - a CNS disorder where there is local
deficiency of dopamine synthesis; symptom: shuffling gait
* L- Dopa (levodopa or sinemet) - important agent in
treatment of Parkinson’s disease since it readily crosses
the BBB (blood brain barrier; you will produce Dopamine
Insulin:
synthesized as a prohormone & modified within
the - cell.
one of the hormones made from larger peptide
precursors made up of: *Angiotensin II is also synthesized from a large precursor;
o Connecting peptide – produced from liver; is also involved in aldosterione regulation
connects a-chains and B-chains *The RAS is involved in the regulation, of BP and
o a-chains – has a intra-sulfide bond (Cys11 electrolyte metabolism (thru aldosterone production)
– Cys6)
o B-chains – *In the diagram below, Angiotensinogen is converted by
Renin to Angiotensin I. Angiotensin - converting Enzyme
*a-chains & B-chains - has 2 separate inter-sulfide bonds converts Angiotensin I to II which is acted upon by
(bet. Cys20 of alpha and Cys19 of Beta and bet. 2 Cys7) Aminopeptidase to for Angiotensin III. Degradation products
*insulin in the market is modified in the B-chains. are formed by angiontensinases from angiotensin III. The
active form is the angiotensin II.
HYPOTHALAMIC HORMONES
•VASOPRESSIN and OXYTOCIN
•OTHER HORMONES that regulate the synthesis and
release of hormones from the anterior pituitary
Pro-opiomelanocortin (POMC) Peptide Family - can result from drugs that inhibit dopamine
action: antipsychotic drugs (Thorazine)
consists of peptides that act as hormones (ACTH,
LPH, MSH) & others that may serve as *Galactorrhea – letting down of milk; spontaneous flow of
neurotransmitters or neuromodulators (endorphins) mlik
Products of POMC cleavage:
o ACTH •GROWTH HORMONE (GH):
a-MSH
CLIP (corticotropin-like - Stimulates release of insulin-like growth factors
intermediate lobe peptide) (somatomedin)
o B-LPH (lipotropin) - Antagonizes the effects of insulin on
y-LPH carbohydrates and fat metabolism
B-endorphin
B-MSH - its release is inhibited by somatostatin
y-Endorphin
a-Endorphin
•THYROID - STIMULATING HORMONE
- Stimulates the release of T3 and T4 from the
thyroid gland.
Diversity in the Storage of Hormones - released from anterior pituitary through the signal
Hormone Supply Store Cell of the TSHRH from hypothalamus
Steroid and 1,25 (OH)2-D3 None - used to screen patients for thyroid disease.
- elevated levels suggest hypothyroidism (negative
Catecholamines and PTH Hours
feedback)
Insulin Days
- low levels suggest hyperthyroidism (negative
T3 and T4 Weeks feedback)
*no patient will suffer from hypo or hyperthyroidism *If patient has hyperthyroidism, the feedback mechanism
immediately. Hyperthyroidism is a suttle disease. It can signals the anterior pituitary to decrease the release TSH.
occur years after you have thyroidectomy. The same can be said to those hypothyroidism.
*Type I diabetic patients can survive without insulin for 4-5
days and until day become coma. •LH and FSH:
*Catecholamines and PTH stores for hours that’s why you - stimulates the GONADS to release hormones that are
can have an adrenaline rush for hours and feel week after. involved in reproduction
Comparison of Receptors with Transport Proteins - their release is stimulated by GnRH and inhibited
Feature Receptors Transport Protein by GnIH from the hypothalamus
Concentration Very Low Very High
(thousands/cell) (billions/uL) •Protein product of the PRO-OPIOMELANOCORTIN gene
Binding affinity High (pmol – Low (umol/L - produced in response to CRH from the
nmol/L range) range) hypothalamus
- Generation of ATP id reduced, causing a sense of •Increased vascular fragility : easy bruising
weakness, fatigue, and hypokinesis •Increased intolerance or overt diabetes
-the reduced BMR is assoc with decreased heat •Central obesity: buffalo hump and moon facies
production, causing cold intolerance and decreased
sweating.
•CUSHING SYNDROME
- Less demand for delivery of fuels and oxygen to
peripheral tissues hence circulation is slowed, decreased - If caused by excessive production of cortisol by an
heart rate and BP adrenal tumor or by intake of exogenous glucocorticoids
- detect the presence of hCG in the urine. •Retinol,the transport form,is stored as retinyl esters.
- serum quantitation of hCG levels can be used to •Retinal is a funtional component of the visual cycle
differentiate a normal intrauterine pregnancy from an reactions.
ectopic pregnancy. •Retinoic acid is involved in growth and also in
•Pitocin – synthetic form of OT that can be administered differentiation and maintenance of epithelial tissue
during labor to initiate or augment labor.
HORMONES THAT REGULATE CALCIUM METABOLISM
The Action of FSH and LH on the Testis •Parathyroid hormone (PTH), 1,25-DHC,and Calcitonin are
the major regulators of Ca metab.
BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1 Page 9
•PTH, produced in response to low Ca levels,acts to •GASTRINOMAS
increase Ca levels in the ECF. - gastrin-secreting endocrine tumors associated
•1,25-DHC stimulates the synthesis of a protein involved in with Zollinger-Ellison syndrome.
Ca absorption by intestinal epithelial cells. - increased hydrochloric acid production with
Calcitonin lowers Ca levels by inhibiting its release from resultant recurrent peptic ulcers.
bone and stimulating its excretion
•VIPomas
- rare tumors that secrete VIP
•HYPERPARATHYROIDISM- patients can present with
- watery diarrhea, hypokalemia, and achlorhydria
fractures of long bones,renal stones, GI
disturbance,lethargy and weakness.
1. Primary – the result of tumor of the INSULIN AND GLUCAGON
parathyroid gland. •INSULIN
2. Secondary – as a result of renal failure. - elevated in the fed state
•HYPOPARATHYROIDISM –most often due to trauma to the - promotes storage of fuels: glycogen and
parathyroids during surgery of the thyroids triacylglycerol.
- stimulates glucose transport into muscle and
HORMONES THAT REGULATE UTILIZATION OF NUTRIENTS adipose cells.
- stimulates protein synthesis and growth
GUT HORMONES
•Gastrin from gastric antrum and the duodenum •GLUCAGON
stimulates gastric acid and pepsin secretion. - elevated during fasting
•Cholecystokinin (CCK) from the duodenum and jejunum - increases the availability of fuels (glucose
stimulates contraction of the GB and secretion of and fatty acids) in the blood.
pancreatic enzymes.
- stimulates glycogen degradation in the liver but
•Secretin from duodenum and jejunum stimulates the NOT in muscle.
secretion of bicarbonate by the pancreas.
- stimulates gluconeogenesis and lipolysis in
•Gastric inhibitory polypeptide (GIP) from the small bowel adipose tissue.
enhances insulin release and inhibit gastric acid secretion
Vasoactive intestinal polypeptide (VIP) from the pancreas
relaxes smooth muscles and stimulates bicarbonate <end of transcription>
secretion by the pancreas