2. Objectives
1. Classify the hormones according to their chemical structure.
2. Outline the general mechanisms for synthesis and secretion of
hormones.
3. Describe the role of hormone-binding proteins.
4. Discuss clearance of hormones from blood.
5. Elaborate the methods for measurement of hormone
concentration in blood.
Reference: Guyton&HallTextbookofMedicalPhysiology-12th ed.P,881– 886& 891 – 892.
3. Defn : Hormone is a chemical substance secreted by ductless gland into the blood.
Endocrine hormones :
Released by ductless glands / specialized cells into the circulating blood
& influence the function of target cells at another location in the body.
• EX: TSH,T3,T4,Insulin,PTH,ADH,Steriods,Oestrogen Testosterone
Neuroendocrine hormones :
Secreted by neurons into the circulating blood & influence the function of
target cells at another location in the body.
• EX: Vasopressin, Oxytocin etc.
Function: To integrate with Neural system of body & thus maintain the
homeostasis of the body.
4. Main functions of Endocrine hormones
Maintain Internal Homeostasis
Support Cell Growth
Coordinate Development
Coordinate Reproduction
Facilitate Responses to External Stimuli
7. Based on distance of target cells
1:Paracrines secreted by cells into the extracellular fluid and affect
neighboring target cells of a different type.
2:Autocrines secreted by cells into the extracellular fluid and affect the
function of the same cells that produced them.
3.Intracrine that acts inside a cell, regulating intracellular events
13. Thyroid & adrenal medullary
hormones:
Formed by the actions of enzymes in
the cytoplasmic compartments of the
glandular cells.
3: Hormones Derived From Tyrosine :
14. Ion Channel–Linked Receptors:
• Ach & NE combine with receptors in the postsynaptic membrane.
• Changes the structure of the receptor :opening/closing a channel for 1 or more ions.
• Leading to altered movement of these ions through the channels
• Results in the subsequent effects as configurational changes on the postsynaptic
cells.
Intracellular signaling after hormone receptor activation
15. G Protein–Linked Hormone Receptors:
• Many hormones activate receptors that indirectly regulate the activity of target proteins
(e.g. enzymes / ion channels) by coupling with groups of cell membrane G proteins.
• cAMP is second messenger used by the different hormones.
• Peptide hormones, Ex: ANP.
• Others 1: Calcium ions & associated calmodulin
2: Products of membrane phospholipid breakdown.
16. The cell membrane phospholipid
second messenger system by which
some hormones exert their control
of cell function.
Ex:
DAG, diacylglycerol; IP3,
inositol triphosphate; PIP2,
phosphatidylinositol biphosphate.
18. Locations for the different types of hormone receptors :
1. In or on the surface of the cell membrane:
These are specific mostly for the protein, peptide & catecholamine hormones.
2. In the cell cytoplasm:
These receptors for the different steroid hormones found mainly in the cytoplasm.
3. In the cell nucleus.
Receptors for the thyroid hormones found in the nucleus
Believed to be located in direct association with one or more of the chromosomes.
19.
20.
21. HORMONES : ACT MAINLY ON THE GENETIC MACHINERY OF THE CELL
The full action of the steroid hormone is
delayed for at least 45 minutes—up to
several hours or even days.
Steroid Hormones :
Increase Protein Synthesis in the target
cells.
These proteins then function as enzymes,
transport proteins, or structural proteins,
which in turn provide other functions of the
cells.
22. Thyroid Hormones Increase Gene Transcription in the Cell Nucleus
Two features of thyroid hormone function in the nucleus are important:
1. They activate the genetic mechanisms for the
formation of > 100 types of intracellular proteins.
Most of them are enzymes that promote enhanced
intracellular metabolic activity in
virtually all cells of the body.
2. Once bound to the intranuclear receptors,
the thyroid hormones continue to express
their control functions for days or even weeks.
23. Number and Sensitivity of Hormone Receptors Are Regulated as follows
Up-regulation of receptors and intracellular signaling proteins;
The stimulating hormone induces greater than normal formation of receptor or
intracellular signaling molecules by the target cell
Greater availability of the receptor for interaction with the hormone.
When up regulation occurs, the target tissue becomes progressively more sensitive to the
stimulating effects of the hormone.
.
24. Increased hormone concentration & binding with its target cell receptors decreases number of
active receptors called down-regulation .
(1) Inactivation of some of the receptor molecules;
(2) Inactivation of some of the intracellular protein signaling molecules;
(3) Temporary sequestration of the receptor to the inside of the cell
(4) Destruction of the receptors by lysosomes
(5) Decreased production of the receptors.
Receptor down regulation decreases the target tissue’s responsiveness to the hormone.
25. Hormone Secretion After a Stimulus & Duration of Action of Different Hormones.
• Hormones, like NE & E , secreted within seconds after the gland is stimulated & may develop
full action within another few seconds to minutes.
• Hormones, like T4 or GH, require months for full effect.
Concentrations of Hormones in the Circulating Blood and Hormonal Secretion Rates.
• Incredibly small.
• Ranges: 1 picogram-few mg/ml of blood .
Rate of secretion of the various hormones :Extremely small: μmg or mg/day
26. FEEDBACK CONTROL OF HORMONE SECRETION
Negative Feedback Prevents
Overactivity of Hormone Systems
Negative feedback
28. Periodic variations in hormone release
Influenced by seasonal changes,
Various stages of development
Aging
Diurnal (daily) cycle,
and sleep.
Cyclical Variations Occur in Hormone Release
29. Transport in blood:(Peptides & Catecholamines)
Water-soluble hormones
Dissolved in the plasma
Transported from their sites of synthesis to target tissues
They diffuse out of the capillaries, into the interstitial fluid,
Ultimately to target cells.
30. Transport in blood: Steroid & thyroid hormones
Circulate in the blood bound to plasma proteins.
<10 % hormones in the plasma exist free in solution.
Protein bound hormones cannot diffuse across the capillaries
Gain access to their target cells
Biologically inactive until dissociate from plasma proteins.
serve as reservoirs .
31. Clearance of Hormones
Factors effecting the concentration of a hormone in the blood.
Rate of hormone secretion into the blood and
removal of the hormone from the blood
Metabolic clearance rate =Rate of disappearance of hormone from the
plasma/Concentration of hormone .
32. Hormones are “cleared” from the plasma in several ways:
(1) metabolic destruction by the tissues
(2) binding with the tissues
(3) excretion by the liver into the bile, and
(4) excretion by the kidneys into the urine.
• Hormones bound to plasma proteins are cleared from the blood at slower rates and
remain in the circulation for several hours or even days.
33. Estimation of hormones
• Calorimetric
• Bioassay
• Radio Immunoassay Assay.
• Enzyme Linked Immuno Sorbent Assay.
• Chemiluminescence method.
• Cytochemical Assays-Genesis of hormone can be detected in slices cut out of the
endocrine gland.
34. Bioassay
• Biological assay of hormonal activity is needed when new synthetic products are
compared with natural hormones.
• Minute concentrations can be estimated.
• The various methods are-
• Solvent extraction
• Chromatography
• Molecular sieving
35. Chemical or immunological techniques
• Fluorescence methods for Catecholamines.
• Gas-Liquid Chromatography for steroid hormones.
Radio active isotopes for thyroid hormones.
• Competitive radioassay (RIA)-Protein & Peptide hormones can be estimated in
micrograms or nanograms per litre.
• It is done with antibody as the binding protein.
• This is high sensitivity & highly specific.
36.
37.
38. Advantages of ELISA over RIA
ELISA use excess antibodies so all hormone molecules are captured in antibody
hormone complexes.
Principle: Amount of hormone present in the sample or in the standard is proportional to
the amount of product formed.
1. Widely used in clinical & research laboratories
2. Does not use radioactive isotopes
3. Much of the assay automated
4. Cost effective
5. Accurate method for assessing hormone levels.