1. The Endocrine Physiology Introduction to Endocrinology
Dr. Khalid Alregaiey

2. Endocrine System: Overview
Endcocrinology: It is study of homeostatic functions of substances called HORMONES, that are released from glands called endocrine glands distributed throughout the body.
Hormones: Are secretions of ductless glands that are directly released into the blood stream. They can act on cells in the vicinity or on distant target cells.
Endocrine system – the body’s second great controlling system which influences metabolic activities of cells by means of hormones

3. Endocrine System: Overview
Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus
The pancreas and gonads produce both hormones and exocrine products
The hypothalamus has both neural functions and releases hormones
Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart

4. The Endocrine System

5. Autocrines and Paracrines
Autocrines – chemicals that exert their effects on the same cells that secrete them
Paracrines – locally acting chemicals that affect cells other than those that secrete them
These are not considered hormones since hormones are long-distance chemical signals

6. Types of Hormones
Amino acid based – most hormones belong to this class, including:
Amines (Tyrosine: Caecholamines and Thyroid hormones, Tryptophan: Melatonin)
Polypeptide hormones
protein hormones
Steroids – Derived from Cholesterol, gonadal and adrenocortical hormones
Fatty acid derived: Eicosanoids, derived from arachidonic leukotrienes and prostaglandins

7. A Structural Classification of Hormones

8. Correlation of Plasma Half-Life & Metabolic Clearance of Hormones with Degree of Protein Binding
(ml/minute)
Thyroid
Thyroxine
Triiodothyronine
Steroids
Cortisol
Testosterone
Aldosterone
Proteins
Thyrotropin
Insulin
Antidiuretic hormone
99.97
99.7 94 89 15
little
6 days
1 day
100 min
85 min
25 min
50 min
8 min
0.7 18
140
860
1100 50
800
600
MCR = (mg/minute removed)/(mg/ml of plasma) = ml cleared/minute

9. Circulating Transport Proteins
Principle Hormone
Transported
Transport Protein
Specific
Corticosteroid binding globulin
(CBG, transcortin)
Thyroxine binding globulin (TBG)
Sex hormone-binding globulin
(SHBG)
Nonspecific
Albumin
Transthyretin (prealbumin)
Cortisol, aldosterone
Thyroxine, triiodothyronine
Testosterone, estrogen
Most steroids, thyroxine,
triiodothyronine
Thyroxine, some steroids

10. Determinants of Free Hormone Receptor Binding
Carrier-bound
hormone
Endocrine
cell
Free
Hormone
Hormone
receptor
Hormone
degradation
Biological
effects

11. Hormone Action
Hormones alter target cell activity by one of the following mechanisms:
Ion Channel–Linked Receptors.
G Protein–Linked Hormone Receptors.
Enzyme-Linked Hormone Receptors.
Intracellular Hormone Receptors and Activation of Genes (steroid and thyroid hormones)

12. Hormone Action
Hormones circulate to all tissues but only activate cells referred to as target cells
Target cells must have specific receptors to which the hormone binds

13. Location of receptors:
1. In or on the surface of the cell membrane. The membrane receptors are specific mostly for the protein, peptide, and catecholamine hormones.
2. In the cell cytoplasm. The primary receptors for the different steroid hormones are found mainly in the cytoplasm.
3. In the cell nucleus. The receptors for the thyroid hormones are found in the nucleus and are believed to be located in direct association with one or more of the chromosomes.

14. Cyclic Adenosine Monophosphate (cAMP) Second Messenger Mechanism
Hormone (first messenger) binds to its receptor, which then binds to a G protein
The G protein is then activated as it binds GTP, displacing GDP
Activated G protein activates the effector enzyme adenylate cyclase
Adenylate cyclase generates cAMP (second messenger) from ATP
cAMP activates protein kinases, which then cause cellular effects

15. Cyclic Adenosine Monophosphate (cAMP) Second Messenger Mechanism

16. Cell Membrane Phospholipid: Second Messenger System
Hormone binds to the receptor and activates G protein
G protein binds and activates a phospholipase enzyme
Phospholipase splits the phospholipid PIP2 into diacylglycerol (DAG) and IP3 (both act as second messengers)
DAG activates protein kinases; IP3 triggers release of Ca2+ stores
Ca2+ (third messenger) alters cellular responses

17. Cell Membrane Phospholipid: Second Messenger System

18. Cytokine Receptors & Tyrosine Kinase Receptors

19. The Insulin Receptor & Mechanisms of Insulin Action

20. Protein Hormones - Mechanisms of Action
Tyrosine Kinase/Cytokine Receptor Mechanism
Adenylyl Cyclase Mechanism
Phospholipid Mechanism
Guanylate Cyclase Mechanism
ACTH LH
FSH
TSH
GHRH
Somatostatin
ADH (V2 receptor)
HCG
MSH
CRH
Calcitonin
PTH
Glucagon
GnRH
TRH
Angiotensin II
ADH (V1 receptor)
Oxytocin
ANP
Insulin
IGF-1 GH
Prolactin

21. Steroid and Thyroid Hormones
Steroid hormones and thyroid hormone diffuse easily into their target cells
Once inside, they bind and activate a specific intracellular receptor
The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor protein
This interaction prompts DNA transcription to produce mRNA
The mRNA is translated into proteins, which bring about a cellular effect

22. Steroid & Thyroid Hormones - Mechanism of Action

23. Target Cell Activation
Target cell activation depends on three factors
Blood levels of the hormone
Relative number of receptors on the target cell
The affinity of those receptors for the hormone
Up-regulation – target cells form more receptors in response to the hormone
Down-regulation – target cells lose receptors in response to the hormone

24. Hormone Concentrations in the Blood
Hormones circulate in the blood in two forms – free or bound
Steroids and thyroid hormone are attached to plasma proteins

25. Hormone Concentrations in the Blood
Concentrations of circulating hormone reflect:
Rate of release
Speed of inactivation and removal from the body
Hormones are removed from the blood by:
Degrading enzymes
The kidneys
Liver enzyme systems

26. Interaction of Hormones at Target Cells
Three types of hormone interaction
Permissiveness – one hormone cannot exert its effects without another hormone being present
Synergism – the total effect of two hormones together is greater than the sum of their individual effects
Antagonism – one or more hormones opposes the action of another hormone

27. PLASMA CORTISOL (nmol/L)
Hormonal Rhythms 12
PLASMA GH (mG/L) 8 4 8 12 16 20 4 8
500
400
PLASMA CORTISOL (nmol/L)
300
200
100 8 12 16 20 4 8
CLOCK TIME

28. Control of Hormone Release
Blood levels of hormones:
Are controlled by negative and positive feedback systems
Vary only within a narrow desirable range
Hormones are synthesized and released in response to humoral, neural, and hormonal stimuli

29. Feedback Control
Negative feedback is most common: for example, LH from pituitary stimulates the testis to produce testosterone which in turn feeds back and inhibits LH secretion
Positive feedback is less common: examples include LH stimulation of estrogen which stimulates LH surge at ovulation

30. Feedback Mechanisms Biological effects Biological effects
Negative Feedback
Positive Feedback + +
Target
cell
Target
cell
Endocrine
cell
Endocrine
cell _ +
Biological effects
Biological effects

31. Negative feedback

32. Measurement of Hormone Concentrations
Radioimmunoassay (RIA)
Enzyme-Linked Immunosorbentm Assay (ELISA)