1. Homeostasis and Hormones
稳态与激素
Homeostasis and Hormones
梅文瀚

2. Learning Goals
To understand the definition, characteristics of action, classification, delivery modes, receptors and action mechanism of hormones.
To understand the compositon of endocrine system.
To understand hormone are essential to maintain the internal environment.

3. What is hormone? Definition
Hormones are chemical messengers secreted into blood or extracellular fluid by one cell that affect the functioning of other cells.

4. The common characteristics of hormone action
Transinformation
Relative specificity:
depends on the specificity of target cell receptors
Biological Amplification
The interaction between hormones
Synergistic effect, Antagonistic effect

5. Where are hormones from
Classic Endocrine glands
Diffused endocrine
Cells in other tissue

6. Hormones and their regulation system
Nervous System
Endocrine System
Endocrine glands
Diffused endocrine
Cells in other tissue
Hormones and their regulation system
Metabolic
Process
代谢过程
Organs
Function
器官功能
Growth and
development
生长发育
Reproduction
and aging
生殖衰老

7. Modes of Hormone Delivery
1.Endocrine : Hormones are distributed throughout the body in the bloodstream. 2.Paracrine: Hormones diffuse locally in the extracellular fluid and influence nearby cells。 3.Autocrine: Hormones diffuse locally in the extracellular fluid and influence the same cells that release them.

8. Endocrine

9. Paracrine and Autocrine

10. 4.Neuroendocrine Neurohormones are secreted by neurons and enter the circulation.

11. Classification of Hormones(1)
Three classes of hormones based on chemical properties:
Peptide and protein hormones :
Water-soluble, easily transported in blood
Can be packaged in vesicles and released by exocytosis
e.g.，ACTH, LH, FSH, PTH, TSH, Insulin , Glucagon, IGFs

13. Three classes of hormones based on chemical properties:
Steroid hormones Synthesized from cholesterol
Lipid-soluble; pass easily through cell membranes
Usually bound to carrier molecules in the blood
e.g., cortisone, aldosterone, 1,25(OH)2 D3 ,
androgen, estrogen

15. Three classes of hormones based on chemical properties:
Amine hormones (e.g., epinephrine):
Mostly synthesized from the amino acid tyrosine (e.g., thyroxine)
Some are water-soluble; others are lipid- soluble; their modes of release differ accordingly.

17. Classification of Hormones(2)
Two classes of hormones based on Solubility:
Water-soluble hormones:
can not pass through cell membranes; bind to cells membrane receptors.
e.g.: peptide hormones, amines, prostaglandin
Lipid-soluble hormones:
bind with plasma transport protein; can diffuse through cell membranes; bind to cytoplasmic or nuclear receptors.
e.g.: steroids, thyroid hormone, Vit D, Vit A

18. Two types of hormones receptors and Mechanisms of Hormones Action
Cell-surface receptors--- activate or inhibit enzymes, which may affect protein synthesis.
Intracellular receptors --- stimulate or inhibit protein synthesis directly.（transcription factor）
Based on their location:

19. The structure of cell-surface receptors
Extracellular domain： ligand-binding domain
Transmembrane domain
Cytoplasmic or intracellular domain: play with hormone, product second messenger ,belong to molecular effect domain

20. Second messenger

21. The structure and function of nucleus receptors
Amino acid domain: interacts with other transcription factors
DNA binding area: binding with specific DNA sequence
Carboxyl terminal ligand binding domain: binding with hormone

22. Glucocorticoids

23. Homeostasis
Homeostasis of internal environment (extracellular fluid) is a narrow range of stable and optimal physical and biochemical conditions.
Homeostasis is maintained through control and regulation of activities of organs and organ systems by nervous and endocrine system.
If homeostasis is compromised, cells can be damaged and can die.

24. Homeostasis Maintaining the internal environment. System Hormones
Glucose Balance
↓Insulin ↑Glucagon
Calcium Balance
↑PTH ↓Calcitonin ↑Calcitriol
Water Balance
↑ADH ↓ANH
K+/Na+ Balance
↑ANH ↓Mineralocorticoids

25. The Endocrine System and Nervous System Work Together
The nervous and endocrine systems work together to control and regulate all the physiological and behavioral mechanisms that contribute to homeostasis, survival, and reproduction.
The pituitary gland is attached to the hypothalamus of the brain.The pituitary connects the nervous and endocrine systems and is involved in hormonal control of many processes.

26. Hypothalamic neurons secrete two neurohormones into the posterior pituitary:
Antidiuretic hormone (ADH) increases the water retained by the kidneys when necessary.
Also called vasopressin—it causes the constriction of peripheral blood vessels to elevate blood pressure.

27. Oxytocin stimulates uterine contractions in childbirth and milk flow.
The baby’s suckling stimulates neurons in the mother’s brain that cause secretion of oxytocin.
An example of how the nervous system integrates information that regulates hormonally mediated processes.

28. Neurohormones produced by hypothalamic neurons reach the anterior pituitary via the portal blood vessels that run through the pituitary stalk.
William’s Endocrinology

30. Hypothalamic hormones
Greenspans Basic And Clinical Endocrinology 8e

31. The anterior pituitary secretes tropic hormones that control other endocrine glands.
Thyrotropin (thyroid-stimulating hormone)
Luteinizing hormone
Follicle-stimulating hormone
Corticotropin

32. Anterior pituitary also secretes:
Growth hormone (GH) promotes growth by stimulating cells to take up amino acids, and liver cells to produce signals to stimulate growth of bone and cartilage.
Endorphins and enkephalins are the body’s natural painkillers, acting as neurotransmitters in the brain.
Melanocyte-stimulating hormone (MSH) stimulates the production of the pigment melanin in skin and hair.

33. Hypothalamo-Pituitary-target glands-Axis

34. Hypothalamo-Pituitary-target glands-Axis
Hypothalamus
TRH
CRH
GnRH GH
GHIH
Pituitary
TSH
ACTH LH
FSH GH
Peripheral
Endocrine gland
Thyroid
T3,T4
Adrenal Cortex
Cortisol
Gonads
Androgen
Estrogen
Progesterone
Liver
IGF

35. Hormones Regulate Calcium Metabolism and the Internal Environment
Regulation of calcium levels in the blood is critical to body function.
There are several mechanisms for changing blood calcium levels:
Deposition or absorption of bone
Excretion or retention of Ca by kidneys
Absorption of Ca from digestive tract

36. Hormones Regulate Calcium Metabolism and the Internal Environment
These mechanisms are controlled by 3 hormones: Calcitonin，PTH，Calcitriol
Calcitonin is released by the thyroid parafollicular cells; lowers blood Ca by regulating bone turnover.
Calcitonin decreases the activity of osteoclasts and thus favors removal of Ca from the blood and deposition in bone by osteoblasts..

37. Hormones Regulate Calcium Metabolism and the Internal Environment
Parathyroid hormone (PTH); secreted by the parathyroid glands.
Blood Ca levels control synthesis and release of PTH—when low, PTH is released, which stimulates bone turnover by osteoclasts and osteoblasts and increases blood Ca levels.
PTH also stimulates kidneys to reabsorb Ca.

38. Hormones Regulate Calcium Metabolism and the Internal Environment
Calcitriol is synthesized from vitamin D (calciferol), which is really a hormone.
Calciferol is synthesized from cholesterol when skin cells receive ultraviolet light.
PTH activates conversion of calciferol to calcitriol in the liver and kidneys.
Calcitriol promotes absorption of Ca from the gut.
The combined actions of PTH and calcitriol raise blood calcium levels.

39. Synthesis and Activation of Vit D3 Active form: 1,25(OH)2D3 (Calcitriol)
1α-hydroxylase
25-hydroxylase
from Ganong WF: Review of Medical Physiology, 21st ed. McGraw-Hill, 2005.

40. Hormonal Regulation of Calcium
Figure Hormonal Regulation of Calcium
Calcitonin, parathyroid hormone (PTH), and calcitriol (the active form of calciferol, or vitamin D) regulate Ca2+ levels in the blood.

41. the Internal Environment
PTH also stimulates release of phosphate from bone. Small increases in Ca and phosphate in the blood can result in precipitation of calcium phosphate salts. This can result in kidney stones and hardening of the arteries (Ca deposits). PTH acts on kidneys to eliminate phosphate in the urine.

42. Pentose phosphate pathway Non-carbohydrate substrates
Blood Glucose Balance
( mmol/L)
Sugar in food
digestion，absorption
oxygenolysis
CO2 + H2O
Glycogen
synthesis
Liver(muscle)
Liver glycogen
glycogenolysis
Blood Glucose
Pentose phosphate pathway
Other
sugars
Non-carbohydrate substrates
gluconeogenesis
Lipid synthesis
amino acid synthesis
Fat
Amino Acid

43. Hormones Regulate Glucose Metabolism and the Internal Environment
Islets of Langerhans: Endocrine cells in the pancreas that produce 3 hormones.
Beta (b) cells produce insulin.
Alpha (a) cells produce glucagon—stimulates liver to convert glycogen to glucose when blood glucose levels fall below normal.

44. Insulin
Fasting plasma insulin:35pmol/L

45. Thr
Ser
Ile
Ala
Val
Gly
Human
Cow
Pig
Sheep
Horse
A Chain

46. Process： Preproinsulin Proinsulin Insulin Protein Translattion
NH2
COOH
Preproinsulin
B Chain
Signal Peptide
A Chain C肽
Signal
Peptide
S S
S S
NH2
COOH
Proinsulin
B Chain
A Chain C肽
C Peptide
S S
NH2
COOH
Insulin
B Chain
A Chain

48. Hormones Regulate Glucose Metabolism and the Internal Environment
Diabetes mellitus (type I) is caused by lack of the protein hormone insulin.
Glucose transporters are controlled by insulin.
When insulin binds to cell receptors, transporters move to the cell membrane and facilitate glucose uptake.

49. Glucose Transporters Are Controlled by Insulin

50. Hormones Regulate Glucose Metabolism and the Internal Environment
Adult onset or type II diabetes is associated with obesity, high carbohydrate consumption, and lack of exercise.
Caused either by low production of insulin or insensitivity to insulin.

51. Hormones Regulate Glucose Metabolism and the Internal Environment
In 1921, it was discovered that diabetes could be treated by injecting pancreas extracts.
Today, insulin replacement therapy using manufactured insulin allows people with type I diabetes to lead almost normal lives.
Type II diabetes can be treated with a combination of dietary changes and weight loss.

52. Summary
Hormones are chemical messengers secreted into blood or extracellular fluid by one cell through endocrine , paracrine, autocrine or neuroendocrine, then affect the functioning of target cells.
The endocrine cells can be aggregated to form endocrine glands or diffused in other tissues.
Water-soluble hormones tend to act via binding to membrane receptors and initiating a signal transduction cascade.
Lipid-soluble hormones tend to bind to cytoplasmic or nuclear receptors to directly regulate gene expression.
The endocrine system and nervous system work together. The pituitary gland is the interface between two systems.
Multiple feedback loops regulate hormone secretion.
Hormones regulate metabolism and the internal environment .
The level of calcium in the blood is regulated by Calcitonin ,PTH and Calcitriol.
The level of glucose in the blood is mainly regulated by Insulin and Glucagon.