Download Lecture 8 th week

Department of medical
physiology
th
8 week
Semester: summer
Study program: Dental medicine
Lecture: RNDr. Soňa Grešová, PhD.
Endocrinology
Chemical messengers
• 1. Neurotransmitters
• 2. Endocrine hormones
hormone
Endocrine cell
blood
R
target cell
• 3. Neuroendocrine hormones
hormone
Endocrine cell
axon transport
= nerve cell
blood
R
target cell
Chemical messengers
• 4. Paracrines
hormone
Endocrine cell
R
target cell
• 5. Autocrines
Endocrine cell
= target cell
R
hormone
• 6. Cytokines
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Chemical structure and synthesis of hormones
• 1. Proteins and polypeptides
• e.g. hormones secreted by the anterior and posterior pituitary gland, the
pancreas, the parathyroid gland etc.
• 2. Steroids
• secreted by the adrenal cortex, the ovaries, the testes and the placenta
• 3. Derivatives of the amino acid tyrosine
• secreted by the thyroid and the adrenal medullae
Polypeptide and protein hormones
•
•
•
•
•
Stored in secretory vesicles
Polypeptide hormones <100 AA
Protein hormones > 100 AA
Hormones are water soluble
Synthesis
• the rough end of the endoplasmic
reticulum
• Preprohormones
• Prohormones
• Golgi apparatus for packaging into
secretory vesicles
• Smaller biologically active hormones
• Secretion of the hormones by exocytosis
(Ca, cAMP)
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology.
Philadelphia, PA: Saunders Elsevier.
Steroid hormones
• Synthesized from cholesterol and are
not stored
• Hormones are lipid soluble
• Very little hormone are stored in steroidproducing endocrine cells
• Simply diffusion across the cell
membrane and enter the interstitial
fluid and then to the blood
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of
medical physiology. Philadelphia, PA: Saunders Elsevier.
Amine hormones
• Are derived from Tyrosine
• 1. The thyroid hormones
• synthesized and stored into macromolecules (thyroglobulin) in the thyroid
gland
• secretion - the amines are split from thyroglobulin, and the free hormones
are then released into the blood stream - combine with plasma proteins
(thyroxine- binding globulin), which slowly releases the hormones to the
target tissues
• 2. Epinephrine and norepinephrine (Catecholamines)
• They are in preformed vesicles and stored until secreted (exocytosis)
• in plasma free form or in conjugation with other substances
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Hormone secretion, transport, and clearance
from the blood
• Hormone secretion
• norepinephrine and epinephrine, are secreted within seconds
• Thyroxine or growth hormone require months for full effect
• secretion of the various hormones are extremely small, measured in
micrograms or milligrams per day
• Feedback control of hormone secretion
• negative feedback mechanisms -to prevent oversecretion of the hormone or
overactivity at the target tissue
• positive feedback (e.g. luteinizing hormone - LH)
• Periodic variations in hormone release
• aging, diurnal cycle, sleep
Hormone secretion, transport, and clearance
from the blood
• Feedback control of hormone secretion
• negative feedback mechanisms -to prevent oversecretion of the hormone or
overactivity at the target tissue
biological response
Endocrine
cell
hypothalamus
Target cell
adenohypophysis
R
hormone
tropic H
target gland
Target gland hormone
• positive feedback (e.g. luteinizing hormone - LH)
biological response
Hormone secretion, transport, and clearance
from the blood
• Transport of hormones in the blood
• Water-soluble hormones
• Steroid and thyroid hormones
• plasma proteins
• < 10% free
• “Clearance” of hormones from the blood
• Metabolic clearance rate =
•
•
•
•
Rate of disappearance of hormone from the plasma
Concentration of hormone in each milliliter of plasma
1) metabolic destruction by the tissues,
2) binding with the tissues,
3) excretion by the liver into the bile,
4) excretion by the kidneys into the urine
• by enzymatic processes in their target cells
• by enzymes in the blood and tissues
Hormone receptors and their activation
• Receptors are located:
• on the target cell membrane
• in the cytoplasm
• in the nucleus
• Hormonal receptors are large proteins
• Cell - 2000 to 100,000 receptors
• highly specific for a single hormone
• The locations:
•
•
•
•
•
•
• 1. In or on the surface of the cell membrane (protein, peptide, and catecholamine hormones)
• 2. In the cell cytoplasm (steroid hormones)
• 3. In the cell nucleus (thyroid hormones)
Down-regulation of the receptors
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, away from the site of action of hormones
4) destruction of the receptors by lysosomes
5) decreased production of the receptors
Intracellular signaling after hormone
receptor activation
• Ion channel–linked receptors
• opening or closing a channel for one or more ions (sodium ions, potassium
ions, calcium ions, etc.)
• G protein–linked hormone receptors
• 1) open or close cell membrane ion channels or
• 2) change the activity of an enzyme in the cytoplasm of the cell (adenylyl
cyclase or phospholipase C)
Copyright: Hall, J. E., & Guyton, A. C. (2006).
Guyton and Hall textbook of medical
physiology. Philadelphia, PA: Saunders
Elsevier.
Intracellular signaling after hormone
receptor activation
• Enzyme-linked hormone receptors
• Pass through the membrane only once
• enzymatic activity through associated
enzymes (e.g. Leptin : janus kinase –JAK)
• special transmembrane receptor
(adenylyl cyclase, cAMP, cGMP)
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of
medical physiology. Philadelphia, PA: Saunders Elsevier.
Intracellular signaling after hormone
receptor activation
• Intracellular hormone receptors and
activation of genes
• adrenal and gonadal steroid hormones,
thyroid hormones, retinoid hormones,
and vitamin D
• activates or represses transcription of
specific genes and formation of
messenger RNA
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Second messenger mechanisms
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
The cell membrane phospholipid second
messenger system
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Calcium-Calmodulin second
messenger system
• 1) changes in membrane potential that open calcium channels or
• 2) a hormone interacting with membrane receptors that open calcium
channels
• calcium ions bind with the protein calmodulin – activation or
inhibition of protein kinases
Hormones that act on the genetic machinery
of the cell
• Steroid hormones
• Increase protein synthesis
• 1. The steroid hormone diffuses across the cell membrane and enters the
cytoplasm of the cell, where it binds with a specific receptor protein.
• 2. The combined receptor protein–hormone then diffuses into or is
transported into the nucleus
• 3. The combination binds at specific points on the DNA strands in the
chromosomes, which activates the transcription process of specific genes
to form mRNA
• 4. The mRNA diffuses into the cytoplasm, where it promotes the
translation process at the ribosomes to form new proteins
Hormones that act on the genetic machinery
of the cell
• Thyroid Hormones
• Increase gene transcription in the cell nucleus
• 1. They activate the genetic mechanisms for the formation of many types of
intracellular proteins—probably 100 or more. Many of these 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 can
continue to express their control functions for days or even weeks