Lecture 6 Flashcards
Types of hormones
(1) Steroids, come from
Adrenal glands
Gonads
(2) Non steroid hormones
2a. Amine-derived hormone
is an AA
Melatonin
2b. Peptide hormone
Chains of AAs
TRH, Vasopressin, Insulin
2c. Lipid based, lipid and phospholipid hormones are derives from lipids
Prostaglandins
Mechanisms of action (mediated)
Activates a receptor
Could be inotropic or metabotropic
Could influence cell communication or gene expression
Polypeptide, monoamines, prostaglandins
Direct actions
Enter the cell
Have intracellular receptors
Go into cell nucleus
Induce gene expression through response element on DNA
Changes protein synthesis at the endoplasmic reticulum
Eg thyroid and steroid hormones
Down regulation (3 ways)
Can also…
1 - inactivation
G protein is uncoupled
2 - receptor internalization
Membrane pinches off into vesicle
Engulfs receptor and takes with it
Can be reversed
3 - Permanent destruction (true down-regulation)
Pinched off in an endosome, lysosome joins, destroys receptor (irreversible)
Can also upregulate by adding more receptors
Non-steroid hormone production
Synthesized from AAs at the ribosome
Usually as a preprohormone or a prohormone
Transported to the Golgi apparatus
On the way, enzymes cleave off parts
Made into a prohormone
Packed at the Golgi body into an vesicle with hormone that cleave parts of the prohormone and turn it into a hormone
When ready, joins cytoplasm and releases fully-active hormone out of the cell
Pre-Prohormones and Enzymatic Cleavage Advantages
-Pre-Prohormones and Enzymatic Cleavage
Advantages :
1. Prohormones stabilizes the 3D structures of peptides during synthesis
(act as a wall)
2. Prohormones are easier to transport & package than hormones
(like a moving box…..)
3. Prohormones act as storage reserve (they store active hormones)
4. Prohormones can regulate the amount of hormones released
5. Prohormones are more resistant to degradation than hormones
and they have a longer half-life
Hormone Synthesis of Steroid Hormones
Synthesized from cholesterol in the smooth endoplasmic reticulum
- Cells take up cholesterol from the blood and convert it to pregnenolone in the mitochondria
- Then pregnenolone is converted into progesterone which will:
1. Act as hormone
2. Be used as a prohormone for further steroid synthesis
Hormone Synthesis of Steroid Hormones example
Cholesterol in blood
Crosses into cell (lipophilic)
Metabolized for energy at the mitochondria, makes pregnenolone as a product
Modified at the smooth endoplasmic reticulum into a hormone
Diffuses out of cell
Steroid hormones are made when needed as they cannot be stored because of their lipophilic properties
Common steroid pathways
Primary enzymes in adrenal and gonadal systems
Cholesterol
Made into pregnenolone
Made enzymatically into progesterone
Made into
ADRENAL steroids (aldosterone and cortisol) or GONADAL steroids (test/est)
Both the Adrenal Glands and the Gonads possess ALL enzymes necessary
for steroid synthesis.
-What differentiates them is the expression of these different enzymes
-Some glands express more of certain enzymes compared to other.
In the adrenal system the primary enzyme is hydroxylase
In the gonads, the primary enzyme is aromatase (17-alpha-hydroxylase converts progesterone into prohormones for gonadal hormones but aromatase is the primary hormone)
Hormonal effects in the brain
Brain made Hormones
Hormones that are released in the brain act in the brain
- Oxytocin and vasopressin
- Estrogens synthesized locally
Hormones that are released outside of the brain can also act in the brain but they must cross the blood brain barrier
The blood brain barrier
What makes it
Where is it weaker
History of the discovery of the BBB
- Injected blue dye: every tissue turned blue with the exception of the BRAIN and SPINAL CORD
- Dye into the brain, only the CNS turns blue
Conclusion : Natural barrier protecting the brain from external fluids
BBB : SEMI-PERMEABLE, i.e. let some compounds in, and not others
BBB : Cells tightly packed, so molecules must be SMALL to cross the BBB
BBB : LIPID-Based, so molecules must be LIPOSOLUBLE to cross the BBB
Is made of the feet processes of astrocytes around capillaries. There are 4 sites where the BBB is weak
1) Median eminence
2) Pituitary gland (technically outside the CNS)
3) Pineal glad
4) Area postreama
Cell membranes in the brain
Cell membranes in the brain have the same properties as the BBB
- Lipid-based
- Small Molecules enter
Steroids & Peptides are VERY different molecules…..
STEROIDS PEPTIDES
-small molecules -large molecules
-liposoluble -water soluble
These hormones regulate activity of their target cells
by VERY different receptor mechanisms
First-order feedback loop
Only ONE gland and a non-endocrine target
Enzymes that are synthesized in the hypothalamus and affect tissue at target sites ALSO bind at the hypothalamus and inhibit their own production
Examples: Oxytocin and Vasopressin -Synthesized in hypothalamus - Released from posterior pituitary -Act on target and inhibit secretion from hypothalamus
Second-order feedback loop
2 Endocrine structures than a non-endocrine target site
Ultra-short loop
Hormone released by hypothalamus inhibits its own release
Short loop
Hormone released by pituitary inhibits hypothalamic hormone release
Third-order feedback loop
2 Endocrine structures and an ENDOCRINE target organ
Trophic hormones
Hyp
Pit
Endocrine target cell
Ultra-short loop
Hypothalamic hormone inhibits its own production by binding to receptors on the hypothalamus
Short loop
Hormone released at the pituitary affects endocrine target site and binds to hypothalamus , inhibiting hypothalamic hormone release
Long loop
Hormone released by endocrine target site exerts its effects at the target site but also binds to the pituitary and hypothalamus inhibiting the release of hypothalamic and pituitary hormones
