1. Ch 11: Endocrine System

2. SLOs
Describe the chemical nature of hormones and define the terms pro- and prepro-hormone.
Explain mechanism of action of steroid and thyroid hormones
Create chart to distinguish the the different classes of hormones (steroids, amines, poly peptides, and proteins and glycoproteins) according to how they are synthesized, stored, released, transported in blood, and cellular mechanisms of action.
Predict the classification of an unknown hormone from knowledge of its synthesis, storage and release, transport in the blood, and cellular mechanism of action.
Differentiate between anterior pituitary and posterior pituitary.
List (full spellings and abbreviations) the hormones secreted by the anterior and posterior pituitary and identify the ones that have trophic effects.
Explain how the hypothalamus regulates the anterior and posterior pituitary glands.
Describe negative feedback inhibition in the regulation of hypothalamic and anterior pituitary hormones

3. Endocrine Glands and Hormones
Review anatomy of ES / Major endocrine glands?
What is a hormone?
What is a neurohormone?
__________________: Study of hormones, their receptors, intracellular signaling pathways they invoke, diseases and conditions associated with them.
Physiological processes controlled by hormones?
Compare to Fig 11-1

4. Chemical Classification of Hormones
3 main types:
Steroids derived from __________
__________, __________, __________, __________
Secreted by __________ and __________
Amines, derived from tyrosine and tryptophan
_____________________, T3 and T4, melatonin
Polypeptides, Proteins and Glycoproteins
ADH, insulin, GH, FSH and LH
FSH and LH are glycoproteins
Steroids derived from cholesterol
Secreted by overies and adrenal cortex
Progesterone......aldosterone and cortisol
Where synthesized? Lipophilic or – phobic? Where stored?
How transported in blood?

5. Different classes of hormones differ on basis of synthesis, storage, release, transport and cellular mechanism of action Polar vs. non-polar Lipo______ vs. lipo______
Nonpolar hormone drugs can be taken orally in pill form

6. Biosynthetic Pathway for Steroid Hormones
All derived from _______________
Interstitial
(Leydig) cells C D
Spermatic
cord A B HO O OH
Cholesterol
Testis
Seminiferous
tubules
CH3
CH3 C O O O C O
Androstenedione
Testosterone ?
In testes
In ovaries HO O OH
Pregnenolone
Progesterone ?
CH2OH HO
Secreted by Leydig cells of testes
Secreted by follicles of ovaries
Ovary
In adrenals ?
Estradiol-17 C O HO OH
Follicles
in ovary
Corpus
luteum O
Ovary
Cortisol (hydrocortisone) ?
Adrenal
cortex
Fig 11-2

7. Tyrosine Derivatives I I I I I I I
Compare to Fig 7-6

8. Pro-, Pre-, and Preprohormones
Some hormones are 1st produced as precursor molecules. They must be cut and sometimes spliced together to be active. E.g.: Insulin

9. Common Aspects of Neural & Endocrine Regulation
Many similarities:
Hormones and NTs both interact with specific _________
Leads to change within cell
Signal molecule is either removed or inactivated
Multiple hormones can affect a single target simultaneously
Three types of hormone interactions:
Synergism
Permissiveness
Antagonism

10. Synergism
2 or more hormones work together to produce a particular effect
Effects may be additive, as when E and NE each affect the heart in the same way.
Effects may be complementary, as when each hormone contributes a different piece of an overall outcome.
Combined action of hormones may be more than just additive!

11. Permissiveness Antagonism
One hormone makes target cell more responsive to a second hormone
E.g.: Exposure to estrogen  uterus more responsive to progesterone.
Antagonism
Insulin and glucagon both affect adipose tissue.
Insulin stimulates fat storage
Glucagon stimulates fat breakdown.
Hormone Antagonists and Cancer: Tamoxifen as an exmaple of a SERM (see Clinical App, p. 325)
Mechanisms: competition for same receptor or different opposing metabolic pathway activated

12. Effects of hormone concentrations on tissue response
Hormone half-life
Time for plasma concentration of a given amount of hormone to be reduced by half (mins to days)
Liver removes most hormones from blood  conversion to less active products
Pharmacological hormone levels (?)
binding to receptors of related hormones  widespread side effects. E.g.: Steroid abuse
Upregulation of receptors leads to “priming effect”
Downregulation of receptors due to prolonged exposure to high concentrations of hormone. Desensitization can be avoided by releasing hormones in spurts = pulsatile secretion
Hormone levels too high (pharmacological levels) vs. physiological levels

13. Mechanisms of Hormone Action
Hormones bind to _________on or in _____cells.
Binding is highly specific
Hormone has high affinity
Saturation occurs
Location of hormone receptors? What is determining factor?

14. Nuclear Hormone Receptors for Steroid and Thyroid hormones
Two regions on the receptor:
Ligand-binding domain for the hormone
DNA-binding domain for DNA
These hormones act as transcription factors
many “orphan” receptors without a known ligand.
Fig11.4

15. Steroid Hormone Receptors
Receptor protein
for steroid hormone
Ligand-binding
domain
DNA-binding
domain
Half-sites
(a)
DNA
Hormone-
response
element
Target gene
Dimerization of receptor
Steroid
hormone H H
Steroid
hormone
Fig. 11.5
DNA
Genetic transcription
(b)
mRNA

16. There is also “nongenomic action” involving 2nd messenger systems
Compare to
Fig11.4
Construct flow chart:
Travel to target cells attached to carrier proteins
At the target cell, dissociate from the carrier protein and diffuse across the plasma membrane
Receptors are found within the nucleus and are called because they activate genetic transcription
These hormone receptors serve as transcription factors.
They are activated by the binding of the hormone
The effect of these hormones is therefore to produce new proteins, usually enzymes that change metabolism inside the cell.
Classical mechanism – stimulates genetic transcription
Required at least 30 minutes to work
Better established and understood mechanism
There is also “nongenomic action” involving 2nd messenger systems
Which reaction is faster ?

17. Coactivator and Corepressor...
....molecules often used in addition to the steroid hormone. They bind to nuclear receptor proteins at specific regions  different effects of a given hormone in different cells

18. Thyroid Hormone Action
Cytoplasm
Nucleus
DNA
Thyroid Hormone Action 4
Receptor
protein 5 T3
mRNA T3
mRNA 3
Carrier
protein
(TBG) T4 T3 6
Construct flow chart :
Thyroxine (T4) travels to target cells on thyroxine-binding globulin (TBG).
Some T3 is also released, but is not bonded to a carrier; “free iodine”
Inside the target cell, T4 is converted to T3.
Receptor proteins are located inside the nucleus bound to DNA.
The hormone response element on the DNA has two half-sites, one for a T3 receptor and one for a 9-cis-retinoic acid receptor (a Vit A derivative).
Binding of these molecules forms a heterodimer because there are two different receptors
The binding of T3 will cause corepressor proteins to be removed and coactivator proteins to be recruited.
Vitamin D action in the cell is similar.
Protein
synthesis
Binding
protein 1 T3 7 2
Thyroid
hormone
response T4 T4
Fig. 11.6
Blood
Target cell

19. Hormones That Use 2nd Messengers
Catecholamines, polypeptides, proteins, and glycoproteins
Cannot cross plasma membrane (?)  bind to cell surface receptors
Activate intracellular mediators called 2nd messenger via __________
Know adenylate (adenyl) cyclase / cAMP pathway only
G protein

20. Adenylate Cyclase (cAMP) System
Used by epinephrine and norepinephrine
Binds to a β-adrenergic receptor
G-protein dissociates
Activates adenylate cyclase
Uses ATP to make cAMP
cAMP activates protein kinase
Protein kinase phosphorylates proteins in the target cell to alter cell metabolism
E and NE
Fig. 11.8

21. Pituitary Gland Other name? Anterior lobe (__________________)
Optic chiasma
Anterior lobe
(__________________)
Infundibulum
Posterior lobe
(________________)
Hypothalamus
The pituitary gland is attached to the hypothalamus by the infundibulum
Divided into an anterior lobe (adenohypophysis) and a posterior lobe (neurohypophysis)
The anterior pituitary is glandular epithelium with two parts – pars distalis and pars tuberalis
The posterior pituitary is nervous tissue and also called the pars nervosa
Fig

22. Neurohormones of Posterior Pituitary
Both are peptides (9 aa) transported in secretory vesicles via axonal transport
Stores and releases two hormones made in the hypothalamus:
Antidiuretic hormone (ADH), which promotes the retention of water in the kidneys (also called arginine vasopressin – AVP)
Oxytocin, which stimulates contractions in childbirth and milk let-down in lactation
Release is controlled by neuroendocrine reflexes.
ADH is stimulated by an increase in blood osmolality
Oxytocin is stimulated by suckling
Compare to Fig 11.13

23. Hormones of Anterior Pituitary
6 Hormones (names?)
A Trophic hormone controls the secretion of another hormone. Target gland hypertrophies in response to trophic hormone.
Hypothalamic trophic hormones and the hypothalamo-hypophyseal _________system
Growth hormone (GH)
Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH) – in the male, it is interstitial cell stimulating hormone (ICSH)
Prolactin (PRL)
hypothalamo-hypophyseal portal system.

24. Review Table 11.6 and compare to Fig. 11.14

25. Feedback Control of Anterior Pituitary
Final product regulates secretion of pituitary hormones: negative feedback inhibition
Hypothalamus  anterior pituitary  target tissue axis
Inhibition
at pituitary level, inhibiting response to hypothalamic hormones.
at hypothalamus level, inhibiting secretion of releasing hormones.

26. Negative Feedback Loops in Complex Endocrine Pathways
Hypothalamus
IC1
Ant. pituitary
IC2
Endocrine gland
IC3
Target tissue
Compare to Fig 11.16/17
Hormones serve as negative feedback signals:
Short-loop vs. long-loop negative feedback.
Feedback patterns are important in diagnosis of ES pathologies

27. Higher Brain Controls
Since hypothalamus receives input from higher brain regions, emotions can alter hormone secretion!
Pituitary-gonad axis: At least 26 brain regions and olfactory neurons send axons to the GnRH-producing neurons.
Pituitary-adrenal axis: Psychological stress influences CRH production
Hot field: neuropsychophysiology