Ch 11: Endocrine

System

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

• 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

Endocrine Glands and Hormones

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

Where synthesized? Lipophilic or – phobic? Where stored? How transported in blood?

Different classes of hormones differ on basis of synthesis, storage, release, transport and cellular mechanism of action

Polar vs. non-polar

Lipo______ vs. lipo______

HO

HO

Pregnenolone

Cholesterol

Interstitial

(Leydig) cells

OH

Adrenal

cortex

Ovary

A

C

B

D

Corpus

luteum

O

O C

CH3 CH3

C O

OH O

O O

Testosterone

HO

Estradiol-17

Follicles

in ovary

HO

O

OH

C O

CH2OH

Spermatic

cord

Testis

Seminiferous

tubules

Progesterone

Ovary Cortisol (hydrocortisone)

Androstenedione

Biosynthetic Pathway for Steroid Hormones

Fig 11-2

All derived from _______________

?

?

?

?

Compare to Fig 7-6

Tyrosine Derivatives

I

I I

I

I I

I

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

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

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!

Permissiveness 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.

1)Insulin stimulates fat storage 2)Glucagon stimulates fat breakdown.

Hormone Antagonists and Cancer: Tamoxifen as

an exmaple of a SERM (see Clinical App, p. 325)

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

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?

Fig11.4

Two regions on the receptor:

1)Ligand-binding domain for the hormone

2)DNA-binding domain for DNA

These hormones act as transcription factors

Nuclear Hormone Receptors for Steroid and Thyroid hormones

Fig. 11.5

H

Receptor protein

for steroid hormone

Steroid

hormone

Ligand-binding

domain

DNA-binding

domain Half-sites

Target gene

DNA

Dimerization of receptor

Steroid

hormone

Steroid

hormone

Genetic transcription

mRNA

(a)

(b)

DNA

H H

Hormone-

response

element

Steroid Hormone Receptors

Compare to

Fig11.4

There is also “nongenomic action” involving 2nd messenger systems

Which reaction is faster ?

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

Fig. 11.6

Nucleus

Cytoplasm

Receptor

protein

DNA

4

5

6

7

Blood Target cell

mRNA

mRNA

Thyroid

hormone

response

Protein

synthesis

Carrier

protein

(TBG)

2

1 Binding

protein

3

T4

T4 T4

Thyroid

Hormone

Action

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

Adenylate Cyclase (cAMP) System

Fig. 11.8

E and NE

Fig. 11.12

Optic chiasma

Anterior lobe

(__________________)

Infundibulum

Posterior lobe

(________________)

Hypothalamus

PITUITARY GLAND Other name?

Neurohormones of Posterior Pituitary

2 neurohormones (?)

Both are peptides (9 aa) transported in secretory vesicles via axonal transport Compare to Fig

11.13

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

Review Table 11.6 and compare to Fig. 11.14

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.

Hypothalamus

IC1 Ant. pituitary

IC2

Endocrine gland

IC3 Target tissue

Negative Feedback Loops in Complex Endocrine Pathways

Hormones serve as negative feedback signals:

Short-loop vs. long-loop negative feedback.

Feedback patterns are important in diagnosis of

ES pathologies

Compare to Fig 11.16/17

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