Fig 7-2

__________________: the study of hormones, their receptors, the intracellular signaling pathways they invoke, and the diseases and conditions associated with them.

What are hormones?

Major endocrine glands?

Physiological processes controlled by hormones?

Fig 7-2

Hormones Known since ancient times

Secreted by cells into the blood

Transported to distant targets

Effective at very low concentration

Bind to receptors

Hormone action must be of limited duration

Classification of Hormones 3 main types:

–Peptides and proteins

–Steroids

–Amines

Differ on basis of synthesis, storage, release, transport and cellular mechanism of action (review Table 7-1)

Peptide (Protein) Hormones Synthesis as preprohormonepreprohormone post-

translational modification to prohormoneprohormone then hormonehormone

Storage – release? Short half-life (mins.)

Most common type

Fig 7-4

Fig 7-3

Cellular Mechanism of Action for Peptide Hormones

Lipophobic how does message get into cell?

Usually rapid cellular response because existing proteins are modified

cAMP 2nd messenger system most common

Steroid Hormones

All derived from cholesterol

Where synthesized?

Storage – release?

Transport in blood? Longer half-life

Mechanism of action

Fig 7-6

Fig 7-7

Amine Hormones

Derived from one or two amino acids 3 groups

– Tryptophan Melatonin

– Tyrosine Catecholaminesbehave like peptide hormones

– Tyrosine Thyroid hormones behave like steroid hormones

Fig 7-8

Control of Hormone Release

All endocrine reflex pathways have similar components – Stimulus / input signal– Integration (where?)– Output signal (hormone / neurohormone)– Physiological action– Negative feedback – turns off reflex

One Hormone may follow > 1 reflex pathway pattern

Fig 7-9

Simple Endocrine Reflex

Endocrine cell acts as sensor AND integrating center no afferent pathway responds by secreting hormone

Example: PTH increases [Ca2+] in plasma

Fig 6-31/➅

Fig 7-10

NeurohormoneReflexNH release by modified

neurons upon NS signal

3 major groups of Neurohormones:– Catecholamines from adrenal medulla– Hypothalamic neurohormones from

posterior pituitary– Hypothalamic neurohormones acting on

anterior pituitary

Fig 6-31/②

Neurohormones of Posterior Pituitary

Other name of gland?

2 neurohormones

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

Fig 7-12

Anterior Pituitary Secretes 6 Hormones (names?)

A Trophic (tropic) hormone controls the secretion of another hormone

Hypothalamic trophic hormones and the hypothalamic-hypophyseal portal system

Fig 7-13

HypothalamusIC1

Ant. pituitaryIC2

Endocrine glandIC3 Target tissue

Negative Feedback Loops in the Hypothalamic-anterior pituitary axis

Hormones serve as negative feedback signals:Short-loop vs. long-loop negative feedback.

Feedback patterns important in diagnosis of ES pathologies

Hormone Interactions

Multiple hormones can affect a single target simultaneously

Three types of hormone interactions: Synergism Permissiveness Antagonism

SynergismSynergism Combined action of hormones is

more than just additive!

Example: Blood glucose levels & synergistic effects of glucagon, cortisol and epinephrine

Fig 7-18

PermissivenessPermissivenessHormone A will not exert full effect without

presence of hormone B.

Example: Thyroid hormone & growth hormone

AntagonismAntagonismAntagonistic hormones have opposing

physiological actions – Hormone B diminishes the effect of hormone A (mechanisms?)

Hormone Antagonists and Cancer: Tamoxifen

Endocrine Pathologies

“Unbalance leads to disease”

Due to:1. Hypersecretion (excess)

2. Hyposecretion (deficiency)

3. Abnormal target tissue response

Hypersecretion: Due to ?

– Iatrogenic (could lead to gland atrophy)– ________

Symptoms: Exaggerated Effects

Examples: Cushing’s Syndrome Gigantism Graves disease

Example: HyperthyroidismHyperthyroidism (Review pp. 756 – 761)

Most common cause: Graves' disease

Autoantibodies (TSI) bind to TSH receptor and stimulate thyroid hormone production

This activation by TSI is not subject to the normal negative feedback loop.

Left exophthalmus in Graves disease

Hyposecretion:

Due to ?

Symptoms: Normal effects of hormone diminished or absent

Examples: Addison’s disease Dwarfism Hypothyroidism

Example: HypothyroidismMost common cause in US: chronic

autoimmune thyroiditis (Hashimoto's thyroiditis = Chronic thyroiditis )

Other causes surgical removal of the thyroid gland radioactive iodine treatment external radiation a deficiency in dietary iodide consumption

(=endemic or primary goiter)

Symptoms:During childhood:

stunted growth retardation lethargy low body temp.

In adulthood:Bradycardiaweight gain lethargy low body temp.

Hypothyroidism cont.

Abnormal Tissue ResponsivenessHormone levels normal, target

unresponsive

Due to:

– Abnormal hormone / receptor interaction

– Abnormal signal transduction

Diagnosis of Endocrine Pathologies

Primary Pathology– Defect arises in last integration center in

the reflex– Examples?

Secondary Pathology– Defect arises in one of the trophic

integration centers– Examples?

Patient Serum T4 Serum TSH

A 6 µg/dl 1.5 µU/ml

B 14 µg/dl .25 µU/ml

C 2.5 µg/dl 20 µU/ml

D 16 µg/dl 10 µU/ml

Normal 4.6-12 µg/dl 0.5 - 6 µU/ml

Which of the sets of lab values below would indicate Grave’s disease? Explain.

Graves’ disease