Jan 6 - Endocrinology and Metabolism

Question 1

What does the endocrine system control?

Answer 1

Development and growth
Energy regulation (storage and mobilization)
Internal homeostasis (fluids, ions)
Reproduction (sex, pregnancy, lactation)

Question 2

What is the difference between endocrine, paracrine and autocrine?

Answer 2

Endocrine hormones is borne via the bloodstream
Paracrine hormones act in a local environment
Autocrine hormones act on the secreting cell

Question 3

What is the pituitary gland?

Answer 3

Probably the most important hormone producing organ (size of a chickpea). It produces some of the most important hormones

Question 4

Name the different chemical classes of hormones

Answer 4

Amino hormones (derived from tyrosine)
Peptide and protein hormones (encoded in genes, i.e. insulin)
Steroid hormones (derived from cholesterol)

Question 5

Describe amino hormones

Answer 5

Derived from the amino acid tyrosine
Includes the catecholamines epinephrine and norepinephrine from adrenal medulla
Includes thryoid hormones thryroxine (T4) and trioiodothyronine (T3) and thryoid

Question 6

Describe protein and polypeptide hormones

Answer 6

They are transcribed from genes.
They are translated in rough ER, processed in Golgi, stored in secretory vesicles.
May undergo one or more post-translational modifications including cleavage, glycosylation, disulfide bridging.

Question 7

Explain how protein and polypeptide hormones exit the cells

Answer 7

They are stored in secretory granules and released on stimulation. It is a calcium ion dependant event (exocytosis). They cannot cross membrane freely as they are hydrophilic

Question 8

Describe steroid hormones

Answer 8

Not encoded in genes, but derived from cholesterol through enzymatic reactions. They include glucocorticoids, mineralcorticoids, androgens, estrogens and progestins

Question 9

How do steroid hormones enter the cell?

Answer 9

Steroids are lipophilic molecules that freely cross membranes. Steroids are not stored in endocrine glands but are released as made. Steroids travel in the blood associated with steroid-binding globulins (SBGs)

Question 10

What are the three main axes (feedback loops) involving the hypothalamus and the pituitary control? What do they do?

Answer 10

The hypothalamic-pituitary-thyroid axis (HPT)
The hypothalamic-pituitary-adrenal axis (HPA)
The hypothalamic-pituitary-gonadal axis (HPG)

They control much of the endocrine system and they operate by negative feedback loops

Question 11

Explain the HPG axis

Answer 11

GnRH secreted by the hypothalamus stimulates the secretion of FSH and LH in the pituitary. FSH/LH stimulates the secretion of estrogen and progesterone. Once the levels of estrogen/progesterone are high enough, they travel to the brain to inhibit the secretion of FSH/LH and GnRH

Question 12

What is positive feedback control? Give two examples

Answer 12

It is less common, but used when amplification is needed. Example 1: the mid-cycle surge of gonadotropins (LH and FSH) stimulated by high levels of estrogens. Example 2: Oxytocin (made in the hypothalamus and released by the posterior pituitary) during parturition and suckling

Question 13

Explain the activation of bioactive hormones. Give examples

Answer 13

It requires modifications after synthesis and release. Example 1: 5-alpha reductase converts testosterone (T) to bioactive dihydrotestosterone (DHT). Example 2: Aromatase converts testosterone of estrogen. Example 3: Thyroxine (T4) to triiodotyronine (T3, more active form thyroid hormone)

Question 14

Explain endocrine rhythms

Answer 14

Hormone levels may fluctuate in response to internal (neurotropic) and external stimuli (food, light, activity). Circadian and longer rhythms also exist

Question 15

What is the physiological and clinical significance of pulsatile hormone secretion

Answer 15

It maintains organ sensitivity, e.g. prevents down-regulation of receptors. Abolished pulsatile secretion results in diminished hormone secretion, e.g. GnRH agonist leads to clinical castration

Question 16

What is the mechanism of hormone action?

Answer 16

All hormone action is receptor mediated. Hormone receptors act as allosteric effectors; hormone binding to specific receptor results in conformational change in receptor that conveys a signal to target cell

Question 17

Describe cell surface receptors

Answer 17

Peptide hormones and catecholamines bind to cell surface receptors. Receptors have extracellular, transmembrane and intracellular domains. Extracellular domain contains ligand (hormone) binding site

Question 18

Describe the steps in cell surface receptor binding

Answer 18

The hormone traveling in the blood stream with a binding protein detaches from the binding protein. It binds with the extracellular domain of the receptor. The intracellular domain of the receptor activates a second messenger system causing an altered cell function

Question 19

What are second messengers?

Answer 19

They are released within the cell upon hormone binding to the extracellular domain of the receptor. They can include cAMP or cGMP, the phospholipids diacylglycerol (DAG) and inositol triphosphate (IP3), calcium, etc.

Question 20

Describe the action of the second messenger cAMP

Answer 20

G-protein-coupled receptors activate adenylate cyclase via the alpha domain of the G-protein. Adenylate cyclase converts ATP into cAMP, which goes on to activate other proteins that alter cell function

Question 21

Describe the action of phospholipids as second messengers

Answer 21

Phosphorylation of receptors activates phospholipase C. Phospholipase C converts PIP2 into DAG and IP3. DAG activates other enzymes and IP3 causes release of calcium. Further processing alters cell function

Question 22

Describe the action of kinase receptors via the example of insulin

Answer 22

Insulin binds to the receptors, causing them to dimerise. Dimerised receptors undergoes transautophosphorylation. Linking protein binds to phosphate group. Linking protein activates second messanger systems

Question 23

Describe receptor down-regulation

Answer 23

After hormone binding, receptors may be internalized (coated pits). Leads to reduced responsiveness of target cell (usually temporary). Receptor may be recycled to cell surface or degraded

Question 24

Describe intracellular receptors

Answer 24

Steroid and thyroid hormones act via intracellular receptors. Hormone-receptor complex interacts directly with DNA at the promotor of specific genes

Question 25

Describe the action of intracellular receptors

Answer 25

The steroid hormone diffuses through the cell membrane. The hormone binds to an intracellular receptor either the cytoplasm or the nucleus, forming a hormone-receptor complex. The complex interacts with DNA in the nucleus, altering gene expression and cell function

Question 26

What causes endocrine dysfunction due to changes in hormone levels

Answer 26

It can arise from a variety of factors. Most commonly it results from abnormal plasma concentrations of a hormone caused by inappropriate rates of secretion

Question 27

What is primary hyposecretion? What are the causes?

Answer 27

Too little hormone is secreted due to abnormality within the gland. Causes: genetic, dietary, chemical or toxic, immunologic, other disease processes such as cancer

Question 28

What is secondary hypsecretion?

Answer 28

Gland is normal but too little hormone is secreted due to deficiency of tropic hormone

Question 29

What is primary hypersecretion?

Answer 29

Too much hormone is secreted due to abnormality within gland (e.g. hormone secreting hormones)

Question 30

What is secondary hypersecretion?

Answer 30

Excessive stimulation from outside the gland causes oversecretion

Question 31

What are the two types of endocrine dysfunction at the target cells?

Answer 31

Receptor defects (mutations causing inactivity or constitutive activity, reduced/increased numbers, receptor agonist/antagonist)
Post-receptor signal transduction defects (e.g., second messangers, coupling proteins)