Endo 01: Endocrinology Basics

Front 1

How can hormones be classified?

Back 1

By their chemical nature
- Group 1: Steroids and Thyroid Hormones
- Group 2: Peptides, Proteins, and Glycoproteins

Front 2

What are some of the Group 1 / steroid hormones?

Back 2

- Cortisol
- Aldosterone
- Testosterone (androgens)
- Estrogens
- Progestins
- Calcitriol

Front 3

What are the Group 1 / thyroid hormones?

Back 3

- Thyroxine (T4)
- Triiodothyronine (T3)

Front 4

What are some of the Group 2 / peptide hormones?

Back 4

- Oxytocin
- Vasopressin (ADH)
- Angiotensin
- Somatostatin
- Thyrotropin-Releasing Hormone (TRH)
- Gonadotropin-Releasing Hormone (GnRH)
- Gastrin

Front 5

What are some of the Group 2 / protein hormones?

Back 5

- Insulin
- Glucagon
- ACTH
- Growth Hormone
- Prolactin
- CRH
- GHRH
- PTH
- Calcitonin
- CCK
- Secretin

Front 6

What are some of the Group 2 / glycoprotein hormones?

Back 6

- TSH
- Gonadotropins: FSH, LH, hCG

Front 7

Group 1 Hormones:
- Types
- Solubility
- Transport proteins
- Plasma half-life
- Receptor location
- Mediator

Back 7

Group 1 Hormones:
- Types: steroids and thyroid hormones
- Solubility: lipophilic
- Transport proteins: yes
- Plasma half-life: long (hours to days)
- Receptor location: intracellular
- Mediator: receptor-hormone complex

Front 8

Group 2 Hormones:
- Types
- Solubility
- Transport proteins
- Plasma half-life
- Receptor location
- Mediator

Back 8

Group 2 Hormones:
- Types: peptides, proteins, glycoproteins, catecholamines
- Solubility: hydrophilic
- Transport proteins: rarely
- Plasma half-life: short (minutes)
- Receptor location: plasma membrane
- Mediator: cAMP, cGMP, Ca2+, metabolites of complex phosphinositols, kinase cascades

Front 9

What are steroids all synthesized from?

Back 9

Cholesterol

Front 10

What do thyroid hormones contain?

Back 10

Iodine

Front 11

How do you distinguish between peptide hormones and protein hormones?

Back 11

Peptides generally do not have tertiary structure, whereas proteins do have tertiary (folding) structure

Front 12

What is similar about glycoproteins? How are they distinguished?

Back 12

- Glycoproteins all have the same alpha subunit
- Their specificity is found in the beta subunit

Front 13

What are the two forms a hormone can be in the blood plasma?

Back 13

- Protein bound
- Free

Front 14

What are the implications of a hormone being bound to protein or not being bound when traveling in the blood?

Back 14

- With the bound hormone, only the free fraction is available for tissue uptake
- As the free fraction is depleted, additional hormone dissociates from the plasma-binding protein, making more available to distal portions of the tissue

- All hormones that are not protein bound are quickly extracted in the proximal part of the tissue

Front 15

Which types of hormones are bound to plasma proteins? To which proteins? Implications?

Back 15

Thyroid Hormones:
- >99.5% bound to TBG, Transthyretin, and Albumin
- Plasma half-life is very long (4-6 days) and metabolic clearance is very slow

Steroid Hormones:
- 90-98% bound to plasma proteins (eg, cortisol to CBG and testosterone to SHBG)
- Plasma half-life is 30-60 minutes (shorter than thyroid hormones but still longer than most peptides and proteins)

Front 16

Which types of hormones are NOT bound to plasma proteins? Implications?

Back 16

Peptides and Protein hormones:
- Circulate only in free form
- Plasma half-life is very short, <15 minutes and the clearance is very high
- There are notable exceptions that will be covered in this unit

Front 17

What are the types of cell signaling?

Back 17

- Endocrine
- Paracrine
- Autocrine
- Neurotransmitter
- Neuroendocrine

Front 18

What type of hormones are secreted by endocrine signaling? Mechanism?

Back 18

- Polypeptide (eg, thyrotrophic hormone) or steroid hormones (eg, estrogen)
- Secreted into blood vessels which are then carried to a target cell, which may be located at a considerable distance from the secreting cell

Front 19

What kind of signaling:
- Thyrotrophic Hormone is secreted by the Hypophysis and acts on the Thyroid Gland

Back 19

Polypeptide hormone - endocrine signaling

Front 20

What kind of signaling:
- Estradiol is produced by the Ovaries and acts on the Endometrium

Back 20

Steroid hormone - endocrine signaling

Front 21

What type of hormones are secreted by paracrine signaling? Mechanism?

Back 21

- Hormones or growth factors (eg, glucagon and somatostatin)
- Act on an adjacent cell

Front 22

What type of signaling:
- Glucagon and somatostatin act on adjacent cells of the Islets of Langerhans that secrete insulin

Back 22

Paracrine Signaling

Front 23

What type of hormones are secreted by autocrine signaling? Mechanism?

Back 23

- Some hormones or growth factors (eg, prostaglandins and interleukins)
- Act on originating cell

Front 24

What type of signaling:
- Prostaglandins and interleukins are released from a cell and then act on that same cell

Back 24

Autocrine Signaling

Front 25

What type of hormones are secreted by neurotransmitter signaling? Mechanism?

Back 25

In response to a neural signal, neurons secrete neurotransmitters from the axon terminals to activate adjacent neurons

Front 26

What kind of signaling:
- Neuron secretes a hormone from the axon terminals to activate adjacent neurons

Back 26

Neurotransmitter signaling

Front 27

What type of hormones are secreted by neuroendocrine signaling? Mechanism?

Back 27

- In response to a neural signal, neuroendocrine cells secrete a hormone into the blood to travel to a target organ
- Eg, norepinephrine acting on hepatocytes or adipocytes

Front 28

What kind of signaling:
- Norepinephrine is released from neuroendocrine cells in response to a signal to act on hepatocytes or adipocytes

Back 28

Neuroendocrine Signaling

Front 29

Which hormones mainly act via nuclear receptors to increase transcription and translation? What is the speed of this process?

Back 29

- Thyroid Hormones
- Estrogen (steroid hormone)

- Slow

Front 30

Which hormones act via cytoplasmic receptors to increase transcription and translation?

Back 30

Cortisol (steroid hormone)

Front 31

Which hormones act on cell surface receptors and activate secondary messengers? What is the speed of this process?

Back 31

Water-soluble hormones
- Peptide hormones
- Catecholamines

Rapid effect

Front 32

What determines a hormone or drugs mechanism of action?

Back 32

Chemical nature (lipophilic or hydrophilic)

Front 33

What determines the specificity of hormone action?

Back 33

Expression of appropriate receptor in tissues determines which hormones will act on that tissue

Front 34

What is the relationship between Thyroxine (T4) and Triiodothyronine (T3)?

Back 34

- Thyroxine (T4) and Triiodothyronine (T3) readily diffuse through cell membrane
- Much of T4 is deiodinated / activated to form T3 which interacts with the Thyroid Hormone Receptor

Front 35

Which thyroid hormone has a greater binding affinity for the Thyroid Hormone Receptor? How does it get in this form? Action?

Back 35

T3: Triiodothyronine
- Converted from T4 → T3 by Iodinase
- T3 binds the Thyroid Hormone Receptor, bound as a heterodimer to Retinoid X receptor, which is part of the Thyroid Hormone Response Element of the gene
- This either increases or decreases transcription of genes that lead to formation of proteins

Front 36

What is a way to block thyroid activity?

Back 36

Block Iodinase which converts T4 → T3 (greater activity at thyroid hormone receptor)

Front 37

What is the relationship between Testosterone and Dihydrotestosterone (DHT)?

Back 37

- T converted to DHT by 5α-Reductase in target tissue
- Both T and DHT can bind to the receptor, but DHT has greater activity at receptor
- Both DHT-R and T-R can diffuse into nucleus and stimulate protein synthesis, cell growth, etc.

Front 38

How is Testosterone converted to Dihydrotestosterone (DHT)?

Back 38

5α-Reductase

Front 39

What is the relationship between androgens (eg, Androstenedione) and estrogens (eg, Estrone, E1, and Estradiol, E2)? Effects?

Back 39

- Androgens can be converted to Estrogen by Aromatase in breast tumor tissue and adipose tissue
- Estrogens in breast tumor tissue will stimulate cancer growth
- Also in fat men, the adipose tissue will stimulate conversion to estrogen, leading to feminization

Front 40

How do androgens get converted to estrogens? Where?

Back 40

- Aromatase
- Breast tissue tumor or adipose tissue

Front 41

How can you block growth of a tumor in estrogen-sensitive breast cancer in post-menopausal women?

Back 41

Aromatase inhibitors that inhibit conversion of Androgens (Androstenedione) to Estrogens (Estrone, E1, and Estradiol, E2), which stimulate the cancer growth

Front 42

What is the action of Tamoxifen?

Back 42

- Selective Estrogen Receptor Modulator (SERM)
- Useful for breast cancer by blocking estrogen receptors

Front 43

What happens in the simple feedback loop?

Back 43

- Sensor detects some regulated variable (hormone/metabolite concentration)
- Sensor responds by modulating its secretion of a hormone
- This hormone, in turn, acts on a target to modulate its production of another hormone or a metabolite
- This may affect a second target
- In addition, the other hormone or metabolite feeds back on the original sensor cell

Front 44

What is an example of a simple feedback loop?

Back 44

- Sensor (eg, β cell in a pancreatic islet) detects some regulated variable (e.g., plasma [glucose])
- Sensor responds by modulating its secretion of a hormone (e.g., insulin)
- This hormone, in turn, acts on a target (e.g., liver or muscle) to modulate its production of another hormone or a metabolite (e.g., glucose)
- This may affect a second target (e.g., making glucose available to the brain)
- In addition, the other hormone or metabolite feeds back on the original sensor cell

Front 45

What is an example of the hierarchical control feedback "loop"?

Back 45

- Under the influence of the cerebral cortex, the hypothalamus releases CRH
- CRH stimulates the anterior pituitary to release ACTH
- ACTH stimulates the adrenal cortex to release cortisol
- Cortisol acts on certain effector organs
- In addition, the cortisol feeds back on both the anterior pituitary and the hypothalamus

Front 46

What is the most common type of feedback in the hypothalamic-pituitary-target gland axis? What happens?

Back 46

Negative Feedback:
- The trophic hormones of the anterior pituitary gland has negative feedback effects on the hypothalamus
- The target gland hormone has negative feedback effects on both hypothalamus and the anterior pituitary

Front 47

What is the type of feedback that occurs during late follicular and ovulatory phases of the menstrual cycle? What happens?

Back 47

Positive Feedback:
- High levels of estradiol actually cause greater secretion of the hypothalamic releasing hormone and trophic hormones in that system
- Results in a surge in pituitary hormone release that is responsible for ovulation at midcycle

Front 48

What is the type of feedback that occurs during childbirth? What happens?

Back 48

Positive Feedback:
- Oxytocin is stimulated by distention of cervix toward the term of pregnancy and by contraction of the uterus during parturition
- Signals are transmitted to the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus where they provide a POSITIVE feedback regulation of oxytocin release

Front 49

What allows for the positive feedback response of Oxytocin during childbirth?

Back 49

- Increased number of oxytocin receptors
- Increased number of gap junctions between smooth muscle cells
- Increased synthesis of prostaglandins, enhances the responsiveness of the uterine muscle

Front 50

What is the type of feedback that occurs during breastfeeding? What happens?

Back 50

Positive Feedback:
- The suckling of the nipple of the lactating breast stimulates oxytocin release
- The afferent sensory signals elicit an increase in oxytocin release into the circulation, which stimulates milk production and ejection

Front 51

What is the general term for too much production of the target gland hormone that exerts the systemic effect?

Back 51

Primary Hyperfunction

Front 52

What happens in Primary Hyperfunction?

Back 52

- Too much production of the target gland hormone that exerts the important systemic effect
- Controlling hormone / factor is decreased

Front 53

What is the most common cause of Primary Hyperfunction?

Back 53

Neoplasm (often benign adenoma) in gland of origin that has lost its normal control and now produces too much of its hormone in the absence of its normal stimulation (autonomous secretion)

Front 54

What is the relative amount of the controlling hormone/factor in Primary Hyperfunction? Why?

Back 54

Controlling hormone is decreased because of negative feedback

Front 55

What are some examples of Primary Hyperfunction?

Back 55

- Adrenal Cushing's Syndrome (primary hyperadrenocorticism)
- Graves' Disease (primary hyperthyroidism)

Front 56

What happens in Adrenal Cushing's Syndrome? What is it an example of?

Back 56

- Cortisol overproduction from adrenal adenoma (usually) that suppresses ACTH release from the pituitary
- Diagnosis is made by measuring an increased cortisol and decreased ACTH
- Aka ACTH-independent Cushing's Syndrome

- Primary Hyperfunction

Front 57

What happens in Graves' Disease? What is it an example of?

Back 57

- Excess thyroid hormone production independent of TSH
- Diagnosis is made by measured increased thyroid hormone and decreased TSH

- Primary hyperthyroidism / hyperfunction

Front 58

What is the general term for too much production of the hormone that exerts the important systemic effect because it is being "told" to by overproduction of the stimulator of that hormone?

Back 58

Secondary Hyperfunction

Front 59

What happens in Secondary Hyperfunction?

Back 59

- There is overproduction of the normal stimulator (this can be "within the reference range", however it should be suppressed, thus it is inappropriately not suppressed)
- This causes the hormone that exerts the important systemic effect to be overproduced

Front 60

What are some examples of Secondary Hyperfunction?

Back 60

Cushing's Disease

Front 61

What happens in Cushing's Disease? What is it an example of?

Back 61

- Pituitary hypersecretion of ACTH causes ACTH-dependent Cushing's Syndrome
- Because cortisol is increased, pituitary secretion of ACTH should be suppressed, like in Adrenal Cushing's Syndrome
- ACTH is not suppressed (although often in the reference range for ACTH) - inappropriately not suppressed maintains cortisol hypersecretion and adrenal hypertrophy

Front 62

What is the general term for loss of target gland function due to a pathophysiological process directly in the gland?

Back 62

Primary Hypofunction

Front 63

What happens in Primary Hypofunction?

Back 63

- Target gland hormone will be low
- Normal stimulator of that hormone will be increased in an attempt to restore target gland function

Front 64

What can cause Primary Hypofunction?

Back 64

Pathophysiological process directly in the gland:
- Auto-immune destruction
- Surgical removal

Front 65

What are some examples of Primary Hypofunction?

Back 65

- Primary Adrenal Insufficiency
- Primary Hypothyroidism (Hashimoto's Thyroiditis)
- Menopause
- Male Primary Hypogonadism

Front 66

What happens in Primary Adrenal Insufficiency? What is it an example of?

Back 66

- Irreversible adrenal gland destruction (usually d/t auto-immune or infectious process)
- Cortisol secretion is low and ACTH secretion is high because the pituitary has been relieved of cortisol negative feedback

- Example of Primary Hypofunction

Front 67

What happens in Hashimoto's Thyroiditis? What is it an example of?

Back 67

- Thyroid has been partially or totally destroyed by an auto-immune process
- Thyroid hormone secretion is low and TSH secretion is high because pituitary has been relieved of thyroid hormone negative feedback

- Example of Primary Hypofunction

Front 68

What happens in Menopause? What is it an example of?

Back 68

- Ovarian steroid secretion has ceased
- Estrogen is low and FSH and LH are increased

- Example of Primary Hypofunction

Front 69

What happens in Male Primary Hypogonadism? What is it an example of?

Back 69

- Testicular function is lost (eg, d/t auto-immune process)
- Testosterone secretion is low and FSH and LH are increased

- Example of Primary Hypofunction

Front 70

What is the general term for when a normal stimulator of a target gland is inadequate and the target gland does not produce a normal amount of its hormone (and often atrophies as a result)?

Back 70

Secondary Hypofunction

Front 71

What happens in Secondary Hypofunction?

Back 71

- Normal stimulator of target gland is inadequate and target gland does not produce a normal amount of its hormone
- Target gland may atrophy as a result
- The normal stimulator of the target gland is often "in the reference range" - thus it is "inappropriately not increased"

Front 72

What are some examples of Secondary Hypofunction?

Back 72

Hypopituitarism
- Secondary Adrenal Insufficiency
- Secondary Hypothyroidism
- Secondary (Hypogonadotropic) Hypogonadism

Front 73

What is the term for a loss of anterior pituitary function? What can cause this?

Back 73

Hypopituitarism - can be d/t auto-immune processes, trauma, and infarction

Front 74

What are the implications of hypopituitarism?

Back 74

- Secondary adrenal insufficiency
- Secondary hypothyroidism
- Secondary (hypogonadotropic) hypogonadism

Front 75

What happens in Secondary Adrenal Insufficiency?

Back 75

- Cortisol secretion is low
- Plasma ACTH is not elevated (although it is often "normal" but inadequate to restore adrenal function to normal)

Front 76

What happens in Secondary Hypothyroidism?

Back 76

- Thyroid hormone secretion is low
- Plasma TSH is not elevated (although it is often "normal" but inadequate to restore thyroid function to normal)

Front 77

What happens in Secondary (Hypogonadotropic) Hypogonadism?

Back 77

- Ovarian or testicular steroid secretion is low
- Plasma LH and FSH are not elevated (although it is often "normal" but inadequate to restore gonadal function to normal)

Front 78

Primary Hypofunction:
- Target gland function: ↑/↓/⟷
- Controlling hormone/factor: ↑/↓/⟷

Back 78

- Target gland function: ↓ (cause of problem)
- Controlling hormone / factor: ↑ (loss of negative feedback)

Front 79

Secondary Hypofunction:
- Target gland function: ↑/↓/⟷
- Controlling hormone/factor: ↑/↓/⟷

Back 79

- Target gland function: ↓ (result of problem)
- Controlling hormone / factor: ↓ or ⟷ (loss of negative feedback)

Front 80

Primary Hyperfunction:
- Target gland function: ↑/↓/⟷
- Controlling hormone/factor: ↑/↓/⟷

Back 80

- Target gland function: ↑ (cause of problem)
- Controlling hormone / factor: ↓ (too much negative feedback)

Front 81

Secondary Hyperfunction:
- Target gland function: ↑/↓/⟷
- Controlling hormone/factor: ↑/↓/⟷

Back 81

- Target gland function: ↑ (result of problem)
- Controlling hormone / factor: ↑ or ⟷ (too much negative feedback)