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FHB - Endocrine & Reproductive > Lecture 1 - Cell and molecular physiology > Flashcards

Lecture 1 - Cell and molecular physiology Flashcards

1
Q

What are 3 main components of CLASSIC endocrine glands?

A
  1. ductless
  2. Secrete hormones DIRECTLY into the bloodstream or EC
  3. Entire organ is dedicated to endocrine function
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2
Q

What are the 7 classical endocrine organs?

What is the exception?

A
  1. Pineal Gland - sits on the epithalamus  technically outside of the BBB  can respond to peripheral signals
  2. Pituitary gland
  3. Parathyroid (calcium & phosphate regulation)
  4. Thyroid gland
  5. Adrenal Gland
  6. Pancreas
  7. Ovary
  8. Testes (gonads)
  9. PLACENTA - considered endocrine during fetal development

PANCREAS is the exception since it is both endocrine & exocrine

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3
Q

What are the 6 NON-classical endocrine organs?

A

Brain – especially hypothalamus (“releasing hormones”)

Kidney – Renin, Vitamin D, erythropoietin (EPO)

Heart – atrial/brain natriuretic peptide (ANP, BNP)

Liver – Insulin-like growth factor
(IGF-I)

GI – small intestine, stomach (serotonin, ghrelin)

Adipose Tissue - leptin

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4
Q

What are 2 key concepts in homeostasis?

A

HYPER = overproduction of a hormone and/or hypersensitivity
(at the receptor level or receptor signaling pathway) to hormonal effects

HYPO = underproduction of a hormone and/or insensitivity to hormonal effects.
(ex: insulin resistance - body no longer responding)

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5
Q

What organ is a good example of integration?

Name the 6 organs that affect this

A

THYMUS

  1. Cortisol/adrenalin from ADRENAL glands
  2. Thyroid hormones from thyroid gland
  3. GH/GnRH from CNS
  4. Testosterone
  5. Grhelin - Stomach
  6. Leptin/Adipokinase - Adipose tissue
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6
Q

How are endocrine pathologies characterized?

Why are they often difficult to characterize?

A

Characterized by a hormone imbalance

Defect can be in classical endocrine gland (primary defect) or other organ (secondary/tertiary)

Symptoms can be vague and hard to diagnose
Weight/Appetite changes
Fatigue
Hair loss/Hirsutism
Cognitive (forgetfulness/confusion)
Dizziness
Moodiness (depression/anxiety/aggression)

Symptoms can take a long time to develop and might seem unrelated

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7
Q

What is an example of a CONGENITAL endocrine pathology?

What causes it?

What are the 3 symptoms?

A

CRETINISM

  1. Iodine deficiency during development
  2. Short stature/impaired bone formation
  3. Mental retardation
  4. Delayed motor development
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8
Q

What is MEN (Multiple Endocrine Neoplasia)?

Is this an genetic or congenital pathology?

A

Multiple Endocrine Neoplasia (MEN)

characterized by 2-3 tumors in multiple endocrine glands

(parathyroid, pituitary, entero-pancreatic)

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9
Q

State some examples of the following categories of endocrine pathologies:

  1. Malignant and benign tumors
  2. Infections/immunological problems
  3. Environmental Factors
A

1.Neoplastic tissues
Small lung cell carcinoma

  1. Autoimmune – Diabetes Mellitus Type
  2. PCBs, DES, birth control
    - either compete for receptor or change how hormone delivered to cells
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10
Q

State examples for the following endocrine pathologies:

  1. Trauma/ Stress
  2. Surgical
  3. Therapeutic
A

1.Trauma/stress:

Sheehan’s Syndrome – postpartum hemorrhage/shock; results in massive pituitary cell death
(SMALL GROUP)

  1. Surgical
    Thyroid gland removal (often parathyroid injury)
3.Therapeutic:
Glucocorticoid therapy (Crohn’s disease and others)
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11
Q

What is Diabetes mellitus highly correlated with?

A

Highly correlated with OBESITY

  • correlated with BMI
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12
Q

What are the 3 main mechanisms of hormone action? How do they function?

A
  1. Endocrine
    – hormones secreted into the blood acting on downstream target tissues.
  2. Paracrine
    – hormones secreted into the interstitial space acting at nearby cells.  can be at a synapse (considered a NT)
  3. Autocrine – hormones secreted into the interstitial space acting back on same cell.
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13
Q

______ binds to hormones to facilitate transport.

They generally increase what of the hormone?

What type of hormones uses them most often?

A
  1. Hormone Binding Proteins
  2. Increase the HALF - LIFE of the hormone
  3. Mostly for STEROID hormones (lipophilic)
    Also: IGF-I, GH, T4/T3
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14
Q

If the hormone is bound/unbound there is action in the cell. (choose one)

A

UNBOUND

  • only free hormone has action
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15
Q

What do the following have in common? What do they bind?

  1. Sex hormone binding globulin (SHBG)
  2. Corticosteriod binding globulin (CBG)
  3. Thyroxine binding globulin (TBG) and transthyretin (TTR)
A
  1. Sex hormone binding globulin (SHBG) – binds estrogens and testosterone
  2. Corticosteriod binding globulin (CBG) – binds cortisol/corticosterone
  3. Thyroxine binding globulin (TBG) and transthyretin (TTR) – binds thyroid hormone
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16
Q

What is an example of a nonspecific hormone binder?

A

ALBUMIN

  • binds most lipophilic compounds in blood
  • weak interaction
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17
Q

Why is albumin bound SHBG (sex hormone binding globulin) considered bioavailable?

A

Since the bind to albumin is easily broken, it is considered bioavailable if present in the blood

18
Q

How are extracellular hormones delivered to the target?

A

Scenario #1 –
1. Bound Steroid hormone is released at membrane.

  1. Freely diffuses across lipid bilayer. (lipid soluble)
  2. Finds intracellular targets.
    - FREE INSIDE THE CELL
19
Q

What is the second scenario of hormone delivery to the target?

A

Scenario #2 –

  1. Hormone/protein complex binds to MEGALIN. (both hormone & HBP)
  2. Formation of ENDOCYTIC vesicle.
  3. Hormone dissociates and is released from vesicle.
20
Q

What structure forms an endocytic vesicle when delivering hormones to the target?

A

MEGALIN

21
Q

If there is no _____ there is no action.

A

RECEPTOR

22
Q

The receptor determines what 2 important functions of the hormone?

A
  1. DURATION of hormone activity

2. AUTOREGULATION by hormone itself (up/downregulation depending on hormone levels)

23
Q

Hormones bind to receptors with high _____ and high _____

A
  1. Affinity

2. Specificity

24
Q

What is the difference between affinity and specificity?

A

Specificity: being able to distinguish between similar substances

Affinity:
measured as Kd
- Kd= ligand concentration that occupies 50% of binding sites

Specificity:
Ki = ability to displace ligand at 50% of max capacity

25
Q

If the Ki is smaller, is the specificity greater or less?

A

GREATER SPECIFICITY

- not able to displace the ligand

26
Q

You must reach Kd in order to get a response.

True or False?

A

FALSE

  • you do not need to reach Kd to get a response
27
Q

What did the Binding assays for estrogen related receptor (ERR) and ligand (4-OH tamoxifen) show?

Was the Ki low or high for 4-OHT?

A

Showed that both DES and TAM bind, but 4-OHT shifted left, so indicated a specificity for 4-HT

LOW Ki for 4-OHT showed that there was specificity for 4-OHT

  • adding increased amounts of hormone showed that at a certain Ki the hormone was kicked off and competitively bound by 4-OHT
28
Q

What tells you nothing about action:

Affinity or Specificity?

A

AFFINITY

- only shows that a hormone can bind (Kd shows how much bound at 50%)

29
Q

What are 4 examples of Liphophobic receptors?

What do they bind?

What 2nd messaging pathways are they coupled to?

A
  1. ION CHANNELS
  2. Intracellular signalling - G protein
  3. Receptor- Linked Kinase
  4. Receptor Kinase
    - they are coupled to second messenger signaling pathways (cAMP, IP3/DAG)

rapidly internalized or degraded

30
Q

Ion channels are not receptors, true or false?

What typically activates ION channels?

A

TRUE

  • not receptors, but have receptors that open the channels nearby
    1. Ligand binding causes conformational change that opens channel
  • Neurotransmitters typically activate these types of receptors
31
Q

G protein Lipophobic receptors are mostly bound by what 2 things?

What does ligand binding activate?

A
  1. Proteins & PEPTIDE HORMONES

2. Activates second messenger signaling cascades

32
Q

Which Cell surface lipophobic receptor does not have intrinsic catalytic activity?

A

RECEPTOR Linked KINASES

33
Q

Ligand binding in Receptor-linked Kinases causes what?

What are some examples? (3)

A
  1. DIMER FORMATION
    - activates intracellular kinase

ex:
1. Growth Hormone (GH)
2. prolactin
3. erythropotein

34
Q

Which one has intrinsic catalytic activity:

  1. Receptor Kinases
  2. Receptor - linked Kinases
A

RECEPTOR KINASES

phosphorylate themselves when the ligand binds
- phosphorylated residues serve as scaffolds

35
Q

What two hormones utilize Receptor kinases?

A

INSULIN

& ANP

36
Q

What is the difference between lipophilic and lipophobic receptors?

A

LIPOPHILIC

  • bind mainly INTRACELLULAR receptors
37
Q

Which type of hormone receptors often:

  1. bind large CHAPERON proteins in cytoplasm (heat shock)
  2. Require SLOW biological response (transcription/translation)
  3. Can repress or activate transcription?
A

LIPOPHILIC

38
Q

Which types of receptor (lipophilic/lipophobic) is considered a transcription factor?

A

LIPOPHILIC

39
Q

What is an example of a LIPOPHILIC hormone?

A

THYROID HORMONE

  • not steroid, but bind nuclear receptors already present in the cell
40
Q

When the lipophilic receptor is NOT bound to a ligand, transcription is active. True or False?

A

FALSE

When receptor is NOT bound to ligand = transcriptional repression

Ligand (thyroid hormone) binding activates gene transcription

FHB - Endocrine & Reproductive (17 decks)

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