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ANS 452 Exam 1 > LM1 > Flashcards

LM1 Flashcards

1
Q

Describe the transmembrane receptor involved in Receptor Tyrosine Kinase Signaling

A
  • The extracellular portion has signal-binding site
  • The portion embedded in the membrane is comprised of α-helices
  • The intracellular portion is loaded with tyrosine molecules
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2
Q

Describe the Receptor Tyrosine Kinase Signaling Pathway

A
  • Growth factor (such as epidermal growth factor) binds each monomer causing them to come together as a dimer
  • Once the dimer forms, they autophosphorylate
  • The activated tyrosine kinase receptor then phosphorylates relay proteins
  • Relay proteins move throughout the cell to elicit a cellular response
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3
Q

Describe the energy input and output for receptor tyrosine-kinase activation

A
  • The 6 activated tyrosine-kinase regions use 6 ATP to phosphorylate to become a fully activated receptor tyrosine-kinase
  • This yields 6 ADP
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4
Q

What are the 2 families of RTKs?

A
  • ErbB

* Insulin-IGF

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5
Q

Describe the ErbB Family of RTKs

A

*Receptor monomers must dimerize before autophosphorylation can happen

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6
Q

Describe the IGF-1 Receptor of the Insulin-IGF RTK family

A
  • Contains α and ß subunits which are bound together via disulfide bonds making it already a dimer
  • The α subunit is the majority of the extracellular portion of the receptor and contains the ligand binding domain
  • The ß subunit is some extracellular, but contains the membrane-bound α-helical portion as well as the cytoplasmic tyrosine kinase domain
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7
Q

Describe how the Insulin-IGF RTK family pathway works

A
  • When the hormone binds the extracellular segment of the receptor, it cross-phosphorylates from P1->P2->P3
  • Once phosphorylation completes, it becomes an active tyrosine kinase and phosphorylates other proteins to elicit a cellular repsonse
  • Autophosphorylation occurs immediately upon hormone binding
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8
Q

Describe the Classical Testosterone Signaling Pathway

A
  • T passes through the plasma membrane via diffusion
  • T binds to receptor in cytoplasm activating it
  • The hormone-receptor complex moves into the nucleus and binds to specific genes
  • The bound protein stimulates transcription of the gene into mRNA
  • The mRNA is edited and exits the nucleus to be used as a template for new proteins via translation
  • The new proteins elicit a cellular response
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9
Q

Describe Pathway 1 of the Classical Estradiol Signaling Pathway

A
  • E2 diffuses through the plasma membrane and enters the cytoplasm to bind its receptors
  • The E2 receptors dimerize to enter the nucleus
  • The E2 receptors bind estrogen-response elements (ERE) in the nucleus or other gene promoters to increase the rate of gene expression
  • This is a long term response of hours-days
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10
Q

Describe the 2nd E2 Signaling Pathway

A
  • E2 binds receptors presen on the plasma membrane
  • The hormone-receptor complex stimulate activation of intermediary proteins
  • Intermediary proteins signal other 2nd messengers w/in the cytoplasm resulting in enzyme phosphorylation or gene expression
  • This can also affect RTKs and ion channels
  • This is a short-term cellular response of minutes-hours
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11
Q

Describe the 3rd E2 signaling pathway

A
  • E2 diffuses into cytoplasm
  • E2 directly acts to block molecules that induce cell stress
  • This is an immediate effect within minutes
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12
Q

Describe the 4th E2 signaling pathway

A
  • Other agents such as GFs or dopamine bind their own receptors
  • Protein kinase cascades occur resulting in phosphorylation of ER (estrogen receptors)
  • The activate ERs dimerize and bind DNA promoters
  • This affects gene expression
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13
Q

Name the hormone

  • Source: ovary, placenta, or emrbyo
  • Function: promotes exual behavior, stimulates secondary sex characteristics, growth of reproductive tract, uterine contractions, and mammary gland duct growth, controls gonadotropin release, stimulates calcium uptake in bones, has anabolic effects
  • Class: steroid
A

Estrogens (E)

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14
Q

Name the hormone

  • Source: ovary, placenta
  • Function: acts synergistically with estrogen in promoting estrous behavior and preparing reproductive tract for implantation
  • Class: steroid
A

Progesterone (P)

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15
Q

Name the hormone

  • Source: Posterior pituitary
  • Function: stimulates uterine contractions, parturition, sperm and egg transport, facilitates milk ejection, possible leutolytic function
  • Class: neuropeptide
A

Oxytocin (OT)

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16
Q

Name the hormone

  • Source: ovary, testis
  • Function: inhibit and stimulate FSH
  • Class: Glycoprotein
A

Inhibin-activin

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17
Q

Name the hormone

  • Source: Anterior pituitary
  • Function: Regulating metabolism, provides background for supportive reproductive function
  • Class: Glycoprotein
A

Thyroid Stimulating Hormone (TSH)

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18
Q

Name the hormone

  • Source: Anterior pituitary
  • Function: Regulation of metabolism and parturition
  • Class: Glycoprotein
A

Adrenocorticotropic hormone (ACTH)

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19
Q

Name the hormone

  • Source: Anterior pituitary
  • Function: Regulation of metabolism
  • Class: Protein
A

Growth Hormone (GH)

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20
Q

Name the hormone

  • Source: Anterior pituitary
  • Function: Promotes lactation, stimulates corpus luteum function and progesterone secretion in some species, promotes maternal behavior, promotes tissue and bone growth
  • Class: protein
A

Prolactin (PRL)

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21
Q

Name the hormone

  • Source: Anterior pituitary
  • Function: Stimulates ovulation, corpus luteum function: stimulates secretion of progesterone, estrogen and androgen
  • Class: Glycoprotein
A

Leutenizing Hormone (LH)

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22
Q

Name the hormone

  • Source: Anterior pituitary
  • Function: Stimulates follicular growth, spermatogenesis, estrogen secretion
  • Class: Glycoprotein
A

Follicle Stimulating Hormone (FSH)

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23
Q

Name the hormone

  • Source: Hypothalamus
  • Function: stimulates the release of ACTH
  • Class: Neruopeptide
A

Corticotropin releasing hormone (CRH)

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24
Q

Name the hormone

  • Source: Hypothalamus
  • Function: Stimualtes release of thyroid-stimulating hormone and prolactin
  • Class:Neruopeptide
A

Thyrotropin releasing hormone (TRH)

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25
Q

Name the hormone

  • Source: Hypothalamus
  • Function: inhibits release of growth hormone
  • Class:Neuropeptide
A

Growth hormone inhibiting hormone (GHLH) a.k.a. Somatostatin

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26
Q

Name the hormone

  • Source: Hypothalamus
  • Function: Stimulates release of growth hormone
  • Class :Neuropeptide
A

Growth hormone releasing hormone (GHRH)

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27
Q

Name the hormone

  • Source: Hypothalamus
  • Function: Stimulates release of FSH and LH from anterior pituitary
  • Class: Neuropeptide
A

Gonadotropin Releasing Hormone (GnRH) a.k.a. Leutinizing hormone releasing hormone (LH-RH)

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28
Q

Name the hormone

  • Source: Posterior pituitary
  • Function: vasoconstrictor, helps retain water
  • Class: peptide
A

Vasopressin a.k.a. Anti-Diruetic hormone (ADH)

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29
Q

Name the hormone

  • Source: Hypothalamus
  • Function: inhibits release of prolactin
  • Class: Neuropeptide, biogenic amine
A

Prolactin inhibiting factor (PIF) a.k.a. Dopamine

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30
Q

Name the hormone

  • Source: Testis
  • Function: develops and maintains accessory sex glands, stimulates secondary sexual characteristics, sexual behavior, and spermatogenesis, has anabolic effects
  • Class: steroid
A

Androgens

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31
Q

Name the hormone

  • Source: Uterus
  • Function: causes uterine contractions and is leutolytic
  • Class: Prostaglandin
A

Prostaglandin F2α

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32
Q

Name the hormone

  • Source: Ovary, uterus, embryonic membranes
  • Function: uterine contractions, leutolytic, stimulates secretion of progesterone from CL
  • Class: prostaglandin
A

Prostaglandin E2 (PGE2)

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33
Q

Name the hormone

  • Source: Uterus
  • Function: transfers iron from maternal system to developing embryo during gestation
  • Class: glycoprotein
A

Uteroferrin

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34
Q

Name the hormone

  • Source: placenta
  • Function: LH activity, maintains corpus luteum of pregnancy in primates
  • Class: Glycoprotein
A

Human chorionic gonadotropin (hCG)

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35
Q

Name the hormone

  • Source: Placenta
  • Function: dilates cervix and causes joint relaxation
  • Class: protein
A

Relaxin

36
Q

Name the hormone

  • Source: embryo
  • Function: maternal recognition of pregnancy in ruminants
  • Class:interferon
A

Interferon tau

37
Q

Name the growth factor

  • Stimulates regrowth of epithelium following disruption of ovarian surface at ovulation
  • Human myometrial cells respond to this factor by stimulation of their proliferation: their activites are additive when used in combination and synergistically enhanced by progesterone
  • Class: Protein
A

Epidermal Growth Factor (EGF)

38
Q

Name the growth factor

  • Stimulates proliferation of various cell types required with blastocyst implantation and embryonic development
  • Class: Protein
A

Fibroblast growth factor (FGF)

39
Q

Name the growth factor

  • Regulates steroidogenesis in granulosa cells in large ovarian follicles via aromatase activity
  • Class: Protein
A

Insulin-like growth factor (IGF)

40
Q

Name the growth factor

  • Removal of fetus causes elevated levels of this growth factor but can be reversed by Androgens and Estrogen
  • The fetus, via secretion of estrogen precursors, regulates placental and maternal production of this growth factor during pregnancy
A

Insulin-like growth factor-1 (IGF-1)

41
Q

What hormone initiates granulosa cell’s responsiveness to IGF-1 during follicular development

A

Estrogen

42
Q

Describe the flow through the hypothlamus-Hypohyseal portal system using GnRH and LH as examples

A
  • GnRH is secreted by hypothlamic nerve cells exiting at the axons
  • GnRH enters the Median Eminence
  • Hypohyseal portal vessels carry GnRH to the capillary plexus of the AP
  • GnRH exits the vessels and binds to gonadotropes inducing LH secretion
  • LH leaves the AP via cavernous sinus veins into general circulation
43
Q

What is the hypophysis?

A

Both anterior and posterior pituitary

44
Q

Where is the hypolthalamus located? What type of tissue is it comprised of?

A
  • 3rd ventricle at the base of the brain

* Neural tissue

45
Q

What type of tissue is the anterior pituitary comprised of?

A

Secretory tissue

46
Q

Where is the nerupophysis located? What type of tissue is it comprised of?

A
  • directly connected to hypothalamus

* comprised of neural tissue

47
Q

Describe the location of the Magnacellular neruons including axon termination

A
  • 2 main locations: paraventricular nuclei cells and supraoptic nuclei cell within the hypothalamus
  • Axons extend down hypohyseal nerve tract and terminate within the neurpohysis
48
Q

How is the neuropophysis vascularized?

A

carotid artery

49
Q

Describe the flow of Oxytocin (OT) as a neruopophyseal hormone beginning with synthesis

A
  • OT is synthesized in paraventricular cells
  • 9 OT are produced with each neurophysin
  • OT travels down hypophyseal nerve tract where it is cleaved from neurophysin
  • OT enters neuropophysis and is stimulated to be released via veins into general circulation
50
Q

Describe the neuro-endocrine reflex arc of OT initiated by a suckling calf

A
  • Suckling sends a nerve imulse to the spinal cord and then the impulse reaches the brain
  • Impulse causes supraoptic and paraventricular nuclei to secrete OT
  • OT is released from neuropophysis, enters general circulation, and reaches the mammary gland
  • OT binds to receptors on myoepithelial cells around alveoli
  • Myoepithelial cells contract causing milk let down
51
Q

How is the hypothalamus connected to the posterior and anterior pituitary?

A

posterior: directly
anterior: indirectly via hypohyseal portal plexus

52
Q

Name the type of feedback mechanism

  • Gonadal steroids are secreted by the gonads and enter the bloodstream
  • They enter the hypothalamus to regulate GnRH secretion
  • They can also directly affect the anterior pituitary and LH and FSH secretion
A

Long-loop feedback

53
Q

Name the type of feedback mechanism

  • Secretory products exit the AP and enter circulation
  • Then they have a feedback effect on hypothalamus
  • Ex: ACTH is secreted from anterior pituitary and enters general circulation to act as an endocrine hormone to feedback on CRH secretion on the hypothlamus
  • Ex: TSH feedback on hypothalamus for TRH
A

Short-loop feedback

54
Q

Name the type of feedback mechanism

  • Dominant follicle secretes estradiol to have a paracrine feedback effect on adjacent secondary follicles
  • Gonadal steroids, gonadal proteins (inhibin/activin), and growth factors use this mechanism as well
A

ultra-short loop feedback

55
Q

What 2 hormones use the Adenylate cyclase-protein kinase A (PKA) system?

A

FSH and LH

56
Q

Describe the general PKA system

A
  • LH/FSH bind to its specific receptor that’s coupled with adenylate cycles on the cell membrane
  • Adenylate cyclase converts ATP to cAMP
  • cAMP is 2nd messenger and interacts and activates PKA in the cytoplasm
  • PKA has direct effects on enzymes in cytoplasm via phosphorylation and can influence gene transcription
57
Q

How is the PKA system regulated

A

Phosphodiesterases (PDEs) take free cAMP and converti it to inactive 5’ AMP

58
Q

Describe activation of the PKA holoenzyme

A
  • PKA has 2 catalytic subunits and 2 regulatory subunits
  • Each regulatory subunit has 2 cAMP binding sites so it can bind a total of 4 cAMP
  • Once cAMP binds, the catalytic subunits unbind and become active kinases
  • These kinases then phosphorylate other proteins within the cytoplasm
59
Q

Describe the general role of G-Proteins as intracellular couplers

A
  • Hormone binds to G-protein coupled receptor on the plasma membrane
  • Activated G-protein can transit within the membrane to interact with an enzyme to activate it and create a cellular response
  • The hormone dissociates from its receptor so it becomes inactive
  • G-proteins aren’t destroyed in this process, but shuffle back and forth between inactivated receptors and enzymes
60
Q

Describe G-protein cycling of activation and inactivation

A
  • Inactive G-protein has GDP bound to the α-subunit and the ß and ¥ subunits are still together
  • When hormone binds, GTP replaces GDP to activate the G-protein
  • The GTP-α separate from the ߥ so it can stimulate a protein causing GTP to loose a phosphate and return to GDP
  • The αߥ subunits return together in a resting state
61
Q

Describe how G-proteins are activated by magnesium

A
  • LH receptors are transmembrane receptors
  • Carbohydrates on the extracellular component aid in hormone binding
  • When LH binds, the tail of tis receptor incorporates Mg2+
  • This causes activation of the G-protein
62
Q

What are the 3 levels that cells can control the 2nd messenger PKA system?

A
  • Level of hormone-receptor binding
  • Level of G-proteins (inhibitory vs stimulatory)
  • Level of cytoplasm (phosphodiesterases on cAMP)
63
Q

Describe how the PKA system can affect gene expression

A
  • Active catalytic subunits enter the nucleus and interacts with proteins to stimulate transcription/gene expression
  • Catalytic subunits phosphorylate cAMP response element binding protein (CREB)
  • CREB interacts with DNA inducing accumulation of transcription factors resulting in gene transcription and mRNA production
  • This causes a cellular response
64
Q

What hormone uses the 2nd messenger Ca2+-Calmodulin system?

A

LH for signal transduction

65
Q

What type of binding does Ca2+-Calmodulin use?

A

Cooperative (allosteric)

66
Q

Describe the general Ca2+-Calmodulin system

A
  • 2 Ca2+ bind to Calmodulin (2 at the top and 2 at the bottome)
  • The complex is then activated and has a conformational change
  • The complex interacts with target proteins by wrapping around and phosphorylating the target protein
  • This induces a cellular response
67
Q

Describe the 2 modes of action for Ca2+-Calmodulin

A
  • 1: Ca2+-Calmodulin complex is free in cytosol and interacts with the target protein (phosphodiesterase) to activate
  • 2: Calmodulin is part of an inactive target protein (phosphorylase kinase) and interaction with the 4 Ca2+ ions causes activation of the target protein
68
Q

What are the 5 major cellular targets Ca2+-Calmodulin can affect?

A
  • Enzymes
  • Receptors/ion exchanges
  • Gap junctions
  • Cell shape
  • Metabolic effects
69
Q

What are the 2 major enzymes Ca2+-Calmodulin can affect?

A
  • G-protein subunits

* Adenylate cyclase

70
Q

What are the 2 major receptors/ion exchangers Ca2+-Calmodulin can affect

A
  • EGF receptors

* Na+/K+-Ca2+ exchanger

71
Q

How does Ca2+-Calmodulin affect gap junctions?

A

Affects intracellular communication

72
Q

How does Ca2+-Calmodulin affect cell shape?

A

The complex can bind cytoskeletal proteins

73
Q

How does Ca2+-Calmodulin affect metabolic effects?

A
  • Mitochondrial activity
  • ER activity
  • Gene transcription and other activities within the nucleus
74
Q

What does PI stand for?

A

Phosphptidylinositol

75
Q

What does PIP stand for?

A

Phosphotidylinositol-4-phosphate

76
Q

What does PIP2 stand for?

A

Phosphotidylinositol-4,5-bisphosphate

77
Q

What does IP3 stand for?

A

inositol-1,4,5-trisphosphate

78
Q

What hormones use the phosphatidyinositol 2nd messenger pathway

A

LH, OT and PGF

79
Q

What does DAG stand for?

A

Diacylglycerol

80
Q

Describe pathway 1 of the phosphatidyl inositol 2nd messenger pathway which occurs in the cytoplasm

A
  • Hormone binds to its receptor, activating phospholipase C
  • Phospholipase C cleaves PIP2 into IP3 and DAG
  • IP3 interacts with smooth ER which contains an IP3 sensitive Ca2+ channels to release Ca2+
  • The release of Ca2+ activates calmodulin causing an increase of protein phosphorylation
81
Q

Describe pathway 2 of the phosphatidylinositol 2nd messenger pathway that occurs in the membrane

A
  • LH/PGF binds to its receptor and activates phospholipase C
  • Phospholipase C cleaves PIP2 into IP3 and DAG
  • DAG activates protein kinase C
  • PKC then phosphorylates target protein
82
Q

Describe activation of the Type 1 subtype of PKC

A
  • Hormone binds, activating phospholipase C which cleaves PIP2 into IP3 and DAG
  • IP3 interacts with IP3 sensitive Ca2+ channels, releasing Ca2+ into cytoplasm
  • Ca2+ causes preliminary activation of PKC
  • DAG interacts with Ca2+-activated PKC to complete activation
  • Fully activated PKC can phosphorylate subsrates
83
Q

Describe activation of type 2 subtype of PKC

A
  • Hormone binds, activating phospholipase C which cleaves PIP2 into IP3 and DAG
  • DAG interacts directly with PKC causing a Ca2+ membrane channel to open
  • Ca2+ enters cytoplasm leading to a cellular response
  • GTP-activated G-protein complex has a stimulatory αsubunit which activates Phospholipase C
84
Q

Describe the 3rd pathway of the phosphatidyinositol 2nd messenger pathway

A
  • OT binds its receptor, activating phospholipase C which cleaves PIP2 into IP3 and DAG
  • DAG is the precursor for Arachondonic acid
  • Arachodonic acid is a precursor for prostoglandins
  • Results in formation of prostaglandins
85
Q

Describe how the 3rd pathway of the phosphatidyl inositol 2nd messenger pathway is important for CL destruction

A
  • In ruminants, increase of PGF2α is the main cause of CL destruction
  • OT binds receptors within the uterine endometrium and proceeds with system
  • PGF2α is released from the uterus and travels via counter-current exchange to ovary
86
Q

Describe how the 3rd pathway of the phosphotidylinositol 2nd messenger pathway is important for parturition

A
  • OT interacts with receptors within the uterine endometrium inducing phospholipase C activity and DAG generation
  • DAG is metabolised into PGF2α which works on uterine endometrium and myometirum to stimulate contractions for parturition

ANS 452 Exam 1 (5 decks)

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