Molecular Endocrinology: Peptides I, Ii, & Iii---Jd

Front 1

Glands that secrete hormones directly into the bloodstream and have an effect on distal tissue targets are ________.

Back 1

Endocrine glands

Front 2

Cells that secrete substances into the extracellular space to affect target on nearby cells are classified as _______.

Back 2

Paracrine

Front 3

Cells that secrete substances that affect target on the same cell are classified as _________.

Back 3

Autocrine

Front 4

Cells that make a substance that affects something within the same cell is classified as _________.

Back 4

Intracrine

Front 5

Insulin is secreted into the blood stream to help increase cellular glucose uptake, glycolysis, and glycogen production. This is an example of ____________ glands.

Back 5

Endocrine glands

Front 6

Insulin is secreted to inhibit glucagon secretion from alpha cells. This is an example of what type of gland?

Back 6

Paracrine gland

Front 7

Insulin is released at certain levels works as a negative feedback to inhibit the secretion of more insulin is an example of what type of action?

Back 7

Autocrine

Front 8

Hydrophobic signaling molecules are an example of what type of cell action?

Back 8

Intracrine

Front 9

What are the major hormones produced by the hypothalamus?

Back 9

the hypothalamus secretes releasing hormones:
1. GRH
2. TRH
3. CRH
4. PRH
5. GnRH
6. Norepinephrine

Front 10

Growth hormone, Prolactin, TSH, ACTH, FSH, and LH are major hormones released from what organ?

Back 10

Anterior pituitary

Front 11

What are the major hormones released from the pars intermedia?

Back 11

1. beta-endorphin
2. alpha-MSH
3. CLIP

Front 12

Vasopressin (ADH) and Oxytocin are released from what endocrine organ?

Back 12

Posterior pituitary

Front 13

What hormone does the heart release?

Back 13

Atrial Natriuretic Factor

Front 14

Adipokines is secreted from what type of tissue?

Back 14

Adipose tissue

Front 15

Describe a negative feedback loop.

Back 15

A negative feedback loop uses the final hormone product to inhibit that action of earlier steps within a cascade

Front 16

In the production of cortisol, it feeds back onto ACTH to inhibit the production. This is an example of what type of feedback inhibition?

Back 16

Negative Feedback Inhibition

Front 17

Most peptide hormones are encoded by a single gene--- name three exceptions.

Back 17

TSH, LH, AND FSH are not encoded by a single gene

Front 18

How are the alpha chains of TSH, LH, and FSH related?

Back 18

The alpha chains are all encoded by one common gene.

Front 19

How are the beta chains of TSH, LH, and FSH related?

Back 19

the beta chains are all unique: there are 3 separate genes that encode for each chain

Front 20

Many peptide hormones are processed from longer precursors. What determines where the precursors will be cut?

Back 20

The peptide hormones are usually made as pro-hormones or polypeptides containing multiple hormones that need to be cleaved into the mature form.
- Cleavage typically occurs between two basic amino acids

Front 21

In what subcellular compartment does the cleavage of the precursor hormones occur?

Back 21

Cleavage happens during transport from the ER to the Golgi-where it will be packaged into a vesicle

Front 22

What controls the selective proteolysis of proopiomelanocortin?

Back 22

POMC cleaveage occurs differently in different cells in order to increase the hormone repertoire

Front 23

What physiological process is Beta-endorphin involved in?

Back 23

Beta-endorphin is involved in the response to opiates

Front 24

When exogenous opiates are prescribed, tolerance to the drug develops. What is tolerance, and what molecular process initiates the development of tolerance?

Back 24

Tolerance is the reduced effects of drugs overtime, when given the same dose.
The molecular process that is involved in the development of tolerance typically involves receptor desensitization and down-regulation.

Front 25

What are the symptoms of opiate withdrawal?

Back 25

Withdrawal typically prevents with various symptoms:
severe dysphoria, depression, sweating, nausea, rhinorrhea, fatigue, vomiting, pain

Front 26

How can the symptoms of opiate withdrawal be reduced?

Back 26

Continuing the administration of the opiates, but gradually reducing the dose can dull the symptoms of withdrawal
The time course of withdrawal will depend on the half-life of the drug.

Front 27

In melanocytes, which physiological process is controlled by the melonocortin-1 receptor?

Back 27

The melanocortin-1 receptor controls which pigments are produced

Front 28

Mutations in the MC1R that prevent it from signaling cause what phenotype in humans?

Back 28

Typical phenotype seen in people with the MC1R mutation is red hair and fair skin.

Front 29

What are the clinical ramifications of the phenotype seen with the MC1R mutation?

Back 29

The clinical ramifications of having red hair and fair skin are an increased rate of skin cancer and reduced tolerance to pain.

Front 30

What is the endogenous agonist for MC2R, and where are the receoptors expressed?

Back 30

The agonist of MC2R is the ACTH receptor.
These receptors are found in the adrenal cortex

Front 31

Why is MC4R of clinical interest?

Back 31

MC4R is of clinical interest because it is a receptor for alpha-MSH.
-Mutations in and around the MC4R are associated with insulin resistance and obesity.
-This is only seen in 1-2.5% of people, but it is the most prevalent monogenic cause of obesity

Front 32

What controls the synthesis of PNMT?

Back 32

PNMT synthesis is controlled by CORTISOL

Front 33

What controls the release of epinephrine?

Back 33

Signaling from acetylcholine neurons in the sympathetic system controls the release of epinephrine

Front 34

How does the endocrine action of vasopressin on V2 receptors in the kidney and V1 receptors in the vasculature coordinate to effect blood pressure?

Back 34

Both increase water reabsorption and vasoconstriction in order to increase blood pressure.

Front 35

Vasopressin on V2 receptors

Back 35

V2R:
1. GPSR-alphas are triggered by vasopressin
2. Insert aquaporin 2 into apical surface
3. Increases reabsorption of water

Front 36

Vasopressin on V1 receptors

Back 36

1. GPCR-alpha-r is triggered by vasopressin
2. Affects the vasculature
3. Causes vasoconstriction

Front 37

How do ANF receptors in the kidney and vasculature coordinate to effect blood pressure?

Back 37

ANF's work to increase water excretion and vasodilation to decrease blood pressure.

Front 38

What are the ligands for ErbB receptors?

Back 38

The ligands for ErbB receptors are EGF and Neuregulin

Front 39

ErbB signaling is important for what physiological processes?

Back 39

ErbB signaling is important in the development of the nervous system. It promotes proliferation, differentiation, and migration

Front 40

What is the effect on signaling of an ErbB2 subunit in a receptor dimer?

Back 40

Dimers that include ErbB2 have a strong signal.
They increase the proliferation and decrease apoptosis.
If too much ErbB2 signaling exists than it will promote cancer.

Front 41

Beta cells secrete insulin in response to high blood glucose. How do beta cells sense high blood glucose? How is this coupled with insulin release?

Back 41

Beta cells sense high blood glucose via receptors on the cell surface. When high blood glucose is detected insulin will be released into the bloodstream.

Front 42

What is the role of GLUT2?

Back 42

GLUT2 is used to transport glucose into the cell.

Front 43

What is the role of the ATP dependent Potassium channel?

Back 43

The ATP-dependent channels close when ATP binds. ATP will bind more frequently when there is high blood glucose because it increases the amount of ATP in the system.

Front 44

What is the role of voltage gated Calcium channels?

Back 44

Voltage gated calcium channels open when the cell is depolarized. Increased intracellular calcium causes an increase in insulin

Front 45

What are sulfonylureas?

Back 45

Sulfonylureas bind to SUR1 subunits of ATP-gated Potassium channels and close the channel

Front 46

What is the mechanism of action for sulfonylureas?

Back 46

Sulfonylureas bind to SUR1 subunits of ATP-GATED POTASSIUM CHANNELS and close the channel
-this increases the insulin release

Front 47

What are sulfonylureas?

Back 47

Sulfonylureas bind to SUR1 subunits of ATP-gated channels and close the channel

Front 48

What is the mechanism of action of sulfonylureas?

Back 48

Sulfonylureas bind to SUR1 subunits of ATP-gated channels and close the channel. This increases insulin release

Front 49

How does insulin receptor activation lead to an increase in glucose uptake?

Back 49

1. Phospho-IRS recruits PI 3-kinase which is phosphorylated
2. Activated PI 3-kinase binds to PIP2 on the membrane and converts it to PIP3
3. PIP3 recruits PDK1 and Protein Kinase B to the membranes
4. Once bound PDK1 phosphorylates PKB (PKB is a serine/threonine protease)
5. Activated PKB dissociates from PIP3 to phosphorylate target proteins (one target is glucose transporter GLUT4 in vesicles)
6. Phosphorylatation of GLUT4 promotes its insertion into the plasma membrane

Front 50

How does insulin receptor activation lead to increased rate of glycolysis?

Back 50

1. Fructose 2,6-P2, is a positive allosteric modulator of 6-phosphofructo-1-kinase. --> more fructose 2,6-P2 will stimulate glycolysis
2. Glucagon activates G-alphas & PKA, resulting in the phosphorylation of EnzymeX ----> phosphorylated enzymeX acts as a phosphate and converts fructose 2,6-P2 to Fructose 6-Phosphate ---> less fructose 2,6-P2 slows glycolysis
3. Insulin lowers cAMP levels and activates a phosphate that dephosphorylates EnzymeX----> Dephospho-EnzymeX acts as a kinase and converts fructose-6-phosphate to fructose 2.6-P2

Front 51

How does insulin receptor activation increase glycogen synthesis?

Back 51

1. Insulin binding leads to PKB activation
2. PKB phosphorylates Glycogen Synthase Kinase 3 (GSK3) which inactivates the GSK3---> active GSK3 would phosphorylate glycogen synthesis which lowers its activity
3. Inactive GSK3---> dephosphorylates glycogen synthase, which is more active---> more glycogen synthesis

Front 52

What is GLP-1 and where is it secreted?

Back 52

Glucagon-Like-Peptide is an incretin peptide
It is secreted in the upper gut

Front 53

What four effects does it have on pancreatic beta cells?

Back 53

If effects pancreatic beta cells via:
1. increasing insulin biosynthesis
2. Increasing glucose-dependent insulin release
3. Increasing beta cell proliferation
4. Decreasing beta cell apoptosis

Front 54

How is GLP-1 degraded?

Back 54

GLP-1 is degraded by a DPP-IV

Front 55

What is the pharmacological significance of this pathway?

Back 55

GLP-1 is degraded by DPP-IV --->
this pathway can be used to treat type 2 diabetes

Front 56

What is PPAR-gamma?

Back 56

PPAR-gamma is Peroxisome Proliferator-Activated Receptor

Front 57

What role does PPAR-gamma play in adipocytes? Why is this of therapeutic interest?

Back 57

PPAR-gamma is an adipocyte specific transcription factor that is activated by fatty acids and its derivatives
These are invovled in:
1. Adipocyte differentiation
2. Adipocyte apoptosis
3. Regulating insulin sensitivity
4. Increasing triglyceride clearance
this is of specific interest because of its potential to help with type 2 diabetes and lowering fat retention

Front 58

What is somatostatin? Where is it released? What is its physiological function?

Back 58

Somatostatin is released from the hypothalamus and can inhibit the release of growth hormone

Front 59

Although pituitary adenomas rarely progress to malignancy they can cause serious symptoms. Name two reasons why?

Back 59

1. They are present in most of the population
2. Rarely present clinically
3. Cause serious symptoms because of the area and the secretions that they affect

Front 60

What are the symptoms and molecular causes of DIABETES INSIPIDUS?

Back 60

1. Symptoms: polyuria & polydipsia
2. Can be caused by hypothalamic damage and when the kidneys become insensitive to vasopressin

Front 61

What are the following symptoms a sign of?
1. Polyuria
2. Polydipsia
3. Weight loss
4. Fatigue
5. Blurred Vision
6. Thrush

Back 61

Diabetes Mellitus

Front 62

What does/can Diabetes Mellitus cause?

Back 62

1. Blindness in capable adults
2. End-stage renal failure requiring dialysis
3. Non-traumatic amputation
4. Stroke & Heart Attack

Front 63

What is Type I Diabetes Mellitus molecular cause?

Back 63

Pancreatic Beta Cell destruction. This produces a complete lack of insulin

Front 64

What is Type II Diabetes Mellitus molecular cause?

Back 64

Insulin resistance and insulin deficiency

Front 65

Calorie restriction has been shown to increase lifespan in a variety of organisms, including mammals. What is the major hormonal system that mediates this effect?

Back 65

The major hormonal system that is significant is the insulin/GF signaling pathway

Front 66

How does the starved state affect this hormones signaling?

Back 66

The starved state re-tunes the signaling

Front 67

What are the major hormones produced by the Hypothalamus?

Back 67

1. GRH
2. TRH
3. CRH
4. Norepinephrine
5. PRG
6. GnRH

Front 68

What are the major hormones produced by the anterior pituitary?

Back 68

1. GH
2. TSH
3. ACTH
4. Prolactin
5. FSH
6. LH

Front 69

What are the major hormones produced in the posterior pituitary?

Back 69

1. Oxytocin
2. Vasopressin

Front 70

What are the major hormones produced in the thyroid gland?

Back 70

T3 & T4 thyroid hormones

Front 71

Classic steroid hormones are synthesized from which molecule?

Back 71

Steroid hormones are synthesized from Cholesterol.

Front 72

What are the 3 steps where steroid hormones synthesis is most tightly controlled?

Back 72

Activation of hydrolysis of cholesterol esters, transport into the mitochondria via StAR, and converison to pregnenolone by SCC are the 3 steps where hormone synthesis is the most tightly regulated

Front 73

What hormone synthesis is the most rapidly affected by hormone synthesis?

Back 73

the activation of hydrolysis of the cholesterol esters is the fasted regulated hormone synthesis.

Front 74

On the subcellular level, where does steroid hormone synthesis occur?

Back 74

Steroid synthesis occurs in the cell membrane, cytoplasm, and mitochondria

Front 75

What controls steroid hormone release?

Back 75

the hormonal signal that initiates the synthesis is what controls the release of steroid hormones

Front 76

What does 5-alpha-reductase do?

Back 76

5-alpha-reductase cleaves testosterone into dihydrotestosterone ---> is a much more potent form that is necessary for male differentiation

Front 77

What does Aromatase do?

Back 77

Aromatase is used to synthesize 17-beta-estradiol (estrogen) from androgens like testosterone or dehydroepiandosterone

Front 78

Why are 5-alpha-reductase and Aromatase important?

Back 78

5-alpha-reductase and Aromatase are important because they are used for developing sex specific hormones that are crucial in male/female development

Front 79

How are steroid hormones transported in the blood?

Back 79

Steroid hormones are transferred in the blood through binding (in a reversible fashion) to sex hormone-binding globulin or albumin

Front 80

What is the main mechanism for inactivating steroid hormones?

Back 80

Most steroids are inactivated by being reduced in the liver. The reduction makes them more water soluble so they can be excreted in the urine

Front 81

GnRH secretion is pulsatile. When a long acting GnRH analog is given systemically, what happens to FSH and LH levels in the blood after a few hours?

Back 81

There is a resultant effect of desensitization and down regulation. It affects the ratio of FSH and LH beta subunits that are synthesized

Front 82

What is the molecular mechanism that causes the desensitization and down regulation when a long acting GnRH analog is given systemically?

Back 82

A G-Protein coupled receptor signals through G-alph-q

Front 83

How do FSH and LH affect the testes?

Back 83

1. LH acts on the Leydig cells to help increase the synthesis and release of testosterone----> testosterone is developed in the testes---> promotes maturation of sperm
2. FSH acts on the Sertoli cells to increase the production of aromatase and androgen-binding protein ---> inhibin is also produced and works to feedback and decrease FSH-beta-subunits

Front 84

What are the physiological effects of testosterone in the developing fetus?

Back 84

In the Fetus:
Testosterone causes masculization of the internal and external genital tracts.

Front 85

What are the physiological effects of testosterone in the neonate?

Back 85

In the Neonate:
Testosterone causes masculine organization of the brain

Front 86

What are the physiological effects of testosterone at puberty?

Back 86

At puberty testosterone causes:
1. Growth promoting actions
2. Secondary sexual characteristics
3. Maintain fertility and libido

Front 87

What are the physiological effects of estrogen?

Back 87

1. Growth and development of the female reproductive tract
2. Breast development: stromal & ductal system
3. Feminine fat distribution
4. Early fusion of epiphyseal plates
5. Preparation of the uterus for egg implantation

Front 88

What is the role of Gonadotropin Releasing Hormone in the menstrual cycle/pregnancy?

Back 88

GnRH causes the stimulation of FSH and LH

Front 89

What is the role of Follicle Stimulating Hormone in the menstrual cycle/pregnancy?

Back 89

FSH causes the synthesis and secretion of 17-beta-estradiol and inhibin in the ovary
FSH causes the follicle to mature

Front 90

What is the role of Luteinizing Hormone in the menstrual cycle/pregnancy?

Back 90

LH is expressed by mature follicles.
LH causes ovulation.
LH causes the remnants of the follicle to differentiate and produce progesterone

Front 91

What is the role of 17-beta-estradiol in the menstrual cycle/pregnancy?

Back 91

1. 17-beta-estrodiol exerts a negative feedback on gonadotrophs.
2. Estrogen levels are so high mid-cylce that it ceases to be inhibitory---> mediates positive feedback
3. Estrogen prepares the uterus for implantation
4. Estrogen increases the transcription of progesterone receptors
5. Low levels of Estrogen can cause menses

Front 92

What is the role of Progesterone in the menstrual cycle/pregnancy?

Back 92

1. Progesterone prepares the uterus for implantation
2. Lowered levels of Progesterone can cause menses

Front 93

What is the role of Inhibin in the menstrual cycle/pregnancy?

Back 93

Inhibin exhibits negative feedback on gonadotrophs

Front 94

What is the role of Human Chorionic Gonadotropin in the menstrual cycle/pregnancy?

Back 94

If implantation occurs HCG acts like LH to keep the corpus luteum going in order to continue progesterone secretion

Front 95

In oral contraceptives that contain both estrogen and progesterone, how is pregnancy prevented?

Back 95

With the combination of Estrogen and Progesterone: The constant, low level of estrogen provides negative feedback to gonadotrophs and prevents ovulation

Front 96

In oral contraceptives that contain just progesterone how is pregnancy prevented?

Back 96

Progesterone makes the body think that it is pregnant.

Front 97

What are the physiological effects of progesterone?

Back 97

1. Stimulate secretory activity of glands in the oviduct and uterus
2. Maintain structure of the spiral arteries in the endometrium
3. Suppress muscular contractions of the uterus
4. Increase the viscosity of the cervical mucus
5. Promote breast development, especially during pregnancy but prevents lactogenesis