bi 358 lecture 10 3 prep lectures, then 3 guest lecturers ...€¦ · bi 358 lecture 10. t = 0,...

52
I. Paper Draft Due (step > outline) Next Tues Discussion ! Focus: help especially those presenting on February 18 th . II. Endocrinology Overview G&H ch 75, 76, 77, 78, 79; LS, Fox… A. Endocrine vignette: Cushing’s Syndrome LS B. What’s an endocrine? Hormone criteria & classifications? C. Mechanisms of hormonal action G&H fig 75-6, 75-7... D. Endocrinology focuses on the relationship between the Hypothalamus - Controller Pituitary - Subcontroller E. Endocrine organ, hormonal overview G&H fig 76-1,tab 76-1 F. Hypothalamus-Post & Ant Pituitary G&H fig 76-9, 76-4, 76-2 G. Anterior pituitary hormone functions G&H tab 75-1, Fox, LS H. Negative feedback loops G&H p 929-30, LS I. Growth Hormone (GH/STH) G&H fig 76-5, 76-6, tab 76-3 Body builder's dream or fountain of youth? Neither! III.Peripheral Endocrine Organs G&H ch 77, 78, 79 A. Pancreas: insulin vs. glucagon, diabetes, G&H ch 79 + Fox B. Thyroid: T3 & T4 G&H fig 77-2 thru fig 77-9 + DC C. Adrenal cortices G&H fig 78-1 & 78-2 + DC 3 Prep Lectures, then 3 Guest Lecturers: Dr. Garrett, Dr. Kaplan, Dr. Godfrey! Hooray! BI 358 Lecture 10

Upload: others

Post on 13-Jul-2020

0 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

I. Paper Draft Due (step > outline) Next Tues Discussion!

Focus: help especially those presenting on February 18th.II. Endocrinology Overview G&H ch 75, 76, 77, 78, 79; LS, Fox…

A. Endocrine vignette: Cushing’s Syndrome LS

B. What’s an endocrine? Hormone criteria & classifications? C. Mechanisms of hormonal action G&H fig 75-6, 75-7...

D. Endocrinology focuses on the relationship between the Hypothalamus - Controller Pituitary - Subcontroller

E. Endocrine organ, hormonal overview G&H fig 76-1,tab 76-1

F. Hypothalamus-Post & Ant Pituitary G&H fig 76-9, 76-4, 76-2

G. Anterior pituitary hormone functions G&H tab 75-1, Fox, LS

H. Negative feedback loops G&H p 929-30, LS

I. Growth Hormone (GH/STH) G&H fig 76-5, 76-6, tab 76-3

Body builder's dream or fountain of youth? Neither!III.Peripheral Endocrine Organs G&H ch 77, 78, 79

A. Pancreas: insulin vs. glucagon, diabetes, G&H ch 79 + Fox

B. Thyroid: T3 & T4 G&H fig 77-2 thru fig 77-9 + DC

C. Adrenal cortices G&H fig 78-1 & 78-2 + DC

3 Prep Lectures, then 3 Guest Lecturers:Dr. Garrett, Dr. Kaplan, Dr. Godfrey! Hooray!

BI 358 Lecture 10

Page 2: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

T = 0, near normal T = 4 months later

Cushing’s Syndrome = Hypersecretionof Cortisol: Hypothalamic (CRH),

Pituitary (ACTH), or Adrenal (Cortisol)

Page 3: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Endocrine or Hormone?

Made by gland?1

Secreted into blood?2

Acts on target?3

Page 4: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Endocrine or Hormone ClassificationsEndogenousExogenous

Amino Acid, PP or Protein

Steroid

ThyroidPorcine

Bovine

Recombinant DNA

Page 5: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

G&H 2016 fig 75-3, G&H 2011 fig 74-3

Steroid Hormone Structure: Cholesterol Backbone

Page 6: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Lipophilic (Steroid+Thyroid) Hormone Mechanisms

G&H 2016 fig 75-6

G&H 2011 fig 74-6

Page 7: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Common Hydrophilic (AA, PP, Pro) Mechanism

G&H 2016 fig 75-7

G&H 2011 fig 74-7

Page 8: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Table 74-2 Hormones That Use the Adenylyl Cyclase –

Cyclic AMP Second Messenger System

Adrenocorticotropic hormone (ACTH)

Angiotensin II (ANG II, epithelial cells)

Calcitonin

Catecholamines (β receptors)

Corticotropin-releasing hormone (CRH)

Follicle-stimulating hormone (FSH)

Glucagon

Human chorionic gonadotropin (hCG)

Luteinizing hormone (LH)

Parathyroid hormone (PTH)

Secretin

Somatostatin (SS, GH RIH)

Thyroid-stimulating hormone (TSH)

Vasopressin (ADH, VP, V2 receptor, epithelial cells)

G&H 2016

tab 75-3,

G&H 2011

tab 74-2

Page 9: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

http://www.hhmi.org/bulletin/winter2013/features/index.htmlImage by Wayne Decatur

Robert Lefkowitz, MDDuke University Cardiologist

2012 Nobel Prize in Chemistry

G-Protein Coupled Receptor (blue) sits withinlipid bilayer (green) to respond to hormone (yellow)

Page 10: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

G&H 2016 fig 75-1

G&H 2011 fig 74-1

ANP =Atrial Natriuretic Polypeptide

1

Vasodilation2

BP

Page 11: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Krieger & Hughes 1980

Page 12: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Hypothalamus – Posterior Pituitary Nervous Connection

G&H 2016 fig 76-9

G&H 2011 fig 75-9

ADH/VP

OXY

H2O retentionby kidneys

Contraction ofsexual smooth m

Page 13: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Hypothalamus – Anterior Pituitary Vascular Connection

G&H 2016 fig 76-4

G&H 2011 fig 75-4

Releasing (RH)/Release-Inhibiting (RIH)

Hormones

1 of 6 Trophic/

Nourishing Hormones

Page 14: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Capillary-Venule-Capillary Circulation

Krieger & Hughes 1980

NB:Ensures RH/RIH super-

concentrated upon arrival

@ anterior pituitary!

Page 15: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Krieger & Hughes

1980

Long hypophyseal-portal veins

Pituitaryremoved!

Infin

dib

ulu

m/s

talk

Page 16: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

G&H 2011 tab 74-1

G&H 2016 tab 75-1

Endocrine Glands, Hormones, Structures & Functions

Page 17: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Anterior Pituitary Metabolic Functions

G&H 2011 fig 75-2

G&H 2016 fig 76-2

Page 18: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

SI Fox 2008Hypothalamus

Anterior Pituitary

Page 19: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

LS 1991

Page 20: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Growth Hormone/GH/Somatotrophic Hormone/STH Protein Hormone (191 AA) & Rat Growth

G&H 2016 fig 76-5

G&H 2011 fig 75-5

Page 21: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

LS2 2006

Page 22: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

LS 2012 fig 17-11

Progression & Development of Acromegaly

Page 23: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Growth Hormone ≡

Somatotrophic Hormone

Body Builder’s Dream?

Page 24: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

GH/STH Effects: InsulinResistance/Type II Diabetes?

Amino Acid uptake & Protein synthesis

Lipolysis & Fatty Acid mobilization

Glucose uptake

(skeletal muscle & adipocytes)

Glucose production

(liver glycogenolysis)

Insulin secretion

Mismatch!!

Page 25: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Increase GH naturally with exercise & sleep!!

cf: G&H 2016 fig 76-6

G&H 2011 fig 75-6

0800 1200 1600 2400 0400 0800

Page 26: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Growth Hormone & Protein Deficiency

G&H 2016 fig 76-7

G&H 2011 fig 75-7

Page 27: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Questions + Discussion

Page 28: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Endocrine Pancreas: Insulin (I) & Glucagon (G)

See-Saw Hormones in Regulating Blood Glucose

I G

I

GI

G

LS 2007

Page 29: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Store!

Times of Plenty!!

NB: Diabetics have problems either here or here.

Fox 1987

Page 30: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Insulin Stores Sugar, Glucagon Mobilizes Sugar!

Peripheral Endocrine &

Digestive Organ

~ 4-6 hr of Stored Glucose

Benjamin Cummings 2001

https://ed.ted.com/lessons/what-does-the-pancreas-do-emma-bryce

Page 31: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Proinsulin with C-Connecting Peptide

DO Norris 1980

cf: G&H 2016 fig 79-2

Page 32: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic
Page 33: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Diabetic & Normal Response to Glucose Load

G&H 2000

G&H 2016 fig 79-12Ingest Glucola or eat meal

Page 34: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Normal: 70-99Pre-Diabetes: 100-125Diabetes: ≥ 126 mg/dL

Glucose: Sugar in Blood

Page 35: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Source: Centers for Disease Control, Division of Diabetes Translation, http://www.cdc.gov/diabetes/statistics, S&W 2014 fig 4-15 p139A.

1994 Diabetes Prevalencein the US by State

Page 36: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Source: Centers for Disease Control, Division of Diabetes Translation, http://www.cdc.gov/diabetes/statistics, S&W 2014 fig 4-15 p139B.

2010 Diabetes Prevalencein the US by State

Page 37: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

S&W 2014 tab 4-9 p 140

Page 38: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Diabetics must constantly juggle diet, exercise & medication to control blood glucose!

Exercise

Diet

Medication

Page 39: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

S&W 2011 p 133

Like others, diabetics benefit from whole grains, vegetables, fruits, legumes & non-/low-fat milk products!

Page 40: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

S&W 2011 p 135

Exercise is a must based on its insulin-like effect!

Page 41: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

DC 2003

Page 42: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

DC 2003

Page 43: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

DC 2003

Page 44: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

LS

20

12

fig

17-1

6

Page 45: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

LS 2012 fig 17-17

Page 46: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Inadequate Iodine Promotes Goiter!

T3 + T4

TRH

TSH ≡ Thyrotropin

Iodine present?

IodineG&H 2011 fig 76-7

G&H 2016 fig 77-7

Page 47: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

G&H 2016

fig 77-9,

G&H 2011

fig 76-9

Near

absence of

thyroid-

hormone

function +

myxedema

Page 48: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

DC 2003

Page 49: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

LS 2012 fig 17-18

Adrenals/Suprarenals

Page 50: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

AnteriorPituitary

Glucose, Amino Acids, Fatty Acids

Metabolic Fuels Building Blocks Relieve Stress

CRH = ACTH-RH

SOURCE: Modified after D Chiras 2003

Corticotropin = ACTH

AdrenalCortices

Cortisol

HypothalamusStressDiurnalRhythm

Page 51: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

G&H 2016 fig 78-1

G&H 2011 fig 77-1

Adrenal Cortex ZonesBI 358!!

Epinephrine

80%

+

Norepinephrine

20%

Fight/Flight

Alarm Reaction

Page 52: BI 358 Lecture 10 3 Prep Lectures, then 3 Guest Lecturers ...€¦ · BI 358 Lecture 10. T = 0, near normal T = 4 months later Cushing’s Syndrome = Hypersecretion of Cortisol: Hypothalamic

Questions + Discussion