General Biochemistry II

MOLB4610/5610
Lecture 20
Hormones II
(Lehninger pg. 893- 901)
 Todays lecture
Hormonal control
Hormonal signaling hierarchy
Lipostat theory
Leptin and leptin receptors
Leptin deficient mice
Anorexigenic and orexigenic
neuropeptides
JAK/STAT mechanism

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Theodor Hanekamp 2003
 What regulates the regulator ?
1. Hormones control each other
Hormonal signaling hierarchy
2. Hormones are influenced by external factors
3. Hormone responsiveness is in part
controlled by the genetic make-up
Source:
Lehninger pg. 869

Theodor Hanekamp 2003

Leptin deficient Normal 3
 Hormonal control
1. Some hormones (in part) control their own synthesis
Autocrine hormones
Hormone
receptor

Hormone

2. Some hormones regulate the release of other hormones

Insulin Epinephrine Glucogon

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Theodor Hanekamp 2003
 Hormonal signaling hierarchy
THE ENDOCRINE SYSTEM

Multiple levels
(CNS Hypothalamus)
Pituitary gland
Second targets
Ultimate targets
Hypothalamic hormones
Trophic hormones
Diverse hormones

Sensory input from environment

Neuroendocrine Central nervous system

origins of signals

Hypothalamus 5
Theodor Hanekamp 2003
 Hypothalamic hormones
Small peptides, aka Releasing Factors (RFs)

Neuroendocrine Central nervous system

origins of signals

Hypothalamus

Feedback CRF TRF GNRF GRF

inhibition Hypothamalmic hormones Somatostatin
(Releasing factors) (GRIF) Neural
endings
Anterior pituitary Posterior pituitary
First targets (Adenohypophysis) (Neurohypophysis)
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Theodor Hanekamp 2003
 Trophic hormones
polypeptides, aka tropic hormones

CRF TRF GNRF GRF/GRIF

Anterior pituitary (Adenohypophysis)

ACTH TSH FSH LH Somatotropin

Second Adrenal Thyroid Testes,

targets Cortex Ovaries

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Theodor Hanekamp 2003 Liver, Bone
 Trophic hormones
polypeptides, aka tropic hormones
ACTH TSH FSH LH

Second Adrenal Thyroid Testes,Ovaries

targets Cortex

Adrenocorticol T3, T4 Progesterone

Hormones Estradiol Testosterone

Ultimate Many Muscle, Reproductive

targets Tissues Liver organs

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Theodor Hanekamp 2003
 Hormone signaling hierarchy

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Theodor Hanekamp 2003 Source: Lehninger pg. 893
 Signal amplification
Hypoglycemia, CNS Pain, Fear, Infection
hemorrhage

Hypothalamus

CRH (ng)

Anterior Pituritary
ACTH (g)

Adrenal gland

Cortisol (mg)
Muscle Adipose 10
Theodor Hanekamp 2003 Liver
 Long-term regulation of body mass
Body mass: Average American male gains 20
pounds between age 25 55
Short term: Minute change on a daily basis
Long term: Reduced life expectancy
Economic factor:
Weight-reducing diets
Exercise equipment and programs
Pharmaceuticals that help you loose weight
Medical treatments Liposuction
Research on control of body weight
Health insurance increased health risks
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Theodor Hanekamp 2003
 The Lipostat theory
Based on relative constancy of body mass
A feedback mechanism:
Kicks in when body weight exceeds a set point
Inhibits eating behavior
Increases energy consumption
Signal originates in adipose tissue and
influences brain center that control eating
behavior and activity
Signal is Leptin (1994)
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Theodor Hanekamp 2003
 Leptin
Leptin:
encoded by the OB (obese gene)
protein is 167 amino acid residues long
generated mainly in adipose tissue
messenger reduce fuel intake
increases heart rate, blood pressure, thermogenesis
acts on leptin receptors

Leptin receptor
encoded by the DB (diabetic gene) in mice
located mainly in the hypothalamus
also expressed in cells of the adrenal cortex & beta-cells
binding of hormone to receptor reduces appetite
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 Leptin deficient mice
Leptin deficient homozygous mice (ob gene)
behave like mice that are constantly starving
are 3 times bigger than normal
cant stay warm
resemble diabetic mice(DB)
are insulin-resistant
db/db mice are obese and diabetic
ob/ob

OB/ob or OB/OB 14
Theodor Hanekamp 2003
 Leptin cascade
Appetite suppressing
neuropeptides
(a -MSH) a-melanocyte-stimulating
hormone
(POMC)Proopiomelanocortin
(CRH) Corticotropin releasing
hormone
(CART) Hypothalamic peptide
Appetite stimluating
neuropeptides
(NPY) Neuropeptide Y

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 The JAK/STAT mechanism

Theodor Hanekamp 2003

SOURCE: Lehninger pg. 899 16