April 25, 2014 – Chemical signals and hormones I

1. No pre-lecture quiz2. Cell-to-cell signaling – an introduction3. Endocrine systems & hormones4. Case study: The importance of thyroid hormones (T3 & T4)

Introduction to chemical signals in animals – Major categoriesEndocrine cells may be organized into glands

Neurotransmitters

Introduction to chemical signals in animals – Major categories

Neuroendocrine pathway

Neuroendocrinesignal

Endocrine pathway Neuroendocrine-to-endocrine pathway

Neuroendocrinesignal

Endocrinesignal

Endocrinesignal

Endocrine cell

Effectorcell

Response

Response

Stimulus Stimulus

Feed

back

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bitio

n

Feed

back

inhi

bitio

n Sensor cell

Effectorcell

Feed

back

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bitio

n

Neural signal

CNS

Stimulus

Sensor cell

Neural signal

CNS

Response

Effectorcell

Endocrine cell

Endocrine systems are regulated by negative feedback

Steroids

CortisolEpinephrine

Amino AcidDerivatives

Receptor

Secretin

Peptides and Polypeptides

Receptor

Receptor

Target cell

Most not lipid soluble;bind to receptors onsurface of target cell

Not lipid soluble;bind to receptors onsurface of target cell

Lipid soluble;bind to receptorsinside target cell

Chemical characteristics of hormones – major classes

Hormone Transport and Action on Target

Hydrophobic messengers pass into cell where they bind with transcription factors which affect gene expression.

Hydrophilic hormones bind to a receptor on the cell membrane which causes several reactions known as a signal transductionpathway. This can affect the properties of enzymes/proteins, etc. or it may affect gene expression.

This picture shows a hormone traveling throughthe cell membrane and binding with a transcription factor.

Which of the following statements are true?

A) This is a membrane soluble (hydrophobic) hormone thatalters gene transcription.

B) This is a membrane soluble (hydrophobic) hormone thatalters immediate enzyme activity and cell processes.

C) This is a membrane insoluble (hydrophilic) hormone thatalters gene transcription.

D) This is a membrane insoluble (hydrophilic) hormone thatalters immediate enzyme activity and cell processes.

Barry Bonds was accused of using a steriod ‘the cream’ to increase his athletic performance. He supposedly applied this to his skin. What does this tell you about the nature of this hormone?

A. The hormone was membrane insoluble.B. The hormone was membrane soluble.C. The hormone initiated a signal transduction pathway.D. A and C

Steroids

PolypeptidesAmino acid derivatives

Major endocrine glands

Figure 47-3-1Hypothalamus

Growth-hormone-releasing hormone:stimulates release of GH from pituitarygland

Corticotropin-releasing hormone (CRH):stimulates release of ACTH from pituitarygland

Gonadotropin-releasing hormone:stimulates release of FSH and LH from pituitary gland

Thyroid-releasing hormone: stimulatesrelease of TSH from thyroid gland

Antidiuretic hormone (ADH): promotesreabsorption of H2O by kidneys

Oxytocin: induces labor and milk releasefrom mammary glands in females

Steroids

PolypeptidesAmino acid derivatives

Figure 47-3-3

Pituitary gland

Thyroid-stimulating hormone (TSH):stimulates thyroid gland to secretethyroxine

Prolactin: stimulates mammary glandgrowth and milk production in females

Follicle-stimulating hormone (FSH)and luteinizing hormone (LH): involvedin production of sex hormones;regulate menstrual cycle in females

Growth hormone (GH): stimulates growth

Adrenocorticotropic hormone (ACTH):stimulates adrenal glands to secreteglucocorticoids

Steroids

PolypeptidesAmino acid derivatives

Figure 47-3-2

Adrenal glands

Thyroid gland

Thyroxine: increases metabolic rateand heart rate; promotes growth

Kidneys

Epinephrine: produces many effectsrelated to short-term stress response

Aldosterone: increases reabsorption ofNa+ by kidneys

Cortisol: produces many effects related toshort-term and long-term stress responses

Vitamin D: decreases blood Ca2+

Testes (in males)

Erythropoietin (EPO): increasessynthesis of red blood cells

Testosterone: regulates developmentand maintenance of secondary sexcharacteristics in males; other effects

Steroids

PolypeptidesAmino acid derivatives

Figure 47-3-4

Parathyroid glands

Pancreas (islets of Langerhans)

Ovaries (in females)

Insulin: decreases blood glucose

Glucagon: increases blood glucose

Estradiol: regulates development andmaintenance of secondary sexcharacteristics in females; other effectsProgesterone: prepares uterus for pregnancy

Parathyroid hormone (PTH): increases blood Ca2+

Steroids

PolypeptidesAmino acid derivatives

Thyroid Hormone

Thyroid hormone:- Actually two hormones (T3/T4)

Mammals mainly secrete T4 - but some T4 is converted under certain circumstances- Same receptor binds both, but ↑affinity for T3

T3/T4 are membrane soluble- ↑metabolism in muscles, heart, liver & kidney

T4 T3

Thyroid Gland

Low levels of iodine cause ~90% of goiters.Why?

Figure 47-8

T3

Juvenile frog (tadpole)

T3

LocomotionRespiration

Excretion

Nutrition

Swim via movements of muscular tailGas exchange occurs in gills, across skin,and in lungsMost are herbivorous; have a long gutspecialized for digesting algae and plantsMost nitrogenous wastes excreted asammonia

Adult frog

LocomotionRespiration

Nutrition

Excretion

Gas exchange occurs across skin, and inlungs

Tailless; walk or hop

Most nitrogenous wastes excreted as urea

Most are carnivorous; have a large mouthor long tongue for catching prey; short gutspecialized for digesting proteins

Researchers figured out that tadpoles could be induced to undergo metamorphosis by feeding them ground up thyroid glands from horses.

They could also prevent metamorphosis by surgically removing the tadpoles' thyroid glands.

In juvenile amphibians, cells respond to increased levels of T3 in one of three ways:

(1) They may begin growing and form new structures, such as legs;(2) They may die, as in cells that form the tadpole's tail; or(3) They may change structure and function.

Researchers figured out that tadpoles could be induced to undergo metamorphosis by feeding them ground up thyroid glands from horses.

They could also prevent metamorphosis by surgically removing the tadpoles' thyroid glands.

In juvenile amphibians, cells respond to increased levels of T3 in one of three ways:

(1) They may begin growing and form new structures, such as legs;(2) They may die, as in cells that form the tadpole's tail; or(3) They may change structure and function.

Take home message: The same hormone can multiple physiological effects

Anadromous versus Resident Stream Sticklebacks

Higher metabolic rates

Migrate from ocean to freshwater to breed

Bigger

Lower metabolic rates

Permanent residents in freshwater

Smaller

Anadromous versus Resident Stream Sticklebacks

Higher metabolic rates

Migrate from ocean to freshwater to breed

Bigger

Lower metabolic rates

Permanent residents in freshwater

Smaller

I-Clicker - Which one has higher levels of thyroid hormone?

A) MarineB) Stream

Kitano, J. et al. 2010. Adaptive divergence in the thyroid signaling pathway in the stickleback radiation. Current Biology 20:2124-2130.

Marine Stream

Does T4 really affect metabolism?

Experiment:

For both marine and stream fish . . .

1. Expose some to higher levels of thyroid (T4)

2. Some unmanipulated (control)

3. Expose some to a thyroid inhibitor

Measure Oxygen Consumption.

Experiment:

For both marine and stream fish . . .

1. Expose some to higher levels of thyroid (T4)

2. Some unmanipulated (control)

3. Expose some to a thyroid inhibitor

Measure Oxygen Consumption inboth marine and freshwater fish.

What are the predictions?

Does T4 really affect metabolism?

Experiment:

Expose some to higher levels of thyroid (T4)

Some unmanipulated (control)

Expose some to a thyroid inhibitor

Does T4 really affect metabolism?

Elevated T4 levels in marine fish were associated with upregulation of genes involved in aerobic metabolism (OXPHOS)

Does T4 really affect metabolism?

There are lots of other elements of the fish that differ, possibly due to thyroid hormone.

-initiation of migration (for marine fish)-activity levels

There are lots of other elements of the fish that differ, possibly due to thyroid hormone.

-initiation of migration-activity levels

-DNA polymorphisms in binding sites of TSH

Altering individual behaviors by altering overall thyroid levels seems like a pretty blunt way to go about changing specific phenotypes.

How could this system be fine-tuned to optimize specific traits under different contexts?

A.) changes in TRH expressionB.) changes in TSH expressionC.) alterations of TSH receptorsD.) alteration of T3/T4 receptors in specific cell types.