Hormones in Animals Endocrinology D R Davies School of Biological Sciences Purves Life: the Science...

Hormones in Animals

EndocrinologyD R Davies

School of Biological Sciences

Purves Life: the Science of Biology Chapters 41 (Animal Hormones) and 15 (Cell Signalling)

Lecture 13 Learning Outcomes

At the end of this lecture you should be able to:

• Describe the general properties of hormones, with examples

• Know the location of the major endocrine glands and the types of hormone secreted

• Outline the steps in the study of hormones

• Explain the different types of hormone receptor and describe in outline the transduction mechanism

Communication between cells in multicellular organisms

For a multicellular organism to survive it must be able to respond to changes in the external and internal environment - individual cells must be able to communicate with one another communication between cells occurs via 4 distinct mechanisms

Cell-to-cell communication via gap junctions in the plasma membrane

Paracrine control via locally acting chemical signals Electrical signals via the nervous system By chemical signals (hormones) released into the

bloodstream

Definition of hormone

• A specific chemical substance formed in one organ (endocrine gland) and transported in the bloodstream to another organ (Target Organ)where it affects the metabolism of that organ.

• First coined in 1902 by Bayliss and Starling who were the first to show the existence of the hormone - secretin.

Definition of hormone (2)

• Hormones are information transferring molecules which move from one cell to another for the benefit of the organism as a whole Huxley)

Endocrine Cell

Target CellH

Physiological effects of hormones are proportional to

hormone concentration• Hormones are only

effective over a narrow concentration range

• The EC50 value is the hormone concentration required to produce 50% of the maximal response

100%

50%

Hormones:• do not initiate reactions but rather they

effect the rate of pre-existing metabolic functions in a positive or negative fashion

• some hormones have specific effects on a single cell type, others a more general effect

• hormones are effective at minute concentrations - range 10-12 to 10-8 M

• hormones have a very short half-life in circulation ( ranging from minutes to hours)

Hormone concentration• Hormones are inactivated or degraded to an

inactive form (H*)at a constant rate

• It follows that the level of hormone in circulation is dependent on the rate of secretion

Endocrine Cell

Target Cell[H]

H*

Physiological effects of hormones are timed responses

• The effects of hormones occur in a regulated and timed manner

• Hormone levels increase in response to a physiological signal which results in an increased secretion of hormone

TimeH

orm

one C

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Phys

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Hormone

Physiol.Response

• hormone levels decrease when secretion ceases

Endocrine Glands

What kinds of hormonesdoes each glandproduce?

Fig. 23-20

Hypothalamus: releasing peptide hormone acting on the anterior pituitary : GHRH, CRH, TRH GnRH

Anterior Pituitary: Growth Hormone (GH), Corticotrophin (ACTH), Thyroid Stimulating hormone (TSH), Luteinizing hormone (LH), Follicle stimulating hormone (FSH)

Posterior Pituitary: oxytocin, vasopressin (ADH)

Pancreatic Islets of Langerhans: insulin and glucagon

Adrenal cortex: aldosterone and cortisol

Adrenal Medulla: Adrenaline and Noradrenaline

Thyroid Gland: thyroxine and Tri-iodothyronine

Testis: testosterone (androgen)

Ovary and placenta: oestradiol (oestrogens), progesterone

Hypothalamus and thePituitary Gland

Endocrine action coordinatedhere. It makes sense: it’sright next to your brain.

Fig. 23-22

Different types of hormones

Glycoprotein hormones e.g TSH, LH and FSH

Small peptide hormones : oxytocin, vaspressin (ADH) GnRH

Larger peptide hormones: insulin, ACTH

Catecholamine hormones: adrenaline and noradrenaline (a.k.a. epinephrine and norepinephrine in the USA)

Thyroid hormone: thyroxine and triiodothyronine

Steroid hormones: cortisol, progesterone, testosterone, (o)estradiol

Fatty Acid -based hormones: prostaglandins

Peptide Hormones from the Posterior Pitutary

Insulin Structure

Steroid Hormones

•Lipid hormones

•Cross plasma membranes readily

•Interact with intracellular receptors

•Regulate gene transcription

Adrenaline (epinephrine)

Epinephrine

C C

H

H

H

OH

HO

OH

N

H

CH3

Methods of studying hormones and their effects

Removal of the source of hormones:

If you remove the endocrine gland there is a measurable physiological consequence:• remove pancreas - causes diabetes mellitus (high blood glucose)• destroy -cells in pancreas by injecting streptozotocin - also results in diabetes•castration - results in loss of secondary sexual characteristics

Methods of studying hormones and their effects

Make extracts of the removed tissue and administer the the hormone deficient animal:

there is a measurable reversal physiological consequence:• pancreatic extracts lower blood glucose) in streptozotocin - induced in diabetes• administration of testosterone restores secondary sexual characteristics

•Proof that the endocrine gland secretes a chemical agent with hormonal effects

Methods of studying hormones and their effects

•Identify and characterise the hormone•Make a synthetic version of the hormone and show that it has similar effects•Identify the target tissue (s)•What are the metabolic and physiological effects of the hormone?•Make radiolabelled hormone (e.g. I125-insulin, 3H-oestradiol•Hormone specfically retained in target tissue (by a high affinity receptor)•Examine properties of hormone receptor•Purify and characterise receptor•characterise the metabolic effects of hormone within the target tissue

Hormones which bind to plasma membrane receptors:

• Hormones bind to specific receptors on the outside of the plasma membrane of the cell and exert rapid and specific effects on metabolism and longer term effects gene transcription

G-protein linked receptors e.g. adrenaline and glucagon receptors

Activated!

Second Messenger

Effects

Activation of Insulin Receptor

Effects of Hormones

• In all cases activation of the receptor can lead to a cascade of related and consequential molecular events inside the cell.

• Events including generation of second messengers, changes in ion fluxes, activation or inhibition of protein kinases, activation or inhibition of transcription factors

• eventually lead to the regulation of the activity of key metabolic enzymes or other cellular function or changes in the level of transcription of genes coding for key proteins

Intracellular Signalling Cascades

Signal Transfer

Signal Transformed and Relayed

Signal Amplified

Signal Diverges

Modulated Effect

Signalling via the insulin receptor

Mode of Action of Steroid and Thyroid Hormones

• These hormones are produced continuously • They are not stored in the endocrine gland• The hormones cross cell membranes readily• Bind to receptors in the cytoplasm or nuclei

of target cells• These steroid-receptor complexes act as

transcription factors regulating specific gene expression

• The effects of steroid and thyroid hormones usually take several hours to take effect

Activation of Protein Kinases