Hormone survey getting to know your hormones
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Hormone Survey: Getting to Know Your Hormones. Classification of Hormones Classification by System/Function Classification by Source Classification by Structure - Peptide Hormones -Steroid Hormones -Amino Acid Derivatives Classification of Hormone Receptors.

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Hormone Survey:Getting to Know Your Hormones

  • Classification of Hormones

  • Classification by System/Function

  • Classification by Source

  • Classification by Structure

  • - Peptide Hormones

  • -Steroid Hormones

  • -Amino Acid Derivatives

  • Classification of Hormone Receptors


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Some Things to Know about a Hormone

  • Source (what organ/cell produces and/or secretes it?)

  • What is its target cell(s)?

  • What is the effect on target cells?

  • What regulates its production/secretion?

  • What type of chemical structure?

  • Details of transport/metabolism?

  • What type of receptor/signal transduction?


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Learning Objectives: Classification of Hormones by Function

  • Describe the various functions that the endocrine system regulates.

  • Become familiar with the range of hormones involved in these functions.

  • You are NOT responsible for specific names of these hormones yet.


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Classification of Hormones by Function

  • Reproductive Hormones:

    - estrogens (estradiol), androgens (testosterone), progesterone

    - luteinizing hormone, follicle-stimulating hormone, prolactin, oxytocin

    - inhibin, activin, follistatin

    - gonadotropin-releasing hormone


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Classification of Hormones by Function

  • Growth Hormones:

    - Growth hormone (somatotropin)

    - somatomedins (insulin-like growth factors)

    - somatostatin, growth hormone-releasing hormone

    - nerve growth factor, epidermal growth factor, fibroblast growth factor, etc.


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Classification of Hormones by Function

  • Hormones regulating carbohydrate/energy metabolism:

    Insulin, glucagon, cortisol, growth hormone, epinephrine

  • Hormones regulating general body metabolism: - thyroid hormone (T3, T4)

    - thyroid stimulating hormone (TSH, or thyrotropin)

    - thyrotropin-releasing hormone (TRH)


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Classification of Hormones by Function

  • Hormones involved in stress responses:

    - norepinephrine, epinephrine

    - cortisol

  • Hormones involved in mineral and water balance:

    - aldosterone, renin, vasopressin

    - atrial natriuretic peptide


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Classification of Hormones by Function

  • Regulation of Calcium Metabolism:

    parathyroid hormone, calcitonin, vitamin D, others….

  • Regulation of Digestion

    cholecystokinin, gastrin, secretin, somatostatin

  • Regulation of Blood Formation:

    erythropoietin, erythrocyte differentiation factor


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Classification of Hormones by Source

  • Hypothalamus (brain): acts on the pituitary to control the release of pituitary hormones:

    -gonadotropin-releasing hormone (GnRH)

    -thyrotropin-releasing hormone (TRH)

    -corticotropin-releasing hormone (CRH)

    -prolactin-inhibiting factor (probably dopamine?)

    -somatostatin

    -growth hormone-releasing hormone (GHRH)


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Classification of Hormones by Source

  • Anterior Pituitary (anterior lobe):

    - luteinizing hormone (LH)

    - follicle-stimulating hormone (FSH)

    - thyroid-stimulating hormone (TSH)

    - growth hormone (GH; or somatotropin)

    - prolactin (PRL)

    - adrenal corticotropic hormone (ACTH, or corticotropin)


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Classification of Hormones by Source

  • Posterior Pituitary (posterior lobe):

    - oxytocin

    - vasopressin (antidiuretic hormone, ADH)

  • Intermediate Lobe (absent in adult human):

    - melanocyte-stimulating hormone


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Classification of Hormones by Source

  • Thyroid gland:

    - thyroid hormones (T3, T4)

    - calcitonin

  • Parathyroid gland:

    - parathyroid hormone


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Classification of Hormones by Source

  • Ovary and testis:

    - estrogens, androgens, progesterone

    - inhibins, activins, follistatin

    - relaxin

  • Placenta:

    - human chorionic gonadotropin (hCG)

    - placental lactogen

    - steroid hormone


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Classification of Hormones by Source

  • Adrenal cortex:

    - glucocorticoids (cortisol, corticosterone)

    - mineralocorticoids (aldosterone)

    - androgens (androstenedione)

  • Adrenal medulla:

    - epinephrine, norepinephrine


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Classification of Hormones by Source

  • Pancreas (endocrine):

    - insulin

    - glucagon

  • Kidney:

    - erythropoietin

  • GI Tract:

    - gastrin

    - cholecystokinin

    - secretin

    - somatostatin

  • Heart:

    - atrial natriuretic peptide


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Reminder….

  • At this point, do NOT memorize the preceding lists of hormone sources and functions.

  • DO understand the following information on hormone structure….


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Classification by Structure

  • Hormones can be classified based on their structure as steroid hormones, peptide hormones, or amino acid derivatives.

  • The structure of the hormone determines:

    • How it is made (gene product; cholesterol derivative; amino acid derivative)

    • How it is transported (binding protein?)

    • How it interacts with receptors on target cells (hormone-receptor interactions)


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Hormone-Receptor Interactions

  • Hormones and receptors bind due to noncovalent bonding between them.

  • This also involves a three-dimensional “lock and key” conformation

    BUT, there is a caveat – this analogy breaks down:

    Receptor Affinity

    Receptor Number


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Hormone-Receptor Interactions

  • Only specific regions of the hormone and receptor interact.

    • Some regions determine hormone binding

    • Other regions allow signal transduction

  • Small changes in hormone or receptor structure can prevent hormone binding and/or hormone activity


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Peptide Hormones: Water Soluble Gene Products

Recall that proteins are gene products:

gene (DNA)

transcription

mRNA

translation

protein


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Structure of Peptide Hormones

  • Proteins are made up of amino acids, connected to each other by peptide bonds.

  • Peptide hormones may be very short (three amino acids) to very long (over one hundred amino acids) in length.

  • They typically have an amino terminus (NH2) and a carboxyl terminus (-COOH).

NH2 COOH


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Structure of Peptide Hormones

  • Peptides have primary, secondary, tertiary, and quaternary structure:


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a

LHb

TSHb

FSHb

LH FSH TSH

Peptide Hormones: Subunit Structure

  • Peptide hormones may consist of two subunits joined together, usually by disulfide bonds at cysteine residues.

    Example: LH, FSH and TSH are composed of a common alpha subunit, and distinct beta subunits:


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Peptide Hormones

  • The shape of peptide hormones may be influenced by and strengthened by disulfide bridges.

  • Peptides may also form ring structures, such as oxytocin.


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Peptide Hormones: Glycosylation

  • Peptide hormones may be glycosylated (have carbohydrate side chains).

  • This glycosylation can affect:

    - assembly of hormone subunits

    - secretion from the endocrine cell

    - clearance of the hormone from the circulation

    - biological activity (receptor binding and biological response of the target cell)


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Peptide Hormones: Species Homology

  • The primary amino acid sequence of peptide hormones may differ slightly from species to species. Hormones obtained from one species may not necessarily interact with receptors for hormones of a different species.

    Example: The human FSH receptor does not respond well to FSH from other species.


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Endocrine Bioinformatics

  • Bioinformatics: The utilization of information (ie, databases) to solve biological problems.

  • Example: Suppose you were studying the hormone prolactin, and wanted to see what chromosome it was located on, and if there were any undiscovered hormones which were similar in structure.

  • Approach: Compare the human prolactin sequence to the human genome database at

    http://www.ncbi.nlm.nih.gov/genome/seq/HsBlast.html


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- Anderson et al., 2001

Actions of Peptide Hormones

  • The effects of peptide hormones are relatively quick, but short-lived.


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Half-life of Peptide Hormones

  • The half-life of peptide hormones in the circulation is relatively short (water soluble, no binding proteins).

- Fares et al., 1992


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Steroid Hormones

  • Steroid hormones are NOT made up of amino acids. They have a characteristic four ring structure, derived from cholesterol:

Examples: estrogens, androgens, progesterone, cortisol,

aldosterone


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Characteristics of Steroid Hormones

  • Steroid hormones are not glycosylated.

  • The structure of steroid hormones is the same in all species (estradiol in rats is the same as estradiol in humans).

  • Is there a gene for testosterone? How is testosterone made? How is its production regulated?


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- Luo et al., 2003

Characteristics of Steroid Hormones

  • Steroid hormones have more gradual and long-lasting effects than peptide hormones (in general).


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- Charmandari et al., 2001

Characteristics of Steroid Hormones

  • Steroid hormones have a relatively longer half life in the circulation (in general, compared with peptide hormones); reflects plasma binding proteins.


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Amino Acid Derivatives (Amines)

  • There are other hormones which are not steroids and not peptides, but are derived from amino acid precursors.

  • Epinephrine (adrenaline): Derived from tyrosine.


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Amino Acid Derivatives

  • Thyroid hormones (triiodothyronine, thyroxine); are also produced from tyrosine.

  • In this case, get lipid soluble hormones (not water soluble)


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Water soluble

hormones

Lipid soluble

hormones

gene

mRNA

peptide hormones

synthesis

synthesis

stimulus

amino acid

derivatives

(epinephrine,

norepinephrine)

cholesterol

steroid hormone

amino acid

derivative

(thyroid

hormone)

secretion

storage

diffusion

secretion

free hormone

free hormone

binding protein

Hormone

Level

Hormone

Level

Time

Time

plasma membrane

receptors

ion flux

target

DNA

second

messengers

(cAMP,

cGMP)

phosphorylation

mRNA

protein

cellular response

cellular response


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Types of receptors

  • Receptors for the water soluble hormones are found on the surface of the target cell, on the plasma membrane.

    • These types of receptors are coupled to various second messenger systems which mediate the action of the hormone in the target cell.

  • Receptors for the lipid soluble hormones reside in the nucleus (and sometimes the cytoplasm) of the target cell.

    • Because these hormones can diffuse through the lipid bilayer of the plasma membrane, their receptors are located on the interior of the target cell


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Hormone

Class of hormone

Location

Amine (epinephrine)

Water-soluble

Cell surface

Amine (thyroid hormone)

Lipid soluble

Intracellular

Peptide/protein

Water soluble

Cell surface

Steroids and Vitamin D

Lipid Soluble

Intracellular

Hormones and their receptors


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Second messenger systems

  • Receptors for the water soluble hormones are found on the surface of the target cell, on the plasma membrane. These types of receptors are coupled to various second messenger systems which mediate the action of the hormone in the target cell


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Second messengers for cell-surface receptors

  • Second messenger systems include:

    • Adenylate cyclase which catalyzes the conversion of ATP to cyclic AMP;

    • Guanylate cyclase which catalyzes the conversion of GMP to cyclic GMP (cyclic AMP and cyclic GMP are known collectively as cyclic nucleotides);

    • Calcium and calmodulin; phospholipase C which catalyzes phosphoinositide turnover producing inositol phosphates and diacyl glycerol.



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Second messenger systems

  • Each of these second messenger systems activates a specific protein kinase enzyme.

    • These include cyclic nucleotide-dependent protein kinases

    • Calcium/calmodulin-dependent protein kinase, and protein kinase C which depends on diacyl glycerol binding for activation.

      • Protein kinase C activity is further increased by calcium which is released by the action of inositol phosphates.


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Second messenger systems

  • The generation of second messengers and activation of specific protein kinases results in changes in the activity of the target cell which characterizes the response that the hormone evokes.

  • Changes evoked by the actions of second messengers are usually rapid


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Activation of adenylate cyclase

Inhibition of adenylate cyclase

Increased phospho-inositide turnover

Tyrosine kinase activation

b-adrenergic

a2-adrenergic

a1-adgrenergic

Insulin

LH, FSH, TSH, hCG

Opioid

Angiotensin II

Growth factors (PDGF, EGF, FGF, IGF-1

Glucagon

Muscarinic cholinergic – M2

Muscarinic cholinergic – M3

Growth hormone

Vasopressin- V2

Vasopressin –V1

Prolactin

ACTH

Signal transduction mechanisms of hormones



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G-protein coupled receptors

Adenylate cyclase, cAMP and PKA


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Amplification via 2nd messenger


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Transmembranekinase-linked receptors

  • Certain receptors have intrinsic kinase activity. These include receptors for growth factors, insulin etc. Receptors for growth factors usually have intrinsic tyrosine kinase activity

  • Other tyrosine-kinase associated receptor, such as those for Growth Hormone, Prolactin and the cytokines, do not have intrinsic kinase activity, but activate soluble, intracellular kinases such as the Jak kinases.

  • In addition, a newly described class of receptors have intrinsic serine/threonine kinase activity—this class includes receptors for inhibin, activin, TGFb, and Mullerian Inhibitory Factor (MIF).



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Receptors for lipid-soluble hormones reside within the cell

  • Because these hormones can diffuse through the lipid bilayer of the plasma membrane, their receptors are located on the interior of the target cell.

  • The lipid soluble hormone diffuses into the cell and binds to the receptor which undergoes a conformational change. The receptor-hormone complex is then binds to specific DNA sequences called response elements.

  • These DNA sequences are in the regulatory regions of genes.


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Receptors for lipid-soluble hormones reside within the cell

  • The receptor-hormone complex binds to the regulatory region of the gene and changes the expression of that gene.

  • In most cases binding of receptor-hormone complex to the gene stimulating the transcription of messenger RNA.

  • The messenger RNA travels to the cytoplasm where it is translated into protein. The translated proteins that are produced participate in the response that is evoked by the hormone in the target cell

  • Responses evoked by lipid soluble hormones are usually SLOW, requiring transcription/translation to evoke physiological responses.



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Receptor control mechanisms

  • Hormonally induced negative regulation of receptors is referred to as homologous-desensitization

  • This homeostatic mechanism protects from toxic effects of hormone excess.

  • Heterologous desensitization occurs when exposure of the cell to one agonist reduces the responsiveness of the cell any other agonist that acts through a different receptor.

  • This most commonly occurs through receptors that act through the adenylyl cyclase system.

  • Heterologous desensitization results in a broad pattern of refractoriness with slower onset than homologous desensitization


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