Introduction to the Endocrine System General Features and Definitions Types of Hormones Functions of the Endocrine System Components of the Endocrine System Chemical Structure of Hormones Homeostasis Endocrine vs. Nervous Systems Control of Endocrine Activity Regulation of Hormone Secretion Transport and Distribution of Hormones Mechanism of Hormone Action Regulation of Hormone Receptors

General Features of the Endocrine System Endocrine glands are ductless Endocrine glands have a rich supply of blood. Hormones, produced by the endocrine glands are secreted into the bloodstream. Hormones travel in the blood to target cells close by or far away from point of secretion. Hormones receptors are specific binding sites on the target cell. Here is a list of 5 general features of endocrine systems. First, endocrine glands are ductless. Points 2 and 3 go to together. It is important for endocrine glands to have a rich supply of blood because the hormones that these glands produce are then secreted into the bloodstream. Because hormones can travel anywhere in our bodies through the bloodstream, their effects are seen in all organ systems and tissue types. Finally, hormones can only exert their physiologic actions on target cells that contain appropriate receptors. The traditional view of hormone-receptor interactions is that a receptor is inactive (turned off) in the absence of a particular hormones.

Important Definitions: Endocrine System Endocrine--endo means within. This is a system which controls body function through hormones. Endocrine System is composed of a number of glands. Glands are specialized tissues that produce a hormone or product.

Important Definitions What are hormones? Hormones are organic chemical messengers produced and secreted by endocrine cells into the bloodstream. Hormones regulate, integrate and control a wide range of physiologic functions. Silverthorn, Human Physiology, 3rd edition Figure 6-1&2

Important Definitions What are endocrine glands? Endocrine glands are ductless glands comprised of endocrine cells. This means that these glands do not have ducts that lead to the outside of the body. For example, sweat glands are NOT endocrine glands (they are instead exocrine glands) because sweat glands have ducts that lead to the outside surface of your skin (that’s how the sweat gets out). The fact that endocrine glands are ductless means that these glands secrete hormones directly into the blood stream (instead of to the outside of your body).

Important Definitions What are target cells? Target cells refer to cells that contain specific receptors (binding sites) for a particular hormone. Once a hormone binds to receptors on a target cell, a series of cellular events unfold that eventually impact gene expression and protein synthesis. Silverthorn, Human Physiology, 3rd edition Figure 6-1&2

Important Definitions What are hormone receptors? Hormone receptors are binding sites on the target cell (either on the surface or in the cytoplasm or nucleus of the target cell) that are activated only when specific hormones bind to them. If a hormone does not/cannot bind to it’s receptor, then no physiologic effect results. See next slide for a picture of a hormone bound to its receptor

This particular receptor is activated when growth hormone binds to it This particular receptor is activated when growth hormone binds to it. The physiologic effect of this particular hormone binding to this particular type of receptor may be that a person experiences linear growth. Notice, the receptor pictured here is specific to growth hormones because the shape of the hormones fits nicely into the shape of the receptor. A good analogy is a specific key being able to fit into a specific lock. Growth hormone regulates cell growth by binding to growth hormone receptors on target cells.

Types of Hormones Protein Hormones These are made of amino acids. Steroid Hormones These are all derived from cholesterol. Examples: testosterone, estrogen, progesterone, mineralicoids, glucocorticoids. Steroids can cross the plasma membrane! Other kinds of lipids. Protein Hormones These are made of amino acids. Examples: Insulin, hypothalmus-signaling hormones. Protein hormones cannot cross the plasma membrane!

Chemical Structure of Hormones Two general classes of hormones: water soluble and lipid soluble. Water soluble (polar): proteins, glycoproteins, polypeptides, amino acid derivatives. Lipid soluble (nonpolar): steroids, amino acid derivatives, fatty acids. Different classes have different mechanisms of action, different modes of transport through the body, and differing stability in the circulation.

Examples of Water Soluble Hormones Proteins: growth hormone, prolactin, insulin Glycoproteins: follicle-stimulating hormone (FSH), luteinizing hormone (LH) , thyroid-stimulating hormone (TSH) Polypeptides: arginine vasopressin, oxytocin, somatostatin Amino acid derivatives:epinephrine, melatonin

Examples of Lipid-Soluble Hormones Steroids: estrogen, progesterone, testosterone, glucocorticoids, mineralocorticoids Amino acid derivatives: Thyroid hormones (T3, T4) Fatty acids: prostaglandins, thromboxanes

Classes of Hormones Steroids vs. Peptide Hormones Hormones fall into 2 general classes based on their molecular structure and synthesis. All steroid hormones are made initially from the precursor (precursor = first step in biosynthetic pathway) cholesterol. See next slide for a diagram of the biosynthetic pathway of steroid hormones from cholesterol.

Steroid Hormones Steroid hormones are produced by the gonads and adrenal cortex. Thyroid hormones are not steroids, but will be categorized with steroids for simplicity. Steroid hormones are made from cholesterol in the smooth endoplasmic reticulum and mitochondria of endocrine cells.

Steroid Hormones Steroid hormones cannot be stored in vesicles in the endocrine cells that produce them. As soon as steroid hormones are produced, they diffuse out of the endocrine cell and enter the bloodstream. Steroid hormones are lipid soluble and their receptors are located inside their target cell.

Peptide Hormones Peptide hormones are comprised of chains on amino acids. Like most proteins, peptide hormones are synthesized on ribosomes of the (rough) endoplasmic reticulum of endocrine cells. Peptide hormones can be stored in vesicles in endocrine cells until they are needed at some later point.

Peptide Hormones Peptide hormones do not readily pass through cell membranes (lipid bilayers) and they are referred to as water soluble. Receptors for peptide hormones are found on the cell surface of their target cells.

Some General Actions of Hormones Hormones cause cells to change. Hormones can result in changes in gene expression (DNA-RNA-Protein). Hormones can result in enzyme cascades which control our metabolism. Hormones drive our reproductive systems.

Some Specific Actions of Hormones Fetal development and differentiation Cell growth and cancer Metabolism Cardiovascular function Renal function Skeletal function Reproductive function Immune function Central nervous system function Hormones have widespread effects on multiple systems throughout development. Here is a list of some general classes of hormone action. In future classes, we will consider each of these actions in detail.

Homeostasis Definition: the maintenance of a constant environment (internal). Parameters regulated: Temperature, osmolarity, pH, nutrient levels, hormone levels, etc. Homeostasis is critical for cell viability and proper functioning. Loss of homeostasis results in disease/death. Homeostasis is maintained by feedback mechanisms (primarily negative feedback).

Another Example: Regulation of LH Release in the Male LH increases production of testosterone from the testis. Testosterone feeds back upon the pituitary to inhibit LH release. pituitary LH (-) testis testosterone

Another Example of Homeotasis: Regulation of Blood pH Levels 7.5 7.3

Feedback control Negative feedback is most common: for example, LH from pituitary stimulates the testis to produce testosterone which in turn feeds back and inhibits LH secretion Positive feedback is less common: examples include LH stimulation of estrogen which stimulates LH surge at ovulation

Negative feedback effects of cortisol

Substrate-hormone control Glucose and insulin: as glucose increases it stimulates the pancreas to secrete insulin

Feedback control of insulin by glucose concentrations

Endocrine overview Hormones are released by glands. Hormones are released by feedback. Our body works to carefully regulate hormone levels. Negative feedback usually controls hormone secretion.

Homeostasis and Controls Successful compensation Homeostasis reestablished Failure to compensate Pathophysiology Illness Death Figure 1-5: Homeostasis

Figure 6-26: Negative and positive feedback Feedback Loops Figure 6-26: Negative and positive feedback

Negative Feedback Controls: Long & Short Loop Reflexes

Endocrine Reflex Pathways: Overview

Pathologies: Over or Under Production

Pathologies: Due to Receptors

Endocrine vs. Nervous System Major communication systems in the body Integrate stimuli and responses to changes in external and internal environment Both are crucial to coordinated functions of highly differentiated cells, tissues and organs Unlike the nervous system, the endocrine system is anatomically discontinuous.

Nervous system The nervous system exerts point-to-point control through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast.

Functions of the Endocrine System Contributes to and interacts with the control and integration functions of the nervous system Important in the maintenance of homeostasis (set points), usually through negative feedback Occasionally involved in processes with controlled movement away from set point (positive feedback)

Why Two Systems? Comparison of Nervous and Endocrine Systems The nervous system responds to changes in the environment quickly, the endocrine system more gradually. The effects of nervous system action are short-lived, while the effects of endocrine changes persist longer. The nervous signal (neurotransmitter) is highly localized (at the synapse), the endocrine signal (hormone secretion) is systemic. The magnitude of nervous system effects are dependent upon the frequency of action potentials (frequency modulated); the magnitude of endocrine effects are dependent upon the amount of hormone released (amplitude modulated).

Hormones travel via the bloodstream to target cells The endocrine system broadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular fluid. Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.

A cell is a target because is has a specific receptor for the hormone Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells. A target cell responds to a hormone because it bears receptors for the hormone.

Principal functions of the endocrine system Maintenance of the internal environment in the body (maintaining the optimum biochemical environment). Integration and regulation of growth and development. Control, maintenance and instigation of sexual reproduction, including gametogenesis, coitus, fertilization, fetal growth and development and nourishment of the newborn.

Types of cell-to-cell signaling Classic endocrine hormones travel via bloodstream to target cells; neurohormones are released via synapses and travel via the bloostream; paracrine hormones act on adjacent cells and autocrine hormones are released and act on the cell that secreted them. Also, intracrine hormones act within the cell that produces them.

Response vs. distance traveled Endocrine action: the hormone is distributed in blood and binds to distant target cells. Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood. Autocrine action: the hormone acts on the same cell that produced it.

Major hormones and systems Top down organization of endocrine system. Hypothalamus produces releasing factors that stimulate production of anterior pituitary hormone which act on peripheral endocrine gland to stimulate release of third hormone Specific examples to follow Posterior pituitary hormones are synthesized in neuronal cell bodies in the hypothalamus and are released via synapses in posterior pituitary. Oxytocin and antidiuretic hormone (ADH)

Regulation of hormone secretion Sensing and signaling: a biological need is sensed, the endocrine system sends out a signal to a target cell whose action addresses the biological need. Key features of this stimulus response system are: ·        receipt of stimulus ·        synthesis and secretion of hormone ·        delivery of hormone to target cell ·        evoking target cell response ·        degradation of hormone

Some Specific Types of Chemical Signaling Hormones: chemicals released into the blood stream, act at a distant site Autocrine factor: chemical signal is released from a cell type, and acts upon that same cell type chemical

Some Specific Types of Chemical Signaling Paracrine factor: chemical is released from one cell type, and acts locally on another cell type (in same tissue) chemical

Some Specific Types of Chemical Signaling Pheromone: chemical is released into the environment, can affect other individuals

Some Specific Types of Chemical Signaling Neurotransmitter: chemical released into synaptic cleft, influences postsynaptic cell Neurohormone: chemical released from neuron into bloodstream, acts at distant site

What determines the size of hormone effects? 1) The amount of hormone in the circulation (reaching the target tissue) - the more hormone, the greater the effect 2) The presence and number of receptors for that hormone on the target tissue. - no receptor, no response - some receptors, some response - many receptors, higher response

How do you regulate hormone levels? Hormones are generally not secreted at a constant rate. Regulation of hormone levels involves: - regulation of hormone production - regulation of hormone secretion (often a separate step) - sometimes, regulation of hormone metabolism

Mechanisms of Hormone Regulation Neural Regulation: neurons synapse with cells producing hormone (ie, norepinephrine release from the adrenal gland). Endocrine Regulation: hormones bind to endocrine cells, regulating release of another hormone (ie, FSH stimulates estrogen release) Regulation by other factors (humoral): endocrine cells respond to levels of other factors in the circulation (ie, glucose causes increased insulin secretion from the pancreas)

Role of Feedback in Secretion The secretion of hormones is usually dependent upon feedback mechanisms Negative feedback: a stimulus causes an endocrine response (hormone secretion) which will decrease the level of that stimulus Positive feedback: a stimulus causes a response which will increase the level of that stimulus

Patterns of Hormone Secretion There are three basic patterns of secretion: pulsatile, acute, and cyclic. Pulsatile: relatively constant level of hormone, over a long period Acute: rapid increase in hormone level for a short time in response to a stimulus Cyclic: hormone increases and decreases in a constant pattern

Patterns of Secretion Pulsatile Acute Cyclic

Cyclic Increases in Reproductive Hormones Rat Ovulatory Cycle LH E2 Hormone Level FSH Diestrus Diestrus Proestrus Estrus Day 1 Day 2

How are hormones transported through the body to their target cells? Some hormones are bound to proteins (binding proteins) in the bloodstream hormone + binding protein <----> complex - hormone must unbind to act on tissues: binding affects activity of hormone - binding proteins may increase the time the hormone stays in the circulation -some binding proteins highly specific, some less specific Other hormones circulate freely in the blood (no binding proteins)

Where are Hormones Distributed to? Hormones are distributed in the general circulation to all parts of the body that receive blood flow.

What is a half-life? Hormones are eventually broken down (metabolized) and/or excreted from the body. The rate of removal from the circulation is fairly constant for a given hormone. The length of time it takes to remove half of the amount of hormone from the circulation is the half-life of that hormone. 100% Amount of Hormone 50% 0% Time

What is a half-life? In general, water-soluble hormones have shorter half-lives than lipid soluble hormones (rapid degradation in kidney, liver, lungs) Hormones with short half-lives exhibit rapid changes in hormone levels. Lipid soluble Water soluble TIME 0 30 60 0 30 60

Conjugation of Hormones Some hormones (ie, steroids) are modified by the liver (conjugation). Water-soluble groups are added on (sulfate, glucuronic acid),decreasing activity and increasing the water solubility of the hormone. Increasing water solubility increases the rate at which the hormone is excreted by the kidney.

Mechanism of Hormone Action: Receptors For hormones to act on a cell, that cell must have a receptor for that hormone. Receptors bind the hormone, resulting in a biological response. Receptors are found only in target tissues for that hormone. Receptors are very specific (they only bind a specific hormone, not all hormones) Receptors have high affinity for their hormone (bind hormone at very low hormone concentration).

What Receptors Do Activate second messenger systems (cyclic AMP, cyclic GMP). Phosphorylate cellular proteins, affecting their activity. Control ion channels. Regulate gene transcription.

Types of Membrane-Bound Receptors

Types of Receptors Membrane Bound: For hormones which do not enter the cell, the receptor is on the surface of the cell membrane. These typically affect second messengers, kinases, and ion channels. FSH protein kinase A FSH cAMP

Types of Receptors (the other kind) Intracellular Receptor: Steroid hormones, thyroid hormone, and vitamin D cross the plasma membrane and bind to receptors within the cell. This hormone:receptor complex binds DNA, regulating gene expression. E2 E2:R E2:R:DNA +,- mRNA protein

Regulation of Receptors The responsiveness of a target cell to a hormone is dependent upon the number of receptors present. By increasing or decreasing receptor number, you can regulate the hormonal activity on the target cell. Up-regulation: increase in receptor number due to increased synthesis. Down-regulation: decrease in receptor number due to decreased synthesis and/or increased degradation. More about receptors in the next lecture…

Next Lecture..… Hormone Survey