The Endocrine System Dr Khalid Alregaiey Learning Objectives

The Endocrine System Dr. Khalid Alregaiey

Learning Objectives • List the general chemical categories of hormones and give examples of hormones within each category. • Explain how different hormones can exert synergistic, permissive, or antagonistic effects. • Explain how hormone concentrations in the blood are regulated • Describe the mechanisms of actions of hormones

Endocrine System: Overview • Endocrine system – the body’s second great controlling system which influences metabolic activities of cells by means of hormones • Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus • The pancreas and gonads produce both hormones and exocrine products

Endocrine System: Overview • The hypothalamus has both neural functions and releases hormones • Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart

Endocrine System: Overview • 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. • 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.

Major Endocrine Organs

The Endocrine System

Autocrines and Paracrines • Autocrines – chemicals that exert their effects on the same cells that secrete them • Paracrines – locally acting chemicals that affect cells other than those that secrete them • These are not considered hormones since hormones are long-distance chemical signals

Hormones • Hormones – chemical substances secreted by cells into the extracellular fluids • Regulate the metabolic function of other cells • Have lag times ranging from seconds to hours • Tend to have prolonged effects • Are classified as amino acid-based hormones, or steroids

Types of Hormones • Amino acid based – most hormones belong to this class, including: • Amines (Tyrosine: Caecholamines and Thyroid hormones, Tryptophan: Melatonin) • Polypeptide hormones • protein hormones • Steroids – Derived from Cholesterol, gonadal and adrenocortical hormones • Fatty acid derived: Eicosanoids, derived from arachidonic leukotrienes and prostaglandins

A Structural Classification of Hormones

Hormone Action • Hormones alter target cell activity by one of two mechanisms • Cell membrane receptors: • G Protein-coupled receptors • Tyrosine kinase receptors • Cytokines Receptors • Cytoplasmic or nuclear receptors: Direct gene activation involving steroid hormones • The precise response depends on the type of the target cell

Mechanism of Hormone Action • Hormones produce one or more of the following cellular changes in target cells • Alter plasma membrane permeability • Stimulate protein synthesis • Activate or deactivate enzyme systems • Induce secretory activity • Stimulate mitosis

Amino Acid-Based Hormone Action: c. AMP Second Messenger • Hormone (first messenger) binds to its receptor, which then binds to a G protein • The G protein is then activated as it binds GTP, displacing GDP • Activated G protein activates the effector enzyme adenylate cyclase • Adenylate cyclase generates c. AMP (second messenger) from ATP • c. AMP activates protein kinases, which then cause cellular effects

Amino Acid-Based Hormone Action: c. AMP Second Messenger

Amino Acid-Based Hormone Action: PIP-Calcium • Hormone binds to the receptor and activates G protein • G protein binds and activates a phospholipase enzyme • Phospholipase splits the phospholipid PIP 2 into diacylglycerol (DAG) and IP 3 (both act as second messengers) • DAG activates protein kinases; IP 3 triggers release of Ca 2+ stores • Ca 2+ (third messenger) alters cellular responses

Amino Acid-Based Hormone Action: PIP-Calcium

Tyrosine Kinase Receptors (RTK)

Steroid and Thyroid Hormones • Steroid hormones and thyroid hormone diffuse easily into their target cells • Once inside, they bind activate a specific intracellular receptor • The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor protein • This interaction prompts DNA transcription to produce m. RNA • The m. RNA is translated into proteins, which bring about a cellular effect

Steroid and Thyroid Hormones

Target Cell Specificity • Hormones circulate to all tissues but only activate cells referred to as target cells • Target cells must have specific receptors to which the hormone binds • These receptors may be intracellular or located on the plasma membrane

Target Cell Specificity • Examples of hormone activity • ACTH receptors are only found on certain cells of the adrenal cortex • Thyroxin receptors are found on nearly all cells of the body

Target Cell Activation • Target cell activation depends on three factors • Blood levels of the hormone • Relative number of receptors on the target cell • The affinity of those receptors for the hormone • Up-regulation – target cells form more receptors in response to the hormone • Down-regulation – target cells lose receptors in response to the hormone

Hormone Concentrations in the Blood • Hormones circulate in the blood in two forms – free or bound • Steroids and thyroid hormone are attached to plasma proteins • Others are unbound

Hormone Concentrations in the Blood • Concentrations of circulating hormone reflect: • Rate of release • Speed of inactivation and removal from the body • Hormones are removed from the blood by: • Degrading enzymes • The kidneys • Liver enzyme systems

Interaction of Hormones at Target Cells • Three types of hormone interaction • Permissiveness – one hormone cannot exert its effects without another hormone being present • Synergism – more than one hormone produces the same effects on a target cell • Antagonism – one or more hormones opposes the action of another hormone

Control of Hormone Release • Blood levels of hormones: • Are controlled by negative and positive feedback systems • Vary only within a narrow desirable range • Hormones are synthesized and released in response to humoral, neural, and hormonal stimuli

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

Humoral Stimuli • Humoral stimuli – secretion of hormones in direct response to changing blood levels of ions and nutrients • Example: concentration of calcium ions in the blood • Declining blood Ca 2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone) • PTH causes Ca 2+ concentrations to rise and the stimulus is removed

Humoral Stimuli

Neural Stimuli • Neural stimuli – nerve fibers stimulate hormone release • Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines

Hormonal Stimuli • Hormonal stimuli – release of hormones in response to hormones produced by other endocrine organs • The hypothalamic hormones stimulate the anterior pituitary • In turn, pituitary hormones stimulate targets to secrete still more hormones

Hormonal Stimuli

Major Endocrine Organs: Pituitary (Hypophysis) • Pituitary gland – two-lobed organ that secretes nine major hormones • Neurohypophysis – posterior lobe (neural tissue) and the infundibulum • Receives, stores, and releases hormones from the hypothalamus • Adenohypophysis – anterior lobe, made up of glandular tissue • Synthesizes and secretes a number of hormones

Major Endocrine Organs: Pituitary (Hypophysis)

Pituitary-Hypothalamic Relationships: Posterior Lobe • The posterior lobe is a downgrowth of hypothalamic neural tissue • Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract) • Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH) • These hormones are transported to the posterior pituitary

Pituitary-Hypothalamic Relationships: Anterior Lobe • The anterior lobe of the pituitary is an outpocketing of the oral mucosa • There is no direct neural contact with the hypothalamus

Major Endocrine Organs: Pituitary (Hypophysis)

Pituitary-Hypothalamic Relationships: Anterior Lobe

Adenophypophyseal Hormones • The six hormones of the adenohypophysis: • Are abbreviated as GH, TSH, ACTH, FSH, LH, and PRL • Regulate the activity of other endocrine glands • In addition, pro-opiomelanocortin (POMC): • Has been isolated from the pituitary • Is enzymatically split into ACTH, opiates, and MSH

Activity of the Adenophypophysis • The hypothalamus sends a chemical stimulus to the anterior pituitary • Releasing hormones stimulate the synthesis and release of hormones • Inhibiting hormones shut off the synthesis and release of hormones

Hormones of the hypothalamus 1. Thyrotropin-releasing hormone (TRH), which causes release of thyroid-stimulating hormone 2. Corticotropin-releasing hormone (CRH), which causes release of adrenocorticotropin 3. Growth hormone–releasing hormone (GHRH), which causes release of growth hormone, and growth hormone inhibitory hormone (GHIH), alsocalled somatostatin, which inhibits release of growth hormone 4. Gonadotropin-releasing hormone (Gn. RH), which causes release of the two gonadotropic hormones, luteinizing hormone and follicle-stimulating hormone 5. Prolactin inhibitory hormone (PIH), which causes inhibition of prolactin secretion

Activity of the Adenophypophysis • The tropic hormones that are released are: • Thyroid-stimulating hormone (TSH) • Adrenocorticotropic hormone (ACTH) • Follicle-stimulating hormone (FSH) • Luteinizing hormone (LH)

Gonadotropins • Gonadotropins – follicle-stimulating hormone (FSH) and luteinizing hormone (LH) • Regulate the function of the ovaries and testes • FSH stimulates gamete (egg or sperm) production • Absent from the blood in prepubertal boys and girls • Triggered by the hypothalamic gonadotropinreleasing hormone (Gn. RH) during and after puberty

Functions of Gonadotropins • In females • LH works with FSH to cause maturation of the ovarian follicle • LH works alone to trigger ovulation (expulsion of the egg from the follicle) • LH promotes synthesis and release of estrogens and progesterone

Functions of Gonadotropins • In males • LH stimulates interstitial cells of the testes to produce testosterone • LH is also referred to as interstitial cellstimulating hormone (ICSH)

Growth Hormone (GH) • Produced by somatotropic cells of the anterior lobe that: • Stimulate most cells, but target bone and skeletal muscle • Promote protein synthesis and encourage the use of fats for fuel • Most effects are mediated indirectly by somatomedins

Growth Hormone (GH) • Antagonistic hypothalamic hormones regulate GH • Growth hormone–releasing hormone (GHRH) stimulates GH release • Growth hormone–inhibiting hormone (GHIH) inhibits GH release

Metabolic Action of Growth Hormone • GH stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors • Direct action promotes lipolysis and inhibits glucose uptake

Metabolic Action of Growth Hormone

Thyroid Stimulating Hormone (Thyrotropin) • Tropic hormone that stimulates the normal development and secretory activity of the thyroid gland • Triggered by hypothalamic peptide thyrotropinreleasing hormone (TRH) • Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH

Adrenocorticotropic Hormone (Corticotropin) • Stimulates the adrenal cortex to release corticosteroids • Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm • Internal and external factors such as fever, hypoglycemia, and stressors can trigger the release of CRH

Prolactin (PRL) • In females, stimulates milk production by the breasts • Triggered by the hypothalamic prolactin-releasing hormone (PRH) • Inhibited by prolactin-inhibiting hormone (PIH) • Blood levels rise toward the end of pregnancy • Suckling stimulates PRH release and encourages continued milk production

Physiology of posterior Pituitary gland • Posterior pituitary hormones • ADH also known as Vasopressin • Oxytocin • These hormones are synthesized in the neuron cell bodies in the hypothalamus and packed in secretory vesicles with neurophysin (carrier protein)

Posterior. Pituitary pituitary Gland gland • Does not synthesize hormones • Consists of axon terminals of hypothalamic neurons

Antidiuretic Hormone (ADH) (vasopressin)

Synthesis of ADH • It is synthesized as pre-prohormone and processed into a nonapeptide • ADH synthesized in the cell bodies of hypothalamic neurons(supraoptic nucleus) • ADH is stored in the posterior pituitary

Receptors of ADH (vasopressin) • There are 2 types of receptors for ADH: • V 1 • V 2 V 1 receptors mediate vasoconstriction V 2 receptors are located in the principle cells in distal convoluted tubule and collecting ducts in the kidneys

Mechanism of action of ADH: Antidiuresis • ADH binds to V 2 receptors on the principle cells of the distal convoluted tubules and collecting ducts. • Via adenylate cyclase/c. AMP induces production of specific proteins into the luminal membrane and enhances permeability of cell to water. • Increased membrane permeability to water permits back diffusion of free water, resulting in increased urine osmolality (concentrates urine).

Mechanism of action of ADH

Control of ADH Release • Osmotic pressure: • Osmoreceptors in the hypothalamus • osmotic pressure ADH secretion • osmotic pressure ADH secretion • Blood volume : • Baroreceptor in carotid artery and aortic arch, and Stretch receptors in left atrium • blood pressure ADH secretion

Function of ADH (vasopressin)

ADH V 1 receptor Increased Blood Pressure

Oxytocin

Synthesis of Oxytocin • Oxytocin is synthesized in the cell bodies of hypothalamic neurons(paraventricular nucleus) • Oxytocin is stored in the posterior pituitary

Functions of oxytocin q Suckling during breast-feeding o Contracts the myoepithelial cells of the alveoli q Childbirth (Parturition) o In late pregnancy, uterine smooth muscle (myometrium) becomes sensitive to oxytocin (positive feedback)

Summary of posterior pituitary hormones actions