The Endocrine System Second controlling system of the

The Endocrine System • Second controlling system of the body • Nervous system is the fast-control system • Uses chemical messengers (hormones) that are released into the blood • Hormones control several major processes: • Reproduction • Growth and development • Mobilization of body defenses • Maintenance of much of homeostasis • Regulation of metabolism

Hormone Overview • Hormones are produced only by endocrine glands, but exocrine glands produce others as , sweat , sebum &mucous. • Cells secrete hormones into extracellular fluids directly as they have no ducts(ductless), compared to the exocrine glands that have ducts • Blood transfers hormones to target sites • These hormones regulate the activity of other cells

The Chemistry of Hormones • Hormones are classified chemically as • Amino acid–based, which includes: • Proteins • Peptides • Amines • Steroids—made from cholesterol • Prostaglandins—made from highly active lipids

Mechanisms of Hormone Action • Hormones affect only certain tissues or organs (target cells or target organs) • Target cells must have specific protein receptors • Hormone-binding alters cellular activity

Effects Caused by Hormones • Changes in plasma membrane permeability or electrical state • Synthesis of proteins, such as enzymes • Activation or inactivation of enzymes • Stimulation of mitosis • Promotion of secretory activity

The Chemistry of Hormones • Two mechanisms in which hormones act: • Direct gene activation • Second-messenger system

Direct Gene Activation (Steroid Hormone Action) • Diffuse through the plasma membrane of target cells • Enter the nucleus • Bind to a specific protein within the nucleus • Bind to specific sites on the cell’s DNA • Activate genes that result in synthesis of new proteins

Steroid hormone Nucleus Cytoplasm 1 Receptor protein 2 3 Hormonereceptor complex 4 DNA m. RNA 5 New protein Plasma membrane of target cell (a) Steroid hormone action 6 Figure 9. 1 a

Steroid hormone Cytoplasm Nucleus 1 Figure 9. 1 a, step 1

Steroid hormone Nucleus Cytoplasm 1 2 Receptor protein Figure 9. 1 a, step 2

Steroid hormone Nucleus Cytoplasm 1 Receptor protein 2 3 Hormonereceptor complex Figure 9. 1 a, step 3

Steroid hormone Nucleus Cytoplasm 1 Receptor protein 2 3 Hormonereceptor complex 4 DNA Figure 9. 1 a, step 4

Steroid hormone Nucleus Cytoplasm 1 Receptor protein 2 3 Hormonereceptor complex 4 DNA m. RNA 5 Figure 9. 1 a, step 5

Steroid hormone Nucleus Cytoplasm 1 Receptor protein 2 3 Hormonereceptor complex 4 DNA m. RNA 5 New protein Plasma membrane of target cell 6 Figure 9. 1 a, step 6

Second-Messenger System (Nonsteroid Hormone Action) • Hormone binds to a plasma membrane receptor • Hormone does not enter the cell • Sets off a series of reactions that activates an enzyme • Catalyzes a reaction that produces a secondmessenger molecule (such as c. AMP) • Oversees additional intracellular changes to promote a specific response

Nonsteroid hormone (first messenger) Cytoplasm Enzyme ATP 3 1 2 Receptor protein Plasma membrane of target cell Second c. AMP messenger 4 Effect on cellular function, such as glycogen breakdown (b) Nonsteroid hormone action Figure 9. 1 b

Nonsteroid hormone (first messenger) Cytoplasm 1 Receptor protein Figure 9. 1 b, step 1

Nonsteroid hormone (first messenger) Cytoplasm Enzyme 1 2 Receptor protein Figure 9. 1 b, step 2

Nonsteroid hormone (first messenger) Cytoplasm Enzyme ATP 3 1 2 Second c. AMP messenger Receptor protein Figure 9. 1 b, step 3

Nonsteroid hormone (first messenger) Cytoplasm Enzyme ATP 3 1 2 Receptor protein Plasma membrane of target cell Second c. AMP messenger 4 Effect on cellular function, such as glycogen breakdown Figure 9. 1 b, step 4

Control of Hormone Release • Hormone levels in the blood are mostly maintained by negative feedback • A stimulus or low hormone levels in the blood triggers the release of more hormone • Hormone release stops once an appropriate level in the blood is reached like insulin & thyroid hormones

1. Hormonal Stimuli of Endocrine Glands • Most common stimuli , using the negative feed back • Endocrine glands are activated by other hormones(tropic or trophic hormone) • Examples: • Anterior pituitary hormone, TSH, or thyrotropic hormone travels to target glands, such as the thyroid gland, to prompt the release of a particular hormone, such as thyroid hormone

(a) Hormonal stimulus 1 The hypothalamus secretes hormones that… Hypothalamus 2 …stimulate the anterior pituitary gland to secrete hormones that… Thyroid gland Anterior pituitary gland Adrenal Gonad (Testis) cortex 3 …stimulate other endocrine glands to secrete hormones Figure 9. 2 a

2. Humoral Stimuli of Endocrine Glands • Changing blood levels of certain ions stimulate hormone release • Humoral indicates various body fluids such as blood and bile • Examples: • Parathyroid hormone and calcitonin are produced in response to changing levels of blood calcium levels • Insulin is produced in response to changing levels of blood glucose levels

(b) Humoral stimulus 1 Capillary blood contains low concentration of Ca 2+, which stimulates… Capillary (low Ca 2+ in blood) Parathyroid glands Thyroid gland (posterior view) Parathyroid PTH glands 2 …secretion of parathyroid hormone (PTH) by parathyroid glands Figure 9. 2 b

3. Neural Stimuli of Endocrine Glands • Nerve impulses stimulate hormone release • Most are under the control of the sympathetic nervous system • Examples: • The release of norepinephrine and epinephrine by the adrenal medulla

(c) Neural stimulus 1 Preganglionic sympathetic fiber stimulates adrenal medulla cells… CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary 2 …to secrete catecholamines (epinephrine and norepinephrine) Figure 9. 2 c

Major Endocrine Organs • Pituitary gland • Thyroid gland • Parathyroid glands • Adrenal glands • Pineal gland • Thymus gland • Pancreas • Gonads (Ovaries and Testes) • Hypothalamus

Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Thymus Adrenal glands Pancreas Ovary (female) Testis (male) Figure 9. 3

Pituitary Gland • Size of a pea • Hangs by a stalk from the hypothalamus in the brain, located in hypophyseal fossa of the sphenoid bone • Has two functional lobes • Anterior pituitary—glandular tissue (adenohypophysis. ) • Posterior pituitary—nervous tissue (neurohypophysis) • Often called the “master endocrine gland”

Hormones of the Anterior Pituitary • Six anterior pituitary hormones • Two affect non-endocrine targets • Growth hormone • Prolactin • Four stimulate other endocrine glands (tropic hormones) • Thyroid-stimulating hormone (thyrotropic hormone)TSH • Adrenocorticotropic hormone(ACTH) • Two gonadotropic hormones(FSH, LH)

Hormones of the Anterior Pituitary • Characteristics of all anterior pituitary hormones • Proteins (or peptides) • Act through second-messenger systems(non steroidal) • Regulated by hormonal stimuli, mostly negative feedback

Releasing hormones secreted into portal circulation Hypothalamus Anterior pituitary Posterior pituitary Hypophyseal portal system Adrenocorticotropic hormone (ACTH) Growth hormone (GH) Bones and muscles Prolactin (PRL) Follicle-stimulating hormone (FSH) and luteinizing Mammary hormone (LH) glands Thyrotropic hormone (TH) Adrenal cortex Thyroid Testes or ovaries Figure 9. 4

Hormones of the Anterior Pituitary • 1. Growth hormone • General metabolic hormone • Major effects are directed to growth of skeletal muscles and long bones • Plays a role in determining final body size • Causes amino acids to be built into proteins • Causes fats to be broken down for a source of energy

Hormones of the Anterior Pituitary • Growth hormone (GH) disorders • Pituitary dwarfism results from hyposecretion of GH during childhood • Gigantism results from hypersecretion of GH during childhood, affecting long bones • Acromegaly results from hypersecretion of GH during adulthood, affecting flat bones

Pituitary dwarf (left), Giant (center), Normal height woman (right) Figure 9. 5

Hormones of the Anterior Pituitary • 2. Prolactin (PRL) • Stimulates and maintains milk production following childbirth by increasing # of milk ducts & milk glands, no realse of milk • 3. Adrenocorticotropic hormone (ACTH) • Regulates endocrine activity of the adrenal cortex • 4. Thyroid-stimulating hormone (TSH) • Influences growth and activity of the thyroid gland

Hormones of the Anterior Pituitary • 5. Gonadotropic hormones • Regulate hormonal activity of the gonads • A. Follicle-stimulating hormone (FSH) • Stimulates follicle development in ovaries, the grafian follicle that secretes estrogen • Stimulates sperm development in testes • B. Luteinizing hormone (LH) • Triggers ovulation of an egg in females, it acts on the corpus lutium to secrete progestron • Stimulates testosterone production inmale

Pituitary–Hypothalamus Relationship & posterior pit. hormones • Post. Pit. Hormonal release is regulated by releasing and inhibiting hormones produced by the hypothalamus • Hypothalamus produces two hormones • These hormones are transported to the posterior pituitary • 1. Oxytocin • 2. Antidiuretic hormone • The posterior pituitary is not strictly an endocrine gland, but does release hormones

Hormones of the Posterior Pituitary • Oxytocin • Stimulates contractions of the uterus during labour, sexual relations, and breastfeeding • Causes milk ejection in a nursing woman after suckling

Hormones of the Posterior Pituitary • Antidiuretic hormone (ADH) • Inhibits urine production by promoting water reabsorption by the kidneys • In large amounts, causes vasoconstriction leading to increased blood pressure • Also known as vasopressin

Hypothalamic neurosecretory cells Hypothalamus Optic chiasma Axon terminals Arterial blood supply Posterior lobe Capillary bed Venous drainage Anterior lobe of the pituitary ADH Oxytocin Kidney tubules Mammary glands Uterine muscles Figure 9. 6

Thyroid Gland • Found at the base of the throat • Consists of two lobes and a connecting isthmus • Produces two hormones • Thyroid hormone • Calcitonin

Thyroid cartilage Epiglottis Common carotid artery Isthmus of thyroid gland Trachea Brachiocephalic artery Left subclavian artery Left lobe of thyroid gland Aorta (a) Gross anatomy of the thyroid gland, anterior view Figure 9. 7 a

Thyroid Gland • Thyroid hormone • Major metabolic hormone • Composed of two active iodine-containing hormones • 1. Thyroxine (T 4)—secreted by thyroid follicles • 11. Triiodothyronine (T 3)—conversion of T 4 at target tissues

Colloid-filled Follicle cells follicles Parafollicular cell (b) Photomicrograph of thyroid gland follicles (125×) Figure 9. 7 b

Thyroid Gland • Thyroid hormone disorders: • Goiters • Thyroid gland enlarges due to lack of iodine • Salt is iodized to prevent goiters • Types: simple nodular, toxic(Graves disease) & malignant • A. Hyposecretion: • 1. Cretinism • Caused by hyposecretion of thyroxine during childhood

Figure 9. 8

Thyroid Gland • Thyroid hormone disorders (continued) • 2. Myxedema • Caused by hypothyroidism in adults • Results in physical and mental slugishness with rapid increase in weight • B. Hypersecretion • Graves’ disease( toxic goiter) • Caused by hyperthyroidism • Results in increased metabolism, heat intolerance, rapid heartbeat, weight loss, and

Figure 9. 9

Thyroid Gland • 111. Calcitonin • Decreases blood calcium levels by causing its deposition on bone • Antagonistic to parathyroid hormone • Produced by parafollicular cells • Parafollicular cells are found between the follicles

Colloid-filled Follicle cells follicles Parafollicular cell (b) Photomicrograph of thyroid gland follicles (125×) Figure 9. 7 b

Parathyroid Glands • Tiny masses on the posterior of the thyroid(4 glands) • Secrete parathyroid hormone (PTH)0 r parathrmone • Stimulate osteoclasts to remove calcium from bone to blood stream • Stimulate the kidneys and intestine to absorb more calcium • Raise calcium levels in the blood • Hyper secretion causes stones all over the body

Calcitonin stimulates calcium salt deposit in bone. Thyroid gland releases calcitonin. Stimulus Rising blood Ca 2+ levels IMB ALA NC E Calcium homeostasis of blood: 9– 11 mg/100 ml BALANCE IMB ALA NC E Stimulus Falling blood Ca 2+ levels Thyroid gland Osteoclasts degrade bone matrix and release Ca 2+ into blood. Parathyroid glands PTH Parathyroid glands release parathyroid hormone (PTH). Figure 9. 10

Adrenal Glands • Sit on top of the kidneys • Two regions • Adrenal cortex—outer glandular region has three layers • Mineralocorticoids secreted by outermost layer(zona glumerulosa)as aldosterone • Glucocorticoids secreted by middle layer(z. faciculata) as cortison • Sex hormones secreted by innermost layer(z. reticularis)

Adrenal gland Capsule Mineralocorticoidsecreting area Kidney Glucocorticoidsecreting area Adrenal gland • Medulla • Cortex Kidney Adrenal cortex Sex hormone secreting area Adrenal medulla Medulla Figure 9. 11

Hormones of the Adrenal Cortex • Mineralocorticoids (mainly aldosterone) • Produced in outer adrenal cortex • Regulate mineral content in blood • Regulate water and electrolyte balance, it keeps Na(with water) &release K • Target organ is the kidney • Production stimulated by renin • Production inhibited by atrial natriuretic hormon (ANH) • Hyposecretion causes diabetes insepedis

Decreased Na+ or increased K+ in blood Stress Hypothalamus Decreased blood volume and/or blood pressure Corticotropinreleasing hormone Anterior pituitary Increased ACTH blood pressure or blood volume Kidney Renin Indirect stimulating effect via angiotensin Angiotensin II Direct stimulating effect Heart Atrial natriuretic peptide (ANP) Inhibitory effect Mineralocorticoidproducing part of adrenal cortex Enhanced secretion of aldosterone targets kidney tubules Increased absorption of Na+ and water; increased K+ excretion Increased blood volume and blood pressure Figure 9. 12

Hormones of the Adrenal Cortex • Glucocorticoids (including cortisone and cortisol) • Produced in the middle layer of the adrenal cortex • Promote normal cell metabolism(antiinflammatory)& antiallergic • Help resist long-term stressors(antidepressant) • Released in response to increased blood levels of ACTH of the hypothalamus • Hyperfunction causes Cushing syndrom

Short term More prolonged Stress Hypothalamus Releasing hormones Spinal cord Nerve impulses Corticotropic cells of anterior pituitary Preganglionic Adrenal sympathetic medulla fibers ACTH Mineralocorticoids Short-term stress response Catecholamines (epinephrine and norepinephrine) 1. Increased heart rate 2. Increased blood pressure 3. Liver converts glycogen to glucose and releases glucose to blood 4. Dilation of bronchioles 5. Changes in blood flow patterns, leading to increased alertness and decreased digestive and kidney activity 6. Increased metabolic rate Adrenal cortex Glucocorticoids Long-term stress response 1. Retention of sodium and water by kidneys 2. Increased blood volume and blood pressure 1. Proteins and fats converted to glucose or broken down for energy 2. Increased blood sugar 3. Suppression of immune system Figure 9. 13

Hormones of the Adrenal Cortex • Sex hormones • Produced in the inner layer of the adrenal cortex • Small amounts are made throughout life • Mostly androgens (male sex hormones) are made but some estrogens (female sex hormones) are also formed

Adrenal Glands • Adrenal cortex disorders • Addison’s disease • Results from hyposecretion of all adrenal cortex hormones • Bronze skin tone, muscles are weak, burnout, susceptibility to infection • Hyperaldosteronism • May result from an ACTH-releasing tumor • Excess water and sodium are retained leading to high blood pressure and edema

Adrenal Glands • Adrenal cortex disorders • Cushing’s syndrome • Results from a tumor in the middle cortical area of the adrenal cortex • “Moon face, ” “buffalo hump” on the upper back, high blood pressure, hyperglycemia, weakening of bones, depression • Masculinization • Results from hypersecretion of sex hormones • Beard and male distribution of hair growth

Hormones of the Adrenal Medulla • Produces two similar hormones (catecholamines) • Epinephrine (adrenaline) • Norepinephrine (noradrenaline) • These hormones prepare the body to deal with short-term stress (“fight or flight”) by • Increasing heart rate, blood pressure, blood glucose levels • Dilating small passageways of lungs

Adrenal gland Capsule Mineralocorticoidsecreting area Kidney Glucocorticoidsecreting area Adrenal gland • Medulla • Cortex Kidney Adrenal cortex Sex hormone secreting area Adrenal medulla Medulla Figure 9. 11

Pancreatic Islets • The pancreas is a mixed gland has both endocrine and exocrine functions located in the concavity of the duodenum. Has head, body & tail, it produces: • Insulin—allows glucose to cross plasma membranes into cells from beta cells • Glucagon—from alpha cells , transforms glucose to glycogen , stored in liver &muscles, it can be changed to glucose. • These hormones are antagonists that maintain blood sugar homeostasis

Stomach Pancreas (a) Figure 9. 14 a

Exocrine cells of pancreas (b) Pancreatic islets Figure 9. 14 b

Exocrine cells of pancreas Alpha (α) cells Capillaries Cord of beta (β) cells secreting insulin into capillaries (c) Figure 9. 14 c

Uptake of glucose from blood is enhanced in most body cells Insulin-secreting cells of the pancreas activated; release insulin into the blood Tissue cells Insulin Glucose Glycogen Pancreas Elevated blood sugar level IMB ALA Liver takes up glucose and stores as glycogen Stimulus Blood glucose level (e. g. , after eating four jelly doughnuts) NC E BALANCE: Normal blood glucose level (about 90 mg/100 ml) IMB ALA Blood glucose rises to homeostatic set point; stimulus for glucagon release diminishes Liver breaks down glycogen stores and releases glucose to the blood Blood glucose falls to homeostatic set point; stimulus for insulin release diminishes NC E Stimulus Blood glucose level (e. g. , after skipping a meal) Low blood sugar level Glucagon-releasing cells of pancreas activated; release glucagon into blood Glucose Glycogen Liver Glucagon Figure 9. 15

Pineal Gland • Found on the third ventricle(epithalamus) of the brain • Secretes melatonin • Helps establish the body’s wake and sleep cycles • Believed to coordinate the hormones of fertility in humans

Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Thymus Adrenal glands Pancreas Ovary (female) Testis (male) Figure 9. 3

Thymus Gland • Located posterior to the sternum • Largest in infants and children • Produces thymosin • Matures some types of white blood cells • Important in developing the immune system(Tlymphocyte production)

Gonads • 1. Ovaries • Produce eggs • Produce two groups of steroid hormone • Estrogens • Progesterone • 2. Testes • Produce sperm • Produce androgens, such as testosterone

Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Thymus Adrenal glands Pancreas Ovary (female) Testis (male) Figure 9. 3

Hormones of the Ovaries • Estrogens • Stimulate the development of secondary female characteristics • Mature female reproductive organs • With progesterone, estrogens also • Promote breast development • Regulate menstrual cycle

Hormones of the Ovaries • Progesterone • Acts with estrogen to bring about the menstrual cycle • Helps in the implantation of an embryo in the uterus • Helps prepare breasts for lactation

Hormones of the Testes • Produce several androgens • Testosterone is the most important androgen • Responsible for adult male secondary sex characteristics • Promotes growth and maturation of male reproductive system • Required for sperm cell production

Other Hormone-Producing Tissues and Organs • Parts of the small intestine • Parts of the stomach • Kidneys • Heart • Many other areas have scattered endocrine cells

Endocrine Function of the Placenta • Produces hormones that maintain the pregnancy • Some hormones play a part in the delivery of the baby • Produces human chorionic gonadotropin (h. CG) that turns pregnancy test positive, in addition to estrogen, progesterone, and other hormones

Developmental Aspects of the Endocrine System • Most endocrine organs operate smoothly until old age • Menopause is brought about by lack of efficiency of the ovaries • Problems associated with reduced estrogen are common • Growth hormone production declines with age • Many endocrine glands decrease output with age