Chapter 18: Endocrine system

Hormone

A mediator molecule that is released in one part of the body but regulates the activity of cells in other parts of the body by entering interstitial fluid and then the bloodstream; exert effectors by binding to receptors on or in their "target" cells; some also act as Nt's, ex. norepinephrine; most take several minutes or more to cause a response (slower but longer lasting than nervous system); helps regulate all types of body cells

Exocrine glands

One of two types of body glands; secrete their products into ducts that carry the secretions into body cavities, into the lumen of an organ, or to the outer surface of the body; Ex. sweat, oil, mucous, digestive glands

Endocrine glands

One of two types of body glands; secrete their products (hormones) into the interstitial fluid surrounding the secretory cells rather than into ducts; hormones diffuse into blood capillaries and blood carries them to target cells in body; most vascular tissues in body, dependence on cardiovascular system to distribute; include pituitary, thyroid, parathyroid, adrenal, pineal glands; organs with hormone-secreting cells, such as hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine, skin, heart, adipose tissue, placenta

Endocrine system

All endocrine glands and hormone-secreting cells

Receptors

Specific binding spots for hormones, allowing hormones to influence their target cells; made of proteins; a target cell has 2000 to 100,000 for a particular hormone

Down regulation

Decreasing the number of target-cell receptors if a hormone is present in excess; makes a target cell less sensitive to a hormone

Up regulation

Increasing the number of target-cell receptors if a hormone is deficient; makes a target cell more sensitive to a hormone

RU 486

Mifepristone; used to induce abortion; synthetic hormone that blocks the receptors for naturally occurring hormones by binding to receptors for progesterone and preventing progesterone from exerting its normal effect; uterine conditions needed for nurturing an embryo are not maintained and embryonic development stops

Circulating hormones

Most endocrine hormones; pass from the secretory cells that make them into interstitial fluid and then into the blood; lasts longer than local hormones; eventually inactivated by the liver and excreted by the kidneys

Local hormones

Act locally on neighboring cells or on the same cell that secreted them without first entering the bloodstream; paracrines and autocrines; usually inactivated quickly

Paracrines

Local hormones that act on neighboring cells

Autocrines

Local hormones that act on the same cell that secreted them; receptors receive hormone from its own cell

Interleukin 2

IL-2; local hormone released by helper T cells during immune responses; paracrine - helps activate other nearby immune cells; autocrine - stimulates same cell that released it, generating more helper T cells that can secrete even more IL-2 and thus strengthen the immune response

Hormone chemical classes

2 classes: lipid-soluble hormones, water-soluble hormones

Lipid soluble hormones

One of two chemical classes of hormones; Include 1. steroid hormones, 2. thyroid hormones, 3. nitric oxide; most are bound to transport proteins, 0.1-10% are free fraction (not bound); receptors located inside target cells

Steroid hormones

1 of 3 lipid-soluble hormones; derived from cholesterol; unique based on different chemical groups attached at various sites on the four rings at the core of its structure -\> large diversity of functions

Thyroid hormones

1 of 3 lipid-soluble hormones; T3 and T4, synthesized by attching iodine to the amino acid tyrosine; presence of 2 benzene rings within a T3 or T4 molecule makes it very lipid-soluble

Nitric oxide

1 of 3 lipid-soluble hormones; both a hormone and Nt; synthesis is catalyzed by the enzyme nitric oxide synthase

Water soluble hormones

One of two chemical classes of hormones; include 1. amine hormones, 2. peptide and protein hormones, 3. eicosanoid hormones; circulate in watery blood plasma in a "free" form (not attached to other molecules); receptors are part of the plasma membrane of target cell (not inside cell)

Amine hormones

1 of 3 water-soluble hormones; synthesized by decarboxylating and modifying certain amino acids; retain an amino group; catecholamines w/ tyrosine, histamine w/ histidine, serotonin w/ tryptophan

Peptide (protein) hormones

1 of 3 water-soluble hormones; amino acid polymers; peptide hormones are 3 to 49 amino acids, protein hormones are 50 to 200 a.a.'s; attachment of carbohydrate group makes it glycoprotein hormone

Eicosanoid hormones

1 of 3 water-soluble hormones; derived from arachidonic acid, a 20-carbon fatty acid; 2 major types: prostaglandins (PGs) and leukotrienes (LTs); important local hormones

Transport proteins

Synthesized by cells in the liver; lipid-soluble hormone molecules are bound to these; 3 functions: 1. make lipid-soluble hormones temporarily water-soluble, increasing their solubility in blood, 2. retard passage of small hormone molecules through the filtering mechanism in the kidneys, slowing the rate of hormone loss in urine, 3. provide a ready reserve of hormone, already present in the bloodstream

Free fraction

0.1-10% of lipid-soluble hormone molecules; diffuses out of capillaries, binds to receptors, and triggers a response; transport proteins release their hormone molecules when free fraction binds to receptors in order to replenish free fraction hormone molecules

Hormone responses

Synthesis of new molecules, changing permeability of plasma membrane, stimulating transport of a substance into or out of target cells, altering the rate of specific metabolic reactions, causing contraction of smooth or cardiac muscle; various target cells respond differently to the same hormone

Lipid soluble mechanism

1. Free lipid-soluble hormone molecule diffuses from blood -\> interstitial fluid -\> lipid bilayer of plasma membrane -\> cell, 2. if cell is a target cell, the hormone binds to and activates receptors located within the cytosol or nucleus -\> activated receptor-hormone complex alters gene expression, turning specific genes of nuclear DNA on or off, 3. As DNA is transcribed, new mRNA forms, leaves the nucleus, and enters cytosol -\> directs synthesis of a new protein on the ribosomes, 4. New proteins alter cell's activity and cause responses typical of that hormone

Water soluble mechanism

1. Water-soluble hormone (first messenger) diffuses from blood -\> interstitial fluid -\> binds to receptor at exterior surface of target cell's plasma membrane -\> activates G protein -\> activates adenylate cyclase, 2. adenylate cyclase converts ATP into cAMP in cytosol of cell, 3. cAMP (second messenger) activates protein kinases, and ATP donor converted to ADP, 4. activated protein kinases phosphorylate one or more cellular proteins, activating some and inactivating others, 5. different phosphorylated proteins cause reactions that produce physiological responses, 6. phosphodiesterase inactivates cAMP and cell's response is turned off unless new hormone molecules continue to bind to receptors at plasma membrane

Lipid soluble mechanism (brief)

1. Lipid-soluble hormone diffuses into cell, 2. activated receptor-hormone complex alters gene expression, 3. newly formed mRNA directs snthesis of specific proteins on ribosomes, 4. new proteins alter cell's activity

First messenger

When a water-soluble hormone binds to its receptor at the outer surface of the plasma membrane; causes production of a second messenger (ex. cAMP) inside the cell, where specific hormone-stimulated responses take place

Water soluble mechanism (brief)

1. binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase, 2. activated adenylate cyclase converts ATP to cAMP, 3. cAMP serves as a second messenger to activate protein kinases, 4. activated protein kinases phophorylate cellular proteins, 5. millions of phosphorylated proteins cause reactions that produce physiological responses, 6. phosphodiesterase inactivates cAMP

Adenylate Cyclase

Converts ATP into cAMP

Phosphodiesterase

An anzyme which inactivates cAMP

G proteins

Common feature of most second-messenger systems; Activate adenylate cyclase; unless they are further stimulated by binding of more hormone molecules to receptors, they slowly inactivate -\> decrease activity of adenylate cyclase -\> stop hormone response;

Target cell response

Responsiveness of target cell to a hormone depends on: 1. the hormone's concentration in the blood (more responsive at higher concentrations, kinda like up regulation), 2. the abundance of the target cell's hormone receptor, 3. influences exerted by other hormones

Permissive effect

When actions of some hormones on target cells require a simultaneous or recent exposure to a second hormone; second hormone has this kind of effect; effect of thyroid hormones on epinephrine; can promote the synthesis of an enzyme required for the expression of first hormone or increase the number of receptors for the first hormone

Synergistic effect

When the effect of two hormones acting together is greater or more extensive than the effect of each hormone acting alone; the two hormones have this effect; Ex. development of oocytes requires follicle-stimulating hormone and estrogen - neither hormone alone is sufficient

Antagonist effects

When one hormone opposes the actions of another hormone, the two hormones have this effects; Ex. insulin promoting synthesis of glycogen by liver cells and glucagon stimulating breakdown of glycogen in the liver

Hormone secretion regulation

Hormone secretion regulated by 1. signals from nervous system, 2. chemical changes in the blood, 3. other hormones

Hormone secretion control

Release of most hormones occurs in short bursts, with no secretion in between; when stimulated, an endocrine gland releases its hormone in more frequent bursts, increasing the concentration of the hormone in the blood

Hypothalamus

Small region of the brain below the thalamus; major link between nervous and endocrine systems; cells here synthesize at least 9 different hormones; important role in regulation of all aspects of growth, development, metabolism, homeostasis

Pituitary gland

Pea-shaped structure in hypophyseal fossa of the sella turcica of sphenoid bone; attached to hypothalamus by infundibulum (stalk); secretes seven different hormones; split into two parts, anterior and posterior

Anterior pituitary

1 of 2 parts of pituitary gland; 75% of total weight of gland; composed of epithelial tissue; consists of two parts: pars distalis (larger portion) and pars tuberalis (forms sheath around infundibulum); release of hormones here is stimulated by RELEASING HORMONES and suppressed by INHIBITING HORMONES from the hypothalamus

Posterior pituitary

1 of 2 parts of pituitary gland; composed of neural tissue; consists of two parts: pars nervosa (larger bulbar portion) and infundibulum (stalk connecting hypothalamus and pituitary gland); does NOT synthesize hormones, but STORES and RELEASES two hormones (oxytocin and ADH); consists of axons and axon terminals of more than 10,000 hypothalamic neurosecretory cells

Infundibulum

stalk that attaches pituitary gland to hypothalamus

Portal system

Blood flows from one capillary network into a portal vein, and then into a second capillary network before returning to the heart; name of portal system indicates the location of the second capillary network

Hypophyseal portal system

Blood flows from capillaries in the hypothalamus into portal veins that carry blood to capillaries of the anterior pituitary; superior hypophyseal arteries -\> hypothalamus -\> primary plexus -\> hypophyseal portal veins -\> secondary plexus

Superior hypophyseal arteries

Branches of the internal carotid arteries; bring blood INTO the HYPOTHALAMUS during the hypophyseal portal system

Primary plexus

Capillary network formed from divided arteries at the junction of the median eminence of the hypothalamus and the infundibulum; part of hypophyseal portal system

Hypophyseal portal veins

From primary plexus, blood drains here, then passes down the outside of the infundibulum; divides and forms another capillary network called the secondary plexus; part of hypophyseal portal system

Neurosecretory cells

Clusters of specialized neurons above the optic chiasm; they synthesize the hypothalamic releasing and inhibiting hormones in their cell bodies and package the hormones inside vesicles, which reach the axon terminals by axonal transport

Hypophyseal hormone tract

Neurosecretory cells synthesize hypothalamic hormones -\> hormones in vesicles -\> vesicles to axon terminals -\> vesicles do exocytosis -\> hormones diffuse to primary plexus -\> portal veins -\> secondary plexus; allows hypothalamic hormones to act quickly and directly on anterior pituitary cells

Tropic hormones

Tropins; anterior pituitary hormones that act on other endocrine glands; pass into secondary plexus capillaries -\> drain into anterior hypophyseal veins -\> out to general circulation -\> travel to target tissues throughout body

Anterior pituitary cells

Five types that secrete seven hormones; Cells: 1. somatotrophs, 2. thyrotrophs, 3. gonadotrophs, 4. lactotrophs, 5. corticotrophs; Hormones: 1. human growth hormone (hGH), 2. thyroid-stimulating hormone (TSH), 3. follicle-stimulating hormone (FSH), 4. luteinizing hormone (LH), 5. prolactin (PRL), 6. adrenocorticotropic hormone (ACTH), 7. melanocyte-stimulating hormone (MSH)

Somatotrophs

1 of 5 anterior pituitary cells and most numerous; secretes human growth hormone (hGH) (most plentiful of anterior pituitary hormones) in bursts every few hours, which stimulates several tissues to secrete insulinlike growth factors (IGFs), small protein hormones that stimulate general body growth and regulate aspects of metabolism via bloodstream or locally

Thyrotrophs

1 of 5 anterior pituitary cells; secretes thyroid-stimulating hormone (TSH), which controls the secretions and other activities of the thyroid gland

Gonadotrophs

1 of 5 anterior pituitary cells; secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which both act on gonads, stimulating secretion of estrogens and progesterone and the maturation of oocytes in the ovaries; stimulate sperm production and secretion of testosterone in the testes

Lactotrophs

1 of 5 anterior pituitary cells; secretes prolactin (PRL), which initiates milk production in the mammary glands

Corticotrophs

1 of 5 anterior pituitary cells; secretes adrenocorticotropic hormone (ACTH), which stimulates the adrenal cortex to secrete glucocorticoids, such as cortisol; also secretes melanocyte-stimulating hormone (MSH)

IGF

Insulinlike growth factors; functions: 1. cause cells to grow and multiply by increasing uptake of amino acids into cells and accelerating protein synthesis, causing growth of skeleton and skeletal muscles, 2. enhance lipolysis in adipose tissue, resulting in increased use of released fatty acids for ATP production by body cells, 3. influence carbohydrate metabolism by decreasing glucose uptake, decreasing the use of glucose for ATP production by body cells

Hypoglycemia

Abnormally low blood glucose concentration

Hyperglycemia

Abnormally high blood glucose concentration

GHRH on hGH

1. Low blood glucose (hypoglycemia) stimulates release of GHRH -\> 2. GHRH stimulates secretion of hGH by somatotrophs -\> 3. hGH and IGFs speed up breakdown of liver glycogen into glucose, which enters blood faster -\> 4. blood glucose level rises to normal (90mg/100mL)

GHIH on hGH

1. High blood glucose (hyperglycemia) stimulates release of GHIH -\> 2. GHIH inhibits secretion of hGH by somatotrophs -\> 3. low level of hGH and IGFs decreases rate of glycogen breakdown in the liver and glucose enters blood slower -\> 4. blood glucose level falls to normal (90mg/100mL)

Diabetogenic effect

Causes diabetes mellitus (lack of insulin activity) by excess secretion of hGH; excessive stimulation of pancreas to secrete insulin continually - if it lasts for weeks or months can cause "beta-cell burnout," a greatly decreased capacity of pancreatic beta cells to synthesize and secrete insulin

Thyroid stimulating hormone

TSH; releasd by thyrotrophs; stimulates the synthesis and secretion of T3 and T4; Thyrotropin-releasing hormone (TRH) from the hypothalamus controls TSH secretion; high levels of T3 in blood inhibit secretion of TRH

Follicle stimulating hormone

FSH; released by gonadotrophs; initiates development of several ovarian follicles, saclike arrangements of secretory cells that surround a developing oocyte; stimulates follicular cells to secrete estrogens; stimulates sperm production; gonadotropin-releasing hormone (GnRH) from hypothalamus stimulates FSH release - suppressed by estrogens and testosterone

Luteinizing hormone

LH; released by gonadotrophs; triggers ovulation in females, the release of a secondary oocyte by an ovary; stimulates formation of the corpus luteum in the ovary and secretion of progesterone; with FSH, stimulates secretion of estrogens by ovarian cells; controlled by gonadotropin-releasing hormone (GnRH)

Estrogens

With progesterone, prepare the uterus for implantation of a fertilized ovum and help prepare the mammary glands for milk secretion

Prolactin

PRL; released by lactotrophs; initiates and maintains milk production by the mammary glands (weak effect on its own); has both inhibiting (PIH) and excitatory (PRH) hormones from hypothalamus

Lactation

Milk production by prolactin and ejection by oxytocin; oxytocin is released by posterior pituitary, while prolactin released by lactotrophs in anterior pituitary

Adrenocorticotropic hormone

ACTH; released by corticotrophs; controls production and secretion of cortisol and other glucocorticoids by the cortex of the adrenal glands; secretion stimulated by corticotropin-releasing hormone (CRH), stress-related stimuli, and interleukin-1; glucocorticoids inhibit CRH and ACTH release

Melanocyte stimulating hormone

MSH; released by corticotrophs; increases skin pigmentation in amphibians by stimulating the dispersion of melanin granules in melanocytes; little circulating MSH in humans, but we have MSH receptors in brian; stimulated by excessive CRH levels, inhibited by dopamine

Paraventricular (supraoptic) nuclei

Location in hypothalamus of cell bodies of the neurosecretory cells

Hypothalamohypophyseal tract

formed by axons of neurosecretory cells; begins in hypothalamus and ends near blood capillaries in posterior pituitary

Posterior pituitary hormones

Oxytocin and ADH (vasopressin), hormones synthesized in neuronal neurosecretory cell bodies of both the paraventricular and supraoptic nuclei; after production, packaged into secretory vesicles moved by fast axonal transport to axoon terminals in posterior pituitary, where they are stored until nerve impulses trigger exocytosis and release of the hormone

Inferior hypophyseal arteries

Supplies blood to the posterior pituitary; branches from the internal carotid arteries; in posterior pituitary, these arteries drain into the capillary plexus of the infundibular process, and then to the posterior hypophyseal veins -\> target cells in other tissue

Posterior pituitary pathway

Internal carotid arteries -\> inferior hypophyseal arteries -\> posterior pituitary -\> capillary plexus of the infundibular process -\> posterior hypophyseal veins -\> target cells in tissue

Oxytocin

Affects mother's uterus and breasts during and after delivery of a baby; stimulated by stretching of cervix of the uterus - enhances contraction of smooth muscle cells in wall of uterus; stimulates milk ejection from mammary glands in response to suckling infant; has actions with brain that foster parental caretaking behavior toward offspring

Antidiuretic hormone

ADH (vasopressin); conserves body wataer by decreasing urine production - causes kidneys to return more water to the blood; secretion inhibited by alcohol; decreases water lost by sweating and causes constriction of arterioles, which increase BP

ADH pathway

1. High blood osmotic pressure stimulates hypothalamic osmoreceptors (neurons in hypothalamus that monitor blood osmotic pressure) -\> 2. osmoreceptors activate the neurosecretory cells that synthesize and release ADH -\> 3. nerve impulses liberate ADH from axon terminals in posterior pituitary into bloodstream -\> 4. kidneys retain more water, decreases urine output -\>

5. low blood osmotic pressure inhibits hypothalamic osmoreceptors -\> 6. inhibition of osmoreceptors reduces or stops ADH secretion

Thyroid gland anatomy

30g butterfly-shaped, located inferior to larynx; composed of right and left lateral lobes (one on either side of trachea) that are connected by an isthmus anterior to trachea; small third lobe (pyramidial lobe) in some; made up of spherical sacs called thyroid follicles - wall of follicles consist of cells called follicular cells that extend to the lumen (internal space) of the follicle; basement membrane surrounds each follicle; parafollicular cells lie between follicles and produce calcitonin; only endocrine gland to STORE its secretory product in large quantities

Follicular cells

In thyroid gland; low cuboidal to squamous when inactive, cuboidal to low columnar when active; produce 2 hormones: T3 and T4

Parafollicular cells

C cells in thyroid gland; lie between follicles; produce the hormone CALCITONIN, which helps regulate calcium homeostasis

Secretion of thyroid hormones

1. Iodide trapping, 2. synthesis of thyroglubulin, 3. oxidation of iodide, 4. iodination of tyrosine, 5. coupling of T1 and T2, 6. pinocytosis and digestion of colloid, 7. secretion of thyroid hormones, 8. transport in the blood

Thyroglobulin

TGB; a large glycoprotein that is produced in the rough ER, modified in the Golgi complex, and packaged into secretory vesicles; synthesized by follicular cells when trapping iodide in thyroid gland

Colloid

The TGB (thyrooglobulin) with attached iodine atoms; forms a sticky material that accumulates and is stored in the lumen of the thyroid follicle

Thyroid hormone actions

1. Thyroid hormones increase basal metabolic rate (BMR), the rate of oxygen consumption under standard or basal conditions, by stimulating the use of cellular oxygen to produce ATP - when basal metabolic rate increases, cellular metabolism incresaese; 2. stimulate synthesis of additional Na+/K+ pumps, which use large amounts of ATP to continually eject Na+ ions from cytosol into extracellular fluid and K+ ions from extracellular fluid to cytosol; 3. stimulate protein synthesis and increase the use of glucose and fatty acids for ATP production, increase lipolysis and reduce blood cholesterol levels; 4. enhance some actions of the catecholamines ((nor)epinephrine) because they upregulate beta receptors; 5. accelerate body growth - nervous and skeletal systems - deficiency of thyroid hormones cause stunted growth

Calorigenic effect

As cells produce and use more ATP, more heat is given off, and body temperature rises; associated with thyroid gland and Na+/K+ pumps

Thyroid hormone release

1. Low blood levels of T3 and T4 or low metabolic rate stimulates release of TRH -\> 2. TRH, carried by hypophyseal portal veins to anterior pituitary, stimulates release of TSH by thyrotrophs -\> 3. TSH released into blood stimulates thyroid follicular cells -\> 4. T3 and T4 released into blood by follicular cells -\> 5. elevated T3 inhibits release of TRH and TSH

Thyroid hormone actions (summary)

1. Increase basal metabolic rate, 2. stimulate synthesis of Na+/K+ ATPase, 3. increase body temperature (calorigenic), 4. stimulate protein synthesis, 5. increase use of glucose and fatty acids for ATP production, 6. stimulate lipolysis, 7. enhance some action of catecholamines, 8. regulate development and growth of nervous tissue and bones

Calcitonin

Hormone produced by parafollicular cells of thyroid gland; can decrease level of calcium in the blood by inhibiting the action of osteoclasts, the cells that break down bone extracellular matrix; lowers amount of blood Ca2+ and phosphates by inhibiting bone resorption

Parathyroid glands

40mg, one superior and one inferior attached to each lateral thyroid lobe, so 4 total; small, round masses of tissue partially embedded in the posterior surface of the lateral lobes; contain 2 kinds of epithelial cells - chief cells and oxyphil cells

Chief cells

Principal cells; in parathyroid glands; more numerous of the 2 parathyroid epithelial cells; produces PARATHYROID HORMONE (PTH)

Oxyphil cell

1 of 2 epithelial cells in parathyroid glands; function not known, but presence helps identify parathyroid gland b/c unique staining characteristics; secrete excess PTH in a cancer of parathyroid glands

Parathyroid hormone

Produced by chief cells of parathyroid glands; major regulator of the levels of CALCIUM, magnesium, and phosphate ions in the blood; INCREASES number and activity of OSTEOCLASTS -\> elevated bone resorption -\> releases Ca2+ and phosphates into blood; also affects kidneys - slows rate at which Ca2+ is lost from blood into urine, increases loss of phosphates from blood into urine, and promotes formation of calcitriol

Calcitriol

Active form of vitamin D; increases the rate of Ca2+, phosphates, and Mg2+ absorption from the GI tract into the blood; PTH promotes formation

PTH and calcitriol pathway

1. High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT (calcitonin) -\> 2. CT inhibits osteoclasts, decreasing blood Ca2+ level -\>

3. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH -\> 4. PTH promotes release of Ca2+ from bone extracellular matrix into blood and slwos loss of Ca2+ in urine, increasing blood Ca2+ levels -\>

5. PTH also stimulates kidneys to release calcitriol, which stimulates increases absorption of Ca2+ from foods, which increases blood Ca2+ level

Adrenal glands

Lie superior to each kidney in retroperitoneal space, flattened pyramidal shape, 3.5g; two distinct regions: adrenal cortex and adrenal medulla; highly vascularized; connective tissue capsule;

Adrenal cortex

Part of adrenal glands; subdivided into 3 zones (outer to inner): zona glomerulosa, zona fasciculata, zona reticularis

Zona glomerulosa

Outer zone of adrenal cortex; has closely packed cells that secrete MINERALOCORTICOIDS - aldosterone hormone, which affects mineral homeostasis