Endocrine System

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Levels of Organization

hormones = chemical messengers of the endocrine system

amount of hormone circulating in the system is affected by:

rate of hormone production

rate of secretion from endocrine glands

rate of blood flow delivering hormone to its target cells with specific receptors

availability and number of hormone receptors

rate of biochemical degradation and elimination of the hormone

3 classes of hormones:

lipid-derived hormones

steriod hormones - primary class of lipid hormones in humans

derived from cholesterol and are structurally similar to cholesterol

e.g., estrogen and testosterone (released by reproductive organs), aldosterone and cortisol (adrenal glands)

insoluble in water so they bind to transport proteins in order to circulate through the blood

as a result, they typically stay in circulation longer than other classes of hormones

eicosanoids

derived from polyunsaturated fatty acids

typically released as paracrine signals upon stimulation and are only active for a few seconds

amino acid-derived hormones - circulation ranges from few minutes to days

thyroid hormones - derived from amino acid thyrosine

catecholamines- derived from thyrosine

epinephrine

norepinephrine

melatonin - derived from tryptophan

serotonin - derived from tryptophan

peptide hormones - short peptides (peptides are usually made up of fewer than 50 amino acids), polypeptide chains, proteins

examples

antidiuretic hormone

oxytocin

growth hormone

follicle-stimulating hormone

can be released as they're produced or stored and released in response to stimulus

most are water soluble and easily transported in blood plasma, but some bind to transport proteins

most have a half life of minutes

Control of Hormone Production

hormone production regulated by positive or negative feedback pathways

positive feedback - oxytocin during childbirth to stimulate contractions and increase pressure on cervix; increased pressure signals pituitary gland to release more oxytocin

hormone production is regulated by three mechanisms:

humoral regulation - humoral refers to body fluids such as blood and other extracellular fluids

humoral stimuli regulate release of hormones in response to specific changes in extracellular fluids, such as concentration of a particular ion or solute in the blood or even the overall solute levels in the blood

hormonal regulation -

tropic hormonal stimuli - hormone is produced and released by an endocrine gland in response to another hormone (known as "tropic hormones")

tropic - hormones that control the release of another hormone

trophic - hormones that stimulate non-endocrine cell growth and development (growth hormone, estrogen, testosterone)

neural regulation - nervous system directly stimulates endocrine glands to release hormones

Distance of hormonal signaling:

autocrine signaling - affects the cells that released the signaling molecule

paracrine signaling - affects local cells other than secreting cells

endocrine signaling - all-inclusive term including both paracrine and autocrine signaling

Hormone Receptors

receptors - hormones must bind to receptors in order to mediate changes in cells

target cell - a cell that has the receptor for a specific hormone

changes in number of receptors that respond to a hormone (can increase or decrease cell sensitivity):

up-regulation - increase in number of cell receptors (increased cellular response)

down-regulation - decrease in number of cell receptors (reduced cellular response)

receptor location:

intracellular receptors - inside the cell

hormone binds to a receptor in the cytoplasm, on the ER, or within the nucleus

the receptor/hormone complex then binds to a specific site on DNA and acts as a transcription regulator to increase or decrease the synthesis of particular mRNA molecules

this determines the amount of corresponding protein that is synthesized

plasma membrane receptors - on the cell's surface

most peptide and amino acid hormones are polar and therefore can't diffuse through plasma membrane, so they bind to plasma membrane receptors

most hormones that bind at surface receptor must remain outside the target cell; must use intermediate molecules (called second messengers) in order to exert effects on transcription

some hormones are taken into the cell by endocytosis to initiate cellular response from within vesicles

hormone that initiates the signaling pathway is known as the first messenger

G-protein-coupled receptors- class of trans-membrane cell surface proteins that can be activated by hormones or ions and other chemicals for cell signaling

inactive G-proteins bind with GDP on cytoplasmic side of cell

when a hormone binds to the cell surface receptor, the GDP is replaced by GTP

GPCR = G-protein coupled receptor

functions vary depending on the hormone receptor:

open a membrane protein channel

can stimulate movement of ions across the membranes (potassium, sodium, calcium, or chloride)

release a small molecule

activate a membrane-bound enzyme

example: adenylate cyclase - catalyzes conversion of ATP to cyclic AMP (cAMP)--second messenger, which in turn activates a class of enzymes called protein kinases; kinases transfer a phosphate group from ATP to a substrate molecule (phosphorylation), which activates the substrate molecule

reaction cascade - the chain of reactions resulting from hormone binding to GPCR

other second messengers (resulting from hormone binding to cell membrane receptor)

cyclic GMP (derived from guanosine triphosphate)

tyrosine kinases

inositol phospholipids

calcium ions

cellular responses to hormone binding to cell membrane receptor include:

membrane permeability

activating metabolic pathways

stimulating synthesis of proteins and enzymes

hormone release

binding of a hormone at a single cell membrane receptor causes the activation of many G-proteins, which can catalyze many reactions simultaneously

effect of a peptide hormone is amplified as the signaling cascade progresses

small amount of hormone can trigger the formation of a large amount of cellular product

hormone activity is stopped when the cascading chemical reaction is interrupted

example: cAMP is deactivated by cytoplasmic enzyme phosphodiesterase (PDE); PDE is always present in the cell and breaks down cAMP spontaneously, preventing overproduction of cellular products

Pituitary Gland & Hypothalamus

pituitary-hypothalamus axis - links nervous system with endocrine system

hypothalamus - coordinates signals from internal organs and other regions of the brain and regulates a response from the endocrine system via the pituitary

secretes releasing hormones (stimulate the anterior pituitary to secrete a hormone)

secretes inhibiting hormones (inhibit release of a hormone from the anterior pituitary)

pituitary gland - pea-sized gland at base of brain attached to the hypothalamus via a stalk called the infundibulum

regulated primarily by nerve impulses or hormones released by neurosecretory cells of the hypothalamus

releases hormones based on these signals that either have a direct effect on target cells or regulate hormone production by other endocrine glands (tropic hormones)

two distinct regions:

anterior pituitary (adenohypophysis) - secretes 7 different peptide or protein hormones

growth hormone (GH)

prolactin (PRL)

thyroid-stimulating hormone (TSH) - tropic hormone

adrenocorticotropic hormone (ACTH) - tropic hormone

follicle-stimulating hormone (FSH) - tropic hormone

luteinizing hormone (LH) - tropic hormone

melanocyte stimulating hormone (MSH)

posterior pituitary - releases hormones produced by the hypothalamus

antidiuretic hormone (ADH) - also known as vasopressin

oxytocin

these regions do not look visibly different externally, but on a cellular and tissue level, they are quite distinct

Anterior Pituitary

anterior pituitary = adenohypophysis ("adeno" refers to gland)

surrounded by capillary network, which is part of the hypophyseal portal system that carries substances from the hypothalamus directly to the anterior pituitary

portal systems - move material from one capillary bed to another without returning it to the main circulation

production of hormones in the anterior pituitary is controlled by regulatory hormones produced by hypothalamus

negative feedback mechanisms regulate how much of the regulatory hormones are released and how much anterior pituitary hormone is secreted

Posterior Pituitary

contains mostly axons of secretory neurons and neuroglial cells

cell bodies of these neurons are located in the hypothalamus

posterior pituitary + infundibulum = neurohypophysis

does not produce hormones itself, but stores hormones produced by the hypothalamus (antidiuretic hormone and oxytocin) and releases them into the bloodstream

ADH and oxytocin produced by neurons in hypothalamus and transported within these axons along the infundibulum to the posterior pituitary

ADH and oxytocin are released into posterior pituitary capillaries in response to neural signaling from the hypothalamus

Thyroid Gland

composed of two lobes connected by the isthmus

main function: synthesis and storage of thyroid hormones involved in maintaining metabolic homeostasis

made up of spherical thyroid follicles lined with simple cuboidal epithelium

colloid - viscous fluid inside follicles

thyroglobulin - a glycoprotein that is stored in the colloid; precursor to the two thyroid hormones; not normally released into circulation unless the thyroid gland is damaged

iodide molecules are added to thyroglobulin to produce 2 hormones:

thyroxine (T4) - has 4 iodine atoms

triiodothyronine (T3) - has 3 iodine atoms

iodide ions are actively transported into the follicular lumen from the capillaries by follicle cells

parafollicular cells - located between adjacent follicles and produce calcitonin (involved in blood calcium homeostasis)

parafollicular cells (C cells) - produce calcitonin

calcitonin released when blood calcium ion concentrations increase

calcium ions bind to a receptor on C cells that stimulate release of calcitonin

lowers blood calcium levels in children when levels get too high

causes decreased tubular reabsorption of Ca2+ in the kidneys, leading to calcium loss in the urine

inhibits bone resorption activity of osteoclasts

inhibits calcium absorption in intestine

suspected to have an indirect effect in stimulating osteoblast activity and development

plays a minor role in adult calcium homeostasis

may play a role during times of high calcium demands, such as pregnancy and lactation

stores large amounts of some of the hormones it synthesizes (unlike most endocrine glands)

follicle cells are stimulated to release stored T3 and T4 from the lumen into blood capillaries by thyroid stimulating hormone (TSH), which is produced in the anterior pituitary

follicle cells are also stimulated by TSH to begin synthesizing more T3 and T4

Parathyroid Glands

the 4 parathyroid hormones are located on the posterior surface of the thyroid gland (exact number and location can vary from person to person)

named for their proximity to the thyroid gland ("para" means next to), but their cells are distinct from those of the thyroid gland

each gland is covered by connective tissue

chief cells - secretory cells located in each parathyroid gland

synthesize and secrete parathyroid hormone (PTH)

oxyphil cells - another type of cell in the parathyroid but are not clearly understood; appear to increase during renal failure

PTH - maintains blood calcium levels by increasing blood calcium levels when calcium ion levels fall below normal

calcium ions bind to receptors on chief cells to inhibit release of PTH

when blood calcium levels are low, calcium ions don't bind to chief cells and this stimulates release of PTH

PTH stimulates reabsorption of calcium from filtrate during urine formation, increased absorption in the intestines from digested products, and increased activity of osteoclasts to release calcium (and phosphate) from bone matrix into the plasma

may indirectly inhibit osteoblast activity

parathyroid adenoma - benign tumor of parathyroid gland that can cause an overproduction of PTH leading to hyperparathyroidism; usually only one of the glands is affected and can be removed without any adverse effects -- removal of all parathyroid glands would cause an imbalance in blood calcium levels and lead to death

hyperparathyroidism - results in hypercalcemia, which can lead to kidney stones; increased rate of bone resorption may also lead to osteoporosis

Adrenal Glands

functions of adrenal glands:

regulate body's response to stress

control blood pressure

maintain the body's water, sodium, and potassium levels

located on the superior surface of each kidney (which is why they're also called suprarenal glands)

consists of:

outer adrenal cortex (cortex means outer layer)

composed of endocrine cells

produces steroid hormones

inner adrenal medulla (medulla means middle)

composed of neurosecretory cells

produces catecholamine hormones

Adrenal Cortex

made up of layers of epithelial cells and associated capillary networks

layers form 3 distinct regions that secrete different steroid hormones:

zona glomerulosa - outer layer; produces mineralocorticoids (influence salt and water balance)

aldosterone - regulates concentration of ions in urine, sweat, and saliva; release of this hormone can be triggered by a number of things, including a decrease in blood concentrations of sodium ions, blood volume, or blood pressure, or an increase in blood potassium levels

zona fasciculata - middle layer; produces glucocorticoids (impact metabolism and inflammation)

3 main hormones:

cortisol

corticosterone

cortisone

stimulate synthesis of glucose from non-glycogen sources

promote release of fatty acids from adipose tissue

increase blood glucose levels to maintain levels within a normal range between meals

secreted in response to ACTH (adrenocorticotropic hormone)

zona reticularis - inner layer; produces androgens (regulate catabolism and sexual characteristics)

androstenedione - intermediary molecule in synthetic pathway of the following (and other) steriod hormones:

testosterone

progesterone - gets converted to testosterone in post-menopausal women

estrogen

Adrenal Medulla

inner layer of the adrenal glands

contains chromaffin cells - large, irregularly shaped cells that are closely associated with blood vessels

innervated by autonomic (involuntary) nerve fibers from CNS, which allow for quick hormone release

produce two hormones:

epinephrine (adrenaline)

primary hormone, accounting for 75-80% of secretions

norepinephrine (noradrenaline)

both hormones increase heart rate, breathing rate, cardiac muscle contractions, and blood glucose levels; accelerate breakdown of glucose in skeletal muscles and stored fats in adipose tissue

both are stored in vesicles or granules in the adrenal medulla

release of epinephrine and norepinephrine into blood is stimulated by neural impulses from the sympathetic nervous system

nerve impulses originate from the hypothalamus in response to stress to prepare body for fight-or-flight response

adrenal glands have a large blood supply from renal, phrenic, and suprarenal arteries; arterial blood enters at the adrenal cortex and drains into venules in the adrenal medulla

Pineal Gland

consists of secretory cells (pinealocytes)

pinealocytes secrete melatonin

melatonin is derived from serotonin a is regulated in response to light and dark (diurnal cycle)

retinas of eyes detect photons (packets of light), which initiates a nerve impulse that is detected by the pineal gland

target cells for melatonin located in suprachiasmatic nucleus (SCN) of brain

SCN functions as a biological clock that regulates the sleep-wake cycle, appetite, and body temperature

Pancreas

pancreas plays a central role in energy metabolism, storage, and utilization of glucose

contains both exocrine cells (excrete digestive enzymes) and endocrine cells (release hormones)

99% of pancreatic cells are exocrine cells arranged around ducts in clusters called acini

pancreatic islets (islets of Langerhans) - clusters of endocrine cells that have associated capillaries

contain two main cell types:

alpha cells - produce hormone glucagon (when blood glucose levels decline below set point)

causes breakdown of glycogen in liver

causes gluconeogenesis in liver from amino acids

causes enhanced lipolysis

beta cells - produce hormone insulin (when blood glucose levels rise)

causes glucose uptake into fat and muscle

causes glycogen synthesis in liver and muscle

causes glucose synthesis in the liver

two minor cell types:

delta cells - secrete somatostatin

F (PP) cells - secrete pancreatic polypeptide (after a high protein meal or fasting), which inhibits pancreatic exocrine secretion and stimulates gastric juice secretion, as well as stimulates both alpha and beta cells

Gonads

testes in males and ovaries in females

function in the production of gametes (sperm and ovum) and steroid hormones

testes

produce androgen (most prominently testosterone)

testosterone stimulates development of male secondary sex characteristics and production of sperm cells

also produce the hormone inhibin

inhibits release of tropic hormone follicle-stimulating hormone (FSH) from anterior pituitary needed for development of sperm (spermatogenesis)

ovaries

produce estrogen and progesterone, which stimulate development of female secondary sex characteristics, regulate menstrual cycle, and prepare body for childbirth

also produce inhibin, which inhibits release of FSH

placenta - endocrine organ that supplies necessary nutrients to the fetus

synthesizes and secretes hormones crucial for the maintenance of pregnancy

includes human chorionic gonadotropin hormone (hCG) - used in pregnancy tests

placenta takes over the production of estrogen and progesterone during pregnancy

high level of estrogen facilitates growth of the uterus and mammary glands

progesterone suppresses maternal immune response to fetus and inhibits uterine smooth muscle contraction

produces relaxin - affects collagen metabolism and softens the public symphysis to facilitate birthing

produces lactogen - role still being investigated

Overview of Endocrine Glands/Hormones

anterior pituitary

growth hormone - promotes growth of body tissues

prolactin - promotes milk production

thyroid-stimulating hormone (TSH) - stimulates thyroid hormone release

adrenocorticotropic hormone (ACTH) - stimulates hormone release by adrenal cortex

follicle-stimulating hormone (FSH) - stimulates gamete production

luteinizing hormone (LH) - stimulates androgen/estrogen production by gonads

posterior pituitary

antidiuretic hormone (ADH) or vasopressin - stimulates water reabsorption by kidneys

oxytocin - stimulates uterine contractions during childbirth

thyroid

thyroxine (T4) and triiodothyronine (T3) - stimulate metabolism

calcitonin - reduces blood Ca2+ levels, primarily in children

parathyroid

parathyroid hormone (PTH) - increases blood Ca2+ levels

adrenal cortex

aldosterone - increases blood Na+ levels and related water conservation by kidneys; decreases blood K+ levels

cortisol, corticosterone, and cortisone - increase blood glucose levels

adrenal medulla

epinephrine and norepinephrine - stimulate fight-or-flight response

pineal

melatonin - regulates sleep cycles

pancreas

glucagon - increases blood glucose levels

insulin - decreases blood glucose levels

testes

testosterone - stimulates development of male secondary sex characteristics and sperm production

inhibin - inhibits secretion of FSH

ovaries

estrogen and progesterone - stimulate development of female secondary sex characteristics, egg production, and preparation of the body for childbirth

inhibin - inhibits secretion of FSH

Organs w/ Secondary Endocrine Function

heart and cardiovascular system

specialized cardiac muscle cells in walls of atria are endocrine cells that respond to increased blood volume by releasing the hormone atrial natriuretic peptide (ANP)

high blood volume causes cells to stretch and open stretch-activated membrane channels, resulting in hormone release

ANP acts on kidneys to reduce reabsorption of Na+, causing Na+ and water to be excreted in the urine

ANP also reduces amount of renin released by the kidneys and aldosterone released by the adrenal cortex, further preventing retention of water

By doing this, ANP reduces Na+ concentration in blood and causes reduction in blood volume and blood pressure

BNP (brain natriuretic peptide) released from heart ventricle enhances the effect of ANP

endothelial cells lining cardiovascular system produce paracrine hormones:

endothelin (vasodilator and stimulator of ANP secretion)

nitric oxide (vasodilator and inhibitor of ANP secretion)

digestive system

endocrine cells located in mucosa of GI tract throughout stomach and small intestine

hormone secretion is controlled by receptors monitoring chemical content

hormones that trigger release of digestive juices that help break down and digest food:

gastrin - stomach

secretin

cholecystokinin CCK - small intestine

hormones secreted in response to glucose in the intestinal lumen:

glucose-dependent insulinotropic peptide (GIP) - stomach

glucagon-like peptide 1 (GLP-1) - small intestine

GIP and GLP-1 target cells are beta cells in the pancreas, which are stimulated to release insulin, and alpha cells that are inhibited from releasing glucagon

stomach produces ghrelin (mediates hunger, stimulating appetite and growth hormone release)

liver produces:

insulin-like growth factor (IGFs) - work with growth hormone to regulate cell metabolism

thrombopoietin (THPO) - triggers formation of platelets in the blood

prohormones - angiotensinogen and calcidiol (vitamin D)

plasma proteins that transport many of the hormones

kidneys and urinary system

renin - released in response to decreased blood volume or pressure

part of the renin-angiotensin system responsible for formation of angiotensin II and ultimately leads to release of aldosterone

angiotensin II and aldosterone cause retention of Na+ and water, raising blood volume

calcitriol - aids in absorption of Ca2+

erythropoietin (EPO) - protein hormone that triggers formation of red blood cells in bone marrow

released in response to low oxygen levels to increase oxygen delivery throughout the body

adipose tissue

leptin - produced in response to food intake

binds to neuropeptide Y in the CNS neurons, producing feeling of satiety after eating

skin

cholecalciferol - inactive hormone form of vitamin D3 produced when cholesterol molecules in the skin are exposed to UV radiation; modified by liver to form calcifediol; modified by kidneys to form calcitriol

bone

osteocytes produce two hormones (fibroblast growth factor 23 and osteocalcin) that act on kidney, pancreas, and other body tissues influencing Vitamin D and glucose homeostasis

thymus

part of the immune system involved in maturation and immunocompetence of T-lymphocytes

produces thymosins - have an anti-inflammatory effect and stimulate tissue repair; involved in neuroplasticity

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Homeostasis & Integration of Systems

Fluid Balance

ADH - hormone produced by the hypothalamus and secreted by the posterior pituitary

osmoreceptors - receptors in the hypothalamus that detect the concentration of electrolytes in the blood

electrolyte concentration increases when body loses water through perspiration, inadequate water intake, or blood loss

when electrolyte levels increase, osmoreceptors send a neural signal to the hypothalamus

hypothalamus produces ADH (vasopressin) and transports it to the posterior pituitary where it is released

target cells = distal tubule cells in the kidneys, which are stimulated to absorb more water from urine, which results in an increase in the water level in the blood and urine becomes more concentrated

diabetes insipidus - results from chronic underproduction of ADH

if posterior pituitary does not release enough ADH, water cannot be retained by the kidneys and is therefore eliminated in the urine

results in increased thirst, but because water is lost, water must be continually consumed

severe cases can lead to electrolyte imbalances due to dehydration

aldosterone - steroid hormone produced by the adrenal cortex

maintains proper water balance by enhancing Na+ reabsorption from extracellular fluids

aldosterone is an example of a mineralocorticoid (affects concentrations of minerals)

release is stimulated by decrease in blood Na+ levels, blood volume, or blood pressure, or an increase in blood K+ levels

blood pressure - cells in juxtaglomerular apparatus of kidney detect drop and release renin

renin - reacts with a protein in the liver called angiotensinogen, producing angiotensin I, which is then converted to angiotensin II

angiotensin II impacts water and Na+ reabsorption and causes the release of aldosterone by the adrenal cortex

together with aldosterone, these increase blood pressure

angiotensin also causes an increase in ADH and increased thirst, which both help to increase fluids and raise blood pressure

targets renal tubules of kidneys, where it causes reabsorption of Na+ from urine and secretion of K+ into urine

prevents loss of Na+ from sweat, saliva, and gastric juice

reabsorption of Na+ results in osmotic reabsorption of water, which alters blood volume and blood pressure

Reproductive System

General

reproductive system regulated by hormones in 3 glands:

pituitary gland

adrenal cortex

gonads

puberty - hypothalamus produces gonadotropin-releasing hormone (GnRH) -> stimulates release of FSH and LH

gonadotropins - hormones that regulate the gonads (FSH and LH)

FSH - stimulates gamete production

LH - stimulates production of hormones by the gonads

negative feedback loop - increase in gonad hormone levels inhibits GnRH production

Male reproductive system

FSH and LH regulate maturation of sperm cells

FSH stimulates support cells -- Sertoli (sustentacular) cells -- in testes

Sertoli cells

nourish and regulate maturation of sperm

produce androgen binding hormone (ABP)

ABP - keeps level of testosterone high within the testes relative to plasma levels

also release inhibin, which inhibits FSH production

LH stimulates production of sex hormones (androgens) by interstitial or Leydig cells of the testes, which is why LH is also called interstitial cell-stimulating hormone (ICSH)

testosterone - most important androgen in males

promotes production and maturation of sperm and determines secondary sex characteristics

adrenal cortex in males & females also produces small amounts of testosterone

Female reproductive system

FSH stimulates development of support cells around the egg, which develop into structures called follicles

LH regulates the development and release of the egg from the follicle

Follicle cells initially produce estrogen (which has effects on hypothalamus, anterior pituitary, and uterus)

LH stimulates egg to mature within the growing follicle

as estrogen levels rise, it triggers the anterior pituitary to release a surge of LH that stimulates ovulation

follicle cells become the corpus luteum and produce estrogen, progesterone, and inhibin, all of which inhibit the anterior pituitary

estrogen and progesterone prepare the body for pregnancy and regulate the uterine menstrual cycle

estrogen produces secondary sex characteristics in females

Childbirth

prolactin (PRL) produced in anterior pituitary - stimulates production of milk in mammary glands after childbirth

PRL levels are regulated by hypothalamic hormones prolactin-releasing hormone (PRH) and prolactin-inhibiting hormone (PIH) (also known as dopamine)

normally PRL production is inhibited, but PRH + estrogen + infant suckling stimulation removes the inhibition

males can produce small amounts of PRL

oxytocin produced by posterior pituitary - stimulates contractions during childbirth

uterine smooth muscles aren't very sensitive to oxytocin until late in the pregnancy when # of oxytocin receptors peaks

stretching of uterine and vaginal tissues stimulates oxytocin release in childbirth

contractions increase in intensity as blood levels of oxytocin rise until birth is complete

also stimulates contraction of myoepithelial cells around milk-producing cells of mammary glands, which forces milk from secretory alveoli into milk ducts and is ejected from the breasts in a milk let-down reflex

oxytocin release is stimulated by the suckling of an infant, which triggers synthesis of oxytocin in the hypothalamus and its release into circulation at the posterior pituitary

Metabolism

insulin and glucagon are the two hormones primarily responsible for homeostasis of blood glucose levels; additional regulation through thyroid hormones

insulin (produced by beta cells in pancreas) released when blood glucose levels rise

enhances glucose uptake by most target body cells, which utilize glucose for ATP production

stimulates liver to convert glucose to glycogen, which is stored for later use

insulin-mediated increase in # of glucose transporter proteins in cell membranes allows cells to increase their glucose uptake

stimulates conversion of glucose to fat in adipocytes

stimulates synthesis of proteins

hypoglycemic effect - actions of insulin which cause blood glucose concentrations to fall

negative feedback loop - drop in blood glucose inhibits further insulin release

diabetes mellitus - caused by decreased insulin production or reduced sensitivity of cells to insulin

prevents glucose from being absorbed by cells, causing high levels of blood glucose (hyperglycemia)

high blood glucose levels make it hard for kidneys to reabsorb all the filtered glucose, which means glucose is lost in the urine

leads to increased water loss in urine because water is retained in urine to osmotically balance high levels of excess glucose

increased urination may lead to dehydration

high blood glucose levels can cause nerve damage to eyes and peripheral body tissues over time, as well as damage to the kidneys and cardiovascular system

hypoglycemia - caused by over-secretion of insulin leading to low blood glucose levels; leads to muscle weakness and can sometimes cause unconsciousness or death if untreated

glucagon (produced by alpha cells of pancreas) is released when blood glucose levels fall below normal (usually between meals or when glucose is used rapidly during exercise)

raises blood glucose levels (hyperglycemic effect) by stimulating breakdown of glycogen to glucose in skeletal muscle cells and liver cells

glycogenolysis (glycogen-splitting)

stimulates absorption of amino acids from the blood by the liver, which then converts them to glucose

gluconeogenesis (new glucose formation)

stimulates adipose cells to release fatty acids into the blood

thyroid hormones

basal metabolic rate (amount of calories required by the body at rest) is determined by T3 and T4

cross plasma membranes of target cells and bind to receptors on mitochondria, resulting in increased ATP production

T3 and T4 also activate genes in the nucleus involved in energy production and glucose oxidation

calorigenic effect - increased rate of metabolism and body heat production

hypothyroidism - under activity of thyroid hormones causes low metabolic rate, which leads to weight gain, sensitivity to cold, and reduced mental activity

in children, can cause cretinism, which causes mental retardation and growth defects

hyperthyroidism - over activity of thyroid hormones causes increased metabolic rate, causing weight loss, excess heat production, sweating, and an increased heart rate

goiter - thyroid enlargement caused by absence of iodine, which means thyroid hormones cannot be produced and colloid storage increases

Blood Calcium Homeostasis

regulation of blood calcium concentration is important for proper muscle contractions and release of neurotransmitters; calcium also affects voltage-gated plasma membrane ion channels

when plasma calcium levels are too high, membrane permeability to sodium decreases and membranes become less responsive

when plasma calcium levels are too low, membrane permeability to sodium increases and convulsions or muscle spasms can result

PTH (produced by parathyroid gland) regulates blood calcium levels

released in response to low blood Ca2+ levels

PTH increases Ca2+ levels by targeting the skeleton, kidneys, and intestine

skeleton - stimulates osteoclasts to break down bone and release Ca2+ into the blood and inhibits osteoblasts to reduce bone deposition

kidneys - stimulates kidneys to increase Ca2+ reabsorption

intestine - stimulates formation of calcitriol (active form of vitamin D), which acts on intestines to increase absorption of dietary calcium

inhibited by rising blood calcium levels

hyperparathyroidism - results from overproduction of PTH; results in excessive calcium being removed from bones and being introduced into blood circulation; causes structural weakness of bones and nervous system impairment (due to high blood Ca2+ levels)

hypoparathyroidism - underproduction of PTH; results in extremely low levels of blood calcium; causes impaired muscle function and may result in tetany (severe sustained muscle contraction)

calcitonin (produced by parafollicular cells (C cells) of thyroid)

decreases blood Ca2+ levels by inhibiting osteoclasts, stimulating osteoblasts, and stimulating calcium excretion by kidneys

results in calcium being added to bones to promote structural integrity

appears to play a major plasma calcium homeostasis role in children and in pregnant women to reduce maternal bone loss

Growth

GH accelerates the rate of protein synthesis, particularly in skeletal muscle and bones

direct mechanisms of action

stimulates fat breakdown (lipolysis) and release into blood by adipocytes, resulting in switch by most tissues from using glucose as an energy source to utilizing fatty acids (glucose-sparing effect)

glucose-sparing effect - switch to utilizing fatty acids instead of glucose for energy

stimulates glycogen breakdown in liver and release of glucose into the blood

blood glucose levels increase as most tissues are metabolizing fatty acids instead of glucose

diabetogenic effect - GH-mediated increase in blood glucose levels

indirect mechanisms of action

insulin-like growth factors (IGFs) - family of growth-promoting proteins produced by liver

IGFs stimulate uptake of amino acids from the blood, allowing the formation of new proteins, particularly in skeletal muscle, cartilage, and other target cells

GH release stimulated by GHRH and inhibited by GHIH produced by hypothalamus

gigantism - oversecretion of GH in children causing excessive growth

acromegaly - oversecretion of GH in adults causing bones still capable of growth (face, hands, and feet) to enlarge

pituitary dwarfism - results from underproduction of GH in children

Stress

hypothalamus regulates stress response

short-term stress - hypothalamus signals adrenal medulla via nerve impulses

adrenal medulla releases catecholamines (epinephrine and norepinephrine)

these hormones increase blood glucose levels by stimulating the liver and skeleton muscles to breakdown glycogen and by stimulating glucose release by liver cells

increase oxygen availability by increasing heart rate and dilating the bronchioles

increase bloody supply to essential organs such as the heart, brain, and skeletal muscles by stimulating certain blood vessels to relax or by constricting other blood vessels to divert blood away from nonessential organs such as skin, digestive system, and kidneys

long-term stress - hypothalamus signals adrenal cortex via ACTH

stimulates release of corticosteroids

glucocorticoids (cortisol, cortisone, and corticosterone)

affect glucose metabolism by stimulating glucose synthesis

stimulate redistribution of fat stored in adipose tissue for use in meeting long-term energy requirements

anti-inflammatory properties through inhibition of immune system

mineralocorticoids (aldosterone)

stimulates reabsorption of water and sodium ions in the kidneys, which results in increased blood pressure and volume

Cushing's disease - hypersecretion of glucocorticoids unrelated to normal stress response

causes accumulation of adipose tissue in the face and neck and excessive glucose in the blood

Addison's disease - hyposecretion of corticosteroids unrelated to normal stress response may result in low blood sugar levels and low electrolyte levels