Endocrine system controls and regulates:

• Reproduction
• growth and development
• maitnence of electrolyte, water and nutrient balance of blood
• requlation of cellular metabolism and energy balance
• mobolization of body defences

Exocrine glands

Produce no hormonal substances

ex: sweat and saliva

• have ducts to carry secretion to membrane surface

Endocrine glands

Produce hormones and lack ducts

Endocrine glands

• Pituitary glands
• thyroid glands
• parathryroid glands
• adrenal glands
• pineal glands

Neuroendocrine

The hypothalamus is a _______ organ

Pancreas, gonads and placenta

have both endocrine and exocrine functions

Produce hormones

Adipose cells, thymus, and cells in walls of small intestine, stomach, kidneys and heart

Hormones

Long-distance chemical signals; travel in blood or lymph

Autocrines

Chemicals that exert effects of same cells that secrete them

Paracrines

Locally acting chemicals that affect cells other than those that secrete them

Local

Autocrines and Paracrines are ____ chemical messengers

Amino-acid-based and steroids

Two main classes of hormones

Amino-acid-based hormones

Amino acid derivatives p, peptides and proteins

Steroids

gonadal and adrenocortical hormones

Cholesterol

Steroid hormones are synthesized from

Eicosanoids

Possible third class of hormones; considered a hormones by some but most classify it as a Paracrine

Circulate systemically

Though hormones ______ _______, only cells with receptors for that hormones are affected.

Target cells

Tissues with receptors for a specific hormone

Hormones

______ alter target cell activity

Hormones action on target cells may be to:

• Alter plasma membrane permeability and/or membrane potential by opening or closing ion channels
• stimulate synthesis of enzymes or other protiens
• activate or deactivate enzymes
• induce secretory activity
• stimulate mitosis

Chemical nature and receptor location

Hormones act in one of two ways depending on what?

Water-soluble hormones

• All amino acid-based hormones except thyroid hormones
• act on plasma membrane receptors
• actvia G protein second messengers
• cannot enter cell

Lipid-soluble hormones

• Steroid and thyroid hormones
• act on intacellular receptors that directly activate genes
• can enter cell

Second messenger systems

Amino acid based hormones,except thyroid hormone, exert effects through ____ ___ ___.

Two main:

• Cyclic AMP
• PIP₂ -calcium

Cyclic AMP (cAMP) signaling mechanism

• Phosphorlyated protiens are then either activated or inactivated
• cAMP is rapjdly degraded by enzyme phosphodiesterase, stomping cascade
• cascades have huge amplification effect

PIP₂ -calcium signaling mechanism

• Hormone-activated G protein activates a different effector enzyme: phospholipase C
• activated phospholipase C splits membrane protein, PIP₂, into two second messengers:

1. diacylglycerol (DAG) activates protein kinases
2. inositol trisphosphate (IP₃) causes Ca²⁺ release from intracellular storage sites

PIP2 -calcium signaling mechanism

• Calcium ions act as another second messenger
• Ca2+ alters enzyme activity and channels, or binds to regulatory protein calmodulin
• Calcium-bound calmodulin activates enzymes that amplify cellular

Intacellular receptors

Lipid-soluble steroid hormones and thyroid hormone can diffuse into target cells and bind with

DNA

Receptor-hormone complex enters nucleus and binds to specific region of

mRNA

Helps initiate DNA transcription to produce

Protein

mRNA is then translated into specific _____
- Proteins synthesized have various functions
-Examples: metabolic activities, structural purposes, or exported from cell

Negative feebback systems

Blood levels of hormones are controlled by ______

• Increased hormone effects on target organs can inhibit further hormone release
• Levels vary only within narrow, desirable range

Hormone

_____ release is triggered by:
Endocrine gland stimuli
Nervous system modulation

Endocrine glands

_______ are stimulated to synthesize and release hormones in response to one of three stimuli:

• Humoral stimuli
• Neural stimuli
• Hormonal stimuli

Humoral (humor - fluid) stimuli

Changing blood levels of ions and nutrients directly stimulate secretion of hormones

• Example: Ca2+ in blood
  - Declining blood Ca2+ concentration stimulates parathyroid glands to secrete PTH (parathyroid hormone)
  - PTH causes Ca2+ concentrations to rise, and stimulus is removed

Neural stimuli

Nerve fibers stimulate hormone release

• Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines

Hormonal stimuli

Hormones stimulate other endocrine organs to release their hormones

Hypothalamic hormones

stimulate release of most anterior pituitary hormones

Anterior pituitary hormones

stimulate targets to secrete still more hormones

Hypothalamic-pituitary-target

Endocrine organ feedback loop

Anterior pituitary

Hormones from final target organs inhibit release of ______ ______ hormones

Nervous system

can make adjustments to hormone levels when needed
- Can modify stimulation or inhibition of endocrine glands

-can override normal endocrine controls

"Fight or flight"

Nervous system prepares body for ________

Increase

Under severe stress, hypothalamus and sympathetic nervous system override insulin to allow blood glucose levels to ______

Target cells

______ must have specific receptors to which hormone binds
- Example: ACTH receptors are found only on certain cells of adrenal cortex, but thyroxin receptors are found on nearly all cells of body

Target cell activation

_____ ____ ______ depends on three factors:
1. Blood levels of hormone
2. Relative number of receptors on/in target cell
3. Affinity (strength) of binding between receptor 
 and

Up-regulation

target cells form more receptors in response to low hormone levels

Down-regulation

target cells lose receptors in response to high hormone levels
- Desensitizes the target cells to prevent them from overreacting to persistently high levels of hormone

Hormones

______ circulate in blood either free or bound

Concentration of circulating hormone reflects:
- Rate of release
- Speed at which it is inactivated and removed from body

Plasma protiens

Steroids and thyroid hormone are attached to _______.

- All others circulate without carriers

Removed

Hormones can be _______ from blood by:

- degrading enzymes

- kidneys

- liver

Half-life

Time required for level of hormone in blood level to decrease by half

- varies anywhere from fraction of a minute to a week, depending on hormone.

Response times

Hormones have different ______ ___ :

-Some responses are immediate

-Some, especially steroid, can take hours to days

- Some are inactive until they enter target cells

Limited

The duration of response is usually ______:
- Ranges from 10 seconds to several hours
- Effects may disappear rapidly as blood levels drop, but some may persist for hours at low blood levels

Water or lipid soluble

Half-life, onset, and duration of hormone activity are dependent on whether the hormone is ____ or ____ _____

Permissiveness

one hormone cannot exert its effects without another hormone being present
- Example: reproductive hormones need thyroid hormone to have effect

Synergism

more than one hormone produces same effects on target cell, causing amplification
- Example: glucagon and epinephrine both cause liver to release glucose

Antagonism

one or more hormones oppose(s) action of another hormone
- Example: insulin and glucagon

Infundibulum

Hypothalamus is connected to pituitary gland (hypophysis) via stalk called

Has two major lobes:

- Posterior Pituitary

- Anterior Pituitary

Eight

The pituitary glands secrete at least __ major hormones.

Posterior

______ pituitary: composed of neural tissue that secretes neurohormones

Neurohypophysis

Posterior lobe, along with infundibulum make up the

Anterior

______ pituitary: (adenohypophysis) consists of glandular tissue

hypothalamic-hypophyseal tract

Posterior lobe is neural tissue derived from a down growth of the hypothalamus
- Maintains neural connection to hypothalamus via ______-______ tract
- Tract arises from neurons in paraventricular and supraoptic nuclei in hypothalamus
- Runs through infundibulum

Neurohormone

Stores and secretes two _______ (oxytocin and ADH)
- Hormones are stored in axon terminals in posterior pituitary and are released into blood when neurons fire
- ________ a hormone produced by nerve cells and secreted into the circulation

glandular

Anterior lobe is _____ tissue derived from an outpocketing of oral mucosa

hypophyseal portal system

Anterior lobe:

• Vascularly connected to hypothalamus via ____ _____ _____ consisting of:
  - Primary capillary plexus
  - Hypophyseal portal veins
  - Secondary capillary plexus

Hypothalamus

______ secretes releasing and inhibiting hormones to anterior pituitary to regulate hormone secretion

Hypothalmic

Posterior pituitary consists of axon terminals of neurons from ______ neurons:

Oxytocin

Paraventricular neurons produce ______

Supraoptic

_____ neurons produce antidiuretic hormone (ADH)

Nine

Oxytocin and ADH
- Each composed of ____ amino acids
- Almost identical but differ in two amino acids

Oxytocin

- Strong stimulant of uterine contractions released during childbirth
- Also acts as hormonal trigger for milk ejection
- Both are positive feedback mechanisms
- Acts as neurotransmitter in brain
-Uses PIP2-calcium second messenger system

Antidiuretic hormone (ADH)

- Hypothalamus contains osmoreceptors that monitor solute concentrations
- If concentration too high, posterior pituitary triggered to secrete ADH
- Targets kidney tubules to reabsorb more water to inhibit or prevent urine formation
-Release also triggered by pain, low blood pressure, and drugs
-Inhibited by alcohol, diuretics
-High concentrations cause vasoconstriction, so also called

Osmoreceptors

Hypothalamus contains ___ that monitor solute concentrations

Vasopressin

High concentrations cause vasoconstriction, so also called

Antidiuretic hormone (ADH)

Inhibited by alcohol, diuretics

Urine formation

ADH targets kidney tubules to reabsorb more water to inhibit or prevent _____

Diabetes insipidus

- ADH deficiency due to damage to hypothalamus or posterior pituitary
- Must keep well hydrated

Syndrome of inappropriate ADH secretion (SIADH)

-Retention of fluid, headache, disorientation
- Fluid restriction; blood sodium level monitoring

Peptide

Anterior pituitary: All six hormones are _____ hormones.

Anterior Pituitary Hormones

• All except growth hormone (GH) activate target cells via cAMP second-messenger system
• Four are tropic hormones (tropins) that regulate secretion of other hormones
  - Growth hormone (GH)
  - Thyroid-stimulating hormone (TSH) (tropic)
  - Adrenocorticotropic hormone (ACTH) (tropic)
  - Follicle-stimulating hormone (FSH) (tropic)
  - Luteinizing hormone (LH) (tropic)
  - Prolactin (PRL

tropic hormones (tropins)

- Thyroid-stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
- Follicle-stimulating hormone (FSH)
- Luteinizing hormone (LH)

Growth hormone (GH)

- Also called somatotropin as it is produced by somatotropic cells
- Has direct actions on metabolism and indirect growth-promoting actions

Decrease

Anterior pituitary hormones Direct actions on metabolism:
Glucose-sparing actions ______ rate of cellular glucose uptake and metabolism (anti-insulin effects)

Break down

Anterior pituitary hormones Direct actions on metabolism:
Triggers liver to ____ _____ glycogen into glucose

cellular protein synthesis

Anterior pituitary hormones Direct actions on metabolism:
- Increases blood levels of fatty acids for use as fuel and encourages _____ ______ _____

Indirect actions on growth

• GH triggers liver, skeletal muscle, and bone to produce insulin-like growth factors (IGFs)
• IGFs then stimulate:
  - Cellular uptake of nutrients used to synthesize DNA and proteins needed for cell division
  - Formation of collagen and deposition of bone matrix
• GH stimulates most cells to enlarge and divide, but major targets are bone and skeletal

Hypothalamic

Regulation of secretion:
GH release or inhibition regulated by _______ hormones

Releasing / R

Growth hormone–________ hormone (GH_H) stimulates GH release
-Triggered by low blood GH or glucose, or high amino acid levels

Inhibiting / I

Growth hormone–________ hormone (GH_H) (somatostatin) inhibits release
- Triggered by increase in GH and IGF levels

Ghrelin

_____ (hunger hormone) also stimulates GH release

Hypersecretion

_______ of GH is usually caused by anterior pituitary tumor

Gigantism

Hypersecretion of GH
In children results in _______:
- Can reach heights of 8 feet

acromegaly

Hypersecretion of GH

In adults results in ______:
- Overgrowth of hands, feet, and face

Pituitary dwarfism

Hyposecretion of GH
In children results in ________ _______:
- May reach height of only 4 feet

No problems

Hyposecretion of GH In adults usually causes

Thyroid-stimulating hormone (TSH)

- Tropic hormone that is also called thyrotropin as it is produced by thyrotropic cells
- Stimulates normal development and secretory activity of thyroid
- Release triggered by thyrotropin-releasing hormone from hypothalamus
- Inhibited by rising blood levels of thyroid hormones that act on both the pituitary and hypothalamus
- Also inhibited by GHIH

Adrenocorticotropic hormone (ACTH)

- Also called corticotropin as it is secreted by corticotropic cells
- Precursor to corticotropin is pro-opiomelanocortin
- ACTH stimulates adrenal cortex to release corticosteroids
- Regulation of ACTH release
- Triggered by hypothalamic corticotropin-releasing hormone (CRH) in daily rhythm
- Highest levels in morning
- Internal and external factors that alter release of CRH include fever, hypoglycemia, and stressors

Gonadotropins

-Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are secreted by gonadotropic cells of anterior pituitary

FSH Follicle-stimulating Hormone

___ stimulates production of gametes
-Gametes are sex cells
-Two types of gametes -egg or sperm

LH Luteinizing Hormone

__ promotes production of gonadal hormones
-In females, ___ helps mature follicles of egg, triggers ovulation and release of estrogen and progesterone
-In males, ___ stimulates production of testosterone

Blood

LH and FSH both are absent from ____ in prepubertal boys and girls
- Regulation of gonadotropin release

Hypothalamus

Triggered by gonadotropin-releasing hormone (GnRH) during and after puberty
-GnRH is released from the ________
-Suppressed by gonadal hormones (feedback)

Hypothalamus

PIH is released from the

Polactin (PRL)

- Secreted by prolactin cells of anterior pituitary

Dopamine

PIH is ______

Prolactin-inhibiting hormone (PIH)

Regulation of prolactin primarily controlled by ______.

Prolactin

Stimulates milk production in females; role in males not well understood

Lactation

PIH prevents release of PRL until needed, with decreased levels leading to ______.

Increased

Prolactin: _______ estrogen levels stimulate PRL
- Reason behind breast swelling and tenderness during menstrual cycle

Blood levels

Prolactin: ____ ____ rise toward end of pregnancy

Suckling

_____ stimulates PRL release and promotes continued milk

More

Hypersecretion of prolactin is ____ common than hyposecretion

Hyposecretion

________ is not a problem in anyone except women who choose to nurse

Hyperprolactinemia

__________ is the most frequent abnormality of anterior pituitary tumors

• Clinical signs include:
  - inappropriate lactation
  -lack of menses
  -infertility in females
  -impotence in males

Thyroid Gland

Butterfly-shaped gland in anterior neck on the trachea, just inferior to larynx, that consists of:
-Isthmus
-Follicles
-Colloid
-Parafollicular cells

Isthmus

median mass connecting to two lateral lobes

Follicles

hollow sphere of epithelial follicular cells that produce glycoprotein thyroglobulin

Colloid

fluid of follicle lumen containing thyroglobulin plus iodine
- is precursor to thyroid hormone

Parafollicular cells

produce hormone calcitonin

Thyroid hormone

Body’s major metabolic hormone

• Found in two forms:
  1. T4 (thyroxine)
  2. T3 (triiodothyronine)
• Both are iodine-containing amine hormones

T4 (thyroxine)

major form that consists of two tyrosine molecules with four bound iodine atoms

T3 (triiodothyronine)

Form that has two tyrosines with three bound iodine atoms
- Must be converted to T4 at tissue level

Thyroid

_______ hormone affects virtually every cell in body
-Enters target cell and binds to intracellular receptors within nucleus
-Triggers transcription of various metabolic genes

Effects of thyroid hormone include:

-Increases basal metabolic rate and heat production
-Referred to as calorigenic effect
-Regulates tissue growth and development
-Critical for normal skeletal and nervous system development and reproductive capabilities
-Maintains blood pressure
-Increases adrenergic receptors in blood vessels

Thyroid hormone synthesis

Seven steps involved in synthesis of TH:

1. Thyroglobulin is synthesized and discharged into follicle lumen
2. Iodide is trapped: iodide ions (I–) are actively taken into cell and released into lumen
3. Iodide oxidized: electrons are removed, converting it to iodine (I2)
4. Iodine is attached to tyrosine: mediated by peroxidase enzymes
5. Iodinated tyrosines link together to form T3 and T4
6. Colloid is endocytosed by follicular cells
7. Lysosomal enzymes cleave T3 and T4 from thyroglobulin

follicular

Colloid is endocytosed by _______ cells
- Vesicle is then combined with a lysosome

Lysosomal enzymes

______ ______ cleave T3 and T4 from thyroglobulin
- Hormones are secreted into bloodstream
- Mostly T4 secreted, but T3 is also secreted
- T4 must be converted to T3 at tissue level

Iodinated tyrosines link together to form T3 and T4

- If one MIT and one DIT link, T3 is formed
- If two DITs link, T4 is formed

Follicle lumen

Thyroid gland stores hormone extracellularly in _____ _____ until triggered by TSH to release

Monoiodotyrosine (MIT)

formed if only one iodine attaches

Diiodotyrosine (DIT)

Diiodotyrosine (DIT): formed if two iodines attach

Thyroxine-binding globulins

T4 and T3 are transported by ____-_____ _____ (TBGs) and other transport proteins
-Both bind to target receptors, but T3 is 10 times more active than T4
-Peripheral tissues have enzyme needed to convert T4 to T3
-Enzyme removes one iodine

Negative feedback

TH release is regulated by _____ _______

• Falling TH levels stimulate release of thyroid-stimulating hormone (TSH)
  -Rising TH levels provide negative feedback inhibition on TSH
  - TSH can also be inhibited by GHIH, dopamine, and increased levels of cortisol and iodide
• Hypothalamic thyrotropin-releasing hormone (TRH) can overcome negative feedback during pregnancy or exposure to cold, especially in infants

Goiter

If due to lack of iodine, a ______ my devolop

Myxedema

Hyposecretion of TH in adults can lead to _______

• Symptoms include low metabolic rate, thick and/or dry skin, puffy eyes, feeling chilled, constipation, edema, mental sluggishness, lethargy
• If due to lack of iodine, a goiter may develop

Iodine

Lack of ______ decreases TH levels, which triggers increased TSH secretion, triggering thyroid to synthesize more and more unusable thyroglobulin
- Thyroid enlarges

Cretinism

Hyposecretion in infants leads to ______

• Symptoms include intellectual disabilities, short and disproportionately sized body, thick tongue and neck

Grave's disease

Hypersecretion of TH: most common type is _____ _____:

- Autoimmune disease: body makes abnormal antibodies directed against thyroid follicular cells
- Antibodies mimic TSH, stimulating TH release
- Symptoms include elevated metabolic rate, sweating, rapid and irregular heartbeats, nervousness, and weight loss despite adequate food

Exophthalmos

Graves disease:

_______ may result: eyes protrude as tissue behind eyes becomes edematous and fibrous
-Treatments include surgical removal of thyroid or radioactive iodine to destroy active thyroid cells

Autoimmune disease

Body makes abnormal antibodies directed against thyroid follicular cells

Parafollicular (C)

Calcitonin is produced by ___________ cells in response to high Ca2+ levels

Calcitonin

Antagonist to parathyroid hormone (PTH)

Calcitonin

No known physiological role in humans at normal physiological levels, but at higher-than-normal doses:
-Inhibits osteoclast activity and prevents release of Ca2+ from bone matrix
-Stimulates Ca2+ uptake and incorporation into bone

Parathyroid gland

Four to eight tiny yellow-brown glands embedded in posterior aspect of thyroid
- Contain oxyphil cells (function not clear) and parathyroid cells that secrete parathyroid hormone (PTH), or parathormone

PTH

____ is the most important hormone in Ca2+ homeostasis

Skeleton, kidneys and intestine

Parathyroid glands target organs are ______, _____, and ______.

Low

Parathyroid hormone is secreted in response to ____ blood levels of Ca²⁺

Rising

PTH is inhibited by rising levels of Ca²⁺

Functions of the parathyroid hormone

- Stimulate osteoclasts to digest bone matrix and release Ca2+ to blood
- Enhances reabsorption of Ca2+ and secretion of phosphate (PO43-) by kidneys
- Promotes activation of vitamin D by kidneys, which leads to increased absorption of Ca2+ by intestinal

Hypoparathyroidism

________ following gland trauma or removal can cause hypocalcemia

Hyperparathyroidism

_______ due to parathyroid gland tumor
- Calcium leaches from bones, causing them to soften and deform
- Elevated Ca2+ depresses nervous system and contributes to formation of kidney stones

Osteitis fibrosa cystica

severe form resulting in easily fractured bone

Hypocalcemia

A condition in which the blood has too little calcium.
- Results in tetany, respiratory paralysis, and death

Adrenal Gland

Paired, pyramid-shaped organs atop kidneys
- Also referred to as suprarenal glands
- Structurally and functionally it is two glands in one

Adrenal cortex

three layers of glandular tissue that synthesize and secrete several different hormones

Adrenal medulla

nervous tissue that is part of sympathetic nervous system

corticosteroids

The adrenal cortex produces over 24 different hormones collectively called _________.

Not

Steroid hormones are ___ stored in cells

Synthesis

Rate of release depends on rate of ______

Mineralocorticoids

Zona glomerulos produce

Glucocorticoids

Zona fasciculata produce

Gonadocorticoids

Zona reticularis produce

Mineralocorticoids

Regulate electrolyte concentrations (primarily 
Na+ and K+) in ECF

Aldosterone: most potent mineralocorticoid
Stimulates Na+ reabsorption by kidneys
Results in increased blood volume and blood pressure
Stimulates K+ elimination by kidneys
Effects of aldosterone are short lived
Stimulates synthesis and activation of Na+-K+ ATPase transport pumps
Pump exchanges Na+ for K

Na+

____ affects ECF volume, blood volume, blood pressure, and levels of other ions (K+, H+, HCO3− and Cl−)

K+

sets resting membrane potential of cells

Aldosterone

most potent mineralocorticoid
-Stimulates Na+ reabsorption by kidneys
-Results in increased blood volume and blood pressure
-Stimulates K+ elimination by kidneys
-Effects of aldosterone are short lived
-Stimulates synthesis and activation of

Na+-K+ ATPase transport pumps

-Pump exchanges Na+ for K+

Aldosterone

Factors that regulate ______ secretion:
- Renin-angiotensin-aldosterone mechanism
- Plasma concentration of K+
- ACTH
- Atrial natriuretic peptide

Renin-angiotensin-aldosterone mechanism

1. Decreased blood pressure stimulates special cells in kidneys
2. These cells release renin into blood
3. Renin cleaves off part of plasma protein, angiotensinogen, that triggers enzyme cascade, resulting in conversion to angiotensin II
   - Angiotensin II is a potent stimulator of aldosterone release

Plasma concentration of K+

- Increased K+ directly influences zona glomerulosa cells to release aldosterone
- Increased K+ directly stimulates aldosterone release; low levels inhibit it

ACTH

Can cause small increases of aldosterone during periods of increased stress

Atrial natriuretic peptide (ANP)

- Secreted by heart in response to high blood pressure
- Blocks renin and aldosterone secretion to decrease blood pressure

Aldosteronism

hypersecretion usually due to adrenal tumors
- Results in two major problems:
1. Hypertension and edema due to excessive Na+
2. Excretion of K+, leading to abnormal nonresponsive neurons and muscle

Glucocorticoids

- Influence metabolism of most cells and help us resist stressors
- Keep blood glucose levels relatively constant
- Maintain blood pressure by increasing action of vasoconstrictors

Glucocorticoid hormones include:

- Cortisol (hydrocortisone); only glucocorticoid in significant amounts in humans
- Cortisone
- Corticosterone

Cortisol

_______ is released in response to ACTH

- ACTH released in response to corticotropin-releasing hormone (CRH)
- CRH released in response to low cortisol levels
- Increased cortisol levels inhibit ACTH and CRH through negative feedback

Cortisol secretion cycles

_____ _____ ______ are governed by patterns of eating and activity

Acute stress

(infection, physical or emotional trauma) interrupts cortisol rhythm

CNS

____ can override cortisol inhibition of ACTH and CRH, leading to more cortisol

Increase

cortisol causes an ______ in blood levels of glucose, fatty acids, and amino acids

gluconeogenesis

Prime metabolic effect is ________, formation of glucose from fats and proteins
- Encourages cells to use fatty acids for fuel so glucose is “saved” for brain

vasoconstriction

Other function is to enhance ________
- Causes rise in blood pressure to quickly distribute nutrients to cells

Excessive

_______ levels of glucocorticoids:
1. Depress cartilage and bone formation
2. Inhibit inflammation by decreasing release of inflammatory chemicals
3. Depress immune system
4. Disrupt normal cardiovascular, neural, and gastrointestinal functions

inflammatory diseases

Glucocorticoid drugs can control symptoms of many _______ _____ (arthritis, allergies) but can also cause undesirable side effects

Cushing’s

Hypersecretion—________ syndrome/disease
- Depresses cartilage/bone formation and immune system; inhibits inflammation; disrupts neural, cardiovascular, and gastrointestinal function
- Causes: tumor on pituitary, lungs, pancreas, kidney, or adrenal cortex; overuse of corticosteroids
Cushingoid signs: “moon” face and “buffalo hump”
- Treatment: removal of tumor, discontinuation of drugs

Addison's

Hyposecretion—_______ disease
- Also involves deficits in mineralocorticoids
- Decrease in glucose and Na+ levels
- Weight loss, severe dehydration, and hypotension
- Treatment: corticosteroid replacement therapy

Gonadocortoids

(adrenal sex hormone)

• Weak androgens (male sex hormones) converted to testosterone in tissue cells, some to estrogens
  - Example: androstenedione and dehydroepiandrosterone (DHEA)
• May contribute to:
  - Onset of puberty and appearance of secondary sex characteristics
  - Sex drive in women
  - Source of estrogens in postmenopausal women

Adrenogenital

Hypersecretion
______ syndrome (masculinization)
- Not noticeable in adult males
- Already masculinized with testosterone, so no effect
- Females and prepubertal males
Boys: reproductive organs mature; secondary sex characteristics emerge early
Females: beard, masculine pattern of body hair; clitoris resembles small

Medullary chromaffin

_______ _____ cells synthesize catecholamines epinephrine (80%) and norepinephrine (20%)

catecholamines

Effects of _______:
- Vasoconstriction
- Increased heart rate
- Increased blood glucose levels
- Blood diverted to brain, heart, and skeletal muscle

Epinephrine

Both hormones have basically same effects, but:
_________ is more a stimulator of metabolic activities
- Example: bronchial dilation, and blood flow to skeletal muscles and heart

Norepinephrine

_______ has more of an influence on peripheral vasoconstriction and blood pressure

Breif

Adrenal Medulla: Responses to stressors are ____, unlike adrenal cortical

Hyposecretion

Epinephrine and norepinephrine are not essential to life; therefore there are no problems associated with hyposecretion

Hypersecretion

Leads to symptoms of uncontrolled sympathetic nervous system, such as:
- Hyperglycemia, increased metabolic rate, rapid heartbeat, palpitations, hypertension, intense nervousness, and sweating
- Can be due to pheochromocytoma, tumor of medullary chromaffin cells

Pineal gland

Small gland hanging from roof of third ventricle

Serotonin

Pinealocytes secrete melatonin, derived from ________

Melatonin

_______ may affect:
- Timing of sexual maturation and puberty
- Day/night cycles
- Physiological processes that show rhythmic variations (body temperature, sleep, appetite)
- Production of antioxidant and detoxification molecules in cells

Pancreas

Triangular gland located partially behind stomach
Has both exocrine and endocrine cells

Acinar cells

(exocrine) produce enzyme-rich juice for digestion

Pancreatic islets

(islets of Langerhans) contain endocrine cells

Alpha (α) cells

produce glucagon
- hyperglycemic hormone
- Raises blood glucose levels

Beta (β) cells

produce insulin
- hypoglycemic hormone
- Insulin lowers blood glucose

Glucagon

Extremely potent hyperglycemic agent

• Triggered by
  - decreased blood glucose levels
  - rising amino acid levels
  - sympathetic nervous system
• Raises blood glucose levels by targeting liver to:
  - Break down glycogen into glucose
  - Glycogenolysis
  - Synthesize glucose from lactic acid and other noncarbohydrates
  - Gluconeogenesis
  -Release glucose into blood

Insulin

• Secreted when blood glucose levels increase
• Synthesized as proinsulin that is then modified
• Insulin lowers blood glucose levels in three ways:
  - Enhances membrane transport of glucose into fat and muscle cells
  - Inhibits breakdown of glycogen to glucose
  - Inhibits conversion of amino acids or fats to glucose

Insulin

- Not needed for glucose uptake in liver, kidney, or brain
- Plays a role in neuronal development, learning, and memory
- Binding to tyrosine kinase enzyme receptor triggers cell to increase glucose

Insulin

_____ also triggers cells to:
- Catalyze oxidation of glucose for ATP production: first priority
- Polymerize glucose to form glycogen
- Convert glucose to fat (particularly in adipose tissue)

Release

Factors that influence insulin _____:
- Elevated blood glucose levels: primary stimulus
- Rising blood levels of amino acids and fatty acids
- Release of acetylcholine by parasympathetic nerve fibers
- Hormones glucagon, epinephrine, growth hormone, thyroxine, glucocorticoids
- Somatostatin and sympathetic nervous system inhibit insulin

Diabetes mellitus (DM)

______ ______ can be due to:
- Hyposecretion of insulin: Type 1
- Hypoactivity of insulin: Type 2
- When blood glucose levels remain high, person feels nauseated, leading to sympathetic response
- Fight-or-flight response acts to further increase blood glucose levels

Glycosuria

Excess glucose is spilled into urine

Polyuria

Huge urine output

- glucose acts as osmotic pressure

Polydipsia

Excessive thirst

- from water loss due to Polyuria

Polyphagia

Excessive hunger and food consumption

- cells cannot take up glucose and are "starving"

lipidemia

When sugars cannot be used as fuel, as in DM, fats are used, causing ______: high levels of fatty acids in blood

ketones

Fatty acid metabolism results in formation of ______: (ketone bodies)
- Ketones are acidic, and their build-up in blood can cause ketoacidosis
- Also causes ketonuria: ketone bodies in urine
- Untreated ketoacidosis causes hyperpnea, disrupted heart activity and O2 transport, and severe depression of nervous system that can possibly lead to coma and death

Hyperinsulinism

Excessive insulin secretion
- Causes hypoglycemia: low blood glucose levels
- Symptoms: anxiety, nervousness, disorientation, unconsciousness, even death
- Treatment: sugar ingestion

Reduced amounts

Gonads produce the same steroid sex hormones as those of adrenal cortex in ______ _______.

Ovaries

______ produce estrogens and progesterone
Estrogen:
- Maturation of reproductive organs
- Appearance of secondary sexual characteristics
- With progesterone, causes breast development and cyclic changes in uterine mucosa

testosterone

Testes produce ________:
- Initiates maturation of male reproductive organs
- Causes appearance of male secondary sexual characteristics and sex drive
- Necessary for normal sperm production
- Maintains reproductive organs in functional state

Placenta

_____ secretes estrogens, progesterone, and human chorionic gonadotropin (hCG)

Adipose cells release

- Leptin
- Resistin
- Adiponectin

Leptin

appetite control; stimulates increased energy expenditure

Resistin

insulin Antagonist

Adiponectin

enhances sensitivity to insulin

Gastrointestinal tract

Enteroendocrine cells secrete these hormones:
- Gastrin stimulates release of HCl
- Ghrelin from stomach stimulates food intake
- Secretin stimulates liver and pancreas
- Cholecystokinin (CCK) activates pancreas, gallbladder, and hepatopancreatic sphincter
- Incretins enhance insulin release and inhibit glucagon

Gastrin

Stimulates release of HCL

Ghrelin

From stomach stimulates food intake

Secretin

Stimulates liver and pancreas

Cholecystokinin (CCK)

Activates pancreas, gallbladder, and hepatopancrieatic sphincter

Incretins

Enhance insulin release and inhibit glucagon

Heart

Atrial natriuretic peptide (ANP) decreases blood Na+ concentration, therefore blood pressure and blood volume

Kidneys

Erythropoietin signals production of red blood cells
Renin initiates the renin-angiotensin-aldosterone mechanism

Skeleton

• Osteoblasts in bone secrete osteocalcin
  - Prods pancreas to secrete more insulin; restricts fat storage; improves glucose handling; reduces body fat
  - Activated by insulin
  - Low levels of osteocalcin are present in type 2 diabetes: perhaps increasing levels may be new treatment

Skin

Cholecalciferol, precursor of vitamin D
Calcitriol: active form of vitamin D that helps absorb calcium from intestine
-Also modulates immunity, decreases inflammation, and may act as anticancer agent

Thymus

• Large in infants and children; shrinks with age
• Thymulin, thymopoietins, and thymosins may be involved in normal development of T lymphocytes in immune response
  - Classified as hormones but act as paracrines

Environmental Pollutants

Effects of _____ _______:
- Exposure to pesticides, industrial chemicals, arsenic, dioxin, and soil and water pollutants disrupts hormone function
- Sex hormones, thyroid hormone, glucocorticoids are all vulnerable to effects of pollutants
- Interference with glucocorticoids may help explain high cancer rates in certain areas

Hormone-producing

____-______ glands arise from all three germ layers

Endocrine Function throughout Life

- Most endocrine organs operate well until old age
- GH levels decline with age: accounts for muscle atrophy with age
- TH declines with age, contributing to lower basal metabolic rates
- PTH levels remain fairly constant with age, but lack of estrogen in older women makes them more vulnerable to bone-demineralizing effects of PTH

Endocrine Function throughout Life

- Glucose tolerance deteriorates with age
- Ovaries undergo significant changes with age and become unresponsive to gonadotropins; problems associated with estrogen deficiency occur
- Testosterone also diminishes with age, but effect is not usually seen until very old age