HP LEC 12: Adrenal Glands/ Tyroid and Parathyroid Glands/Pancreas & Other Endocrine glands

Structure/location of Adrenal glands

• located above the kidneys

• consist of an outer adrenal cortex and an inner adrenal medulla that functions as seperate glands

Adrenal Medulla

• is neuroendocrine tissue and secretes epinephrine & norepinephrine in response to sympathetic neural stimulation

• outer

Adrenal cortex

• is glandular epithelium and secretes steriod hormones (cortisol, aldosterone, etc…) in response mostly to ACTH (released by the anterior pituitary gland) or other hormones

3 Layers:

a) Zona Glomerulosa

b) Zona fasciculata

c) Zona Reticularis

Functions of the Adrenal Cortex

• secretes hormones made from cholesterol; called corticosteriods or corticoids

3 Categories of corticosteroids

a) Mineralocorticoids

b) glucocorticoids

c) adrenal androgens

Mineralocorticoids

• from the zona glomerulosa

• regulate Na+ and K+ balance

• ex: aldosterone

Glucocorticoids

• from the zona fasciculata

• systemic fuel metabolism

• the immune system and the stress response

• ex: cortisol

Adrenal Androgens

• from the zona reticularis

• are “weak” sex hormones that supplement those made in gonads

• ex: DHEA

Functions of the Adrenal Cortex: Aldosterone

1) aldosterone is one of the most potent of the mineralcorticoids

2) plays a central role in the regulation of blood pressure mainly by acting on organs such as the kidney and the colon to INCREASE the amt of salt reabsorbed into the bloodstream and to increase the amt of K+ excreted in the urine

Aldosterone Hormone- what does aldosterone cause?

1) adrenocorticotropic hormone (ACTH) can stimulate aldosterone secretion acutely and transiently under normal conditions, but to a lesser extent that the reninangiotensin- aldosterone system

2) aldosterone causes an INCREASE in salt & water reabsorption into the bloodstream from the kidney thereby increasing the blood volume, restoring salt levels & blood pressure

Too Much Aldosterone?

• causes high blood pressure

• low blood levels of potassium

• abnormal increase in blood volume

Not enough aldosterone

• causes Addison’s disease

• in addisons diease there is a general loss of adrenal function resulting in LOW blood pressure, lethargy, and in increase in postassium levels in the blood

Functions of the Adrenal Cortex: Cortisol

• cortisol production is regulated by hypothalamus & pituitary gland (hypothalamic pituitary-adrenal axis)

a) corticotropin releasing hormone (CRH)

b) adrenocorticotropic releasing hormone (ACTH)

Cortisol actions (7)

• almost every cell contains receptors for cortisol, so it can have lots of different actions depending on which cell its acting upon

1. controlling the body blood sugar levels

2. regulating metabolism

3. acting as an anti-inflammatory

4. influencing memory formation

5. controlling salt & water balance

6. influencing blood pressure

7. helping development of the fetus

What are exogenous glucocorticoids used for?

• exogenous glucocorticoids are used medically to suppress immune response & inhibit inflammation; can have many negative side effects

Stress & the Adrenal Gland (how does the body respond to stress?)

• stress INcreases secretion of ACTH, which results in increased cortisol release

• the stress hormone are glucocorticoids, but also norepinephrine & epinephrine (fight or flight)

• Body responds to stress by the general adaptation syndrome (GAS)

Stages of GAS (general adaptation syndrome)

1. Alarm Reaction

2. Stage of Resistance

3. Stage of Exhaustion

Stages of Gas: Alarm Rxn

1) Alarm Rxn: activates the adrenal glands- this natural rxn prepares you to either flee or protect yourself in dangerous situations

• heart rate increases

• adrenal medulla releases cortisol, you receive a boost of adrenaline (released by adrenal cortex)- increases energy

• fight or flight response occurs in the alarm rxn stage

Stages of Gas: Stage of Resistance

2) readjustments in response

• body begins to repair itself

• it releases a lower amt of cortisol

• heart rate and blood pressure begin to normalize

However, some stressful situations continue for extended periods of time, your body remains on high alert, it eventually adapts and learns how to live with a higher stress level

Stages of Gas: Stage of Exhaustion

3) stage of exhaustion:

• may lead to sickness or death

• this stage is the result of prolonged or chronic stress

Stress & the adrenal gland- (what does Chronic Stress lead to? what can cortisol act on?)

Chronic stress leads to an INcreased risk of illness

1. cortisol may act on higher brain regions, contributing to depression,  anxiety, memory

2. By stimulating the liver to release glucose, insulin receptors may become resistant, making it harder to treat people with diabetes

Cushing’s Syndrome (what does it result from? what does it cause?)

• resulting from chronically HIGH levels of glucocorticoids (stress hormone)

• it causes lipolysis & a redistribution of fat that can produce a “buffalo hump” (a fatty deposit between the shoulders and below the back of the neck), a '“moon face” (round) and other symptoms

When does Cushing’s Syndrome commonly occur?

• commonly occurs when a person takes sustained high does of glucocorticoid medicine, but it can be produced by either:

1) a pituitary tumor that secretes excessive ACTH

2) a benign tumor of the adrenal that secretes excessive cortisol without requiring ACTH stimulation

hypothalamus and anterior pituitary gland hormone review

Thyroid Glands (location, structure)

• located just below the larynx

• has two lobes on either side of the trachea, connected by the isthmus

• hypothalamus signals the pituitary glands which signals the thyroid glands

Thyroid Hormones (4)

1. TRH- thyroid releasing hormone

2. TSH- thyroid stimulating hormone

3. T3- Triiodothyronine hormone

4. T4- Thyroxine hormone

Thyroid Gland consists of: T3, T4, and calcitonin

Photomicrograph of the Thyroid Gland

• consists of hollow spaces called thyroid follicles lined with simple cuboidal epithelium composed of follicular cells that produce thyroxine (T4) and Triiodothyronine (T3)

• outside of the follicles are parafollicular cells that secrete calcitonin

Production & Action of Thyroid Hormone- pt 1

1) Thyroglobulin (precursor of T3 & T4) is made by the follicular cells

a) thyroid follicles- actively accumulate iodide (I-) and secrete it into the colloid; the enzyme thyroid peroxidase catalyzes the oxidation of iodide ions to molecular iodine (I2 oxidized iodide)

Production & Action of Thyroid Hormone- pt 2

b) the iodine is attached to tyrosine within the thyroglobulin

1) one iodine produces monoidotyrosine (MIT)

2) two iodine produces diiodotyrosine (DIT)

enzymes within the colloid attach MIT & DIT together

• DIT +DIT= T4 (tetraiodothyronine/ thyroxine)

• DIT +MIT= T3 (triiodothyronine)

Production & Action of Thyroid Hormone- pt 3

c) these are still bound to thyroglobulin

• they dissociate from thyroglobulin when the thyroid gland is stimulated by TSH & secreted into the blood

Action of Thyroid Hormone (4)

1. stimulates protein synthesis

2. promotes maturation of the nervous system

3. increases rates of cellular respiration

4. elevates basal metabolic rate

How Iodine Deficiency Causes a Goiter (enlargement of the thyroid gland in the neck)- what can it lead too

1) iodine deficiency (low) leads to overstimulation of the thyroid gland (no negative feedback on pituitary gland) and growth of a goiter (endemic goiter)

2) can also lead to hypothyroidsm: LOW metabolic rates, weight gain, lethargy, poor adaptation to cold stress, & myxedema (accumulation of fluids in subcutaneous connective tissues)

Other causes of hypothyroidism (4)

1. Pituitary disorder

2. Pregnancy

3. Autoimmune diease (hasimoto)

4. Medication (lithium)

What disease does hypothyroidism cause?

• Graves disease is an autoimmune disorder which autoantibodies bind to the receptors for TSH on thyroid gland follicular cells

What does graves disease cause

a) this causes growth of the thyroid ( a goiter) and stimulates the excessive secretion of thyroid hormones

b) although TSH levels are very low bc of negative feedback, the thyroid continues to be stimulated by the thryotropin receptor antibodes to grow & secrete thyroxine

c) the hyperthyroidism produces symptoms such as sensitivity to heat, palpitations and others

d) graves disease is the most common cause of hyperthyroidism and is 5 to 10 times more common in women than men

Parathyroid Glands (what is it, location?)

• generally 4 glands embedded in the BACK of the thyroid gland

Parathyroid Glands (function)

1. secretes parathyroid hormone (PTH)

2. PTH promotes a RISE in blood calcium by acting on bones, kidneys, and intestine

Pancreas (what is it? location?)

1) the pancreas is both an ENdocrine and an EXocrine gland

2) ENdocrine cells are located in pancreatic islets (islets of Langerhans)

• Alpha cells: release glucagon

• Beta Cells: release insulin

Pancreas: Insulin (what is it? what is it secreted by? its purpose?

1) Insulin is a primary hormone regulating plasma glucose concentration

2) insulin is secreted by beta cells when blood glucose levels rise after a sugary or carbohydrate meal

3) its purpose is to lower blood glucose levels to the “normal” range

Action of Insulin

1) Insulin binds to receptors on target cells

• vesicles with GLUT4 carrier proteins bind to membrane

• glucose diffuses through GLUT4 channels by facilitated diffusion

• occurs mostly in adipose tissue, skeletal muscle, and the liver

2) INdirectly stimulates the enzyme glycogen synthase in liver and skeletal muscles to promote sugar storage

3) Stimulates adipose tissue to store fat

Pancreas: glucagon (what is it, secreted by, purpose?)

1) antagonistic (opposite to insulin)

2) secreted b alpha cells when blood glucose levels are LOW

3) purpose is to raise blood glucose levels to a “normal” range

Action of Glucagon

1) stimulates liver to hydrolyze glycogen into glucose & release it into the blood

2) stimulates gluconeogenesis conversion of noncarbohydrates (amino acids, lactate) into glucose

3) stimulates lipolysis in adipose tissue so fat is released and used as a fuel source instead of glucose

Glucose homeostasis

Diabetes Mellitus (what is it characterized by, two major forms?)

• Diabetes mellitus is characterized by fasting hyperglycemina and the presence of glucose in the urine

Two major forms of this disease:

1. Type 1 diabetes

2. Type 2 diabetes

Type 1 Diabetes

• caused by destruction of the BETA cells (production of insulin) and the resulting lack of insulin secretion

a) environmental factor: possibly a viral infection or a nutritional factor during childhood or early adulthood- causes the immune system to destroy the insulin- producing cells of the pancreases

b) genetic predisposition: makes some people more susceptible to an environmental factor

Type 2 Diabetes

• caused largely by insulin resistance, or decreased tissue sensitivity to the effects of insulin

• insulin resistance is when cells in muscles, body fat and liver, starts “resisting” or “ignoring” the signal that insulin is trying to send out- which is to grab glucose out of the bloodstream and put it into the cells

a) gestational diabetes occurs in about 4% of pregnancies due to insulin secretion that is inadequate to meet the increased demand imposed by the fetus and the anti-insulin effect of certain placental hormones

Other Endocrine Glands (3)

1. Gastrointestinal Tract

2. Gonads

3. Placenta

Endocrine Gland: Gastrointestinal Tract

• several hormones are made in the stomach & small intestine to regulate digestive processes; includes gastrin, secretin, cholecystokinin

Endocrine Gland: Gonads

• produce testosterone, estrogen, and progesterone to regulate production of gametes & secondary sexual characteristics

Endocrine Gland: Placenta

• produces human chorionic gonadotropin (hCG) and samatomammotropin to regulate pregnancy

Autocrine Vs Paracrine Signals

1) both are involved in short-range signaling between neighboring cells within an organ

2) Autocrine signals: the sender & receiver are the same cell type( cell A to cell A)

3) Paracrine signals: the sender & receiver are different cell types/tissues (cell A to cell B)

Ex of Autocrine Regulation

1) many regulatory molecules are called cytokines or growth factors

• cytokines regulate cells of the immune system

• growth factors promote growth & cell division

• given specific names depending on where they are found & what they do- for ex: lymphokines, neurotrophins

2) most control gene expression in the target cell