Endocrine Physiology

Gian Carlo Delante, PhB PTRP RPT

Function of the Endocrine System• Maintenance of the internal

environment (body temperature, body fluid volume, osmolality, etc), adaptation to stress, control of growth and metabolism, and control of reproduction

• In contrast to the nervous system – slower to take effect yet lasts longer and are generally more widespread throughout the body; can indirectly affect many organs at a distance by secreting chemicals into the blood

Endocrine VS Exocrine Glands• Exocrine glands

– have ducts– secrete onto a surface

• Examples:– sebaceous and sweat glands (surface of the skin)– salivary glands (surface of the mouth)– Pancreas (surface of duodenum)

• Endocrine glands– do not have ducts– secretions (hormones) are secreted into the blood stream (internal)

• Advantages:– the hormones can act over long distances– The hormones can reach any organ in the body to co-ordinate activity

• Often there is a specific 'target' organ that the hormone acts on

Glands

• Endocrine gland– Group of specialized cells that synthesize, store,

and release a very special chemical into the blood– This chemical is called a hormone– The hormone is released into the bloodstream and

circulates throughout the body to specific target cells that have receptors for the hormone

– The hormone can either stimulate or inhibit cell activity

Hormones

• 3 basic categories based on chemical make up• Hormones derived from amino acid TYROSINE

– Thyroxine (T4), triidothyronine (T3)– Secreted from thyroid gland

• Hormones derived from proteins– Calcitonin, parathyroid hormone, pituitary and pancreatic

hormones, and most of the releasing & inhibiting hormones from the hypothalamus

• Hormones derived from cholesterol - Steroid hormones– Cortisol, aldosterone, estrogen, progesterone, testosterone

Hormones – receptors for hydrophobic hormones

• Since hydrophobic (lipid soluble) hormones (steroid and thyroid hormones) can diffuse through the cell membrane, the receptor will be located in the cytoplasm or in the nucleus. However, the hormone first must be released by its carrier protein before it can enter the cell.

Hormones—Receptors for Hydrophilic Hormones

• Hydrophilic (protein) hormones are unable to diffuse through the membrane and therefore must be able to alter the activity of the cell from the "outside.“

• The receptors for protein hormones are located on the cell membrane. When the hormone attaches to the receptor, it initiates a sequence of chemical reactions that will eventually alter the activity of the cell.

• There are three ways in which the receptor can affect the cell: through a second messenger system, through tyrosine kinase, and through G-proteins

Hormones—The Second Messenger

• In this situation, when the hormone binds to its receptor, it causes a G-protein on the inside of the membrane to produce a "second messenger“ (the first messenger is the hormone).

• The most widely studied second messenger is called cyclic adenosine monophosphate (cAMP).

• This second messenger, released into the cytoplasm, will rapidly alter proteins already present inside the cell.

• These altered proteins will then trigger a sequence of reactions inside the cell, which will lead to a variety of intracellular responses — including the release of proteins

Hormones—Tyrosine Kinase

• In this case, the hormone receptor complex activates tyrosine kinase on the inside surface of the membrane

• The tyrosine kinase, like the second messenger, then alters existing proteins that will then alter the activity of the cell

Hormones—G-Proteins

• When the hormone attaches to its receptor, a G-protein is activated that lies within the cell membrane

• This G-protein can then open adjacent ion channels

• If the ion is calcium (Ca++), it can act as a second messenger to alter existing proteins once it diffuses into the cell

The Hypothalamus—Structure and Function

• The hypothalamus is located at the base of the brain just above the pituitary gland and below the thalamus

• Involved with some of the body's homeostatic mechanisms, including: – regulation of body temperature, water balance,

and energy production– also involved in regulating the behavioral drives of

thirst, hunger, and sexual behavior• In order to perform all of these complex and

widespread functions, the hypothalamus receives large amounts of information from all around the body, including metabolic, hormonal, temperature, and neural information

The Hypothalamus—Hormones and Releasing Factors

• The hypothalamus secretes many types of hormones—sometimes called releasing factors into a special portal system– Prolactin Releasing Hormone (PRH)– Prolactin Inhibiting Hormone (PIH)– Thyrotropin Releasing Hormone (TRH)– Corticotropin Releasing Hormone (CRH)– Growth Hormone Releasing Hormone (GHRH)– Growth Hormone Inhibiting Hormone (GHIH)– Gonadotropin Releasing Hormone (GnRH)

• referred to as releasingor inhibiting hormones because they cause the release or inhibition of a hormone from the anterior pituitary gland

The Pituitary Gland—Structure

• The pituitary gland is divided into two distinct regions—the anterior and posterior pituitary– The anterior pituitary is made up of endocrine

tissue – The posterior pituitary develops from neural tissue

• Endocrine cells in this area secrete pituitary hormones directly into the blood– Regulated by the hypothalamus through a very

special circulatory system called the hypothalamic-hypophyseal portal system

The Pituitary Gland—Structure

• The posterior pituitary develops from neural tissue at the base of the brain– Contains the axons and nerve terminals of

neurons whose cell bodies lie in the hypothalamus– Hypothalamic-hypophyseal tract

• Posterior pituitary neurohormones– antidiuretic hormone (ADH) and oxytocin

The Pituitary Gland—Anterior Pituitary Hormones

• Thyroid releasing hormone (TRH) from hypothalamus causes the release of thyroid stimulating hormone (TSH) from the anterior pituitary– Stimulates the thyroid gland to secrete triiodothyronine (T3) and thyroxine (T4)

• Corticotropin releasing hormone (CRH) stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary– Stimulates the adrenal glands to secrete cortisol. ACTH also has a minor effect in the

secretion of adrenal androgens and aldosterone• Growth hormone (GH) is under the control of two hypothalamic hormones –

growth hormone releasing hormone (GHRH) and growth hormone inhibiting hormone (GHIH—also known as somatostatin).

• Gonadotropin releasing hormone (GnRH) stimulates the anterior pituitary to secrete both luteinizing hormone (LH) and follicle stimulating hormone (FSH)– Both of these hormones act on the testes in the male and ovaries in the female.

• Prolactin (PRL) release from the anterior pituitary is under the control of two hypothalamic hormones—prolactin releasing hormone (PRH) and prolactin inhibiting hormone (PIH)

The Pituitary Gland—Posterior Pituitary Hormones

• The hormones secreted from the posterior pituitary– manufactured by nerve cells whose cell bodies lie in

the hypothalamus– The hormones are carried down to the terminal end of

the nerve and are released in response to action potentials—much like neurotransmitters are released.

• Neurohormones: antidiuretic hormone (ADH—also called vasopressin) and oxytocin– ADH causes the reabsorption of water in the kidney. – Oxytocin is responsible for the ejection of milk from the

breasts and causes the uterus to contract during birth

The Pituitary Gland—Regulation by Negative Feedback

Pituitary Gland—A Quick Review

Pituitary Gland—A Quick Review

The Thyroid Gland—Structure

• The thyroid gland lies directly below the larynx (or voice box)

• consists of two lobes that almost completely surround the trachea

• made up of follicles, which are the functional units of the gland

• Lying between the follicles are parafollicular cells or C cells

The Thyroid Gland—Function

• Follicular cells– T3 & T4– Increases basal metabolic

rate• Parafollicular cells– Calcitonin– Decreases calcium levels in

the blood

The Thyroid Gland—Effects of T3 and T4 on the Body

The Thyroid Gland—Diseases

• Before or after birth and even during childhood, insufficient amounts of thyroid hormones (hypothyroidism) will result in cretinism– characterized by dwarfism and mental retardation and

can be prevented with thyroid hormone treatments• Can be caused by a congenital lack of a thyroid

gland, inability of gland to produce T3 or T4 due to a genetic defect or lack of iodine in the diet

The Thyroid Gland—Diseases

The Thyroid Gland—Calcitonin• Protein hormone secreted by the parafollicular cells (also

called C cells—"C" for calcitonin) of the thyroid– These cells make up roughly 0.1% of the thyroid gland in humans

• Calcitonin helps regulate calcium levels in the blood– secreted when blood calcium levels rise above normal– Calcitonin's role is to decrease these high levels by decreasing the

number and activity of special bone-dissolving cells called osteoclasts

– Osteoclasts: responsible for enzymatically breaking down bone into calcium that is then released into the blood

• Calcitonin also stimulates the secretion of calcium in the urine and can therefore also decrease blood calcium levels

The Parathyroid Glands and Parathyroid Hormone

• The parathyroid glands– located on the posterior side of the thyroid

• Secrete parathyroid hormone (PTH) when blood calcium levels are low

• PTH performs this by two principal effects: – (1) increasing the number and activity of the bone-dissolving

osteoclast cells, which will release calcium into the blood– (2) decreasing the excretion of calcium in the urine by

reabsorbing it out of the filtrate• Without PTH, the kidney would continually excrete calcium

and this would eventually deplete the extracellular fluid and bones of this vital mineral.

The Adrenal Glands—Structure• The body has two adrenal glands, each resting on top of a kidney. Like

the pituitary gland, they consist of neural tissue and glandular tissue. • Inner medulla

– composed of neural tissue– under the control of the sympathetic nervous system

• Outer cortex– endocrine in nature (glandular tissue)– under the control of pituitary hormones

• The adrenal cortex is divided into three different layers: – the outer zona glomerulosa– the middle zona fasciculata– and the inner zona reticularis

• Each layer looks different under a microscope because each contains a different cell type that secretes a different hormone

The Adrenal Glands—Function• The three regions of the cortex each secrete a different

hormone all of which are steroid hormones and thus hydrophobic

• The outer zona glomerulosa – secretes the hormone aldosterone, a mineralocorticoid– helps to regulate mineral & fluid volume by the kidney

• The zona fasciculata – secretes the hormone cortisol, a glucocorticoid– helps in glucose metabolism

• The inner zona reticularis – secretes small amounts of androgens (a general term for the sex

steroids)

Adrenal Cortex – Zones

The Adrenal Glands—Function• The medulla of the adrenal gland – secretes the

hormone epinephrine (also called adrenaline)

• You should now understand why this part of the adrenal gland is under the influence of the sympathetic nervous system (recall the fight or flight reflex)

The Adrenal Glands — Production of Hormones

• When stimulated by the sympathetic nervous system, epinephrine is secreted from the adrenal medulla into the blood. – SNS is activated in fight or flight situations– The epinephrine will increase heart rate and force of contraction as

well as increase blood flow to the heart and skeletal muscle• Aldosterone is secreted by the adrenal glands in response to:

– (1) angiotensin II– (2) low Na+ levels and high K+ levels in the blood– (3) adrenocorticotropic hormone (ACTH)– *Aldosterone stimulates the reabsorption of Na in the nephron

• Androgens (sex steroids) are released from the zona reticularis in response to ACTH.

The Adrenal Glands—Cortisol• Cortisol is always being secreted from the adrenal glands in small

amounts. Certain conditions like stress, however, will increase its production and secretion.

• Stress– physical (extreme hot or cold)– physiological (pain, loss of blood, or low blood sugar)– emotional (fear or anxiety)– social(personal conflicts)

• Stress -- hypothalamus secretes corticotropin releasing hormone (CRH) -- anterior pituitary secretes adrenocorticotropic hormone (ACTH) -- adrenal glands produce cortisol (as well as aldosterone and androgens)

• Cortisol can feed back to the hypothalamus and anterior pituitary to decrease the release of CRH and ACTH, respectively

The Adrenal Glands—Hormone Production—Cortisol

• Cortisol is secreted when the body is under stress in order to increase glucose levels in the blood

• Essentially, most of its effects will be catabolic– stimulating the breakdown

of stored energy molecules to produce glucose

• Cortisol also suppresses the immune system making the individual more susceptible to infections

The Adrenal Glands—Diseases• Cushing's Syndrome.

– Excess secretion of cortisol – essentially catabolic, promoting the

breakdown of most energy stores including protein and fat.

• Symptoms:– Wasting of muscles, resulting in weakness– Thin skin, resulting in easy bruisability– Poor wound healing– Fat deposits in cheeks, resulting in "moon

face"– Fat deposits in abdomen, resulting in obesity– Depression

The Pancreas—Structure• Lies parallel to and beneath the stomach• contains both endocrine tissue & exocrine tissue• Endocrine portion

– consists of 1 million to 2 million pancreatic islets (also called Islets of Langerhans), each about 0.3 mm (0.01 inches) in diameter

– contain three principal types of cells:• alpha cells make up 25% of the islets and secrete GLUCAGON• beta cells make up 60% of the islets and secrete INSULIN and AMYLIN• delta cells make up 10% of the islets and secrete SOMATOSTATIN

• Exocrine portion– consists of pancreatic acinar cells and ducts

The Pancreas—Structure

The Pancreas—Function—Insulin

• Insulin– a protein hormone secreted by the BETA cells of the Islets of Langerhans – causes cells throughout the body to rapidly take up, store, and use

glucose—as a result, it will cause glucose levels in the blood to decrease• Secreted when glucose levels in the blood increase

– for example: after a meal• Although virtually all cells of the body respond to insulin, the liver,

muscle, and adipose tissue (also called fat tissue) respond maximally to it

• Once the cells take up the circulating glucose, blood glucose levels will decrease which will then cause insulin release from the pancreas to decrease

The Pancreas—Function—Glucagon

• Glucagon– works in opposition to insulin– Secreted by ALPHA cells of the Islets of Langerhans– increases blood glucose concentrations

• Secreted when blood glucose levels decrease and when amino acid levels in the blood increase

• Once in the blood it will primarily stimulate the liver where it will cause both glycogenolysis and gluconeogenesis– Glycogenolysis

• breakdown of glycogen into glucose– Gluconeogenesis

• formation of new glucose molecules from non-glucose fuel sources (such as amino acids)

The Pancreas—Function—Somatostatin

• Somatostatin is protein hormone – secreted by the DELTA cells of the pancreas– also released in the digestive tract and by the hypothalamus, where

it is also referred to as growth hormone inhibiting hormone (GHIH)• Released from the pancreas when blood glucose levels rise,

when amino acid levels in the blood increase, and when there is an increase in blood born fats (called fatty acids)

• Primary function– to reduce the secretion of BOTH insulin and glucagon

• It is believed that somatostatin is trying to prevent the extremely rapid storage of food and trying to make it available to the entire body for a longer period of time

The Pancreas—Importance of Blood Glucose Regulation

• The blood glucose level in a normal fasted individual (before breakfast)– roughly between 80 and 90 mg/dL of blood

• Roughly 1 hour after a meal, blood glucose levels can increase to 120–140 mg/dL of blood– blood glucose levels return rapidly to normal with the help of

insulin• During periods of starvation– glucagon stimulates gluconeogenesis to help maintain blood

glucose levels around 80 to 90 mg/dL of blood• Importance: Glucose is the primary fuel source for the

brain, retina, and some cells in the gonads

• hypothyroidism• hyperthyroidism• Cushing's syndrome• Addison's disease• DM type I• DM type II• Diabetes Insipidus