AP II Chapter 17(The Endocrine System)

1. Introduction: (17.1).

1. In the human body, two major organ systems participate in relatively “long distance” communication: the nervous system and the endocrine system. Together, these two systems are primarily responsible for maintaining homeostasis in the body. 

Neural and Endocrine Signaling

2. Structures of the Endocrine System: The endocrine system consists of cells, tissues, and organs that secrete hormones as a primary or secondary function.

The body contains two kinds of glands: 

1. Exocrine (outside/to secrete) glands secrete their products into ducts, and the ducts carry the secretions to the target site.

• E.g. to outside of body (sweat & sebum)   

• E.g. into a cavity (mucous) (nasal cavity) or lumen of organs (digestive juices)

2. Endocrine (inside/to secrete) glands secrete their products (hormones) into the blood.

3. Endocrine glands (and organs with hormone secreting cells) constitute the endocrine system and include the pituitary, thyroid, parathyroid, adrenal, pancreas, kidneys, gastrointestinal organs, pineal glands, hypothalamus, ovaries, testes, heart, skin, and adipose tissue.

3. Other Types of  Chemical Signaling:

1. Local hormones are hormones that act locally without first entering the blood stream.

1. Paracrines act on neighboring cells

2. Autocrines act on the same cell that secreted them.

4. Career Connections:

Endocrinologists

1. Endocrinology is a specialty in the field of medicine that focuses on the treatment of endocrine system disorders. 

2. Endocrinologists—medical doctors who specialize in this field—are experts in treating diseases associated with hormonal systems, ranging from thyroid disease to diabetes mellitus. 

2. Hormones: (17.2). Although a given hormone may travel throughout the body in the bloodstream, it will affect the activity only of its target cells (cells with receptors for that hormone)

1. The Major Hormones of the Body and their Effects:

2. Types of Hormones: Hormones are classified into groups based on their chemical structure:

1.  Amino Acid Derivatives: 

a. Thyroid hormones (thyroxine -T4)

b. Catecholamines (Epinephrine, norepinephrine, dopamine)

c. Tryptophan Derivatives (Melatonin)

2.  Peptide and Protein Hormones:

      Peptide hormone are synthesized as prohormones- inactive molecules that are converted to active      hormones. (short peptides-ADH and oxytocin; small proteins-hGH and prolactin; glycoproteins-TSH, LH, and FSH)

3. Lipid Derivatives: Consists of carbon rings and side chains built either from fatty acids or cholesterol.

a. Eicosanoids (paracrine factors that coordinate cellular activities and enzyme processes- leukotrienes and prostaglandins)

b. Steroid hormones (reproductive-testosterone and estrogens, adrenal cortex-corticosteroids, and kidneys-calcitriol) All are bound to transport proteins in the blood.

C. Pathways of Hormone Action: 

• The message a hormone sends is received by a hormone receptor.

• A protein is located either inside the cell or in the cell membrane. 

• The receptor will process the message by initiating other signaling events or cellular mechanisms that result in the target cell’s response.

• If a cell has a receptor that will bind a particular hormone, that cell (target cell) will respond to that hormone (if no receptor then the cell will not respond to that hormone).

Pathways of Hormone Action Involving Intracellular Hormone Receptors:

1. Action of Lipid-Soluble Hormone:  

1. Lipid-soluble hormones bind to and activate receptors within cells.

2. The activated receptors then alter gene expression which results in new proteins.

3. The new proteins alter the cells activity, causing the physiological response of the hormone.

Pathways of Hormone Action Involving Cell Membrane Hormone Receptors:

1. Action of Water-Soluble Hormones:

Water-soluble hormones alter cell functions by activating plasma membrane receptors on the outside of cells, which set off a cascade of events inside the cell.

1. The water-soluble hormone that binds to the cell membrane receptor is the first messenger.

2. A second messenger is released inside the cell where hormone stimulated response takes place.

• Cyclic AMP is a very common second messenger.

• cAMP then can activate protein kinase which triggers a wide variety of intracellular effects, from nutrient metabolism to the synthesis of different hormones and products.

• Since hormones that bind to plasma membrane receptors initiate a cascade of events, they can induce their effects at very low concentrations.

4. Factors Affecting Target Cell Response: the presence of a high level of a hormone circulating in the bloodstream can cause its target cells to decrease their number of receptors for that hormone (downregulation).

• This causes cells to become less reactive to the excessive hormone levels. 

• When the level of a hormone is chronically reduced, target cells engage in upregulation to increase their number of receptors and the cells sensitivity to the hormone.

Two or more hormones can interact to affect the response of cells in a variety of ways.

1. Permissive effect: target cell needs simultaneous or recent exposure by another hormone. (E.g. Epinephrine does not change the rate of energy consumption in a tissue unless thyroid is present).

2. Synergistic effect:  The net result is greater than the effect that each would bring acting along (two hormones acting together for greater effect) e.g. the enhancement of the glucose-sparing action of growth hormone in the presents of cortisol.

3. Antagonistic effect:  Two hormones with opposite effects (insulin promotes glycogen formation in the liver and glucagon stimulates glycogen breakdown).

5. Regulation of Hormone Secretion: Feedback loops govern the initiation and maintenance of most hormone secretion in response to various stimuli.

1. Negative Feedback loops: 

• The more common method of hormone regulation is the negative feedback loop. 

• It is characterized by the inhibition of further secretion of a hormone in response to adequate levels of that hormone.

6. The Role of Endocrine Gland Stimuli:

1. Osmoreceptors in the hypothalamus detect changes in blood concentration of solutes (E.g. sodium).

2. High blood glucose levels cause the release of insulin from the pancreas.

3. Hormones can also be released in response to neural stimuli (adrenal medulla).

3. The Pituitary Gland and Hypothalamus: (17.3). The hypothalamus–pituitary complex can be thought of as the “command center” of the endocrine system.

1. The pituitary gland consists of an anterior and posterior lobe, with each lobe secreting different hormones in response to signals from the hypothalamus.

2. Posterior Pituitary Gland (neurohypophysis) [means=nerve/undergrowth](See Table 1)

1. Although the posterior pituitary gland does not synthesize hormones, it does store and release two hormones (ADH and Oxytocin).

2. There is a neural connection between the hypothalamus and the neurohypophysis.

3. Hormones made by the hypothalamus and stored in the posterior pituitary are:

1. Antidiuretic hormone (ADH)- a peptide

• Stimulates water reabsorption by the kidneys         

• Decrease urine volume and conserve body water (concentrated the urine).

• Controlled primarily by osmotic pressure of the blood (osmoreceptors in hypothalamus).

2. Oxytocin (OXT)- a peptide

• Stimulates contraction of the uterus. 

• Ejection (let-down) of milk from the breasts. Nursing a baby after delivery stimulates oxytocin release promoting uterine contractions and the expulsion of the placenta.

3. Anterior Pituitary: The pituitary gland is located in the sella turcica of sphenoid bone and is differentiated into the anterior pituitary and the posterior pituitary. 

• Many hormones of the anterior pituitary are called tropic hormones because they "turn on" endocrine glands to produce other hormones.

1. The vascular connection between the hypothalamus and the anterior lobe of the pituitary gland is called the hypophyseal portal system (two capillaries connected by a blood vessel).

2. Anterior Pituitary Gland (Adenohypophysis)  (means=gland/undergrowth) 

1. Human growth hormone (hGH)- a protein

• The most plentiful anterior pituitary hormone.

• Stimulate stem cell division in tissues.

• It acts indirectly on tissues by promoting the synthesis and secretion of small protein hormones called insulin-like growth factors (IFGs), which stimulate general body growth (new proteins).

• Stimulate the breakdown of fats which are used for energy, sparing glucose.

2.  Thyroid-stimulating hormone (TSH)- a protein.

• TSH is released in response to thyrotropin-releasing hormone from the hypothalamus. 

• Regulates thyroid gland (TSH stimulates the synthesis & secretion of thyroid hormone) Control of TSH by negative feedback by thyroid hormone.

3. Adrenocorticotrophic hormone (ACTH) and melanocyte-stimulating hormone

(MSH). Hypothalamus releasing hormones stimulate secretion of ACTH.

• Both peptides

• ACTH controls the cortex of the adrenal gland. 

4. Gonadotropins: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)- proteins      

    1). Follicle-stimulating hormone (FSH)

    Females: 

• Initiates egg follicle development.

Males: 

• Stimulates sperm production in the testes.

2). Luteinizing hormone (LH)

     Releasing hormones from hypothalamus produce LH

Females

• Secretion of estrogen

• Ovulation of 2nd oocyte from ovary

• Formation of corpus luteum

• Secretion of progesterone

 Males 

• Stimulates the testes to secrete testosterone.

5. Prolactin (PRL) Together with other hormones initiates and maintains milk secretion by the mammary glands.- a peptide

6.  Melanocyte-stimulating hormone (MSH) 

4. Pituitary Gland Disorders (Not in text):

1. Dwarfism- hyposecretion of hGH.

2. Hypersecretion of hGH 

• If in childhood (before epiphyseal plate closes) 🡺 gigantism. 

• If in adulthood (after epiphyseal plate closes) 🡺 acromegaly.

3.   Diabetes insipitus- Absent ADH, resulting in polyuria and thirst.

4. Thyroid Gland: (17.4). Thyroid hormones regulate metabolism, heat production, protein synthesis.

        Thyroid Hormone:

1.  Location just below the larynx and has right and left lateral lobes connected by an isthmus. 

2.  Follicle cells synthesize thyroglobulin (contains T3 and T4) and store it in the colloid of the thyroid   follicles.  From here the T3 and T4 are released into the blood stream.

  3. Thyroid hormones are primarily transported across the plasma membrane. (Not in text)

• Once inside they bind to receptors on mitochondria stimulating the production of more ATP.

• Thyroid-receptor complexes travel into the nucleus and bind the DNA of a specific gene.

• Similar to steroids they alter the target cells activity by altering specific enzyme production

4.  Functions of Thyroxine (T₄) and (T₃): (🡹 means increases)

•  🡹 oxygen use and basal metabolic rate (🡹 ATP production, 🡹ATP use, and 🡹 body temperature).

• Stimulate RBC formation, enhancing oxygen delivery.

• 🡹 heart rate and force of contraction which 🡹 BP. 🡹 sensitivity to sympathetic stimulation.

5. Regulated by a negative feedback system.  Low blood levels of hormones stimulate hypothalamus 🡺   stimulates pituitary to release TSH 🡺 stimulates thyroid gland to raise blood level.

• Secretion of thyroid hormone is controlled by the level of TSH.

6. Thyroid Gland Disorders

1. Cretinism hyposecretion of thyroid hormones during fetal life or infancy 

2. Graves’ disease hyperthyroidism (autoimmune-antibodies against TSH; stimulates these receptors on cells behind eye🡺inflammation and edema; more often in women)

3. Goiter an enlarged thyroid gland often due to iodine deficiency outside the US.

V.   Calcitonin:

1. Calcitonin (CT) secreted by Clear (C) cells aids in regulation of calcium ions.

2. Calcitonin is released in response to a rise in blood calcium levels. It appears to have a function in decreasing blood calcium concentrations by:

1. Inhibiting the activity of osteoclasts, bone cells that release calcium into the circulation

2. 🡹 osteoblastic activity. 

3. 🡻 calcium absorption in the intestines. 

4. 🡹 calcium loss in the urine.

6. Parathyroid: (17.5). Location embedded on the posterior surfaces of the lateral lobes of the thyroid (4 glands).

1. Parathyroid hormone (PTH) increases blood level of calcium.

• Activates osteoclast cells.

• Stimulates kidneys to produce activated Vitamin D₃ (Calcitriol).

• Enhances reabsorption of calcium by the kidneys. 

2. Blood calcium level directly controls the secretion of calcitonin and parathyroid hormone

3. Calcitonin and PTH have opposing effects on levels of calcium ion in body fluids

• Calcitonin (from thyroid gland) lowers calcium.

• PTH (from parathyroid glands) raises calcium.

4. Abnormally high activity of the parathyroid gland can cause hyperparathyroidism, a disorder caused by an overproduction of PTH that results in excessive calcium reabsorption from bone.

• Hyperparathyroidism can significantly decrease bone density, leading to spontaneous fractures or deformities.

7. The Adrenal Glands: (17.6). Wedges of glandular and neuroendocrine tissue adhering to the top of the kidneys. The adrenal glands have a rich blood supply and with one of the highest rates of blood flow in the body.

1. The General Adaptation Syndrome: The body responds in different ways to short-term stress and long-term stress: 

1. Fight or Flight Response (alarm phase)

1. Initiated by nerve impulses from the hypothalamus to the sympathetic division of the autonomic nervous system and adrenal medulla.

2. Responses are:

• 🡹 breathing, 🡹 heart rate, 🡹 glucose mobilized from breakdown of glycogen. 🡻 nonessential activities E.g. digestion, urination and reproduction.

2. The Resistance Reaction (If stress lasts more than a few hours)

1. Initiated by regulating hormones secreted by the hypothalamus 

• Corticotropin RF 🡺 ACTH 🡺 Cortisol (dominant hormone in this phase)

2. Resistance reactions are long-term. 

3. Exhaustion

1. Results from dramatic changes during “fight or flight” and resistance reactions.

2. Caused mainly by loss of potassium, depletion of adrenal glucocorticoids, and weakened organs. If stress is too great, it may lead to death.

2. Three zones, each of which secretes different hormones.

1. Zona glomerulosa (outer zone) secretes mineralocorticoids.

• Primarily the hormone aldosterone.

• Targets kidneys affect mineral homeostasis 🡹 Na⁺ and H₂0 reabsorption and 🡻 K⁺ reabsorption (E.g. Renin-angiotensin-aldosterone system)        

2. Zona fasciculata (middle zone) secretes glucocorticoids.

• Primarily  the hormone cortisol.

• Promote formation of glucose, breakdown of proteins and lipids, resistance to stress, anti-inflammatory effects, and depression of the immune system 

3. Zona reticularis (inner zone) secretes androgens.

• Secretes only small amounts of androgens.

     Stimulate the development of pubic hair in bays and girls before puberty.

• Aldosterone, cortisol, and androgens are all lipid-soluble steroid (from cholesterol)

hormones

3. Adrenal medulla -secrete epinephrine (adrenaline) and norepinephrine (NE)

1. Really a modified sympathetic ganglion.

2. Produce effects similar to sympathetic responses (fight or flight). They are released by direct innervation from the autonomic nervous system. 

• 🡹 Cardiac activity, 🡹 BP, 🡹 Glycogen breakdown, raising blood glucose levels.

4. Adrenal Disorders:

1. Hypersecretion:

1. Cushing’s syndrome hypersecretion of cortisol by the adrenal cortex.

• Cortisol causes breakdown of proteins- muscle wasting

• Impaired glucose metabolism

2. Addison’s disease: Hyposecretion of corticosteroids

1. A rare disorder that causes low blood glucose levels and low blood sodium levels.

8. Pineal Gland: (17.7).

  A.  The pineal gland lies in the posterior portion of the roof of the 3rd ventricle. Special secretory cells     synthesize melatonin.

• Collaterals from the visual pathway enter the pineal gland and affect the rate of melatonin secretion (lowest during daylight and highest at night)

B.  Functions of melatonin in humans:

• In some mammals melatonin inhibits reproductive functions.  The role in humans is unclear.

• Melatonin is a very effective antioxidant that may protect the CNS neurons from free radicals.

• Sets the circadian rhythm (day-night pattern).

9. Gonadal and Placental Hormones: (17.8). Hormonal role of the gonads—the male testes and female ovaries— which produce the sex cells (sperm and ova) and secrete the gonadal hormones.

Ovaries and Testes:

1. Ovaries produce sex hormones:

1. Estrogens and progesterone: development and maintenance of female sexual characteristics, reproductive cycle, pregnancy, lactation, and normal reproductive functions. (Both steroids)

2. Inhibin: inhibits FSH. (polypeptide)

3. Relaxin: loosens up the coxal bones for childbirth

2. Testes produce sex hormones: 

1. Testosterone: (steroid)

• Development and maintenance of male sexual characteristics 

• Sperm production. 

2. Inhibin: inhibits FSH. (polypeptide)

3. Placenta: 

1. Human chorionic gonadotropin (hCG). 

• hCG hormone promotes progesterone synthesis and reduces the mother’s immune function to protect the fetus from immune rejection.

10. The Endocrine Pancreas: (17.9). Flattened organ located posterior and slightly inferior to the stomach.

A. Endocrine -pancreatic islets (islets of Langerhans)

Cell Types in the Pancreatic Islets: 

1. Alpha cells 🡺glucagon 

• 🡹 Blood glucose levels by breaking down liver glycogen. 

2. Beta cells 🡺 insulin

• 🡻 Blood glucose levels by increase uptake by cells and 🡹 glycogen synthesis by skeletal muscle and liver.

3. Delta cells 🡺 similar to growth hormone-inhibiting hormone

• Acts to inhibit the secretion of insulin and glucagon.

4. PP-cells 🡺 pancreatic polypeptide 

• Regulates release of pancreatic digestive enzymes and inhibits gallbladder contraction.

B.  Insulin (from beta cells) and glucagon (from alpha cells) are the primary hormones responsible for the regulation of blood glucose levels.

3. Diabetes Mellitus is caused by genetic abnormalities or mutations that result in:

• Inadequate insulin production

• The synthesis of abnormal insulin molecules

• Defect insulin-receptor production.  

      1.  Characteristics of DM:

• Hyperglycemia is the presents of abnormally high blood glucose.

• Glycosuria is glucose in the urine.

• Polyuria is excessive urine volumes.

      2.  Types of DM:

1. Type I diabetes (insulin-dependent) caused by a deficiency of insulin from beta cells.

• Cause: genetic

2. Type II diabetes (insulin-independent) insulin levels are initially normal, but their tissues respond poorly (insulin resistance).  

• Cause: 🡹 weight related 

• Can damage skin, kidneys (diabetic nephropathy), nervous system (diabetic neuropathy),    circulatory system (reduced blood flow to limbs) and eyes (diabetic retinopathy).

11. Organs with Secondary Endocrine Functions: (17.10). Many organs have secondary endocrine functions. 

1. Hormone-producing activities of the heart, gastrointestinal tract, kidneys, skeleton, adipose tissue, skin, and thymus.

2. Development and Aging of the Endocrine System: (17.11). The endocrine system arises from all three embryonic germ layers

1. Development:

• The endocrine glands that produce the steroid hormones, such as the gonads and adrenal cortex, arise from the mesoderm. 

• Endocrine glands that arise from the endoderm and ectoderm produce the amine, peptide, and protein hormones. 

• The anterior pituitary gland and posterior pituitary gland both arises from the ectoderm.

2. Aging:

• hGH declines with age, resulting in 🡻muscle mass in the elderly.

• An example of the aging process affecting an endocrine gland is menopause.

• Testosterone levels also decline with age, a condition called andropause.

• As the body ages, the thyroid gland produces less of the thyroid hormones, causing a gradual decrease in the basal metabolic rate.

Nearly one third of Americans aged 65 and older have diabetes.