Parathyroid Hormones Calcitonin (Thyrocalcitonin) is made by the parafollicular (C-cells) of the thyroid gland and when secreted lowers the blood calcium level An increase in blood calcium will stimulate the C-cells of the thyroid to secrete calcitonin Increased calcitonin will cause a negative feedback inhibition of parathyroid hormone (PTH) which causes a decrease in blood calcium and an increase in blood phosphate levels

PARATHYROID HORMONES (Interactions Animation) Calcitonin You must be connected to the internet to run this animation

Parathyroid Hormones Parathyroid hormone (PTH) is made by the more numerous chief (principal) cells of the gland PTH increases absorption of Ca2+ from the GI tract and stimulates osteoclastic activity so that Ca2+ is released from bone into the blood

PARATHYROID HORMONES (Interactions Animation) You must be connected to the internet to run this animation

Calcium Regulation 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. PARATHYROID HORMONE (PTH) promotes release of Ca2+ from bone extracellular matrix into blood and slows loss of Ca2+ in urine, thus increasing blood Ca2+ level. 3 4 2 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. 3 2 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. 2 1 PTH also stimulates the kidneys to release CALCITRIOL. High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. PARATHYROID HORMONE (PTH) promotes release of Ca2+ from bone extracellular matrix into blood and slows loss of Ca2+ in urine, thus increasing blood Ca2+ level. 3 4 2 5 1 CALCITRIOL stimulates increased absorption of Ca2+ from foods, which increases blood Ca2+ level. PTH also stimulates the kidneys to release CALCITRIOL. High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. PARATHYROID HORMONE (PTH) promotes release of Ca2+ from bone extracellular matrix into blood and slows loss of Ca2+ in urine, thus increasing blood Ca2+ level. 3 4 2 5 6

The Adrenal Glands There are two adrenal glands, one superior to each kidney (also called the suprarenal glands). During embryonic development, the adrenal glands differentiate into two structurally and functionally distinct regions the adrenal cortex the adrenal medulla Steroid hormones like cortisol Catecholamines like norepinephrine

The Adrenal Glands

The Adrenal Cortex The adrenal cortex is peripherally located and makes up 80-90% of the total weight of the gland The cortex is subdivided into three zones, each of which secretes a different group of steroid hormones, all formed from the cholesterol molecule

Adrenocortical Hormones Just deep to the CT capsule, the cells of the zona glomerulosa synthesize mineralocorticoid hormones The middle zone, or zona fasciculata, secrete mainly glucocorticoid hormones, primarily cortisol The inner zona reticularis is the site of synthesis of weak androgens (masculinizing hormones)

Adrenocortical Hormones Mineralocorticoids regulate the concentrations of Na+ and K+ in the blood (affects blood volume/pressure) Aldosterone is the major hormone in this group Glucocorticoids influence glucose metabolism and the ability to resists the effects of stress Cortisol is the major hormone in this group Weak androgens (masculinizing sex hormones) have little effect in men, but play an important role in promoting libido in women

RAAS The most important effects of aldosterone is seen in the renin-angiotensin-aldosterone system (RAAS) The RAAS is stimulated by a decrease in blood volume and/or blood pressure – as in cases of dehydration or hemorrhage. Low BP stimulates juxtaglomerular cells in the kidney to secrete the enzyme renin

RAAS Renin converts the plasma protein angiotensinogen (produced in the liver) into angiotensin I. As angiotensin I circulates to the lungs, an enzyme called angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II Angiotensin II stimulates the adrenal cortex to secrete aldosterone (salt and H20 resorption indirectly increases BP), and it is a potent vasoconstrictor (which directly increases BP)

RAAS

Glucocorticoids Glucocorticoids (mainly cortisol) regulate metabolism by promoting the breakdown of proteins and fats to form glucose (gluconeogenesis). Increased blood sugar levels assist the body to cope with stress Their inflammatory effects result from inhibiting white blood cells. Unfortunately they also retard tissue repair and slow wound healing glucocorticoids are very useful in the treatment of chronic inflammatory disorders such as Lupus, though long term side-effects are severe

Glucocorticoids High levels of circulating cortisol, as seen with corticosteroid drugs (prednisone), or tumors (adrenal cortex, pituitary gland) is called Cushing’s syndrome Manifestations include hyper- glycemia, poor wound healing, osteoporosis, dermatitis, fat redistribution (spindly arms and legs, moon face, buffalo hump at the neck), and truncal obesity

Glucocorticoids In adults, hyposecretion of glucocorticoids and aldosterone, usually as a result of an autoimmune disorder, is called Addison’s disease The physiologic effects include hypoglycemia, Na+ loss, low BP, dehydration, and muscle weakness only after his death did the world learn that President Kennedy suffered from Addison’s disease Many people know that U.S. President John F. Kennedy (1917-1963) suffered from back pain most of his life and that he was assassinated in 1963. But it was not until after his death that the public learned that President Kennedy also had Addison's disease. Addison's disease is a chronic condition that results when the adrenal glands are unable to produce enough of certain important hormones. This can lead to fatigue, low blood pressure, loss of appetite, and darkening of the skin. It is a rare condition that results when the body fails to produce enough of certain hormones* that help regulate important body functions. Image from http://www.humanillnesses.com/original/images/hdc_0001_0001_0_img0007.jpg

The Adrenal Medulla The inner region of the adrenal gland, the adrenal medulla, is a modified sympathetic ganglion that develops from the same embryonic tissue as all other sympathetic ganglia of the ANS and is innervated by sympathetic preganglionic neurons The catecholamines epinephrine (80%), and norepinephrine (20%), are secreted at the adrenal medulla and serve to prolong the sympathetic response

ADRENAL MEDULLA HORMONES (Interactions Animation) Epinephrine/Norepinephrine You must be connected to the internet to run this animation

The Pancreas The pancreas is both an endocrine and an exocrine gland. It is located posterior and inferior to the stomach. We will discuss its endocrine functions here and its exocrine functions in detail in chapter 24 The tail is contained within the splenorenal ligament but all the other parts of the pancreas are retroperitoneal.

The Pancreas Most of the exocrine cells of the pancreas are arranged in clusters called acini and produce digestive enzymes which flow through ducts into the GI tract Distributed among the acini are clusters of endocrine tissue called pancreatic islets (islets of Langerhans)

Pancreatic Hormones Each pancreatic islet contains four types of hormone-secreting cells: alpha (A), beta (B), delta (D), and F cells Alpha cells secrete glucagon which increases blood glucose levels by acting on hepatocytes to convert glycogen to glucose Beta cells secrete insulin

Pancreatic Hormones Insulin is an anabolic hormone - it decreases blood glucose levels by acting on hepatocytes to convert glucose to glycogen and then facilitating diffusion of glucose into the cells Insulin and glucagon are counter- regulatory hormones in that their actions act to balance one another in terms of blood glucose

Pancreatic Hormones Somatostatin acts in a paracrine manner to inhibit both insulin and glucagon release from neighboring beta and alpha cells. It also inhibits the secretion of hGH The interactions of the four pancreatic hormones are complex and not completely understood

Glucose/Insulin Regulation 1 5 2 3 4 6 1 5 2 3 4 6 7 1 5 2 3 4 6 7 8 1 Insulin acts on various body cells to: • accelerate facilitated diffusion of glucose into cells • speed conversion of glucose into glycogen (glycogenesis) • increase uptake of amino acids and increase protein synthesis • speed synthesis of fatty acids (lipogenesis) • slow glycogenolysis • slow gluconeogenesis Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete INSULIN GLUCAGON 1 5 2 3 4 6 Insulin acts on various body cells to: • accelerate facilitated diffusion of glucose into cells • speed conversion of glucose into glycogen (glycogenesis) • increase uptake of amino acids and increase protein synthesis • speed synthesis of fatty acids (lipogenesis) • slow glycogenolysis • slow gluconeogenesis Blood glucose level falls Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete INSULIN GLUCAGON 1 5 2 3 4 6 7 Insulin acts on various body cells to: • accelerate facilitated diffusion of glucose into cells • speed conversion of glucose into glycogen (glycogenesis) • increase uptake of amino acids and increase protein synthesis • speed synthesis of fatty acids (lipogenesis) • slow glycogenolysis • slow gluconeogenesis If blood glucose continues to fall, hypoglycemia inhibits release of insulin Blood glucose level falls Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete INSULIN GLUCAGON 1 5 2 3 4 6 7 8 Low blood glucose (hypoglycemia) stimulates alpha cells to secrete 1 GLUCAGON Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete GLUCAGON 1 5 2 3 4 INSULIN Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Low blood glucose (hypoglycemia) stimulates alpha cells to secrete GLUCAGON 1 2 Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal Low blood glucose (hypoglycemia) stimulates alpha cells to secrete GLUCAGON 1 2 3 Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete GLUCAGON 1 2 3 4 Glucose/Insulin Regulation

PANCREATIC HORMONES (Interactions Animation) Insulin You must be connected to the internet to run this animation

Gonadal Hormones The ovaries are paired oval bodies located in the female pelvic cavity. They produce several steroid hormones including two estrogens (estradiol and estrone), progesterone, relaxin, and inhibin Estrogens, along with FSH and LH from the anterior pituitary, regulate the menstrual cycle, maintain pregnancy, and prepare the mammary glands for lactation

Gonadal Hormones Ovarian hormones also promote enlargement of the breasts and widening of the hips at puberty, and help maintain these female secondary sex characteristics Progesterone prepares the uterus lining for implantation of a fertilized ovum

OVARIAN HORMONES (Interactions Animation) Hormonal Regulation of Female Reproductive System You must be connected to the internet to run this animation

Gonadal Hormones The male gonads, the testes, are oval glands that lie in the scrotum. The main hormone produced and secreted by the testes is testosterone, an androgen (male sex hormone) Testosterone is needed for production of sperm and maintenance of male secondary sex characteristics

TESTICULAR HORMONES (Interactions Animation) Hormonal Regulation of Male Reproductive Function You must be connected to the internet to run this animation

The Pineal Gland The pineal gland is a small endocrine gland attached to the roof of the third ventricle – it is part of the epithalamus The pineal gland secretes the hormone melatonin, which contributes to maintaining the biological clock (seasonal and daily cycles) more melatonin is secreted in darkness; the pineal gland is very developed in nocturnal animals

The Thymus gland The thymus gland secretes thymosin, which promotes the proliferation and maturation of T cells T cells are a type of white blood cell (lymphocyte) that destroys microorganisms and foreign substances through direct cellular contact

General Adaptation Syndrome The general adaptation syndrome (GAS) or stress response refers to the consequences of failure to respond appropriately to emotional or physical threats, whether actual or imagined Interestingly, stressful situations can be events normally considered to be “good”, as well as bad for instance, a marriage can be as stressful as a divorce, a birth as stressful as a death, etc. Psychologist Hans Selye described the General Adaptation Syndrome (GAS) where initial observations about infectious reactions led to the discovery that stress can lead to infection, illness, disease and death. There are three stages that he discovered: Alarm, Resistance and Exhaustion. Alarm When we are surprised or threatened, we have an immediate physical reaction, often called the Fight-or-Flight reaction. This prepares the body for life-threatening situations, channeling away resources from such as the digestive and immune system to more immediate muscular and emotional needs. This leads to the immune system being depressed, making us susceptible to disease. Resistance As we become used to the stress levels, we initially become more resistance to disease, which leads us to believe we can easily adapt to these more stressful situations. However, this is only the immune system fighting to keep up with demands and expectations, but requires it to work at abnormally high levels. Exhaustion Eventually reality kicks in and our bodies give up on trying to maintain a high level of stress. Parts of the body literally start to break down and we become very unwell. If we continue to fight this situation, we may even die.

General Adaptation Syndrome It is impossible to remove all of the stress from our everyday lives, and some levels of stress actually help us perform well and be productive. Regardless, the body’s homeostatic mechanisms attempt to counteract stress, and maintain a constant internal environment whenever possible If stress is extreme, unusual, or long lasting, the normal mechanisms may not be enough, and they may elicit a series of changes called the stress response or GAS

General Adaptation Syndrome There are three stages to a prolonged stress response: alarm reaction, resistance reaction, and exhaustion The alarm reaction is the short-lived fight-or-flight response initiated by the hypothalamus and mediated by the sympathetic division of the ANS it brings huge amounts of glucose and oxygen to the brain, the lungs, and skeletal muscles the RAAS is also activated to maintain blood volume and BP

THE ALARM REACTION (Interactions Animation) You must be connected to the internet to run this animation

General Adaptation Syndrome The three stages to the GAS continued… The resistance reaction is initiated in large part by hypothalamic releasing hormones and is a longer-lasting response. The release of high levels of cortisol and thyroid hormones assures that the tissues of the body can sustain necessary metabolic needs

General Adaptation Syndrome The alarm reaction leads to a resistance response.

General Adaptation Syndrome The three stages to the GAS continued… Exhaustion occurs when the body’s reserves become so depleted that they cannot sustain the resistance stage Prolonged exposure to high levels of cortisol and other hormones causes wasting of muscle, suppression of the immune system, ulceration of the GI tract, and failure of pancreatic beta cells… disease often ensues

THE GAS (Interactions Animation) General Adaptation Syndrome You must be connected to the internet to run this animation

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