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THE ENDOCRINE SYSTEM

INTRODUCTION

1.All cells are sensitive to changes in their environment, and all cells release chemicals, including prostaglandins, into their surroundings.

2. Hormones are chemical messengers produced by endocrine cells for distribution by the circulatory system.

3. The endocrine system includes all of the endocrine cells and tissues of the body.

HORMONE STRUCTURE AND FUNCTION

1. Hormones fall into three basic categories: (1) amino acid derivatives (catecholamines, thyroid hormones, melatonin), (2) peptides, and (3) steroids (derivatives of cholesterol).

Mechanisms of Hormonal Action

1. Hormones modify intracellular processes by altering the identities, activities, quantities, or properties of intracellular enzymes.

2. To be affected by a particular hormone, the target cell must have appropriate receptor molecules on the cell membrane, in the cytoplasm, or in the nucleus.

3. The hormone/receptor complex may activate or inhibit enzymes, act as a cofactor in some enzymatic reaction, or activate genes that transcribe specific mRNAs.

4. Receptors for catecholamine and peptide hormones are located on the cell membranes of target cells.The hormones act as first messengers that trigger the release of second messengers (often cyclic AMP) into the cytoplasm. The ultimate effects vary depending on the type of enzymes already present in the cytoplasm.

5. Steroids and thyroid hormones affect the activities of genes. Steroids first combine with receptors in the cytoplasm; thyroid hormones target receptors inside the nucleus.

PRINCIPLES OF HOMEOSTATIC CONTROL

1. The nervous system produces rapid, short-term, specific responses to environmental stimuli. The endocrine system directs long-term modifications in cellular activity that affect a variety of tissues simultaneously.

2. The endocrine system: (1) regulates the composition and volume of body fluids, (2) helps to adapt the body to changing temperatures, (3) readies the body for a sudden crisis, and (4) coordinates long-term processes including embryological development, growth, sexual maturation, and reproduction.

3. Activities of the nervous and endocrine systems are usually controlled by negative feedback mechanisms.

4.It is very difficult to distinguish between the nervous and endocrine systems on anatomical or functional grounds.

The Hypothalamus and Endocrine Regulation

1. Hypothalamic nuclei control endocrine function through three mechanisms: (1) direct neural connections (adrenal medulla); (2) by the release of hypothalamic hormones (ADH and oxytocin); and (3) by the production of regulatory factors (releasing or inhibiting).

2. Regulatory factors control secretory activities in the pituitary gland.

ENDOCRINE TISSUES AND ORGANS

The Pituitary Gland

1. The pituitary is a small oval gland seated in the sella turcica of the sphenoid bone. The infundibulum connects it to the floor of the hypothalamus.

The Posterior Pituitary

1. The posterior pituitary (neurohypophysis) contains the axons of hypothalamic neurons.

2. The supraoptic and paraventricular nuclei of the hypothalamus produce antidiuretic hormone and oxytocin for release into capillaries of the posterior pituitary.

3. ADH release occurs when the electrolyte concentration in the blood rises, and when blood pressure or blood volume declines.ADH reduces the amount of water lost at the kidneys.

4. During delivery, oxytocin stimulates smooth muscle contractions in the uterus and mammary glands.The uterine sensitivity to oxytocin increases as the time of birth approaches and their stimulation by oxytocin contributes to the completion of normal labor.

5. After birth, oxytocin stimulates contractile cells of the mammary glands to force milk along passageways leading to the nipples. This represents the milk let-down reflex.

The Anterior Pituitary

1. The anterior pituitary (adenohypophysis) can be divided into an anterior pars distalis and a posterior pars intermedia.

2.The anterior pituitary secretes seven important hormones, and six are produced by the pars distalis.

3. The anterior pituitary secretes: thyroid-stimulating hormone (TSH), stimulating the release of thyroid hormones; adrenocorticotrophic hormone (ACTH), stimulating the release of glucocorticoids; follicle-stimulating hormone (FSH), stimulating estrogen secretion and egg development in females, and sperm production in males; luteinizing hormone (interstitial cell-stimulating hormone; LH/ICSH), causing ovulation and progesterone production in women, and androgen production in men; prolactin (PRL), stimulating the development of the mammary glands and the production of milk; and mitosis, and the growth of body tissues.

4. Growth hormone (somatotrophin) stimulates cell growth and protein synthesis via the release of somatomedins by the liver. This stimulation occurs almost immediately, at a time when glucose and amino acid concentrations in the blood are elevated.

5. A second effect appears hours later, as glucose and amino acid levels are declining. Under these conditions GH causes the breakdown of glycogen and lipid reserves, and directs peripheral tissues to begin using lipids instead of glucose as an energy source. As a result, blood glucose concentrations rise. These effects appear through an interaction between growth hormone and somatomedins.

6. The pars intermedia produces melanocyte-stimulating hormone (MSH).MSH stimulates the production of melanin in the skin.

The Hypothalamic Control of the Anterior Pituitary

1. Regulatory factors produced by neurons near the median eminence enter the circulation at fenestrated capillaries of the hypophyseal portal system.

2. Releasing factors promote the release of TSH, ACTH, and the gonadotrophic hormones (LH and FSH). The factors involved are called thyroid hormone-releasing factor (TRF), corticotrophin- releasing factor (CRF), and gonadotrophin-releasing factor (GnRF).

3. Inhibiting factors control the release of prolactin and MSH.

4. A releasing factor (GH-RF) and an inhibiting factor (GH-IF) regulate growth hormone secretion.

5. A single releasing or inhibiting factor may have secondary effects on other endocrine cells in the pituitary.

The Thyroid Gland and Associated Endocrine Structures

The Thyroid Gland

1. The thyroid gland lies near the thyroid cartilage of the larynx.

2. Thyroid follicles secrete hormones include thyroxine (tetraiodothyronine, T4) and triiodothyronine (T3). Thyroxine accounts for 90 percent of thyroid gland secretions.

3. Thyroid hormones exert a calorigenic effect, stimulating energy production and utilization by peripheral cells.

4. The follicle cells manufacture thyroglobulin and store it as a colloid filling the lumen of the follicle. The cells also actively transport iodine from the extracellular fluids into the follicular chamber, where they complex with the thyroglobulin molecules.

5. Reabsorbed thyroglobulin is broken down into amino acids and thyroid hormones; the hormones diffuse into the circulation.

6. Most of the thyroid hormones entering the bloodstream are attached to special thyroid-binding globulins. Unbound hormones affect peripheral tissues at once; the binding globulins gradually release their hormones over a week or more.

7. The primary regulatory mechanism involves the production of TSH by the anterior pituitary.

8. The C cells of the follicles produce calcitonin (CT) in response to higher than normal concentrations of calcium ions in the extracellular fluids.

9. Calcitonin stimulates osteoblasts, inhibits osteoclasts, and slows the intestinal absorption and renal conservation of calcium ions.

The Parathyroid Glands

1. There are two pairs of parathyroids embedded in the posterior surface of the thyroid gland.

2. There are several different populations of cells within the parathyroid glands. The chief cells produce parathormone in

response to lower than normal concentrations of calcium ions in the surrounding extracellular fluids.

3. Parathormone stimulates osteoclasts, inhibits osteoblasts, increases intestinal absorption, and reduces urinary excretion of calcium ions.

The Thymus

1. The thymus produces several hormones; thymosin plays a role in the development and maintenance of normal immunological defenses.

The Adrenal Gland

1. The adrenal (suprarenal) glands lie along the superior borders of the kidneys.

2. The adrenals can be subdivided on histological grounds into an outer cortex and an inner medulla.

The Adrenal Cortex

1. The adrenal cortex manufactures steroid hormones called adrenocortical steroids, or simply corticosteroids. The cortex contains three distinct zones, the zona reticularis, zona fasciculata, and zona glomerulosa.

2. The narrow zona reticularis surrounds the adrenal medulla. The zona reticularis produces androgens of uncertain significance.

3. The zona fasciculata extends towards the capsule in a series of radiating cell columns. This zone produces glucocorticoids, notably cortisol (hydrocortisone), corticosterone, and cortisone. These hormones exert glucose-sparing and anti-inflammatory effects.

4. The relatively narrow zona glomerulosa lies just beneath the capsule. It releases mineralocorticoids, principally aldosterone, that restrict sodium and water losses at the kidneys, sweat glands, digestive tract, and salivary glands.

5. The zona glomerulosa responds to the presence of angiotensin II in the circulating blood. This hormone appears following the secretion of the enzyme renin by kidney cells exposed to a decline in blood volume and/or blood pressure.

The Adrenal Medulla

1.The endocrine cells of the medulla are organized in flattened cords separated by blood vessels.

2. The adrenal medulla produces epinephrine (75-80 percent) and norepinephrine (20-25 percent).

The Endocrine Functions of the Kidneys and Heart

1. When exposed to low blood pressure, specialized kidney cells release an enzyme and a hormone into the circulation.

2. Renin, the enzyme, converts angiotensinogen, an inactive protein secreted by the liver, into angiotensin I. In the lungs this compound is converted to angiotensin II, the hormone that stimulates aldosterone production by the adrenal cortex.

3. The kidney hormone, erythropoietin, stimulates red blood cell production, elevating blood volume and improving oxygen delivery to peripheral tissues.

4. Specialized cardiac muscle cells secrete the hormone atrial natriuretic factor (ANF) when the blood volume becomes abnormally large.

5. This hormone suppresses the secretion of ADH, aldosterone, and catecholamines, reduces thirst, encouraging water loss at the kidneys, and lowers blood pressure. The combination reduces blood volume and blood pressure.

Endocrine Tissues of the Digestive System

The Pancreas

1. The pancreas contains exocrine and endocrine cell populations.

2. The endocrine cells are found within the pancreatic islets (islets of Langerhans).

3. Alpha cells secrete glucagon; beta cells produce insulin. These hormones affect glucose metabolism in the body.

4. Insulin lowers blood glucose by increasing the rates of glucose uptake and utilization in peripheral cells. Protein synthesis, fat deposition, and glycogen formation also increases under insulin stimulation.

5. Glucagon elevates blood glucose by increasing the rates of glycogen breakdown andglucose manufacture in the liver. It stimulates the release of fatty acids from adipose tissues, and amino acids from skeletal muscles.

6. Alpha and beta cells monitor the glucose concentrations of the circulating blood.

Endocrine Tissues of the Reproductive System

1. Interstitial cells of the male testes manufacture steroid androgens, notably testosterone.

2. Testosterone promotes the production of functional sperm, maintains the secretory glands of the male reproductive tract, and determines secondary sexual characteristics.

3. Follicle cells in the ovaries produce steroid estrogens while eggs are developing. After ovulation the cells reorganize into a corpus luteum that produces progesterone. If a pregnancy occurs, the placenta will gradually develop endocrine functions of its own.

The Pineal Gland

1. The pineal gland contains pinealocytes that secrete the hormone melatonin.

2.The pineal receives inputs from the visual system, and hormone production rises during the night and falls during the day.

3. Melatonin reduces the rates of melanin synthesis by direct effects on melanocytes and indirectly, by stimulating the release of MSH-IF by the hypothalamus.

4. Melatonin also slows the maturation of sperm and eggs by inhibiting the production of GnRF.

PATTERNS OF HORMONAL INTERACTION

1. The endocrine system functions as an integrated unit, and hormones often interact. Two hormones may have antagonistic, synergistic, permissive, or integrative effects.

Hormones and Growth

1. Normal growth requires GH, TX, insulin, PTH, and gonadal steroids. As the hormonal concentrations change, so do growth patterns.

Hormones and Stress

1. Stresses of many different kinds can produce a characteristic response involving both the nervous and endocrine systems. This response is known as the general adaptation syndrome (GAS).

2. There are three phases to the GAS, the alarm phase, the resistance phase, and the exhaustion phase.

The AlarmPhase

1. The alarm phase is predominately neural in origin and results from sympathetic activation. Epinephrine is the dominant hormone of the alarm phase. During the alarm phase ADH and CRF are also released by the pituitary gland.

The Resistance Phase

1. During the resistance phase energy consumption remains elevated due to the production of glucocorticoids, epinephrine, growth hormone, glucagon, and thyroid hormones.

2. Glucocorticoids are the dominant hormones of the resistance phase.The goals of the resistance phase include: (1) mobilization of lipid and protein reserves; (2) elevation and stabilization of blood glucose levels; and (3) conservation of glucose for neural tissues.

The Exhaustion Phase

1. Exhaustion may result from a depletion of energy reserves, failure to produce the required hormones, or the collapse of one or more vital systems.

Hormones and Behavior

1. Many hormones affect the functional state of the nervous system, producing alterations in mood, emotional states, and various behaviors.

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