PHARMACOLOGY

ENDOCRINE FUNCTION & DYSFUNTION

SUBMITTED BYSHEEMA JAMALSHEZA ZAHEERZARAFSHAN NASIMJAVERIYA KHALIDRAMSHA NAEEMAIMAN IQBL

ENDOCRINE SYSTEM:The endocrine system is the collection of glands that produce hormones that regulate metabolism, growth and development, tissue function, sexual function, reproduction, sleep, and mood, among other things. The word endocrine derives from the Greek words "endo," meaning within, and "crinis," meaning to secrete. In general, a gland selects and removes materials from the blood, processes them and secretes the finished chemical product for use somewhere in the body. The endocrine system affects almost every organ and cell in the body.

HORMONES

A hormone is any member of a class of signaling molecules produced by glands in multicellular organisms that are transported by the circulatory system to target distant organ to regulate physiological and behavioural functions of the body. Hormones are used to communicate between organ and tissues to perform its functions.

ENDOCRINE GLANDS

Endocrine glands are glands of the endocrine system that secrete their products, hormones, directly into the blood rather than through a duct.

The major endocrine glands include:

 Pituitary gland Thymus gland Pineal gland Parathyroid gland Ovaries Testes Adrenal gland

 

Pituitary gland:The pituitary gland is a pea-sized structure located at the base of the brain, just below the hypothalamus, to which it is attached via nerve fibers. It is part of the endocrine system and produces critical hormones, which are chemical substances that control various bodily functions.

The pituitary is divided into three sections: the anterior, intermediate, and posterior lobes.

ANTERIOR LOBE : The anterior lobe is mainly involved in development of the body, sexual maturation, and reproduction. Hormones produced by the anterior lobe regulate growth, and stimulate the adrenal and thyroid glands, as well as the ovaries and testes. It also generates prolactin, which enables new mothers to produce milk.

INTERMEDIATE LOBE:The intermediate lobe of the pituitary gland releases a hormone that stimulates the melanocytes, cells which control pigmentation like skin color through the production of melanin.

POSTERIOR LOBE:The posterior lobe produces antidiuretic hormone, which reclaims water from the kidneys and conserves it in the bloodstream to prevent dehydration. Oxytocin is also produced by the posterior lobe, aiding in uterine contractions during childbirth and stimulating the production and release of milk.

HORMONES:The main hormones produced by the pituitary are:

Prolactin   :It stimulates breast milk production after childbirth. It also affects sex hormone levels from ovaries in women and from testes (testicles) in men, as well as fertility.

Growth hormone (GH) :It stimulates growth in childhood and is important for maintaining a healthy body composition. In adults, GH is important for maintaining muscle mass and bone mass.

Adrenocorticotropin (ACTH) :It stimulates the production of cortisol by the adrenal glands small glands that sit on top of the kidneys. Cortisol, a "stress hormone," is vital to our survival. It helps maintain blood pressure and blood glucose (sugar) levels, and is produced in larger amounts when we’re under stress—especially after illness or injury.

Thyroid-stimulating hormone (TSH) :It stimulates the thyroid gland to produce thyroid hormones, which regulate the body's metabolism, energy balance, growth, and nervous system activity

Luteinizing hormone (LH) :It stimulates testosterone production in men and egg release (ovulation) in women

Follicle-stimulating hormone (FSH) :It promotes sperm production in men and stimulates the ovaries to produce estrogen and develop eggs in women.

The following hormones are stored in the posterior (back part) of the pituitary gland:

Antidiuretic hormone (ADH) : It is also called vasopressin regulates water balance in the body. It conserves body water by reducing the amount of water lost in urine

Oxytocin   : It causes milk to flow from the breasts in breastfeeding women, and may also help labor to progress

MECHANISM OF ACTION:

Hormones elicit a response at their target tissue, target organ, or target cell type through receptors. A good way to visualize the relationship between the hypothalamus and the pituitary gland is like the president and his chief of staff. While the hypothalamus, or president, makes the decisions, the pituitary gland, or chief of staff, executes those decisions by sending out commands to the rest of the body. The

hypothalamus monitors the body through the circulatory and nervous systems. When it detects that something is out of balance, it sends a message to the pituitary gland that a corrective action is needed. When the pituitary gland gets this message from the hypothalamus, it releases specific hormones into the bloodstream that can stimulate other endocrine glands, organs or tissues, depending on what action is needed. The hypothalamus communicating directly with the body, it relies on the pituitary gland to send out the messages. The hypothalamus continues to monitor the state of the body, and when it detects that balance has been restored, it tells the pituitary gland to stop sending out stimulating messages, thereby stopping the corrective action. An example of this process is when we become dehydrated. The hypothalamus is able to detect the increased blood concentration caused by the loss of water. To correct the situation, it uses the posterior pituitary to release anti-diuretic hormone (ADH) into the circulatory system. When ADH reaches the kidneys, it causes more water to be reabsorbed into the bloodstream, diluting the blood. When the hypothalamus detects the return to a normal blood concentration, it stops the release of ADH from the pituitary gland, and the kidneys return to normal functioning.

DISORDER:Prolactin excess:Prolactinomas (benign tumors of the pituitary gland) can cause prolactin to be overproduced. High prolactin levels can cause menstrual periods in women to be irregular or stop, and can cause galactorrhea (abnormal breast milk production). Men suffering from this pituitary disorder may experience impotence (erectile dysfunction, or ED) or a lack of interest in sex. Men may also have enlarged breasts, infertility or a decrease in body hair. If these symptoms go unrecognized and progress, headaches and vision problems can occur.

Pituitary Adenomas:These tumors are the most common type of tumor and pituitary disorder. They do not secrete an extra amount of hormone and until they become a certain size, the person shows no symptoms of pituitary disorders. As the tumor grows, an individual may begin to suffer headaches and vision problems.

Cushing’s syndrome:Cushing's syndrome is the result of the excessive production of corticosteroids by the adrenal glands. An overproduction of corticotropin (the hormone that controls the adrenal gland by the pituitary gland, which stimulates the adrenal glands to produce corticosteroids) may be one cause. In addition, certain lung cancers and other tumors outside the pituitary gland may produce corticotropins. Other causes include benign or cancerous tumors on the adrenal glands.

Acromegaly:Acromegaly is the Greek word for "extremities" and "enlargement." When the pituitary gland produces excess growth hormones the result is excessive growth, called acromegaly. The excessive growth occurs first in the hands and feet, as soft tissue begins to swell. This rare pituitary disease affects mostly middle-aged adults. Untreated, the pituitary disorder can lead to severe illness and death.

Hypopituitarism: Also called an underactive pituitary gland, hypopituitarism is a pituitary disorder that affects the anterior (front) lobe of the pituitary gland, usually resulting in a partial or complete loss of function in that lobe. The resulting symptoms depend on which hormones are no longer being produced by the gland. Because the pituitary gland affects the other endocrine organs, effects of hypopituitarism may be gradual, or sudden and dramatic.

SYMPTOMS:

Pituitary disease symptoms include:

Headaches Vision problems Irregular menstrual periods Abnormal breast milk production Decreased body hair Impotence Enlarged breasts Buildup of fat in the face, back and chest Weakened bones Rapid growth Profuse sweating

Thymus gland:The thymus gland, despite containing glandular tissue and producing several hormones, is much more closely associated with the immune system than with the endocrine system. The thymus serves a vital role in the training and development of T-lymphocytes or T cells, an extremely important type of white blood cell. T cells defend the body from potentially deadly pathogens such as bacteria, viruses, and fungi.

The thymus is a soft, roughly triangular organ located in the mediastinum of the thoracic cavity anterior and superior to the heart and posterior to the sternum. It has two distinct but identical lobes that are each surrounded by a tough, fibrous capsule. Within each lobe is a superficial region of tissue called the cortex and a histologically distinct deep region called the medulla. Epithelial tissues and lymphatic tissues containing dendritic cells and macrophages make up the majority of both regions of the thymus.

THYMUS HORMONES:

Thymosin:

Thymus produces thymosin which stimulates the development of T cells.

Thympoetin:

It makes it possible to distinguish T lymphocytes.

Thymulin:

It enhances T cell Functions.

Thymic humporal factor (THF):

Thymic humporal factor (THF) increase immune responses particularly to viruses.

MECHANISM OF ACTION: Thymus provides the environment where the T cells are developed and trained to

locate different antigen. The function of the thymus is to receive immature T cells that are produces in the red

bone marrow and train them into functional, mature T cell that attack only foreign cell.

T cell first resides within the cortex of thymus where they come in contact with epithelial cells presenting various antigens.

The immature T cells that respond to the antigens are selected to survive and migrate to the medulla for apoptosis and are cleaned up by macrophages. This process is known as positive selection.

Several hormone produces by thymus promote the maturation of the T cells prior to their release into the blood stream.

Then the mature T cells circulate through the body where they recognized and kill pathogens, activate B cells and produce antibody.

DISSORDERS:

Congenital Disorders: Several genetic defects cause thymus problems from birth. A rare condition called severe combined immunodeficiency, or SCID, develops when a person carries a mutation in a gene that regulates development of T cells. Affecting roughly 1 in every 40,000 to 100,000 babies born in the United States, SCID disrupts the normal development of T cells in the thymus and other immune cells. This severely compromises a child's immune system, making him unable to fight off infections. In another rare disorder called DiGeorge syndrome, a piece of a chromosome is missing along with the genes it contains. This leads to poor development of the thymus and other organs in the immune system, causing weak immune responses and frequent illness. The severity of the disorder varies and can cause mild to severe symptoms.

Autoimmune Problems: In disorders called autoimmune diseases, the immune system attacks the body's own cells or substances made by cells, incorrectly perceiving them as foreign and harmful. One of these disorders, myasthenia gravis, is associated with a thymus gland that does not shrink but remains large after birth and functions

abnormally. Although the disorder isn't fully understood, the thymus appears to be abnormally overactive, producing cells that attack a neurotransmitter called acetylcholine, which promotes normal muscle contraction in response to nerve impulses. The disease typically causes muscle weakness, often first seen in the eye muscles. Other symptoms include difficulty swallowing, slurred speech and other problems related to poor muscle function.

Thymus cancer: Although rare, 2 types of cancer can develop it the thymus called thymomas and thymic carcinomas. Both develop in populations of cells on the surface of the thymus, but they differ in other respects. Cells in thymomas grow relatively slowly. Thymic carcinoma cells divide rapidly and can quickly spread to other parts of the body. People with myasthenia gravis and other autoimmune disorders are at increased risk for thymomas. Symptoms of thymus cancer may include a cough that doesn't improve, trouble breathing and chest pain. In some cases, few if any symptoms are present in the early stages of the disease.

TREATMENTS: Each type of thymic disorder can be treated and, in many cases, effectively controlled or cured. Congenital immunodeficiency such as that caused by SCID has been successfully treated through bone marrow transplantation or gene therapy. A severe case of DiGeorge syndrome might be treated with a thymus transplant, with milder forms responding to an infusion of extra immune cells. Treatments for myasthenia gravis depend on disease severity. The condition is often controlled through use of medications that improve muscle function or suppress production of abnormal antibodies made by immune cells. Treatments for thymic cancer vary, depending on whether and how far the cancer has spread. Options include surgery, chemotherapy drugs and radiation therapy.

ADRENAL GLAMD:

The adrenal glands also known as suprarenal glands. It Iies immediately above each kidney.

The adrenal glands are located on both sides of the body in the retroperitoneum, above and slightly medial to the kidneys.

The adrenal glands are surrounded by a fatty capsule and lie within the renal fascia, which also surrounds the kidneys.The adrenal glands are directly below the diaphragm, and are attached to the crura of the diaphragm by the renal fascia.In humans, the right adrenal gland is pyramidal in shape, whereas the left is semilunar and somewhat larger.The glands are usually about 5x3 cm in size, and their combined weight in an adult human ranges from 7 to 10 grams.The glands are yellowish in colour.

Each adrenal gland has two distinct parts, each with a unique function, the outer adrenal cortex and the inner medulla, both of which produce hormones.

BLOOD SUPPLY TO ADRENAL GLANDThe adrenal glands have one of the greatest blood supply rates per gram of tissue of any organ: up to 60 small arteries may enter each gland.[19] Three arteries usually supply each adrenal gland:[7]

The superior suprarenal artery, a branch of the inferior phrenic artery The middle suprarenal artery, a direct branch of the abdominal aorta

The inferior suprarenal artery, a branch of the renal artery

These blood vessels supply a network of small arteries within the capsule of the adrenal glands. Thin strands of the capsule enter the glands, carrying blood to them. [7]

Venous blood is drained from the glands by the suprarenal veins, usually one for each gland:[7]

The right suprarenal vein drains into the inferior vena cava The left suprarenal vein drains into the left renal vein or the left inferior phrenic vein.

The central adrenomedullary vein, in the adrenal medulla, is an unusual type of blood vessel. Its structure is different from the other veins in that the smooth muscle in its tunica media (the middle layer of the vessel) is arranged in conspicuous, longitudinally oriented bundles.[2]

ADRENAL CORTEX

The adrenal cortex is the outermost layer of the adrenal gland. Within the cortex are three layers, called “zones” each layer has a distinct appearance, and each has a different function.The adrenal cortex is devoted to production of hormones, namely aldosterone, cortisol, and androgens collectively termed as corticosteroid hormones that have important effects on the metabolism.

Zona glomerulosa

The outermost layer of the adrenal cortex is the zona glomerulosa. It lies immediately under the fibrous capsule of the gland.This layer is the main site for production of aldosterone, a mineralocorticoid, by the action of the enzyme aldosterone synthase. Aldosterone plays an important role in the long-term regulation of blood pressure.

Zona fasciculate .

The zona fasciculata is situated between the zona glomerulosa and zona reticularis.

Zona reticularis .

The innermost cortical layer, the zona reticularis, lies directly adjacent to the medulla. It produces androgens, mainly dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and androstenedione (the precursor to testosterone) in humans.

HORMONES ASSOCIATED WITH ADRENAL CORTEX:

Hormones released by adrenal cortex are termed as CORTICOSTEROID HORMONES that have many important effects on metabolism of the body.

Important corticosteroids are as follows

1. CORTISOL 2. ALDOSTERONE 3. ANDROGENS

Cortisol:They are involved in glucose metabolism and are produced during Anxiety, Fever and diseases. Corticol promotes the hydrolysis of muscle proteins to aminoacids which are ultimately broken down by the liver into glucose.It also reduces inflammatory responses and pain.

Aldosterone:It increases reabsorption of sodium ions and chloride ions by the kidney.It maintains blood pressure and blood volume.

Androgen:The adrenal cortex also produces another group of corticosteroid hormones ANDROGEN similar to testosterone (mae hormone).It is secreted in both sexes. Androgen cause development of secondary male characterstics such as facial hears, deepening of voice and increase in muscle bulk. Excessive secretion of androgen in females leads to masculinization such as appearance of beared in females.

ADRENAL MEDULLA:

The adrenal medulla is at the centre of each adrenal gland, and is surrounded by the adrenal cortex.The adrenal medulla is uder the influence of sympathetic nervous system. The chromaffin cells of the medulla are the body's main source of the adrenaline (Epinephrine) and noradrenaline (Norepinephrine), released by the medulla.

Epinephrine: Epinephrine, produced by the adrenal medulla, causes either smooth muscle relaxation in the airways or contraction of the smooth muscle in arterioles, which results in blood vessel constriction in the kidneys, decreasing or inhibiting blood flow to the

nephrons.Epinephrine is sometimes given by injections as an emergency treatment in cardiac arrest, aphylatic shock, and acute asthama attacks.

Norepinephrine:Norepinephrine, produced by the adrenal medulla, is a stress hormone that increases blood pressure, heart rate, and glucose from energy stores; in the kidneys, it will cause constriction of the smooth muscles, resulting in decreased inhibited flow to the nephrons

Catecholamine:

Any of a class of aromatic amines derived from pyrocatechol that are hormones produced by the adrenal gland.

DISSORDERS:Cushing`s syndrome: Over production of cortisol results in CUSHING`S SYNDROME.This abnormality of cortisol production characterized by obesity, muscle wasting and diabetesHypertension is also featured.

Addison`s disease:Deficient production of hormones by adrenal gland occurs due to the destruction of adrenal gland.This is usually consequence of autoimmune process.It is characterized by weakness low blood sugar level and reduced blood pressure.

Parathyroid gland:

Parathyroid glands are small glands of the endocrine system which are located in the neck behind the thyroid. Parathyroid glands control the calcium in our bodies--how much calcium is in our bones, and how much calcium is in our blood. Calcium is the most important element in our bodies (we use it to control many systems), so calcium is regulated very carefully. Parathyroid glands control the calcium.

THE ROLE OF THE PARATHYROID GLANDS -- TO REGULATE CALCIUM.

The only purpose of the parathyroid glands is to regulate the calcium level in our bodies within a very narrow range so that the nervous and muscular systems can function properly. This is all they do. They measure the amount of calcium in the blood every minute of every day... and if the calcium levels go down a little bit, the parathyroid glands recognize it and make parathyroid hormone (PTH) which goes to the bones and takes some calcium out (makes a withdrawal from the calcium vault) and puts it into the blood. When the calcium in the blood is high enough, then the parathyroids shut down and stop making PTH.

DISORDERS

As a rule, if the calcium level in the blood is low, the parathyroid glands sense this and release PTH. PTH then causes release of calcium from the bones into the bloodstream, increases vitamin D production from the kidney which ultimately increases absorption of calcium from the intestines. If the calcium level is too high, then PTH secretion should decrease to a very low level. 

Hyperparathyroidism

Hyperparathyroidism exists when the parathyroid glands produce too much parathyroid hormone (PTH). This may be due to multiple reasons, and the reason helps determine the appropriate type of treatment. Sometimes treatment is as simple as replacing

vitamin D when the parathyroid gland is responding appropriately to a problem elsewhere in the body. In other cases, there is an issue with the gland itself and surgery is required. Excess parathyroid hormone can lead to negative effects on the body such as osteoporosis w hich can lead to fractures, kidney stones, decreased kidney function, heart disease, pancreatitis, increased acid secretion in the stomach and ulcers. Many patients experience symptoms of fatigue, depression, anxiety, difficulty concentrating, difficulty with their memory, insomnia, generalized muscle aches and pains, frequent urination (especially at night), and constipation. Because these symptoms may be related to many other disorders, it is never known until after treatment whether or not these will improve.

SYMPTOMS:

Symptoms may be so mild and nonspecific that they don't seem at all related to parathyroid function, or they may be severe. The range of signs and symptoms include:

Fragile bones that easily fracture (osteoporosis)

Kidney stones

Excessive urination

Abdominal pain

Tiring easily or weakness

Depression or forgetfulness

Bone and joint pain

Frequent complaints of illness with no apparent cause

Nausea, vomiting or loss of appetite.

Hypoparathyroidism:

The opposite problem, hypoparathyroidism, occurs when the parathyroid glands do not produce enough PTH. This leads to a low blood calcium level and can adversely affect muscle, nerve and other functions.

OVARIES

The ovaries  are female-only endocrine glands in the humabody. The ovaries produce steroid hormones throughout the woman's life-cycle. The quantities of the different hormones produced change with the women age.

HORMONES OF THE OVARIES

Ovaries produce and release two groups of sex hormones—progesterone and estrogen.There are actually three major estrogens, known as estradiol, estrone, and estriol. These substances work together to promote the healthy development of female sex characteristics during puberty and to ensure fertility.Estrogen (estradiol, specifically) is instrumental in breast development, fat distribution in the hips, legs, and breasts, and the development of reproductive organs. To a lesser extent, the ovaries release the hormone relaxin prior to giving birth. Another minor hormone is inhibin, which is important for signaling to the pituitary to inhibit follicle-stimulating hormone secretion.

 

Progesterone and Estrogen Production and FunctionProgesterone and estrogen are necessary to prepare the uterus for menstruation, and their release is triggered by the hypothalamus.

 After puberty, the ovaries release a single egg each month (the ovaries typically alternate releasing an egg)—this is called ovulation. The hypothalamus sends a signal to the pituitary gland to release gonadotrophic substances (follicle stimulating hormone and luteinizing hormone). These hormones are essential to normal reproductive function—including regulation of the menstrual cycle.

 As the egg migrates down the fallopian tube, progesterone is released. It is secreted by a temporary gland formed within the ovary after ovulation called the corpus luteum. Progesterone prepares the body for pregnancy by causing the uterine lining to thicken. If a woman is not pregnant, the corpus luteum disappears.

 If a woman is pregnant, the pregnancy will trigger high levels of estrogen and progesterone, which prevent further eggs from maturing. Progesterone is secreted to prevent uterine contractions that may disturb the growing embryo. The hormone also prepares the breasts for lactation.Increased estrogen levels near the end of pregnancy alert the pituitary gland to release oxytocin, which causes uterine contractions. 

More hormones are released during pregnancy than at any other time of a woman’s life, but during menopause—which marks the end of fertility—estrogen levels fall fast. This can lead to a range of complications. 

 

DISEASES AND DISORDERS OF THE OVARIES

Osteoporosis: Osteoporosis is commonly associated with menopause, just like mood swings and hot flashes. Menopause is marked by the rapid loss of estrogen. The role estrogen play in bone loss can best be described in terms of a battle between osteoclasts (bone absorbing cells) and osteoblasts (bone producing cells). Estrogen is on the side of the osteoblasts, but as the estrogens diminish, the osteoblasts are discouraged from producing more bone. As such, the osteoclasts win by absorbing more bone than is being produced by the osteoblasts.

Ovarian Cancer: Ovarian cancer is an extremely serious, but rare, disease. Its symptoms usually don’t become apparent until the cancer has progressed into the later stages.

Symptoms of ovarian cancer include: persistent abdominal pain, indigestion, bloating, abnormal uterine bleeding, and pain during sexual intercourse. These are common problems, so in the great majority of cases, they will not indicate cancer.

Ovarian Cysts: Ovarian cysts are fluid-filled sacs that affect women of all ages, though mostly women of child-bearing age. Cysts are very common—and they can range in size from a pea to a grapefruit. The majority of cysts are harmless, though larger cysts (those larger than 5 cm in diameter) may need to be surgically removed because large cysts can twist the ovary and disrupt its blood supply.Cysts can form for a variety of reasons. Oftentimes, they’re simply part of normal menstruation. You may experience no symptoms, and the cysts will go away after a few cycles. These are known as functional cysts.

Polycystic Ovary Syndrome: Polycystic means “many cysts.” Interestingly, the National Institutes of Health (NIH) criteria for diagnosing PCOS do not require the presence of polycystic ovaries by pelvic ultrasound. The NIH criteria are based on signs of hyperandrogenism (or elevated androgens) and oligo/amenorrhea.  Other key

characteristics include infertility, irregular menstruation, acne, and increased hair growth on the face and body.

PCOS is essentially caused by a hormone imbalance—many of the symptoms are caused by increased production of androgens. These patients usually have high free testosterone levels.The ovaries have an immensely important role not only in the female reproductive system but in the endocrine system as a whole. The hormones they secrete ensure the proper development of the female body and promote healthy function.

TESTES:Testes are pair of sperm producing organs that maintain the health of the malle reproductive sstem.The testes are known as gonads.Their female counter part ae the

ovaries .In addition of their role in the male repoductive system,the testes also have the distinction of being an endocrine gland because the secete a homone known as testosterone.The testes are twin oval shaped organs .The are located with inthe scotum,which is the loose pouch of skin.while the location makes the testes vulneable to inju ,and povide a cooler temprtaue for the organs.A cooler enviroment is necessar for health sperm

production.

HORMONES:Testes secrete a hormone known as testosterone.

TESTOSTERONE:It is necessar for proper phsical develoment in boys.It is the primary androgen.During pubet ,testosterone is involved in man of the processes that transit a boy to manhood. Healthy development of male sex organ. Growth of facial and bod hair. Increase in height. Maintain libido. Sperm poduction. Maintianing muscle,strenght and mass.

MECHANISM OF ACTION:The hpothalamus and pituitar gland control how much testosterone the testes poduce and secrete.The hpothalamus sends a signal to the pituitar gland to release gonadotrophic substance(FSH and LH).Leutinizing hormone stimulates testosterone production.If too much testosteone is produced the hpothalamus alerts the pituitary gland to make less LH,which tells the testes to decrease testosterone levels.

Maturation of internal genitalia ,develop and maintain the male secondary sex characteistics,maintain spematogenesis.

DIHYDROTESTOSTEONE:Enlargement of external genitalia,enlargement of prostate and penis at puberty ,facia hair ,acne ,recession of hairline.

TESTICULAR DYSFUNTION:

To some extent, it is possible to change testicular size. Short of direct injury or subjecting them to adverse conditions, e.g., higher temperature than they are normally accustomed to, they can be shrunk by competing against their intrinsic hormonal function through the use of externally administered steroidal hormones. Steroids taken for muscle enhancement (especially anabolic steroids) often have the undesired side effect of testicular shrinkage.

Similarly, stimulation of testicular functions via gonadotropic-like hormones may enlarge their size. Testes may shrink or atrophy during hormone replacement therapy or through chemical castration.

In all cases, the loss in testes volume corresponds with a loss of spermatogenesis

TESTICULAR DISEASE:

Testicular cancer:Like any cancer, testicular cancer happens when cells in the testicle develop mutations that cause them to "misbehave." The cells may multiply recklessly and invade areas where they don't belong. In testicular cancer, this process usually creates a slow-growing painless lump or firmness in one testicle. In most cases, the man himself

discovers it at an early stage. If a man gets medical attention early on, testicular cancer is almost always curable.Testicular torsion:"Torsion" means twisting -- and for a testicle, that's not a good thing. When testicular torsion occurs, the twisting kinks -- like a garden hose -- and blocks the blood vessels to one testicle. Certain men have a developmental problem that makes them susceptible to testicular torsion. Although testicular torsion is rare, it is an emergency. Sudden testicular pain demands an immediate trip to the emergency room. If treatment is delayed, the testicle can die. Torsion is most common during puberty - between ages 10 and 15 .

Epididymitis:The epididymis is a long, coiled tube that sits alongside the testicle. Its job is to store sperm while they mature. Epididymitis occurs when the epididymis become inflamed or infected. Sometimes, this is a sexually transmitted infection. More often, epididymitis comes from injury, a buildup of pressure such as after a vasectomy, or from urine backwashing into the tubules during heavy lifting or straining. Epididymitis can cause symptoms ranging from mild irritation to severe testicle pain, swelling, and fever.

Varicocele:Varicocele is a dilation of the veins above the testicle and is usually harmless. Occasionally, however, varicoceles can impair fertility or cause mild to moderate pain.

Hydrocele:Hydrocele refers to a fluid collection surrounding the testicle and is usually benign. But if it is large enough, it can cause pain or pressure. Though men can develop a hydrocele after injury, the majority of men with hydroceles have no obvious trauma or known cause.

TREATMENT:Testicular cancer is treated according to the type of cancer and how far it has spread. Cancer that has not spread from the testicle can be cured by orchiectomy, a surgery to remove the testicle. If it has spread outside the testicle testicular cancer treatments may include surgery to remove the abdominal lymph nodes, chemotherapy, radiation therapy, or a combination of the three. Testicular cancer is one of the most curable cancers. Even after it has spread, testicular cancer is usually curable. The best chances for cure are when the cancer is detected and treated early.Epididymitis is usually treated successfully with antibiotics and anti-inflammatory drugs. Bed rest, pain medications, using an athletic supporter and ice packs on the scrotum may help more severe cases. The pain can resolve very slowly, sometimes taking weeks or months.

Testicular torsion is a true medical emergency. If caught in time, the affected testicle

can be saved. Emergency surgery is usually required to "untwist" the testicle and to prevent it from happening again. During the surgery, the other side is usually fixed, as the condition tends to be bilateral. Varicoceles usually don't require treatment. But for men with varicoceles and impaired fertility, microsurgery to tie off the dilated veins of the varicocele is effective. Varicoceles can also be corrected without surgery by injecting a tiny coil into the abnormal veins.If a hydrocele is very large or causing pain, surgery can usually correct it. Injecting a special material through the scrotal wall can sometimes fix hydroceles without surgery.Hernias are sometimes mistaken for testicular disease. When a lower part of the abdominal wall muscles are weak, part of the intestine can bulge through it. When the intestine pushes into the scrotum, it's called an inguinal hernia -- although the scrotum swells, and it can appear to be a testicular problem. The solution is surgery to fix the weak part of the abdominal wall.

PINEAL GLAND: The pineal gland, also known as the pineal body, conarium or epiphysis cerebri, is a small endocrine gland in the vertebrate brain. The shape of the gland resembles a pine cone, hence its name. The pineal gland is located in the epithalamus, near the center of the brain, between the two hemispheres, tucked in a groove where the two halves of the thalamus join. The pineal gland is the only midline brain structure that is unpaired (azygous). It takes its name from its pine-cone shape.[8]The gland is reddish-gray and about the size of a grain of rice (5–8 mm) in humans. The pineal gland, also called the pineal body, is part of the epithalamus, and lies between the laterally positioned thalamic bodies and behind the habenular commissure. It is located in the quadrigeminal cistern near to the corpora quadrigemina.[9] It is also located behind the third ventricle and is bathed in cerebrospinal fluid supplied through a small pineal recess of the third ventricle which projects into the stalk of the gland.

HORMONES:

MELTONIN:

 is produced within the pineal gland and synthesized from the neurotransmitter serotonin. It is secreted into cerbrospinal fluid of the third ventricle and is directed from there into the blood. Upon entering the bloodstream, melatonin can be circulated throughout the body. Melatonin is also produced by other body cells and organs including retinal cells, white blood cells, gonads, and skin.Melatonin production is vital to the regulation of sleep-wake cycles (circadian rhythm) and its production is determined by light and dark detection. The retina sends signals about light and dark detection to an area of the brain called the hypothalamus. These signals are eventually relayed to the pineal gland.

The more light detected, the less melatonin produced and released into the blood. Melatonin levels are at their highest during the night and this promotes changes in the body that help us to sleep. Low levels of melatonin during daylight hours help us to stay awake. Melatonin has been used in the treatment of sleep related disorders including jet lag and shift-work sleep disorder. In both of these cases, a person's circadian rhythm is disrupted either due to travel across multiple time zones or due to working night shifts or rotating shifts. Melatonin has also been used in the treatment of insomnia and depressive disorder.

Melatonin influences the development of reproductive system structures as well. It inhibits the release of certain reproductive hormones from the pituitary gland that affect male and female reproductive organs. These pituitary hormones, known as gonadotropins, stimulate gonads to release sex hormones. Melatonin therefore regulates sexual development. In animals, melatonin plays a role in regulating mating seasons.

SEROTONIN:

Serotonin impacts every part of your body, from your emotions to your motor skills. Serotonin is considered a natural mood stabilizer. It’s the chemical that helps with sleeping, eating, and digesting. Serotonin also helps:

reduce depression regulate anxiety heal wounds stimulate nausea maintain bone health

DISSORDER:

Depression, peptic ulcers, and sexual dysfunction may be exacerbated by a deficiency of melatonin. Stress and dietary habits may lead to deficiencies of both serotonin and melatonin. Melatonin inhibits the release of cortisol via the release of vasotocin. Abnormal circadian rhythms of cortisol may occur in states of decreased melatonin. A circannual rhythm of melatonin has troughs associated with peaks in the incidence of peptic ulcers and psychotic depression. Psychotic depression is an apparent disorder of the locus ceruleus and/or dorsal raphe nucleus.