The Endocrine System

Chapter 6

The Endocrine System

 

Introduction 

• The coordinated functioning of body is brought about by two systems working in close association with each other, the nervous system and the endocrine system. These two systems are integrated so thoroughly to regulate body functions that these are sometimes referred as neuroendocrine system.

• Endocrine Glands

• Embryologically, all glands originate from the epithelium and most of the glands retain their connection with epithelium. This connection serves as a duct that carries the secretion of the gland to a particular site. Such glands are known as exocrine glands. The glands which do not retain their connection with epithelium are ductless and they pour their secretions into surrounding tissue, further, to pour these secretions into the blood stream. These ductless glands are known as endocrine glands and their secretions as hormones. Besides endocrine glands certain organs of the body contain endocrine tissue (organ is not exclusively endocrine). The endocrine glands and endocrine tissues together constitute the endocrine system. Fig. 6.1 shows location of endocrine glands and endocrine tissues in the body.

• The Neuroendocrine System

• Certain parts of nervous system (e.g. Hypothalamus) stimulate or inhibit the release of hormones by endocrine glands. Certain hormones may initiate or inhibit nerve impulses, while certain hormones may act as neurotransmitters. Nervous system initiates and controls activities of the body through nerve impulses carried by nerves to the effector organs. The endocrine system releases hormones that are carried by blood to target organs to initiate and control their activities. In general, the nervous system regulates the rapidly changing activities such as skeletal movements, smooth muscle contractions and glandular secretions. The endocrine system regulates the metabolic functions of the body. Moreover, one of the mechanisms by which the hormone secretions of the endocrine glands are regulated is through signals from nervous system.

Hormones 

• The chemical substances which are formed in one particular endocrine gland/endocrine tissue and are carried by blood stream to another organ (target organ) where it has an effect on its functions, growth and nutrition are termed as hormones. Hormones that are carried by blood stream to distant target cells are called circulating hormones. The hormones that act on target cells close to their site of release are called local hormones. Histamine is a local hormone that acts on neighboring cells. Certain local hormones act on the cells that secrete them, such local hormones, e.g. interleukin 2, are known as autocrine. Hormones secreted by variety of endocrine structures differ widely in their chemical nature. Chemically, the hormones can be classified into four classes as follows:

• 1. Steroids: These have steroid nucleus and are derived from cholesterol. They are synthesized on smooth endoplasmic reticulum, e.g. hormones of adrenal cortex: Aldosterone, Cortisol; Hormones of gonads: testosterone, estrogens and progesterone. 

• 2. Biogenic amines: Synthesized from amino acids are: catecholamines - dopamine, noradrenaline, adrenaline histamine and serotonin. 

• 3. Peptides and Proteins: These are synthesized on granular endoplasmic reticulum and consist of chain of amino acids. Hypothalamic releasing and release inhibiting factors: Insulin, Glucagon, Parathormone, Calcitonin. 4. Eicosanoids: They are derived from arachidonic acid (fatty acid). Examples: Prostaglandins, Leukotrienes.

Mechanism of Hormone Action 

• The circulating blood transports the hormones virtually to all cells in the body. Only those cells (target cells) possessing the hormone receptors respond to the hormones and all other cells of the body do not respond. The receptors are macromolecules; protein or glycoprotein on the cell membrane with which the hormones bind chemically and initiate the response. The response to hormone is specific to target cell and various target cells may respond differently to the same hormone. There are several different mechanisms of hormone action.

• (a) Action on Plasma Membrane Receptors The free fraction of hormone (not bound to proteins in blood) diffuse out of the blood capillaries, it binds to the receptors on cell membranes of target cells. This binding of the hormone to its receptor activates many G-protein molecules on the inner surface of the cell membrane. Activated G-protein molecules then activate the intracellular enzyme adenylate cyclase. The activated adenylate cyclase converts ATP (Adenosine Triphosphate) to 3, 5' cyclic adenosine monophosphate (cyclic AMP or CAMP). In this scheme, the hormone is viewed as a first messenger and the cyclic AMP as a second messenger for cell activation. The cyclic AMP then activates protein kinase, activated protein kinase, phosphorylases other enzymes in the cell. Numerous such phosphorylated enzymes catalyze reactions that produce physiological responses. Phosphorylation may activate the enzyme or inactivate it. The result of phosphorylation of a particular enzyme could be regulation of other enzymes, secretion, protein synthesis or changes in the membrane permeability of the cell.

• (b) The Action on Intracellular Receptors The fat-soluble steroidal hormones enter the target cells and bind to the receptors usually present in the nucleus. This hormone-receptor complex then through gene expression forms new messenger RNA (mRNA). Under the direction of mRNA new protein will be synthesized by ribosomes. This new protein initiates change in cell activity which is characteristic of the hormone.

Control of Hormonal Secretions 

• The endocrine glands in general tend to over secrete their hormones. When effects are attained, the gland is inhibited to secrete further. If there is under secretion, the effect also decreases, and the feedback mechanism promotes gland to secrete more hormone. The stimulus to gland for production or inhibition of its hormone is either by direct nervous stimulation, chemical changes in the blood or presence of the other hormones. Most often hormone secretion is regulated by negative feedback mechanism. The anterior pituitary gland secretes hormones that regulate the secretion of hormone of most of the other endocrine glands. 

• The secretion of anterior pituitary hormone is regulated mainly by hypothalamic releasing and inhibiting hormones and negative feedback from target gland hormones. Whenever there is decrease in the level of a hormone in the blood, hypothalamus produces appropriate releasing factor which stimulates release of tropic hormone by the anterior pituitary which in turn stimulates the target gland to produce and release its hormone. When the blood level of hormone rises, it inhibits the secretion of releasing factor by the hypothalamus and vice versa. 

• Hormones once formed do not last longer but are metabolized in liver and excreted in urine. Hepatic and kidney disorders may alter the rate of destruction of hormones.

Pituitary Gland

• The pituitary gland (hypophysis) is located beneath the brain in the Sella Taurica of sphenoid bone. It consists of two lobes derived from the different embryological origins. The anterior lobe (Adenohypophysis) is developed from ectodermic tissue from the roof of the mouth. The posterior lobe (Neurohypophyses) is derived from ectodermic tissue from the floor of the brain. The gland is attached to the hypothalamus by a stalk like structure called infundibulum. 

 Anterior Pituitary Gland (Adenohypophysis)

• The hypothalamic hormones release, and inhibition is regulated by the secretion of hormones by adenohypophysis. Adenohypophysis though not directly connected with hypothalamus; their association is by way of the circulatory system. The blood in the primary capillary plexus within the lower hypothalamic region of brain; by way of hypophysis portal veins flows directly to secondary capillary plexus in the adenohypophysis. Several hormones are secreted by the adenohypophysis regulating wide range of body activities. The target cells for the hormones of adenohypophysis are mainly the other endocrine glands in the body. These hormones influencing activity of the other endocrine glands are known as tropine or tropic hormones. Anterior pituitary secretes seven different hormones: Human growth hormone (somatotrophs), Prolactin (lactotrophs), Adrenocorticotropic hormone (corticotrophin), Thyroid stimulating hormone (Thyrotrophs), Follicle-stimulating hormone (FSH) and luteinizing hormone (Gonadotrophs). 

• Its exact role in human beings is not known. In amphibians, it increases skin pigmentation and hence, darkening of skin.

 Posterior Pituitary Gland (Neurohypophysis)

• Antidiabetic hormone and oxytocin are two hormones released from Neurohypophysis. In fact these are not synthesized in Neurohypophyses but are secreted by specialized neural cells called neurosecretory cells located in the hypothalamus. A carrier protein, neutrophilia transports these hormones to posterior lobe of pituitary gland. These hormones are released in response to the nerve impulses received from different cells in the body.

• 1. Antdiuretic Hormone (ADH) ADH promotes reabsorption of water by Nephron tubules, resulting into reduction in urine output and the retention of fluid within the body. Release of ADH is dependent on the body's state of hydration. In dehydration, with low water content of blood, the osmotic pressure of blood changes and the osmoreceptors in hypothalamus stimulate production and release of ADH. Conversely, when water content of the blood increases, the osmoreceptors inhibit production and release of ADH. ADH also causes constriction of arterioles and raise blood pressure. For this effect it is also called as vasopressin.

•  2. Oxytocin It has a major role to play during and after the birth of a baby. During delivery it stimulates contraction of smooth muscles of uterus. After birth it stimulates contraction of myoepithelial cells surrounding the sac like alveoli of mammary glands resulting into 'let down' of milk. Large amount of oxytocin is released during Laboure and delivery. When baby's head or body stretches the cervix during Laboure, the stretch receptors in the cervix sends impulses to the hypothalamus. These impulses cause posterior pituitary to release oxytocin into blood stream. The milk ejection reflex is initiated when baby starts sucking. Stimulation of touch receptors in the nipple sends impulses to hypothalamus, resulting into release of oxytocin in blood. The role of oxytocin in males and in non-pregnant females is not known.

 Thyroid Gland 

It is one of the largest endocrine glands of the body. It originates in the floor of pharynx as an epithelial thickening. The thickening grows outward from the pharynx and loses its connection with the gastrointestinal tract It further develops as two lobes laterally to trachea, below larynx. The two lobes are connected by a thin band of tissue on the anterior side called as isthmus. The gland is highly vascularized and receives high blood supply. The gland is composed of hollow spherical follicles lined by cuboidal cells. The shape of follicular cells varies with their activity, they become taller and more columnar when actively secreting and flatten when inactive. The follicular cells secrete hormones, thyroxin (Ta) and Triiodothyronine (T3). A few cells lie between follicles and are called as par follicular cells which secrete hormone, calcitonin.

• Synthesis of Thyroid Hormones

•  Iodine absorbed from gastrointestinal tract appears in the blood as inorganic iodide. The follicular cells of thyroid gland take up this iodine (Trapping of Lodine). The iodide ions are oxidized in the follicular cells and the elemental iodine formed is secreted into lumen of the follicle. The follicular cells synthesize thymoglobulin (TGB) that contains tyrosine as one of the amino acids. Follicular cells secrete this thymoglobulin (TGB) into the lumen of the follicle. The lumen containing TGB and iodine is called as colloid. In colloid, the Lodine attaches to tyrosine amino acids of TGB. Binding of one iodine yields monoiodotyrosine (MIT) and second iodination gives diodotyrosine (DIT). Further MIT and DIT join to form Triiodothyronine (T3) and DIT join to form thyroxin. The colloid containing these hormones is then taken up by the follicular cells by Pinocytosis. On stimulation by TSH these hormones are released by diffusion through membrane into blood stream. In blood the thyroid hormones are bound to plasma protein known as Thyroid Binding Globulin (TBG). 

• Disorders of the Thyroid Gland 

• The disorders (Hyposecretion or hypersecretion) of thyroid gland result into variety of pathological conditions depending on the age group of individuals. At younger age, the hyposecretion leads to failure in development of skeleton and brain, this results into cretinism. The cretins thus show dwarfism and mental retardation. There is also retardation of sexual development. 

Parathyroid Glands

• Four small glands located, two on each side, on the dorsal surface of thyroid gland are the parathyroid glands. Structurally, the glands are composed of closely packed epithelial cells receiving rich blood supply. They secrete a protein hormone called as parathyroid hormone or Parathormone. Its role is to maintain the level of calcium in the blood. It enhances absorption of calcium from intestine in presence of vitamin D. It increases reabsorption of both calcium and phosphorous in renal tubules. The excess secretion (hyperparathyroidism) raises plasma calcium level and causes extensive decalcification of bones, leading to deformities and fracture. The hyposecretion effect leads to decrease in calcium level that increases excitability of nervous system resulting into muscular spasm and twitching. 

Adrenal Glands

• Two glands located on superior portion of each kidney are the adrenal or suprarenal glands. Each gland has two distinct parts the inner part called adrenal medulla is surrounded by the outer part, adrenal cortex. The hormones secreted and their functions of two parts of gland are quite different.

• Adrenal cortex: 

• Embryologically, it is developed from mesoderm. It secretes the steroid hormones that are essential for life. The removal of adrenal cortex leads rapidly to death within a week. This is mainly because of deficiency of aldosterone, a hormone that regulates blood sodium (Na+) level. Loss of Na+ leads to hypotensive shock and death. A group of steroid hormones secreted by adrenal cortex are called as corticosteroids. These include mainly two types, the mineral corticoids and glucocorticoids. In addition, it also secretes small quantities of androgenic and estrogenic hormones.

• Adrenal Medulla Embryologically, the adrenal medulla is developed from neural crest cells. It functions in a manner similar to postganglionic sympathetic nerve cells, and hence, may be regarded as a modified sympathetic ganglion. Adrenal Medullary Hormones It secretes two hormones, both having catechol nucleus and amino group. These hormones are called as epinephrine (Adrenaline) and nor-epinephrine (Nor-adrenaline). The physiological effects of these hormones are same as that of sympathetic nervous system; hence these are also called as sympathomimetic amines. They show effect on the organs.

Pancreas 

• It is located in the abdominal cavity behind and slightly inferior to stomach, between duodenum and spleen. It is both exocrine and endocrine gland. The endocrine portion of the gland consists of groups of tiny cells scattered in exocrine portion. These cells are known as islets of Langerhans. Four types of such cells have been identified secreting different hormones.

• (a) Alpha cells secrete the hormone glucagon.

• (b) Beta cells secrete the hormone insulin.

• (C) Delta cells secrete the hormone Somatostatin or Growth Hormone Inhibiting Hormone (GHIH) and (d) F-cells secrete pancreatic polypeptide. The exact origin of these endocrine cells is not known. The pancreatic endocrine cells have rich blood supply and are innervated by both sympathetic and parasympathetic nerves. Pancreatic Hormones 

• 1. Insulin The beta cells of islets of Langerhans produce insulin. Insulin facilitates the transport of glucose into the cells (Glucose uptake). It enhances the glycogenesis (conversion of glucose into glycogen). It accelerates conversion of glucose into fatty acids (Lipogenesis) and reduces gluconeogenesis (formation of glucose from non-carbohydrate sources). All these effects lead to decrease in glucose level of blood. (Hypoglycemia) 

• 2. Glucagon The alpha cells of islets of Langerhans secrete glucagon. It has opposite effects to that of insulin. It increases the blood glucose level. In liver, it accelerates the conversion of glycogen into glucose (Glycogenolysis). It promotes gluconeogenesis and enhances the release of glucose into blood.

• . 3Somatostatin 6.13 The Endocrine System The hormone secreted by delta cells of Islets of Langerhans is Somatostatin. It acts as a peregrine to inhibit the secretion of alpha and beta cells of Islets. 4. The pancreatic polypeptide secreted by F-cells regulates the release of pancreatic digestive enzymes. Release of Pancreatic Hormones Release of Pancreatic hormones is controlled by chemical, hormonal and neural stimuli. The blood glucose level appears to be the major factor that governs the release of both insulin and glucagon. Higher blood glucose level stimulates insulin release while lower blood glucose level stimulates glucagon release. The hormones secreted by cells of gastrointestinal tract such as secretin, gastrin, cholecystokinin promote insulin release. Somatostatin inhibits secretion of both insulin and glucagon. Parasympathetic activity releasing acetylcholine stimulates insulin release while sympathetic transmitters epinephrine and nor-epinephrine inhibit insulin release. 

Pineal Gland 

• A small structure in the brain recognized as a pineal body attached to the roof of third ventricle has an endocrine function. It secretes a hormone called as melatonin. The physiological role of melatonin in human beings is not yet clear.

Thymus Gland

• It is situated in the superior mediastinum, posterior to sternum, between the lungs. Some of the lymphocytes derived in the red bone marrow migrate to thymus gland. They develop and mature there as T' cells. The T' cells then migrate to lymph nodes and spleen. The hormones produced by thymus gland are the thymosin, thyme factor and thymopoietin. These hormones promote maturation of T' cells. The T' cells are involved in development of "cell mediated immunity" of the body.