Hormonal Control

Physiological Mechanisms

Hormonal Control

Dr Smita Bhatia BP-5, II floor, Shalimar Bagh (West) Delhi 110088 Contact: 27483738 Email: [email protected]

1 Learning objectives Chemical nature of hormones Transport of hormones Mechanism of hormone action Hormone interactions Control of hormone secretion Clearance of hormones Major endocrine glands, their secretions and disorders Hypothalamic-hypophyseal axis Thyroid gland Parathyroid glands Adrenal glands Pancreatic islets Gonads and placenta Thymus Pineal gland Other endocrine tissues

In addition to other homeostatic mechanisms of the body, one of the two major regulatory systems of the body is the endocrine system (the other being the nervous system). This system comprises the endocrine glands that release their secretions, called hormones, into the blood stream which transports it to the various target organs on which these hormones act to activate, inhibit or, modify certain functions. Hormones are released into the blood stream rather than directly reaching the target organs because these glands have no ducts (ductless glands) to convey their secretions (also because there could be many target organs for a single hormone so it would not be possible to take these secretions to each and every organ by means of ducts).

Why do hormones act on certain specific organs and not on others?

This is due to the presence of receptors in/on the target cell. These receptors are protein, or glycoprotein molecules, which can bind to the hormone. The location of receptors differs within a cell for different types of hormones. These receptors may be present: • On the cell: For the protein peptide and catecholamine hormones. • In the cytoplasm of the cell: Steroid hormones (since these hormones can readily enter a cell). • In the cell nucleus: Thyroid hormones (as these hormones can readily enter the cell because of their lipid soluble nature) where they directly affect the genes. A specific change occurs after the hormone binds to the receptor (see mechanism of hormone action). The number of receptors on the cell surface is regulated by the concentration of the circulating hormone. If the concentration is very high the number of receptors decreases so

2 that the cell becomes less sensitive to the hormone. This is known as down-regulation. If the concentration of the hormone becomes low, the number of receptors increases to increase the sensitivity of the cell to the hormone. This is known as up-regulation.

Differences between the two major regulatory systems of the body—the endocrine and the nervous system

Nervous system Endocrine system • Neurotransmitters are released which • Hormones are released which can be act locally carried anywhere in the body • Act on muscle cells, gland cells and • Act on a variety of cells other neurons • Effect of hormones may take seconds • Effect of neurotransmitters occurs to hours to days to occur within a short span of time (msec) • Effect may last for a long time (seconds • Effect lasts for a short time (msec) to days)

Functions of hormones

• Help to regulate the chemical composition and volume of the various components of the body, e.g. plasma, interstitial fluid. • Help regulate the metabolism and energy balance. • Help regulate the contraction of smooth and cardiac muscle fibres. • Help regulate glandular secretion and some immune system activities. • Control growth and development. • Regulate the functioning of the reproductive system. • Help establish circadian rhythms. • Help regulate the interaction between the environment and the body. Chemical nature of hormones

Hormones are of different types: Protein or peptide hormones. These are made up of amino acids. They are water soluble. Peptides are made up of 3 to 49 amino acids. e g. oxytocin and insulin. Protein hormones are made up of 50 to 200 amino acids e.g., thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH). These are produced as biologically inactive precursor molecules (pre-prohormones) by the rough endoplasmic reticulum of the gland cell. These pre- prohormones are then cleaved into prohormones which are also biologically inactive. Prohormones are then packaged into vesicles as hormones by the Golgi body. These vesicles

3 are stored in the cytoplasm near the plasma membrane from where they are secreted by exocytosis on an appropriate stimulus. Steroid hormones. These hormones are derived from cholesterol e.g., testosterone, cortisol, progesterone. They are lipid soluble. These are not stored in the cytoplasm but are synthesized from cholesterol when needed and are secreted directly by passing through the plasma membrane as they are lipid soluble. Biogenic amines. They are derived from amino acids. They are of different types:

• Thyroid hormones and catecholamines. Thyroxine (T4) and triiodothyronine (T3) are secreted by the thyroid gland. Catecholamines include epinephrine and non-epinephrine secreted by the adrenal medulla and dopamine secreted by the hypothalamus and other brain cells. They are all derivatives of the amino acid tyrosine. Thyroxine is synthesized in the thyroid follicles where they are stored with thyroglobulin (a glycoprotein). When needed, thyroxin is released from the thyroglobulin into the blood where it combines with the thyroxin-binding globulin. Catecholamines are stored in the vesicles in the cytoplasm which are released by exocytosis when needed. Catecholamines are water soluble while thyroid hormones are lipid soluble because they are iodinated. • Histamine secreted by the mast cells is derived from amino acid histidine. • Serotonin (or 5-hydroxytrptamine, 5-HT) and melatonin. Both are derived from the amino acid tryptophan. Serotonin is secreted by certain brain cells and melatonin is secreted by the pineal gland. • Eicosanoids. These are different types of hormones derived from the fatty acid arachidonic acid containing 20 carbon atoms. Eicosanoids include prostaglandins (like PGF2α), prostacyclins and leukotrienes. These are water-soluble. • Nitric oxide. Though it is a gas, it is produced as a hormone as well as a neurotransmitter. It is lipid soluble. Transport of hormones

The secretion, transport and mechanism of action of these hormones depends on their polar or non-polar nature i.e., whether they are water soluble or lipid soluble. The water-soluble hormones do not need any carrier molecules in the plasma, where they can circulate freely in the aqueous medium. But lipid-soluble hormones cannot be transported as free molecules in the aqueous plasma and are transported by carrier proteins. In addition to transporting these hormones these carrier proteins also, • Prevent filtration of small lipid hormones through the glomerulus in the kidneys thus increasing their half-life. • Provide a readily available stock of these hormones circulating in the blood.

4 Mechanism of hormone action

Sequence of events of the action of a lipid molecule Lipid soluble hormones Lipid hormone is released from the blood into the Lipid-soluble hormones bind to interstitial space the receptors present inside the target cells because these It crosses the plasma membrane of the cell and binds to hormones can cross the plasma specific receptors inside the cell membrane.

The hormone-receptor complex turns certain specific genes on or off.

Synthesis of certain specific mRNA (and hence specific

5 Water soluble hormones Since these hormone molecules cannot enter the cell they bind to receptors on the surface of the target cell and trigger the formation of another molecule within the cell. Here, the hormone molecule is known as the first messenger molecule and the molecule formed within the cell due to its binding is known as the second messenger.

Sequence of events of the action of a water molecule (Figure 1)

Water-soluble molecule binds to the receptor (it is a transmembrane protein) on the surface of the molecule

Hormone-receptor complex activates a membrane bound (bound to the inner side of the plasma membrane) protein—the G-protein (which binds to a GTP molecule and releases a GDP molecule)

G- protein activates enzyme adenylate cyclase

Adenylate cyclase catalyses the conversion of ATP into cyclic AMP (cAMP). (This cAMP is the second messenger)

cAMP activates a protein kinase

Protein kinase phosphorylates other cellular proteins

On phosphorylation some cellular proteins get activated while some other get inhibited

Some physiological processes are stimulated or inhibited (depending upon whether the protein regulating this process has been activated or inhibited)

After some time an enzyme phosphodiesterase breaks down the second messenger to stop this sequence of events till another hormone molecule binds to the receptors to trigger this again.

Fig 1: Mechanism of G-protein mediated action of water soluble hormones

6 Different protein kinases exist in different cells or within the same cell, while one type of protein kinase may stimulate an activity by phosphorylating a protein another protein kinase may inhibit another activity by phosphorylating another protein. In addition to cAMP, other second messengers include cGMP (cyclic guanosyl monophosphate), inositol phosphate (IP3) and diacyl glycerol (DAG). Nitric oxide which causes vasodilation by stimulating the relaxation of smooth muscle fibres in blood vessels acts by stimulating the formation of cGMP (the secondary messenger) which stimulates the transport of Ca2+ into storage areas of the smooth muscle fibre from the cytosol. When cytosol Ca2+ ion concentration decreases it results in the relaxation of muscle fibres. Some hormones cause the opening or closing of specific ion-channels in the cell membrane to initiate the entry or exit of certain ions to produce a specific effect (this effect may be produced through the G-protein). Hormone interactions The action of a hormone is dependent upon • Its concentration in the plasma • The number of receptors of the hormone • Interaction with other hormones

In addition to the concentration of the hormone and the number of receptors present a hormone’s interaction with other hormones also affects its effectiveness. The different types of interactions that a hormone can have with other hormones are: • Permissive effect. When prior exposure to one hormone facilitates the action of another hormone, e.g. exposure of the uterine cells to estrogen and FSH during follicular phase facilitates the action of progesterone during the luteal phase of the menstrual cycle. Exposure to estrogen and FSH also causes the development of receptors for progesterone in the uterine cells. • Synergistic effect. When the effect of two hormones is greater than their independent effects. Thus, these hormones work together to produce an effect, e.g. both FSH and estrogens are required for the development of an ovarian follicle. • Antagonistic effect. When the effect of one hormone is opposite to the effect of another hormone, e.g. parathyroid hormone from parathyroid gland increases blood calcium levels while calcitonin from C cells of thyroid reduces blood calcium levels. Normally, antagonistic hormones are not released at the same time because that would be a waste of energy. Control of hormone secretion Secretion of a particular hormone can be regulated by three mechanisms: • By neural control, e.g., release of epinephrine and nor-epinephrine from the adrenal medulla is controlled by the sympathetic nervous system.

7 • By another hormone, e.g. release of thyroxin from the thyroid gland is stimulated by the thyroid stimulating hormone (TSH) from the anterior pituitary. • Through negative or positive feedback:

Fig 2: Negative feedback control Negative feedback FSH from anterior pituitary

When the secretion of a hormone is inhibited by Follicles in the ovary are stimulated an effect produced in the target cell, e.g. FSH that

stimulates the secretion of estrogen from the – Estrogen secretion ovary is suppressed when estrogen levels reach a particular concentration. The effect produced Increased levels of estrogen (secretion of estrogens) by a hormone (FSH from

the anterior pituitary) inhibits the secretion of the Shows the negative feedback hormone (FSH) that caused it (Figure 2).

Positive feedback

Secretion of certain hormones is stimulated by the effect that it produces, e.g. oxytocin from the posterior pituitary enhances uterine contractions during parturition (birth of a baby). This causes the baby to descend to the cervix, further stretching the cervix which further stimulates the release of oxytocin. The positive feedback cycle is broken by a sudden change in the events of the cycle, e.g. in case of oxytocin, the cycle breaks when the baby is born. In addition to the positive and negative feedback regulation of the hormone secretion there are periodic variations in their secretion also. These variations are dependent on seasonal changes, the circadian rhythm (an inherent rhythm), aging, stages of development and sleep, e.g., the levels of growth hormone increase during early stages of sleep and then reduce. Clearance of hormones

• Binding with tissue. Once a hormone binds to a receptor, it is internalized and the hormone is degraded and the receptors are recycled. • Metabolic destruction by the tissue, e.g. the water soluble hormones (proteins and catecholamines) are degraded by enzymes in the blood and tissues and excreted by the kidneys. • Excretion by liver into bile, e.g. the steroid hormones which are conjugated in the liver and secreted ("excereted") into the bile. • Excreted by the kidneys.

8 Hormones that are bound to plasma proteins have a longer half life. Half-life of a hormone. The time taken for the levels of a hormone to be reduced to half of its original concentration is known as its "half-life". Hormones like angiotensin II have a half-life of less than a minute while others such as the thyroid hormone (bound to proteins) have a half-life of 1 to 6 days.

9 Major endocrine glands, their secretions and disorders

The major endocrine glands include hypothalamus and pituitary (hypothalamo–hypophyseal system), thyroid, parathyroid, adrenal, pancreas, thymus, pineal gland and the gonads (ovary and testis) (Figure 3).

Pineal Hypothalamo–hypophyseal system

Thyroid

Thymus

Adrenal

Pancreas

Ovary

Testis

Fig 3: Position of the major endocrine glands in the body

Hypothalamo–hypophyseal axis For a long time the pituitary gland (hypophysis) was regarded to be the master gland of the body as it secretes hormones that control the secretion of other glands in the body. Then it was discovered that the pituitary itself is regulated by another gland, the hypothalamus, which secretes a set of regulatory hormones that act on the pituitary. Thus this hypothalamo– hypophyseal axis regulates the activity of various glands in the body (Figure 4).

Hypothalamus

10 It is a part of the brain below the thalamus. It is an important connecting link between the nervous system and the endocrine system because it receives neural inputs from different regions of the brain and influences the secretions of the various hormones in the body through the pituitary gland. It integrates all the sensory inputs received by the brain from the body and acts as a regulatory centre for maintaining body temperature, osmotic balance, heart rate, respiratory rate, etc.

Releasing or inhibiting hormones Control and regulation of hormone secretion Thyrotropin releasing hormone (TRH) Stimulates thyrotropin (TSH) Growth hormone releasing hormone Stimulates growth hormone release (GHRH) Growth hormone inhibiting hormone Inhibits growth hormone release (GHIH) Prolactin releasing hormone (PRH) Stimulates prolactin release Prolactin inhibiting hormone (PIH) or Inhibits prolactin release dopamine Adrenocorticotropic hormone releasing Stimulates adrenocorticotropic hormone hormone (CRH) release Melanocyte stimulating hormone releasing Stimulates melanocyte stimulating hormone hormone (MSHRH) release Melanocyte stimulating hormone inhibiting Inhibits melanocyte stimulating hormones hormone (MSHIH) release

Fig 4: Action of releasing and inhibitory hormones from the hypothalamus and hormones of the anterior pituitary gland

Hypothalamo–hypophyseal portal system The hypothalamus secretes stimulatory (releasing) and inhibitory hormones or factors which stimulate or inhibit the release of hormones from the anterior lobe of the pituitary. These factors are synthesized by the neurosecretory cells of the hypothalamus and released on appropriate stimulation. These factors are not released in the general circulation but a special local network of blood vessels between the hypothalamus and hypophysis—the hypothalamo–hypophyseal portal system (Figure 5).

The hypothalamus receives blood supply from the superior hypophyseal arteries that form the primary capillary plexus in the hypothalamus which join to form the hypophyseal portal veins that branch again in the anterior lobe of the pituitary to form a secondary plexus of the hypophyseal system. The releasing or inhibitory factors released by the hypothalamus are directly brought to the hypophysis through this portal system so that they do not get diluted in the general circulation.

Fig 5: Hypothalamo–hypophyseal portal system

Hypothalamus

Primary capillary plexus Median eminence

Infundibulum Pars tuberalis Adenohypophysis Neurohypophysis Pars distalis

Pars nervosa

Secondary capillary plexus Hypophyseal portal veins

Hypophysis (Pituitary) The hypophysis or pituitary gland is connected to the hypothalamus though a stalk, the infundibulum.

The pituitary consists of two lobes, the anterior lobe or adenohypophysis and the posterior lobe or neurohypophysis. The adenohypophysis has two parts, the lower pars distalis and the upper pars tuberalis which forms a covering around the infundibulum. The neurohypophysis has the lobe like pars nervosa and the infundibulum. During embryonic development a third intermediate lobe called the pars intermedia is present which is lost in the adults but some of its cells get integrated into the pars distalis.

13 Adenohypophysis It consists of five types of cells that secrete seven types of hormones (Figure 6). These are:

Somatotroph 1. Somatotrophs that secrete the growth hormone (GH) or somatotropin 2. Thyrotrophs that secrete the thyroid stimulating hormone (thyrotropin) 3. Gonadotrophs secrete the follicle stimulating hormone (FSH) and Thyrotroph the luteinizing hormone (LH). These two hormones together are known as gonadotropins because they stimulate the gonads to produce specific hormones. 4. Lactotrophs secrete the hormone prolactin.

Gonadotroph 5. Corticotrophs secrete adrenocorticotrophic hormone (ACTH) which stimulates the adrenal cortex to produce adrenocorticoids (cortisol, corticosterone, and aldosterone). Some corticotrophs are the remnants of the pars intermedia and they secrete the melanocyte stimulating hormone (MSH).

Lactotroph

Corticotroph

Fig 6: Cell types of the adenohypophysis Neurohypophysis

This region of pituitary does not synthesize any hormones. It stores and then secretes two hormones which are synthesized in the neurons of the hypothalamus. There are two sets of neurons in the hypothalamus, the supraoptic nucleus and paraventricular nucleus which synthesize hormones and convey them to the posterior pituitary through the nerve fibres of these neurons. These nerve fibres form the axon terminals in the posterior pituitary where these hormones are stored and released on appropriate stimulation. These two hormones are: 1. Oxytocin produced by the paraventricular nucleus. 2. Antidiuretic hormone (ADH) or vasopressin produced by the supraoptic nucleus.

14 Part of Principal cell type Hormones Principal actions Target Disorders pituitary organs Adeno- Somatotroph Growth Growth of body cells especially of General Hyposecretion hypophys hormone (GH) bones of limbs, stimulates protein Dwarfism—Reduced secretion of GH from the anterior is synthesis and inhibits protein pituitary results in stunted growth so the person breakdown, stimulates hydrolysis remains a dwarf. In African Pygmies and Lévi-Lorain of fats, retards use of blood dwarfs, however, the secretion of GH from the glucose for ATP production hypothalamo-hypophyseal tract is normal but (diabetogenic effect). Somatomedin C (a mediator of growth hormone action) levels are low. Levels of GH reduce with age.

Hypersecretion Gigantism—This occurs due to overactivity of the somatotrophs or some tumors in this region of the pituitary causes increased secretion of GH. If this happens before adolescence (before the closure of epiphyseal plates) the person is abnormally tall. If this happens after adolescence the bones become thicker and the soft tissue continues to grow. In his condition, called acromegaly, the hands and feet become greatly enlarged, the lower jaw protrudes out, the forehead slants forwards, and the tongue liver and kidneys also become enlarged. Thyrotroph Thyrotropin or Controls secretion of thyroid Thyroid thyroid hormones gland

stimulating

hormone (TSH) Corticotroph Adrenocorticot Controls secretion of adrenal Adrenal ropic hormone cortex hormones. cortex (ACTH)

15 Lactotroph Prolactin (PRL) Along with other hormones Mammary stimulates milk production, glands participates in control of reproduction, osmoregulation, growth and metabolism Gonadotroph Follicle In males, stimulates Gonads stimulating spermatogenesis. In females hormone stimulates growth of ovarian (FSH) follicles. Luteinizing In females, also causes secretion Gonads hormone (LH) of estrogen & proferone and Or together with FSH, it triggers Interstitial cell ovulation, stimulates conversion of stimulating ovarian follicles into corpus hormone luteum. (ICSH) In males stimulates stimulation of testosterone from interstitial cells of Leydig. Neuro- No hormones are Oxytocin (OT) Stimulates contraction of uterine Uterine phypophy synthesized here. Its muscles during birth; initiates muscles and sis hormones are ejection of milk. mammary synthesized in glands hypothalamus Antidiuretic Stimulates reabsorption of water Kidney, Hyposecretion causes diabetes insipidus. Inability hormone and reduction in urine output; blood of the posterior pituitary to secrete enough ADH can (ADH) or stimulates constriction of blood vessels, be due to head injury, some infections or it may be vasopressin vessels to increase blood pressure, sweat congenital. It can result in loss of water from the reduces sweat secretion from glands body due to the formation of very dilute urine as sweat glands. enough water is not reabsorbed by the kidney tubules resulting in severe dehydration.

16 Thyroid gland

The thyroid gland is an H-shaped gland that lies over the trachea below the larynx with the right and left lateral lobes on either side of it. The lobes are connected by a mass of tissue, called the isthmus. The gland consists of microscopic spherical sacs called thyroid follicles. These contain a colloid, composed of the glycoprotein thyroglobulin bound to thyroid hormones triiodothyronine (T3) and tetraiodothyronine or thyroxine (T4), which fills most of the thyroid gland.

Basement membrane Colloidal secretion

Blood capillary

Larynx Parafollicular cells

Thyroid gland Follicular cell

Trachea

Colloidal secretion

Cuboidal epithelium

Blue arrow shows parafollicular or C-cells that The simple cuboidal epithelium lining the secrete calcitonin which helps lower calcium follicles produce the hormones T3 and T4 levels. These C-cells are actually named for which are stored in the follicles with a being "clear" (as it is lightly stained). Notice glycoprotein, thyroglobulin. Notice that the that they are in the interstitium and do not thyroid is the only gland to store its normally touch the follicles. hormones extracellularly.

17 Thyroid Hormone Principle actions Disorders cell type Follicular Triiodothyronine Increases basal metabolic Hypersecretion is called hyperthyroidism and hyposecretion is called hypothyroidism. cells (T3) rate, stimulates synthesis Hyperthyroidism (toxic goiter, thyrotoxicosis or Grave’s disease). Is caused by an of proteins, increases use autoimmune disorder where antibodies bind to receptors to TSH mimicking its action in of glucose and fatty acids stimulating the thyroid gland. These antibodies are called thyroid-stimulating for ATP production, immunoglobulins. Thyroxine or increases heart strength, It may also be caused by a tumour in the thyroid tissue. Symptoms of hyperthyroidism tetraiodothyronine accelerates body growth include a high state of excitability, increased sweating, intolerance to heat, weight loss, hand (T4) and contribute to the tremors, psychic disorders and protrusion of the eyeballs in most patients. development of nervous Hypothyroidism. There is a reduced secretion of thyroid hormones because of another type system in the embryo. of autoimmune disorder where antibodies destroy the secretory cells. It may also be caused by a deficiency of iodine as it is needed for the synthesis of thyroid hormones. The gland enlarges in order to increase the secretion of hormones. This state of enlarged thyroid gland is called goiter. Hypothyroidism in adults causes myxedema where there is accumulation of a gel-like fluid in the interstitial spaces. 0ther symptoms include swelling of the face, bagginess under the eyes, sluggishness, reduced cardiac output, etc. Hypothyroidism in fetal life, infancy or childhood causes a condition called cretinism. It could be congenital or caused by iodine deficiency. Symptoms include mental retardation and improper body growth. Parafollicular Calcitonin (CT) Lowers blood levels of cells (C- ionic Ca2+ and phosphates cells) by inhibiting bone resorption by osteoclasts and stimulates uptake of calcium and phosphates into the bone matrix. This effect is more predominant in children than in adults.

18 Parathyroid glands

These are small masses of tissue, partially embedded in the posterior surface of the lateral lobes of the thyroid gland.

Oxyphil cells Chief cells

Larynx

Thyroid gland

Parathyroid glands

Trachea

Parathyroid cells (Chief cell) in string-like arrangement on the right and large, clear oxyphil cells (whose function is unknown) to the left.

Hormone and Principal actions Disorders source

2+ 2+ Parathyroid Increases blood Ca and PO4 levels. Hypoparathyroidism occurs when the hormone (PTH) Increases bone resorption by osteoclasts; parathyroid hormone is not secreted in from Chief cells and promotes formation of calcitriol, adequate amounts. This results in decrease in which increases rate of dietary Ca2+ and Ca2+ ion concentration of blood; very low levels Mg2+ absorption, decreases the excretion of calcium result in tetany that could be fatal. of calcium from the kidneys. Hyperparathyroidism is increased secretion of parathyroid hormone and results in an increased plasma Ca2+ ion concentration due to increased bone resorption. This results in weakened bones, depressed peripheral and central nervous system, muscle weakness, constipation, lack of appetite and depressed relaxation of the heart muscle during diastole. Secondary hyperparathyroidism may be caused by vitamin D deficiency where there is a compensatory hyperactivity of the parathyroid gland.

19 Adrenal glands

A pair of adrenal (supra-renal) glands are located, one on each side of the spinal cord, above each kidney. Each gland consists of an outer cortex and inner medulla. The cortex has three distinct layers—zona glomerulosa, zona fasciculata and zona reticularis, each secreting different types of steroids. Medulla as groups of large cells which secrete epinephrine and norepinephrine on sympathetic stimulation (that is why adrenal medulla is considered to be an extension of the sympathetic nervous system).

Adrenal medulla

Adrenal glands Adrenal cortex

Kidney

Capsule

Zona glomerulosa Zona fasciculata

Zona reticularis

Medulla

20 Gland part Cell type Hormone Principal action Target Disorders organ Cortex Zona Mineralocorticoid Controls electrolyte and water balance, Kidney Hyposecretion disorder is called hypoadrenalism or

+ glomerulosa s (mainly increases blood levels of Na and H2O, Addison’s disease. This may be caused by atrophy of the cells aldosterone) decreases blood levels of K+ by cortical cells due to an autoimmune disorder. It may also stimulating kidney tubules to reabsorb be caused by tuberculous infection or cancer. It causes more Na+, Cl– and water and less K+. reduced blood volume, hyponatremia, hyperkalemia, Promotes Na+ resorption and K+ and reduced cardiac output, sluggishness, increased

- HCO3 excretion in sweat glands. It also susceptibility to any kind of stress and increased stimulates Na+ resorption in the large pigmentation of the mucous membranes and skin. intestine. Hypersecretion is called hyperadrenalism or Cushing’s syndrome. It may be caused by an abnormal function of the hypothalamus that causes hypersecretion of the corticotrophin releasing hormone which is turn causes an increased secretion of ACTH and cortisol. It may also be due to an abnormally high secretion of ACTH from the pituitary or hypersecretion of cortisol due to an adrenal cortex adenoma. Symptoms include abnormal deposition of fat in the thoracic and upper abdominal regions, edema, acne, hirsuitism (due to increased levels of androgens). Hypersecretion of only aldosterone from the zona glomerulosa of the adrenal cortex caused by a tumour in this region is known as Conn’s syndrome. It is characterized by hypokalemia, hypernatremia, increased blood volume. Muscle paralysis may occur due to hyperkalemia (which interferes with normal transmission of the action potential), It causes an reduced renin secretion from the kidneys due to increased blood volume. Zona Glucocortiocoids Raises blood glucose level, promotes Liver,

21 fasciculata Cortisol (main), gluconeogenesis in the liver and reduces adipocytes cells corticosterone glucose utilization by cells, reduces and other protein stores in all other cells of the body cells body, except liver cells and plasma, promotes mobilization of fatty acids from adipose tissue and enhances oxidation of fatty acids in the cells, provides general resistance to long term stress by blocking inflammatory and allergic responses. Zona Androgens Assists in early growth of axillary and Gonads Hypersecretion of androgens from the zona reticularis reticularis (main), e.g. pubic hairs in both sexes; in females, it because of a tumour in this part of the adrenal cortex cells dihydroepiandros contributes to libido and is a source of causes the adrenogenital syndrome. It causes terone (DHEA) estrogen after menopause masculinization of the body. If it occurs in a female there is and a development of male characteristics such as a beard, a androstienedione deeper voice, deposition of proteins in the muscles, baldness, etc. If it occurs in a prepubertal male it causes precocious development of secondary sexual characters. Medulla Chromaffin Epinephrine Stimulates elevation of blood glucose by Skeletal cells (adrenaline) conversion of liver glycogen to glucose; muscles, Norepinephrine raises blood pressure; accelerates the cardiac (nor-adrenaline) rate and force of heart beat; causes muscles, constriction of skin and visceral smooth capillaries; causes dilation of vessels of muscles, heart and skeletal muscles; increases blood lipid breakdown, oxygen consumption, vessels, fat erection of hair, dilation of pupils; initiate cells stress response

22 Pancreatic islets

The pancreas is both an endocrine and exocrine gland. It is a flattened organ, about 12.5–15 cm long, located in the curve of the duodenum. Roughly 99% of pancreatic cells are exocrine present in clusters called acini. Interspersed among them are a group of endocrine cells forming lobules known as pancreatic islets or Islets of Langerhans. These islets contain four types of cells— alpha (α), beta (β), delta (δ), and F cells.

Pancreas

Types of cells in the Islet of Langerhans

Capillary

F cell

Alpha cell

Beta cell

Delta cell

23 Cell type Hormone Principal action Target organ Disorders Alpha cells Glucagon • Accelerates breakdown of glycogen into glucose Liver adipose Hypersecretion of insulin is (α cells) Causes lypolysis in liver. tissue called hyperinsulinism. It • Promotes conversion of other nutrients, such as may be caused by an amino acids and lactic acid, into glucose in the adenoma of an Islet of liver (gluconeogenesis). Langerhans. It results in • Enhances the release of glucose into blood. hypoglycemia (reduced Beta cells Insulin • Stimulates glucose transport from blood to Liver, muscle, blood glucose levels) which (β cells) muscles and adipose cells, and stimulates liver adipose tissue, and could be fatal. to take up glucose. body cells • Inhibits gluconeogenesis in the liver. Hyposecretion of insulin or • Promotes both oxidation and conversion of hypoinsulinism causes glucose into glycogen in liver and muscle cells. diabetes mellitus (Type I). • Inhibits metabolic breakdown of stored glycogen In Type II diabetes mellitus in liver and muscle cells. the amount of insulin • Promotes synthesis of fats from glucose by secreted by pancreatic β adipose tissue and also inhibits metabolic cells is normal but the breakdown of fat. response of the cells is not • Promotes uptake of amino acids by liver and (insulin resistance). muscle cells, and stimulates protein synthesis Diabetes mellitus causes while inhibiting protein breakdown. hyperglycemia, glycosuria Delta cells Somatostatin (is a Inhibits secretion of glucagon and insulin; reduces Pancreas (α and β (glucose in urine) polyuria (δ cells) paracrine agent) motility of stomach, duodenum and gall bladder; cells), (increased urine output), reduces secretion and absorption in the digestive gastrointestinal tissue injury, increased tract. tract metabolism of fat, F cells Pancreatic Inhibits somatostatin secretion, gall bladder Pancreas, gall ketoacidosis and depletion polypeptide contraction and secretion of pancreatic digestive bladder of body proteins. (is a paracrine agent) enzymes.

24 Gonads and placenta The testis in males and ovaries in females secrete sex hormones during puberty. These hormones are steroids and responsible for controlling various secondary sexual characters during puberty. The placenta also releases some hormones that are responsible for the maintenance and certain changes during pregnancy.

Ovary Testis Placenta

Ovarian follicle Corpus luteum

Progesterone from the corpus luteum maintains T he Graafian follicle is identified by the large the uterus for implantation. Granulosa luteal antrum (A) and the cumulus oophorous (arrow) cells (GL) and theca luteal cells (TL). that surrounds the actual oocyte and projects i nto the antrum.

Testis

Sperms in different stages of development

Seminiferous tubule

Interstitial cells of Leydig

25 Gland type Hormones Principal action Disorders and part Ovary Ovarian follicle Estrogen (estradiol Stimulates the development and maintenance Hypogonadism: when there is reduced estrogen secretion because and estrone) of female sexual characteristics such as high of poorly formed ovaries or genetically abnormal ovaries female pitch, female voice and female pattern and eunuchism occurs. The female secondary sexual characteristics fail distribution of body hair at puberty. to develop and there is a prolonged growth of bones. The ovarian Together with gonadotropic hormones of the cycles are irregular or there may be complete amenorrhoea. anterior pituitary gland they also regulate menstrual cycle and development of Hypersecretion of estrogens: may occur in case of a granulosa cell secondary sex organs. tumour which usually occurs after menopause. Symptoms include hypertrophy of the endometrium and irregular bleeding.

Corpus luteum Progesterone and Progesterone prepares and maintains the estrogen uterine lining for pregnancy, stimulates mucosal lining of the fallopian tubes to secrete a nutrient-rich fluid, prevents the uterine myometrium from undergoing contractions. Prepares the breast for milk secretion. Estrogen stimulates uterine lining for implantation to maintain pregnancy, prepares the mammary glands for lactation and regulates oogenesis. Relaxin Facilitates accommodation of the growing fetus. Relaxes pubic symphysis and helps dilate uterine cervix near the end of pregnancy. Inhibin Regulates oogenesis by inhibiting FSH and GnRH secretion. Testis Interstitial cells Testosterone Stimulates the descent of testis and male Hypogonadism: where there is a loss of testes or if there is a

26 of Leydig pattern of development (before birth); reduced secretion of GnRH from the hypothalamus (adipose genital stimulates development and maintenance of syndrome or Fröhlich’s syndrome or hypothalamic eunuchism). In male sexual characteristics and expression of the absence of testosterone in an adult some of the secondary male characteristics such as beard, sexual characteristics are lost. In a child these characteristics fail to moustache and low-pitch voice; stimulates develop. spermatogenesis, growth spurt, protein synthesis and muscle development, bone Hypergonadism: refers to an increased secretion of testosterone growth, stimulate secretion of erythropoietin due to tumour of Leydig cells. This causes an abnormally increased from the kidneys; increases basal muscle growth, reduced height (as the epiphyseal plates close metabolism. early) and excessive development of male sexual characteristics. Sertoli cells Inhibin Regulates spermatogenesis by inhibiting FSH secretion. Placenta Human chorionic Stimulates progesterone release from the gonadotropin corpus luteum and maintains it. It has an (HCG) interstitial cell stimulating effect in a male fetus. Simulates mammary gland growth or during pregnancy. Has weak growth hormone Human placental like effects. Decreases insulin sensitivity and lactogen glucose utilization by the mother’s cells so that glucose is made available to the fetus. It also mobilizes fatty acids from mother’s fat stores.

27 Thymus The thymus is located behind the sternum. It consists of two lobes separated from one another by a connective tissue capsule. Extensions of this capsule penetrate in the form of septa or trabeculae to divide each lobe into lobules. Each lobule has a lighter staining central medulla surrounded by a darkly staining outer cortex. The cortex contains T cells which proliferate and mature in the thymus; dendritic cells that assist the maturing T cells and epithelial cells with long processes form a framework for the maturing T cells. The medulla consists of more mature T cells, epithelial cells and macrophages. Clusters of flattened degenerate epithelial cells are arranged in concentric layers called Hassall’s (thymic) corpuscles. In infants, the thymus is large but it starts degenerating after puberty and is almost absent in old age. Thymus

Source: http://www.cytochemistry.net/microanatomy/immune_system/lymphoid_tissues.htm © copyright 1998 Gwen V. Childs, Ph.D. URL Address: http://cellbio.utmb.edu/microanatomy/ Gwen V. Childs, Ph.D., WebMistress [email protected]

Thymus Hormones Principal action Thymosin, thymic humoral factor, Promote the proliferation and thymic factor, thymopoietin maturation of T-cells (derived from lymphocytes)

28 Pineal gland It is a small endocrine gland attached to the roof of the third ventricle of the brain at the midline. It is covered by a capsule formed by pia mater and consists of masses of neuroglia and secretory cells called pinealocytes.

It secretes the hormone melatonin, which is believed to help in maintaining the biological clock, as it is produced when no light stimulus is present and its production ceases when eye receives light stimulus.

Cerebral cortex

Pineal gland

Hypothalamus

Pituitary

Pineal gland Hormones Principal action Melatonin Involved with the setting of the biological clock in the body. Controls seasonal fertility in some animals.

Other endocrine tissues Some tissues other than those described already, contain endocrine cells which secrete hormones. Along with these hormones some growth factors are also produced which stimulate cell growth and division.

29 Production site Hormone or Principal action growth factor Gastrointestinal tract G-cells of the stomach Gastrin Promotes secretion of gastric juice and increases motility of the stomach.

Enteroendocrine cells of Glucose-dependent Stimulates release of insulin by pancreatic β cells, inhibits the duodenum insulinotropic peptide gastric secretion. (GIP)

– Secretin Stimulates secretion of pancreatic juice rich in HCO3 ions and bile; reduces gastric secretion and motility. Cholecystokinin Stimulates secretion of pancreatic juice rich in enzymes, (CCK) release of bile from the gall bladder and brings about the feeling of fullness after eating.

Vasoactive intestinal Inhibits gastric secretion and motility polypeptide (VIP)

Oxyntic cells of the Ghrelin Stimulates food intake stomach and cells of the intestine

Liver Angiotensinogen gets Causes vasoconstriction, enhances reabsorption of sodium converted to and chloride ions and water, stimulates the release of angiotensin I which aldosterone from adrenal cortex which further stimulates gets converted to reabsorption of sodium and chloride ions from the kidney angiotensin II tubules. All this results in increased blood volume and blood pressure. Kidneys Erythropoetin (EPO) Increases rate of red blood cell formation. Calcitriol (active Aids in the absorption of dietary calcium and phosphorus. vitamin D) Heart Atrial natriuretic Decreases blood pressure and blood volume by peptide (ANP) stimulating the excretion of Na+ ions from the kidney tubules. Adipose tissue Leptin Suppresses appetite, stimulates the release of corticotropin releasing hormone that decreases food intake, increases sympathetic activity resulting in an increased metabolic rate and energy expenditure, suppresses the release of appetite stimulators from the hypothalamus. Submaxillary salivary Epidermal growth Stimulates proliferation of epithelial cells, fibroblasts, gland factor (EGF) neurons and astrocytes; suppresses some cancer cells and

30 secretion of gastric juice by the stomach. Nerve growth factor Stimulates the growth of ganglia in embryonic life, (NGF) maintains sympathetic nervous system, and stimulates differentiation of neurons. Blood platelets Platelet-derived Found in blood; stimulates proliferation of neuroglial cells, growth factor (PGF) smooth muscle fibres, and fibroblasts; may have a role in wound healing; may contribute to the development or artherosclerosis. Pituitary and brain Fibroblast growth Stimulates proliferation of many cells derived from factor (FGF) embryonic mesoderm (fibroblasts, adrenocortical cells, smooth muscle fibers, chondrocytes and endothelial cells); stimulates cell migration and growth and production of fibronectin (an adhesion protein). Normal and tumor Tumor angiogenesis Stimulates growth of new capillaries, organ regeneration cells factor (TAFs) and wound healing. Various cells Transforming growth Some have activities similar to epidermal growth factor, factors others inhibit proliferation of many cell types.