HORMONES

HORMONES

6.  HORMONES

Have you ever wondered how exactly cells which are far away from each other in the body communicate and coordinate with each other? LET'S TALK about it…
The various functions of the cells, tissues, and organs of the body are coordinated by the several types of chemical messenger systems:
a.     Neurotransmitters are released by neurons and act locally to control nerve cell functions.
b.     Endocrine hormones are released by ductless glands into the blood.
c.     Neuroendocrine hormones are secreted by neurons into the circulating blood.
d.     Paracrines hormones are secreted by cells into the extracellular fluid and affect a different type of neighbouring cells.
e.     Autocrine hormones are secreted by cells into the extracellular fluid and affect the function of the same cells that produced them by binding to cell surface receptors.
f.     Cytokines are peptides secreted by cells into the extracellular fluid which can function as autocrine, paracrine, or endocrine hormones. Examples of cytokines include the interleukins and other lymphokines that are secreted by helper cells and act on other cells of the immune system. Cytokine hormones (e.g., leptin) produced by adipocytes are sometimes called adipokines.
Many of the body’s chemical messenger systems interact with one another to maintain homeostasis. These endocrine hormones are transported by our circulatory system throughout the body and act on various cells depending upon where the receptor of that specific hormone is present. 
Now let’s talk about the chemical nature of these hormones.
These hormones can be Protein/Polypeptide, Steroid or simply derivatives of amino acid tyrosine.
6.1.    Protein/Polypeptide Hormones:
Most of the hormones are made up of proteins and are synthesised in secreting cell as large Pre-Hormone and are cleaved to prohormone in endoplasmic reticulum then packed by Golgi complex and are then stored in vesicles whose enzymes cleave prohormone into the active hormone. Vesicles remain stored in cytoplasm attached to the cell membrane in most cases. When an appropriate signal is received, the concentration of calcium is increased in cell and vesicles release the hormone in the bloodstream by exocytosis. The peptide hormones are water soluble hence easily enter into the circulatory system and they are carried to their target tissues.
Examples: Hormones secreted by the anterior and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone)
6.2.    Steroid Hormone:
These hormones are derived from cholesterol and there is very low storage of these hormones. This is because steroids are lipid soluble and have to be diffused immediately.
Amine Hormones are derived from Tyrosine. 
Mainly there are two types of hormones derived from tyrosine, the thyroid and the adrenal medullary hormones.
Example: T3, T4, Epinephrine, Nor-epinephrine
6.3.    Eicosanoids:- Prostaglandin and leukotrienes are water soluble and derived from arachidonic acid which is a 20 carbon fatty acid.
Now, Since we know the chemical nature of hormones, let’s talk about their concentration and transportation in blood.
Hormones are required in a minute amount in blood ranging from a few picograms to microgram per ml of blood. Their level in blood is controlled by the feedback mechanism. A negative feedback mechanism works, if the amount of hormone increase in blood. In negative feedback, one of hormones product provides an inhibitory effect on its secretion. Also, hormone secretion is increased by the positive feedback of some chemicals. e.g. LH surge is caused by the positive feedback of estrogen.
Apart from this, there is cyclical variation in hormone concentration depending upon age, season etc. Which have a superimposed effect over negative + positive feedback? Once hormones released in blood these can be transported in two ways. Protein and amino acid hormones are transported in water-soluble form while steroid hormones are transported in blood plasma associated form with some plasma proteins. 
6.4.    “Clearance” of Hormones from the Blood
Two factors can increase or decrease the concentration of a hormone in the blood. One of these is the rate of hormone secretion into the blood. The second is the rate of removal of the hormone from the blood, which is called the metabolic clearance rate.
Metabolic clearance rate = Rate of disappearance of hormone from the plasma/Concentration of hormone in each millilitre of plasma
Hormones are “cleared” from the plasma in several ways, including :
(1)     Metabolic destruction by the tissues, 
(2)     binding with the tissues, 
(3)     excretion by the liver into the bile 
(4)     excretion by the kidneys into the urine.
Now let’s talk about the Mechanism of action of these hormones:
The first step of a hormone’s action is to bind to the specific receptors at the target cell. Cells that lack receptors for the hormones do not respond. When the hormone combines with its receptor, this usually initiates a cascade of reactions in the cell, with each stage becoming more powerfully activated so that even small concentrations of the hormone can have a large effect.
The locations for the different types of hormone receptors are the following:
1.    Inside or on the surface of the cell membrane. The membrane receptors are specific mostly for the protein, peptide, and catecholamine hormones
2.    In the cell cytoplasm. The primary receptors for the different steroid hormones are found mainly in the  cytoplasm
3.    In the cell nucleus. The receptors for the thyroid hormones are found in the nucleus and are believed to be located in direct association with one or more of the chromosomes.
These receptors can be of many types. They may be ion-channel linked hormone receptors like in case of neurotransmitters which release acetylcholine, or G- a protein linked hormone receptors or may be linked to some enzyme.
Several hormones, including adrenal and gonadal steroid hormones, thyroid hormones, retinoid hormones, and vitamin D, bind with protein receptors inside the cell rather than on the cell membrane. Because these hormones are lipid soluble, they readily cross the cell membrane and interact with receptors in the cytoplasm or nucleus. The activated hormone-receptor complex then binds with a specific regulatory (promoter) sequence of the DNA called the hormone response element, and in this manner either activates or represses transcription of specific genes and formation of messenger RNA (mRNA).
6.5.    Second Messenger Mechanisms for Mediating Intracellular Hormonal Functions
One of the means by which hormones exert intracellular actions is to stimulate the formation of the second messenger cAMP inside the cell membrane. The cAMP then causes subsequent intracellular effects of the hormone. Thus, the only direct effect that the hormone has on the cell is to activate a single type of membrane receptor. The second messenger does the rest.
Beside cAMP, other secondary messengers are calmodulin and products of phospholipid breakdown. (e.g. IP3).
Now since we have discussed basic functions of hormones, in general, Let’s talk about some important Endocrine.
6.6.    Types of Glands :  
6.6.1.    Pituitary Gland
The pituitary gland lies in a cavity of the skull known as sella turcica. It is also called the hypophysis. The pituitary gland is divisible into two parts: the anterior pituitary (adenohypophysis) and the posterior pituitary (neurohypophysis). Between these, there is a small. The avascular zone called the pars intermedia, which is almost absent in the human being but is much larger and much more functional in some lower animals.

Hormones of anterior pitutors
Adenohypophysis (Anterior Pituitary) and Neurohypophysis (Posterior Pituitary) secrete their respective hormones  
Six important peptide hormones plus several less important ones are secreted by the anterior pituitary :
•     Growth hormone (GH) promotes the growth of the entire body by affecting protein formation, cell multiplication and cell differentiation.
•     Adrenocorticotropin (ACTH) (corticotropin)controls the secretion of some of the adrenocortical hormones. Which affect the metabolism of glucose, proteins and fats.
•     Thyroid-stimulating hormone (TSH) (thyrotropin) controls the rate of secretion of thyroxine and triiodothyronine by the thyroid gland, and these hormones control the rates of most intracellular chemical reactions in the body.
•     Prolactin promotes mammary gland development and milk production.
•     Two different Gonadotropic hormones i.e. follicle-stimulating hormone and luteinizing hormone, control growth of the ovaries and testes, as well as their hormonal and reproductive activities.
The two hormones secreted by the posterior pituitary play other roles.
Hormones of posterior pituitary 
•     Antidiuretic hormone (ADH) (vasopressin) which regulates the amount of water excretion into the urine. Hence, helping in controlling the concentration of water in the body fluids.
•     Oxytocin helps the release of milk from the mammary glands to the nipples during milk sucking and also plays important role in the delivery of the baby at the end of gestation.
Tropic Hormone: Those anterior pituitary hormones that all act on other endocrine glands.

6.6.3.    Development of anterior pituitary :
Anterior Pituitary originally ectodermal in origin arise from a primordial Rathke’s Pouch which comes in contact with cells of the diencephalon. 
Hypothalamus Controls Pituitary Secretion: Almost all secretion by the pituitary is controlled by either hormonal or nervous signals from the hypothalamus. Secretion from the posterior pituitary is controlled by nerve signals that originate in the hypothalamus and terminate in the posterior pituitary. In contrast, secretion by the anterior pituitary is controlled by hormones called hypothalamic releasing and hypothalamic inhibitory hormones (or factors) secreted within the hypothalamus itself and then conducted,  to the anterior pituitary through minute blood vessels called hypothalamic-hypophyseal portal vessels. Hypothalamic releasing and Inhibitory Hormones are Secreted into the Median Eminence.
6.7.    Hypothalamic :
The hypophyseal portal system connects Hypothalamus with anterior pituitary which allows the fast response of hormones between both glands. In this portal system, the blood flows from the primary plexus of the hypophyseal portal system into hypothalamic portal veins and then into secondary plexus present in the anterior pituitary.


6.8.    Hormones of Anterior Pituitary
6.8.1.    Growth Hormone:
Growth hormone or somatotropin exerts its effects directly on all or almost all tissues of the body. It causes the growth of almost all tissues of the body that are capable of growing. It promotes an increase in sizes of the cells, increases in mitosis. Resulting from greater numbers of cells and specific differentiation of certain types of cells such as bone growth cells and early muscle cells.
Aside from its general effect in causing growth, growth hormone has multiple specific metabolic effects, including (1) increased rate of protein synthesis in most cells of the body; (2) increased mobilization of fatty acids from adipose tissue, increased free fatty acids in the blood, and increased use of fatty acids for energy; and (3) decreased rate of glucose utilization throughout the body. Thus, in fact, growth hormone enhances body protein, uses up fat stores, and conserves carbohydrates. 
Growth hormone has the following effects on physiology to increase protein deposition in the body: 
•    Enhancement of Amino Acid transport through the Cell Membranes.
•    Enhancement of RNA Translation to cause Protein Synthesis by the Ribosomes
•    Increase nuclear transcription to form RNA from DNA.
•    Decrease catabolism of Proteins and Amino acids.
Growth Hormone exerts much of Its effect through intermediate substances Called “Somatomedins”(Also Called “Insulin-Like Growth Factors”)
It has been found that growth hormone causes the liver (and, to a much less extent, other tissues) to form several small proteins called somatomedins that have the potent effect of increasing all aspects of bone growth. Many of the somatomedin effects on growth are similar to the effects of insulin on growth. Therefore, somatomedins are also called insulin-like growth factors.
6.8.2.    Regulation of Growth Hormone Secretion
Growth hormone is secreted in a pulsatile pattern. i.e. increasing and decreasing. The precise mechanisms that control the secretion of growth hormone are not fully understood, but several factors related to a person’s state of nutrition or stress are known to stimulate secretion: 
(1)     starvation, especially with severe protein deficiency; 
(2)     hypoglycemia or low concentration of fatty acids in the blood; 
(3)     exercise; 
(4)     excitement; and
(5)     trauma. 

6.8.3.    Abnormalities of Growth Hormone Secretion :
Dwarfism: If growth hormone is not secreted at an early age, proper growth of bone is affected and leads to stunted growth of the child.
Gigantism: Excessive secretion of growth hormones in childhood leads to abnormally large bone size and growth of body and patient is larger than normal body size.
Acromegaly: Excessive secretion of growth hormone in adulthood leads to abnormal growth of long bones, lower jaw etc. giving the gorilla-like appearance to the patient. 
6.9.    Thyroid stimulating hormone:-
TSH is produced when hypothalamus releases a thyrotropin-releasing hormone (TRH). TSH is under the effect of TRH, secreted from cells in the anterior pituitary called thyrotropin. TRH is only 3 amino acids long and it inhibits high blood concentration of thyroid hormone in a classical negative feedback loop.
6.10.    Adrenocorticotropic hormone (ACTH) :
ACTH or corticotropin is recreated by corticotrophin cells of anterior pituitary in response to corticotropin-releasing hormone (CRH) from the hypothalamus. ACTH is an important part of the circadian system. Body stress and the circadian clock of the brain causes the release of CRH which further stimulates the release of ACTH which in turn stimulates adrenal cortex to release cortisol (primary anti-inflammatory stress hormone). It was found that insomniacs have higher ACTH levels than good sleepers.
6.11.    Prolactin:-
Lactotrophs cells secrete prolactin (PRL). Prolactin secretion is regulated by hypothalamic secretion which is prolactin releasing hormone (PRH) and prolactin-inhibiting hormone (PIH), which is also called dopamine. When the menstrual cycle begins, new dopamine level (secretion of PIH) diminishes and prolactin increases but not enough for milk production.
Prolactin controls the milk production (lactogenesis) but not the milk ejection reflex. The rise in prolactin fills the breast with milk in preparation for the next feed.
6.12.    Follicle stimulating hormone:-
FSH release is stimulated by Gonadotropin-releasing hormone (GnRH) from the hypothalamus. Gonadotropin cells of adenohypophysis secrete FSH. In women, each month, it initiates the development of several ovarian follicles in ovaries and stimulates secretion of estrogen from follicular cells. FSH level is highest just before the release of the egg (ovulation).
In men, the amount or level of FSH remains constant and is required for sperm production in testes.
6.13.    Luteinizing hormone:-
LH is also secreted by gonadotrophs cells of adenohypophysis and is regulated by gonadotropin-releasing hormone (GnRH) of the hypothalamus.
In females, it triggers ovulation and stimulates the formation of corpus luteum and secretion of progesterone.
In males, it acts upon Leydig cells of testes and causes the production of testosterone.
Hormones of Posterior Pituitary
Two hormones are released by posterior pituitary namely Oxytocin and Vasopressin. They are originally synthesised by hypothalamic neurons. These hormones are stored in axon terminals situated in posterior lobe called Herring bodies.
Vasopressin is released whenever there is a rise in blood osmotic pressure. It is also known as Anti-Diuretic Hormone (ADH) as it promotes reabsorption of water from urine from Distal Convoluted Tubules of the nephron. In a diseases Diabetes Insipidus, ADH is not released properly and a large amount of water is lost through urine. But even after the increase in urine volume, no significant amount of glucose is observed in urine.
Along with its anti-diuretic function, ADH also causes constriction in arterioles. 
Oxytocin is another hormone of posterior pituitary. It is released by hypothalamus either when there is distention in the uterus during parturition or while the infant is sucking milk from mammary glands. It induces rhythmic contraction in muscles of the uterus which help in childbirth at the end of pregnancy, also it induces contraction in mammary glands which help in ejaculation of milk from the glands. Hence, Oxytocin is also called “Milk Hormone” or “Birth Hormone”.
Note: Pitocin is synthetic oxytocin. It is often given to females at the end of their pregnancy to induce labour.
6.14.    Penial Gland
The pineal gland is often regarded as a vestigial organ in humans. Some call it the third eye because it has light-sensitive cells in lower vertebrates. It is of ectodermal origin and is attached to the roof of the third ventricle at back side of the brain. It is highly vascularized and secretes hormones like Melatonin.
Pineal gland works as a biological clock and neurosecretory transducer. Which converts neural signals. The higher amount of melatonin is produced during the dark and its secretion is reduced in presence of light. This change is regulated by the hypothalamus which receives its signals from eyes. Melatonin secretion is regulated by diurnal cycle and Melatonin, in turn, influences body metabolism, pigmentation, temperature etc.
6.15.    The Thyroid
The thyroid is a large gland present around trachea at the base of the neck. It secretes two main hormones known as Tri-iodothyronine (T3) and thyroxin(T4). These hormones are collectively responsible for the regulation of metabolic rate. Secretion of these hormones is further regulated by TSH of Pituitary gland.
Most of the hormone secreted includes Thyroxine (93%) and only some tri-iodothyronine (7%) but thyroxine at the tissue level converts into tri-iodothyronine. Both these hormones have somewhat similar functions but they differ in their intensity of action. T3 has four times stronger than T4. Both these hormones are the iodinated form of tyrosine amino acid.

The thyroid is the only gland that stores its secretion. This involves iodine metabolism and involve iodine trapping by follicular cells and storing Thyroxin and tri-iodothyronine with help of thyroglobulin.
Also,  Among thyroid follicles there are parafollicular cells also called C-Cells and they release Calcitonin (TCT) and follicular hormone and both of these maintain the level of calcium in the body.


6.15.1.    ROLE of Thyroid hormones
T3 and T4 are both thyroid hormones and have a wide range of functions. Some of them are enlisted here-
•    Thyroid hormones enhance the Basic metabolic rate (BMR) and have a calorigenic effect which increases body heat production.
•    The growth of body tissue is also promoted by thyroid hormones.
•    Thyroid hormones stimulate the differentiation of tissue during development. Metamorphosis in frogs from tadpole to adult is stimulated by thyroid hormone only.
•    Actions of some neurotransmitters like adrenaline and nor-adrenalin are enhanced by thyroid hormones.
•    Thyroid hormones play role in RBC production.
•    They also maintain water-electrolyte balance in the body.


6.15.2.    Disorders of Thyroid hormones
Many times hypersecretion or hyposecretion or any other abnormality leads to various disorders among humans. Some of the major disorders are discussed here,
•    Cretinism: reduced secretion of thyroid hormones during childhood leads to stunted growth of the child and mental retardation. The basic metabolic rate is also highly reduced causing low blood pressure, abnormal skin, and significantly low level of IQ.
•    Myxedema (Gull’s disease):  In adults, reduced level of thyroid hormone causes Myxedema. This causes low metabolic rate, low body temperature, and lower level of intelligence and alertness along with the puffy appearance of the patient.
•    Goitre: In this, due to dietary deficiency of iodine, there is enlargement of thyroid glands and is accompanied by Cretinism or Myxedema.
6.16.    Parathyroid Gland
Parathyroid is a group of four small glands situated near the thyroid. These glands release a hormone called Parathyroid hormone also known as Collip’s Hormone. These regulate blood calcium level through the feedback mechanism. Parathyroid is released whenever there is a reduction in blood calcium level and rise in blood calcium level inhibits secretion of Parathyroid by negative feedback.
Parathyroid increase blood calcium level because it promotes mobilisation of calcium from bone to blood plasma. Along with this, it reduces excretion of calcium ions in urine, it also increases excretion of phosphate ions in urine to maintain their concentration in blood plasma.


6.16.1.    Calcium Homeostasis
Whenever the level of calcium is higher than normal, Parafollicular cells of parathyroid glands release Calcitonin which promotes deposition of Calcium in bones and hence reduces blood calcium level.
Lower levels of calcium promote secretion of Parathyroid hormone (PTH). It promotes the release of calcium and form bones and reduces excretion of calcium in the urine.


PTH also stimulates the release of calcitriol from the kidney. This enhances the absorption of calcium from food in gastrointestinal tract.
6.16.2.    Disorders of Parathyroid gland
6.17.    Hypoparathyroidism: 
When Parathyroid gland fails to secrete sufficient amount of Parathyroid, hormone there is significant reduction in blood calcium level. This eventually affects nerve impulse transduction and muscle contraction, Due to which there is contraction in muscles without external stimulus. This is also called Parathyroid Tetany.
Hyperparathyroidism:
If there is excessive secretion of parathormones due to tumor or any other reason, then there will be too much decomposition of bones to release calcium in blood. This causes high mobilisation of bone minerals and softening of bones. It therefore also causes Osteitis Fibrosis Cystica. 
6.18.    Pancreas
Pancreas is a branched gland located in between the stomach and duodenum which comprises of both exocrine as well as endocrine parts. 
Thus, it perform dual function, the exocrine part acini secretes enzymes through ducts whereas the endocrine part Islets of Langerhans releases hormones into blood. Pancreatic islets appear as clusters of cells which regulates the blood glucose level.


6.19.    Hormones
Different types of pancreatic islets’s cells are involved in the secretion of different hormones. From the endocrine precursor cells, Pax gene directs the formation of alpha and gamma cells whereas the pax-6 gene produces beta and delta cells.
Insulin, glucagon, somatostatin, and pancreatic polypeptide are the hormones released by the Islets of Langerhans of the pancreas. These acts on their particular target organs which are liver, adipose tissues, muscles and the pancreas itself.
6.19.1.    Glucagon: This hormone is released by the alpha cells which increases blood glucose level in different ways
•    Promotes glucose synthesis in the liver by glycogen breakdown.
•    Released between meals when blood glucose level falls and thus, enhances release of glucose into the blood.
•    Promotes gluconeogenesis in the liver under prolonged hypoglycaemic condition.
6.19.2..    Insulin: Insulin is secreted by the beta cells of the pancreas which plays a crucial role in maintaining the blood glucose level. It lowers down the glucose level in blood.
•    Stimulates the transport of glucose from the blood to muscle and adipose cells and stimulate the liver to uptake glucose.
•    Promotes glycolysis and conversion of glucose into glycogen in muscles as in well as liver cells.
•    Promotes protein synthesis and amino acids uptake by liver and muscles. Inhibits protein breakdown.
•    Stimulates fat synthesis from glucose by adipose tissue as well as inhibit lipid breakdown.
•    Inhibits glycogen breakdown in liver and muscles.
6.19.3.    Somatostatin: It is secreted by the delta cells of the pancreas which inhibits the secretion of glucagon and insulin by regulating the alpha and beta cells.
6.19.4.    Pancreatic polypeptide: This hormone is released by the gamma cells which helps in the regulation of pancreatic secretion activities of exocrine as well as endocrine part.
6.19.5.    Disorder of pancreas
Diabetes mellitus (Type-1) Insulin-dependent diabetes: It is an autoimmune disorder in which beta cells are destroyed. This leads to a failure of insulin secretion which causes high blood glucose level. If causes glucosuria (appearance of glucose in urine), polyuria, increased oxidation of fats and proteins.
Diabetes mellitus (Type-2): It is non-insulin dependent in which deficiency of insulin occurs due to non-responsive nature of target cells or sometimes may be due to cells insufficiency of insulin production.


6.20.    The adrenal gland
Adrenals or the suprarenal glands are located above each kidney and their shape resembles conical pyramid-like structure. Similar to kidney it can also be categorised into two distinct structures, the outer one adrenal cortex and the inner one medulla, both of which produces hormones. Adrenal gland synthesizes corticosteroid hormones and catecholamines in response to the stress condition. Synthesis of all these groups of hormones requires the formation of cholesterol.

6.21.    The adrenal cortex
The adrenal cortex is mesodermal in origin and it plays a vital role in survivability of the organism. Damage to the adrenal cortex or its removal causes the death of the organism.
Corticosteroid hormones are released by this part and on the basis of their chemical nature and properties, these form three major groups: mineralocorticoids, glucocorticoids, and sex corticoids.
Adrenal cortex region is further divided into distinct zones and exhibit functional zonation as well. Each zone secretes distinct hormones and has particular enzymes.


6.21.1.    Mineralocorticoids: These are released from the outermost cellular layer, zona glomerulosa of the adrenal cortex. The principal hormone is the aldosterone which performs important functions
•    Regulate salt metabolism and maintains ionic balance in the body.
•    Enhance the active reabsorption of sodium by reducing its elimination from urine, sweat, saliva, and bile.
•    Increases the elimination of potassium from these body fluids.
•    Increases the reabsorption of water from the urine.
6.21.2.    Glucocorticoids: Zona fasciculata, the central portion of the adrenal cortex secretes these group of hormones. It is the widest layer. Cortisol, corticosterone and cortisone are the three main hormone of which cortisol is the most abundant. Corticotropin hormone released by the anterior pituitary stimulates the secretion of glucocorticoids. Glucocorticoids Perform vital roles:
•    Maintains the blood glucose level and stimulates gluconeogenesis, thus involved in the carbohydrate metabolism.
•    Enhances the breakdown of lipids, proteins and inhibit cellular uptake of amino acids.
•    Maintains cardiovascular system and kidney functions.
•    Acts as the stabilizer of lysosomes of phagocytic cells due to anti-inflammatory nature.
•    Used in the transplantation surgery due to immunosuppressive property.
6.21.3.    Sex Corticoids: Zona reticularis, the innermost region releases these hormones. Androstenedione, dehydroepiandrosterone (DHEA), and estrogens are the sex corticoids. These regulate secondary sex determination and stimulate the development of secondary sexual traits.
6.21.4.    The adrenal medulla
The adrenal medulla is the central part of the adrenal gland which is ectodermal in origin. Adrenaline (epinephrine) and noradrenaline (norepinephrine) are collectively called, Catecholamines and these hormones are derived from tyrosine amino acid.
The adrenal medulla secretes these hormones to overcome stress or emergency conditions. The secretion of catecholamines is stimulated by the sympathetic nervous system and these act on adrenergic receptor located on their target organs such as skeletal muscles, cardiac muscles, smooth muscles, blood vessel, fat cells. 
Physical stress (pain, cold, injury, low blood sugar etc.), as well as emotional stress (fear, grief, anger), stimulates their secretion by a sympathetic-adrenal system. Their principal action:
•    Elevation of blood glucose level by converting liver glycogen to glucose.
•    Raises blood pressure.
•    Accelerates rate and force of heartbeat.
•    Dilation of arterioles of heart and skeletal muscles.
•    Increases respiratory rate (oxygen consumption) causing dilation of bronchioles.
•    Enhance lipid breakdown.
•    Erection of hairs (goosebumps).
•    Dilation of pupils and other stress responses.
6.21.5.    Disorder
*    CUSHING’S SYNDROME: In this syndrome, High level of cortisol produced due to the formation of tumour in adrenal cortex that Causes high blood sugar, obesity, electrolyte imbalance, high blood pressure.


*    ALDOSTERONISM (CONN’S SYNDROME): In it, excessive secretion of aldosterone leads to a very high level of sodium and low potassium in plasma, and high blood pressure.
*    ADRENAL VIRILISM: Appearance of male type external sex characters in women due to excessive secretion of sex corticoids, leads to autoimmune disease which causes this disorder.
*    ADDISON’S DISEASE: In it, deficiency of corticosteroids occurs due to the destruction of the adrenal cortex. This damage may be caused by some other diseases like tuberculosis. Low blood sugar, ionic imbalance, nausea, diarrhoea, bronze pigmentation of the skin occurs during this disease.
6.22.    The testes 
The testes or testicles are the primary male reproductive organ or gonads which produces spermatozoa and male sex hormone. In man, these normally remain suspended in a pouch called scrotum outside the abdominal cavity. This maintains two-degree centigrade lesser temperature than body temperature which is required for normal spermatogenesis process.
Testes are developed in the abdomen and descend in the scrotal sac when the foetus is about seven months old and it occurs under the influence of follicle stimulating hormone (FSH) and testosterone. If they fail to descend, the condition called cryptorchidism and leads to sterility. Cremaster muscles and connective tissues form spermatic cord which connects testes to the abdomen as well as the urethra.
6.22.1.    Testes as gland
Apart from the production of reproductive cells (spermatozoa), testes also perform as an endocrine gland.
*    Testosterone, anti-mullerian hormone, inhibin, activin, insulin-like growth factor (IGF), and estradiol are the hormones which are released by the testes. These directly or indirectly influence the reproductive health of the male.  
6.22.2.    Role of testosterone 
Testosterone is the main androgenic hormone which performs several functions
*    Stimulates the descent of testes and a male pattern of development (before birth).
*    Regulates the normal spermatogenesis process.
*    Controls the secondary sex determination and expression of secondary sexual characters such as beard, moustaches, low pitch voice, the growth of Adam’s apple, growth spurt. Primary sex determination is under the control of sex chromosomes.
*    Maintains, muscle strength and bone density during adolescence. 
The release of testosterone is under the control of hypothalamus which secretes gonadotropin-releasing hormone (GnRH). This stimulates anterior pituitary to release interstitial cell stimulating hormone (ICSH) and FSH, both of which acts on its target organ, i.e. testes.
FSH stimulates Sertoli cells of testes to secrete androgen-binding protein (ABP) which concentrates testosterone.
ICSH stimulate Leydig cell to release testosterone.
6.23.    Other hormonal functions
Along with the testosterone hormone, other hormones released by the testes are also required for the normal reproductive functioning.
•    In males, sox 9 gene activates Sertoli cells causing a release of an anti-mullerian hormone (AMH) which triggers the degeneration process in Mullerian duct.
•    Inhibin and activin hormones are also released by the Sertoli cells which control the inhibition and activation of ICSH and FSH production.
•    Leydig cells are also responsible for the secretion of insulin-like growth factor (IGF) and estradiol hormone.
    IGF provides essential signalling process for the control of testes development and its proper functioning.
Estrogen is mainly the female hormone but is also produced in males in lesser amounts and is involved in the maturation of sperms. Its higher levels cause prostate enlargement or prostate cancer.
6.24.    Defects 
*    MALE HYPOGONADISM: It arises due to damage in the hypothalamus, the pituitary, or the testes. It consists of deficient androgen production (hypofunction of Leydig cell), deficient sperm formation (hypofunction of Sertoli cell), or both, before puberty. Represents a lack of development of secondary sexual characters and male musculature.
*    PRECOCIOUS PUBERTY: early maturation of testes with the production of sperm before ten years causes true sexual precocity. High testosterone level due to tumours of the testes or adrenals causes sexual pseudoprecocity.
EUNUCHOIDISM: results from the failure of testosterone secretion. Secondary sex organs remain small in size and infantile. No spermatozoa formation. No expression of secondary sexual characters.
GYNAECOMASTIA: development of breast tissues in males and is usually due to perturbation of estrogen to androgen ratio.
6.25.    The ovaries
The ovaries are the primary female reproductive organ or gonads which produces ova and secretes female sex hormone. These are located near kidneys and remain attached to the lower abdominal cavity through mesovarium. Their structure resembles small, almond-like flattened bodies. Ovaries are connected to the fallopian tubes through finger-like projections called fimbriae and the ova are dumped into the fallopian tubes through the process known as ovulation from the puberty onwards.
Maturation of germ cells takes place in the ovaries by oogenesis process which starts before birth. Primordial cells give rise to oogonia which further forms primary oocytes. At puberty, these oocytes resume their development. Each month, the ovum is ejected from the follicle near the end of the proliferative phase (14th day) or midway during menstruation which is the periodic shedding of the endometrium of the uterus with bleeding. The menstrual cycle is regulated by hormonal balance (Follicle stimulating hormone, luteinizing hormone, estrogen, progesterone).

6.25.1.    The ovary as a gland
Apart from the production and maturation of reproductive cells (ova or egg), ovaries also perform as an endocrine gland.
*    Estrogen, progesterone, relaxin, inhibin, activin are the hormones released by the ovaries during the lifetime of a woman. These hormones collectively influence the reproductive health of the female.
*    Progesterone and estrogen are the primary female sex hormones which are responsible for the development of secondary sexual traits and cause marked cyclic changes in the uterine endometrium. Estrogen is produced by the granulosa cells of developing ovarian follicles.
*    Secretion of these hormones is under the control of hypothalamus which releases gonadotropin-releasing hormone (GnRH). In response to the production of GnRH, anterior pituitary stimulates to release follicle stimulating hormone (FSH) and luteinizing hormone (LH) and both of which acts on its target organ, i.e. ovaries.
*    FSH stimulates follicular growth and maturation of oocytes. It also stimulates ovarian follicle to secrete estrogen which regulates oogenesis.
*    LH leads to the formation of corpus luteum in the ovary which secretes progesterone, estrogen, relaxin, inhibin, activin hormone. Ovulation occurs in the presence of high concentration of LH and estrogen and every month single ovum is released in an alternate manner by the ovaries. The Oogenesis is stimulated by the leutinizing hormone.
6.25.2.    Role of estrogen
Estrogens are the group of steroid hormones that are necessary for the normal reproductive functioning of the female. Normally, estrogens are found in three major forms in women (estrone, estradiol, estriol). Estradiol is the major form found in the females whereas estrone is produced after the menopause. Estriol is the principal hormone observed in pregnant females. Their principal action are summarized below
•    Regulate the oogenesis process.
•    Stimulates development and maintenance of female sexual characteristics like high pitch voice and body pattern, hair distribution at puberty. Primary sex determination is totally under the control of sex hormones.
•    Together with gonadotropic hormones of the anterior pituitary, they also regulate the menstrual cycle.
•    The growth of uterus, ovaries, and breast at the time of puberty.
•    Fat deposition at the different body parts specifically at the hip and belly region.
•    Thickening of the uterine and vaginal wall.
•    Angiogenesis in the endometrium is promoted by estrogen.
6.25.3.    Role of progesterone
Progesterone is also the type of steroid hormone which facilitates the female to maintain its normal reproductive health.
•    Progesterone is released by corpus luteum which is a temporary gland and converts into corpus albicans in ten days if fertilization does not occur.
•    Progesterone is the principal hormone which maintains the pregnancy or the gestation period. So, also called 'Mother hormone'. After the fertilization, corpus luteum is maintained for the whole of the gestation period.
•    It stimulates uterine lining for embryo implantation to maintain pregnancy (foetal development).
•    Prepares the mammary glands for lactation.
•    Regulates oogenesis process and menstrual cycle along with the estrogen hormone.
•    Progesterone inhibits ovulation. So, no menses occurs during the gestation period.

6.25.4.    Other hormonal functions
Apart from the primary female sex hormones, (progesterone, estrogens) other hormones are also released from the ovaries and have certain functions.
*    Corpus luteum secretes relaxin hormone which relaxes pubic symphysis and helps dilate uterine cervix near the end of the pregnancy.
*    Inhibin and activin hormones are released by the corpus luteum controls the inhibition and activation of FSH and GnRH production.
*    Human chorionic gonadotropin (HCG) secreted by the placenta stimulates progesterone release from the corpus luteum and maintains it during gestation.
*    Human placental lactogen stimulates mammary gland growth.
*    Lower amounts of testosterone hormone are also produced by the ovaries which maintain and repair reproductive tissues. Its higher level cause disturbed menstruation.

6.25.5.    Defects
•    FEMALE HYPOGONADISM: damage to the hypothalamus, the pituitary, or the ovary results in it. Hyposecretion of estrogen. Results in the cessation of reproductive cycles, shortage of pituitary gonadotropins or can represent ovary failure.
•    PRECOCIOUS PUBERTY: early maturation and production of ova before the age of nine years in girls without evident cause results in true sexual precocity. Sexual pseudoprecocity in girls arises from the increased level of estrogens due to tumours in adrenals or ovaries.
6.26.    Miscellaneous hormones 
Apart from above discussed endocrine glands, hormones are also secreted by various tissues of the body including heart muscles, kidney and gastrointestinal tract.
Atrial wall of heart release a significant peptide hormone called Atrial Natriuretic Factor (ANF). It decreases blood pressure by dilating blood vessels.
Juxtaglomerular cells of Kidney detect low blood pressure and release another peptide hormone called Erythropoietin.  Which stimulates erythropoiesis i.e. production of RBC.
Endocrine cells of the gastrointestinal tract also secrete various hormones like gastrin, secretin, cholecystokinin and other gastric inhibitory peptides. These hormones together regulate secretion of various enzymes involved in digestion of food.


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