HORMONES

Endocrine cells secrete hormones; neurons secrete neurotransmitters. In each case, the extracellular messenger passes to another cell where it binds to a specific receptor molecule and triggers a change in the activity of the second cell. Hormones are carried rapidly in the blood between distant organs and tissues

A specific chemical compound Produced by a specific tissue of the body Where it is released in the body fluids And carried to a distant target tissue Where it affects a pre-existing mechanism And is effective is small amounts.

 Coordination of systems involve

Nervous System
Rapid response Short lasting Uses neurotransmitters

Endocrine System
Slow response Long lasting Uses hormones

Homeostasis

 Proteins and Polypeptides

Oxytocin Insulin

Biogenic amines
Thyroxine Catecholamines

Steroids
Estrogens Progestins Androgens

Eicosanoids
Prostaglandins Thromboxanes

 Major Endocrine Organs are

Hypothalamus Pituitary gland Thyroid gland Parathyroid gland Thymus Adrenal gland Pancreas Ovaries Testes

 Vascularity of endocrine tissue Autocrine glands - local to same cells that released the hormone Paracrine glands - local to adjacent cells Endocrine-Hormone - release into interstitial space, lymphatics, and blood. Pheromone - into the air

Synthesis of hormons from Tyr

Synthesis of Steroid Hormons

Most of these hormones act through a few fundamentally similar mechanisms.

We first consider one of the best-understood hormone mechanisms involving cAMP as the second messengerwhich mediates the cellular response to epinephrine. We then describe examples of several other fundamental hormone mechanisms, involving different second messengers (cGMP, diacylglycerols, an inositol trisphosphate, Ca2+), The phosphorylation and dephosphorylation of specific proteins are shown to be central to these mechanisms. Finally, we describe how steroid hormones function through the regulation of gene activity.

Mechanisms of Hormones Action

There are two mechanisms: Membrano cytozolic or nondirect, that influence with helping of messengers; Cytosolic niuclear or direct

Prin intermediul nicleotidelor ciclice

Rspuns

Rspuns

H
R
Adenyl Cyclase Gs Protein

ECF

ICF ATP
Inactive c AMP dependant Protein Kinase

c AMP
Active c AMP dependant Protein Kinase

Cells Response

Protein + ATP

ADP + Protein PO4

 Phosphodiestherase (E) descomposes AMP cyclic: AMPc -------------- AMP + H2O Activity of E increases iones of calciu, prostaglandine, insuline. steroides ,Thyroides hormones and methylxantineses ( cofeine , theophyline ) decrease activity of E and support life of AMP - cyclic.

Diacylglycerol and Inozytol 3 phosphate

1. 2. 3. 4. 1. H+R HR 2. HR Gp Gp PhospholipazeiC Phospholipaze C activates to membrane Phospholipids and produce DAG and Iinozitol tri Phosphate DAG activate PK C Inozitol 3 fosfate increase endoplasmatic concentration of Ca

H
R
G Protein
PIP2
Active Protein Kinase C

ECF
Phospholipase C DAG + IP3

ICF
Inactive Protein Kinase C

ER

Ca++

Protein PO4

Protein

Cells Response

Cells Response

Diacilglicerolul i inozitol fosfaii

Mecanismul citozolic de aciune

Action of Steroid Hormones

Steroid hormones (estrogen, progesterone, and cortisol, for example), too hydrophobic to dissolve readily in the blood, are carried on specific carrier proteins from the point of their release to their target tissues. In the target tissue, these hormones pass through the plasma membrane by simple diffusion and bind to specific receptor proteins in the nucleus The hormone-receptor complexes act by binding to highly specific DNA sequences called hormone response elements (HREs) and altering gene expression.

Action of Steroid Hormones

Hormone binding triggers changes in the conformation of the receptor proteins so that they become capable of interacting with specific transcription factors The bound hormone-receptor complex can either enhance or suppress the expression

Classification of Hormones
Classification of Hormones Hormones are classified according to: histological principle - according to the place of their synthesis; chemical structure; biological function; mechanism of action on the target cell.

Histological principle of hormones classification:

hypothalamic hormones - releasing factors: a) liberins b) statins Hypothalamic via posterior pituitary: Oxytocin Antidiuretic hormone (ADH)

Histological principle of hormones classification:

Anterior pituitary hormones tropins: Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin (LTH) Thyroid stimulating hormone (TSH) thyrotropin Adrenocorticotropic hormone (ACTH) Growth hormone (GH) somatotropin Melanocyte-stimulating hormone (MSH) melanotropin

Histological principle of hormones classification:

Thyroid gland hormones: Thyroxin and Triodothyroxin Calcitonin Parathyroid gland hormones Parathyroid hormone Adrenal cortex hormones Mineralocorticoids (aldosterone) Glucocorticoids (cortisol) Adrenal medulla hormones Catecholamines (Adrenalin and Noradrenalin) Pancreas hormones Glucagons Insulin Ovary hormones Estrogens (estradiol) Progestrogen Placenta hormones Chorionic gonadotropin Testes hormones Androgens (testosterone)

Hormone hierarchy
Hormone systems are often linked to each another, giving rise in some cases to a hierarchy of higher-order and lower-order hormones. A particularly important example is the pituitaryhypothalamic axis, which is controlled by the central nervous system (CNS)

Hormone hierarchy
Nerve cells in the hypothalamus react to stimulatory or inhibitory signals from the CNS by releasing activating or inhibiting factors, which are known as liberins (releasing hormones) and statins (inhibiting hormones). These neurohormones reach the adenohypophysis by short routes through the bloodstream. In the adenohypophysis, they stimulate (liberins) or inhibit (statins) the biosynthesis and release of tropines.

Hormone hierarchy
Tropines (glandotropic hormones) in turn stimulate peripheral glands to synthesize glandular hormones. Finally, the glandular hormone acts on its target cells in the organism. In addition, it passes effects back to the higherorder hormone systems. This (usually negative) feedback influences the concentrations of the higher-order hormones, creating a feedback loop.

 Secreia hormonilor adenohipofizei este reglat de ctre peptide elaborate n diverse arii ale hipotalamusului releasing factori (neurohormoni) Liberine i statine Hormonii Hormonii tropi hipotalamici hipofizari 1. 2. 3. 4. 5. 6. 7. 8. 9. somatoliberina corticoliberina tireoliberina folililiberina luliliberina prolactoliberina prolactostatina somatostatin melanostatina + + + + + + somatotropina corticotropina tireotropina folitropina lutropina prolactina

Hormonii hipotalamo-hipofizari

 Hypothalamic Releasing Factors

Release stimulating factor Release inhibitory factor

Each Pituitary Hormone has a set or stimulating and inhibiting factors except the Gonadotropins. Prolactin Release Factor = Gonadotropin Inhibitory factor.

 Releasing factors
Release hormones Release inhibiting hormones

Oxytocin
Milk ejection mechanism Uterine Contraction
Induction of labor Orgasmic responses

Feedback mechanism - Positive

Vasopressin or ADH - AntiDiuretic Hormone

Action on Distal Convoluted tubule and Collecting Duct Pressor effects

 MSH - Intermediate lobe Anterior Lobe Hormones

Basophilic and Acidophilic Trophic and nontrophic hormones Growth Hormone Prolactin Thyroid Stimulating Hormone - TSH AdrenoCorticoTrophic Hormone - ACTH Follicle Stimulating Hormone Lutenizing Hormone

Long Loop and Short Loop Feedback Systems Autocrine Feedback Systems

 Protein mole. wgt. 22,000 Bound to High Affinity Bound protein and Low Affinity Bound protein. Binding compensates for irrating secretion rates. Half life varies 6 to 20 minutes. Somatomedins - produced by liver - polypeptides - growth factors Growth hormone increase IGF-I somatomedin What is growth? Uptake of Amino Acids

 Protein Anabolic Increased plasma phosphorus Increase absorption of gut Diabetogenic Growth Periods Dwarfism Giantism Acromegly

calcium in

 Excessive Production during childhood Different systems respond differently

 Hands Feet Jaws

Prolactin Release Inhibitory Factor Prolactin Release Stimulating Factor Gonadotrophin Release Inhibiting Factor Prolactin hormone - Pregnancy hormone
199 amino acids 20 minute half life Receptor resembles growth hormone receptor Increases milk production Maintains corpus luteum Dopamine controls rate of release

Calcium Homeostasis and Endocrine Regulation of Ca++ concentration

Calcium is required for muscle contraction, intracellular messenger systems, cardiac repolarization. The total quantity of calcium in organism is about 1 kg:
99% of calcium is located in bones as hydroxyapatites 1% of calcium is located in cells and blood In the blood calcium can be in the following state:
In complex with albumin (40% total blood calcium) In complex with anions - Phosphate and Citrate (10% total blood calcium)

In a free form ionic calcium Ca++(50%)

Calcium Homeostasis
The most important hormones for maintaining calcium levels in the body are:
Parathyroid hormone (PTH) produced by Parathyroid gland Calcitriol - 1,25(OH)2D3 (the active form of vitamin D) Calcitonine produced by Parafollicular C cells of Thyroid gland

Parathyroid hormone
The major regulator is Parathyroid hormone, which is part of a negative feedback loop to maintain [Ca++]. PTH secretion is stimulated by hypocalcemia, and it works through three mechanisms to increase Ca++ levels: PTH stimulates the release of Ca++ from bone, stimulating bone resorption. PTH decreases urinary loss of Ca++ by stimulating Ca++ reabsorption. PTH also inhibits phosphate reabsorption. PTH indirectly stimulates Ca++ absorption in the small intestine by stimulating synthesis of 1,25(OH)2D3 in the kidney.

Calcitonine
Produced by Parafollicular C cells of Thyroid in response to increased Ca++ Actions
Inhibit osteoclastic resorption of bone Decrease renal Ca++ excretion and increase renal PO43- excretion

Non-essential hormone. Patients with total thyroidectomy maintain normal Ca++ concentrations

Calcitriol
Sources
Food Vitamin D2 UV light mediated cholesterol metabolism vitamin D3

Metabolism
D2 and D3 are converted to 25(OH)-D in the liver 25(OH)-D is converted to 1,25(OH)2-D in the Kidney

Function
Stimulation of Osteoblasts Increases absorption in intestin of dietary Ca++

Calcitonine
Produced by Parafollicular C cells of Thyroid in response to increased Ca++ Actions
Inhibit osteoclastic resorption of bone Decrease renal Ca++ excretion and increase renal PO43- excretion

Non-essential hormone. Patients with total thyroidectomy maintain normal Ca++ concentrations

Hormones of the pancreas

The endocrine portion of pancreas is represented by clusters of cells called islets of Langerhans. The islets contain four types of cells. In order of abundance, they are: beta cells, which secrete insulin and amylin alpha cells, which secrete glucagon; delta cells, which secrete somatostatin, and gamma cells, which secrete pancreatic polypeptide.

Insulin
Insulin is a small protein consisting of an alpha chain (A chain) of 21 amino acids linked by two disulfide (SS) bridges to a beta chain (B chain) of 30 amino acids. Beta cells secrete insulin in response to a rising level of circulating glucose ("blood sugar"). Insulin major function is to maintain low blood glucose level.

Insulin

Synthesis of insulin
Preproinsulin, the first precursor. The signal peptide at the N-end is deleted, creating proinsulin . Proinsulin differs from insulin in that it has a third peptide, C, which connects the A and B peptides together. The primary sequence of proinsulin goes in the order "B-C-A". This C peptide is spliced from the chain by the action of proteolytic enzymes, known as prohormone convertases. The remaining polypeptides (51 amino acids in total), the B- and A- chains, are bound together by disulphide bonds.

Regulation of insulin secretion:

The secretion of insulin is increased by: The secretion of insulin is decreased by:

Low glucose level in the blood glucose or carbohydrates intake Adrenalin and noradrenalin amino acids from ingested (sympathetic nervous system) proteins (especially alanine, Somatostatin from D-cells of glycine and arginine) pancreas acetylcholine, released from vagus nerve endings (parasympathetic nervous system) cholecystokinin, released by intestinal mucosa gastrin and secretin glucose-dependent insulinotropic peptide (GIP).

Mechanism of insulin action.

Insulin triggers these effects by binding to the insulin receptor a transmembrane protein embedded in the plasma membrane of the responding cells. The insulin receptor is a tyrosine kinase. The activated receptor phosphorylates a number of intracellular proteins (insulin receptor substrate or IRS), which in turn alters their activity, thereby generating a biological response. Activation of insulin receptor leads to internal cellular mechanisms that directly affect glucose uptake by regulating the number and operation of protein molecules in the cell membrane that transport glucose into the cell glucose transporters - GLUT.

Mechanism of insulin action.

The actions of insulin on the global human metabolism level include: Activation of RNA transcription and proteins synthesis; Control of cellular intake and activation of the transmembrane transport of glucose, amino acids, ions; Modification of the activity of numerous enzymes: - activation of enzyme, that catalyze the synthesis of glycogen, fat, proteins. - inactivation of enzyme, that catalyze the reactions of catabolism.

Glucose metabolism differs depending on the type of cell

Muscle and Adipose tussue require the use of glucose transporters GLUT-4, which is only made available in the presence of insulin. Once insulin binds to the receptors the glucose transporters penetrate through the plasma membrane. At this point, glucose can be transported into the cell at a rapid rate. Insulin stimulates skeletal muscle fibers to
take up glucose and convert it into glycogen; use glucose as an energy substrate take up amino acids from the blood and convert them into protein.

Effects of insulin on Liver Tissue

. Insulin acts on liver cells
stimulating them to take up glucose from the blood and convert it into glycogen, inhibiting glycogenolysis and gluconeogenesis, activating glycolysis in order to produce intermediates for glycerol and fatty acid synthesis, activating fat synthesis

Additional Functions of Insulin:

In addition to its role in carbohydrate and lipid metabolism, insulin serves the following functions: Increases amino acid transport into cells- when insulin levels are low, proteins are degraded Regulates transcription, changing the amount of mRNA present in the cell Activates cell growth, DNA synthesis and cell replication Increases the permeability of most cells to potassium, magnesium and phosphate ions Increases the secretion of hydrochloric acid by Parietal cells in the stomach.

Diabetes mellitus
Diabetes mellitus is an insulin deficiency state. Diabetes mellitus is an endocrine disorder characterized by many signs and symptoms. Primary among these are: Hyperglycemia Glucoseuria - a failure of the kidney to reclaim glucose so that glucose spills over into the urine Polyuria - a resulting increase in the volume of urine because of the osmotic effect of this glucose (it reduces the return of water to the blood). polydipsia - increased thirst and consequent increased fluid intake

Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus (also known as Insulin-Dependent Diabetes Mellitus or IDDM) is characterized by little (hypo) or no circulating insulin; most commonly appears in childhood. It results from destruction of the beta cells of the islets. The destruction results from a cell-mediated autoimmune attack against the beta cells. Type 1 diabetes is controlled by carefully-regulated injections of insulin. Acute complications including hypoglycemia, diabetic ketoacidosis, or nonketotic hyperosmolar coma may occur if the disease is not adequately controlled. Serious long-term complications include cardiovascular disease, chronic renal failure, retinal damage, which can lead to blindness, several types of nerve damage, microvascular damage and poor wound healing. Poor healing of wounds, particularly of the feet, can lead to gangrene, possibly requiring amputation.

Type 2 Diabetes Mellitus

Type 2 diabetes mellitus usually strikes in adults and, particularly often, in overweight people. Despite research efforts, the precise nature of the defects leading to type II diabetes have been difficult to ascertain, and the pathogenesis of this condition is plainly multifactorial. Insulin injections are not useful for therapy. Rather the disease is controlled through dietary therapy and hypoglycemic agents. Several drugs, all of which can be taken by mouth, are useful in restoring better control over blood sugar in patients with type 2 diabetes. However, late in the course of disease, patients may have to begin to take insulin. It is as though after years of pumping out insulin in an effort to overcome the patient's insulin resistance, the beta cells become exhausted.

Glucagon
is synthesized and secreted from alpha cells (-cells) of the islets of Langerhans, which are located in the endocrine portion of the pancreas. Glucagon is a linear polypeptide of 29 amino acids. It is synthesized as proglucagon and proteolytically processed to yield glucagon within alpha cells of the pancreatic islets. Glucagon has a major role in maintaining normal concentrations of glucose in blood, and is often described as having the opposite effect of insulin. That is, glucagon has the effect of increasing blood glucose levels.

Effects of Glucagon
Glucagon acts principally on the liver where it stimulates the conversion of: glycogen into glucose (glycogenolysis) and fat and protein into intermediate metabolites that are ultimately converted into glucose (gluconeogenesis)

Hormones of thyroid gland.

Follicular cells in the gland produce the 2 main thyroid hormones, tetraiodothyronine (thyroxine, T4), and triiodothyronine (T3). These hormones act on cells in every body tissue by combining with nuclear receptors and altering expression of a wide range of gene products. Thyroid hormone is required for normal brain and somatic tissue development in the fetus and neonate, and, in all ages, regulates protein, carbohydrate, and fat metabolism.

Synthesis and Release of Thyroid Hormones

The follicular cells surround a space filled with colloid, which contain thyroglobulin - a glycoprotein containing tyrosine. Thyroglobulin is synthesized by thyroid epithelial cells and secreted into the lumen of the follicle colloid. Synthesis of thyroid hormones requires iodine. Iodine, ingested in food and water as iodide, is actively taken up from blood by thyroid epithelial cells, which have on their outer plasma membrane a sodium-iodide symporter or "iodine trap". Once inside the cell, iodide is transported into the lumen of the follicle along with thyroglobulin.

Synthesis and Release of Thyroid Hormones

Sinthesis of thyroid hormones is catalyzed by the enzyme thyroid peroxidase. Thyroid peroxidase catalyzes two sequential reactions: Iodination of tyrosines on thyroglobulin (also known as "organification of iodide"). Synthesis of thyroxine or triiodothyronine from two iodotyrosines. Tyrosine in contact with the membrane of the follicular cells is iodinated at 1 (monoiodotyrosine) or 2 (diiodotyrosine) sites and then coupled to produce the 2 forms of thyroid hormone (diiodotyrosine + diiodotyrosine T4; diiodotyrosine + monoiodotyrosine T3):

Thyroid peroxidase

 Once inside the thyroid follicular cells, T3 and T4 are cleaved from thyroglobulin: colloidladen endosomes fuse with lysosomes, which contain hydrolytic enzymes that digest thyroglobulin, thereby liberating free thyroid hormones. Free T3 and T4 are then released into the bloodstream, where they are bound to serum proteins for transport to target cells.

Mechanism of Action of Thyroid Hormones

The mechanism of action of thyroid hormones is cytosolic-nuclear mechanism. Receptors for thyroid hormones are intracellular DNAbinding proteins that function as hormone-responsive transcription factors, very similar conceptually to the receptors for steroid hormones. Thyroid hormones enter cells through membrane transporter proteins. Once inside the nucleus, the hormone binds its receptor, and the hormone-receptor complex interacts with specific sequences of DNA in the promoters of responsive genes.

Effects of Thyroid Hormones

Metabolism: Thyroid hormones stimulate diverse metabolic activities in most tissues, leading to an increase in basal metabolic rate. One consequence of this activity is to increase body heat production, which seems to result, at least in part, from increased oxygen consumption and rates of ATP hydrolysis. A few examples of specific metabolic effects of thyroid hormones include: Lipid metabolism: Increased thyroid hormone levels stimulate fat mobilization, leading to increased concentrations of fatty acids in plasma. Carbohydrate metabolism: Thyroid hormones stimulate almost all aspects of carbohydrate metabolism, including enhancement of insulin-dependent entry of glucose into cells and increased gluconeogenesis and glycogenolysis to generate free glucose. Growth: Thyroid hormones are clearly necessary for normal growth in children and young animals, as evidenced by the growth-retardation observed in thyroid deficiency.

Other Effects
Cardiovascular system: Thyroid hormones increases heart rate, cardiac contractility and cardiac output. They also promote vasodilatation, which leads to enhanced blood flow to many organs. Central nervous system: Both decreased and increased concentrations of thyroid hormones lead to alterations in mental state. Too little thyroid hormone tends to feel mentally sluggish, while too much induces anxiety and nervousness. Reproductive system: Normal reproductive behavior and physiology is dependent on having essentially normal levels of thyroid hormone. Hypothyroidism in particular is commonly associated with infertility.

Hypothyroidism

Hypothyroidism is the result from any condition that results in thyroid hormone deficiency. Two well-known examples include: Iodine deficiency: Iodide is absolutely necessary for production of thyroid hormones; without adequate iodine intake, thyroid hormones cannot be synthesized. In the case of iodide deficiency, the thyroid becomes inordinately large and is called a goiter. Primary thyroid disease: Inflammatory diseases of the thyroid that destroy parts of the gland are clearly an important cause of hypothyroidism. Common symptoms of hypothyroidism arising after early childhood include lethargy, fatigue, cold-intolerance, weakness, hair loss and reproductive failure. If these signs are severe, the clinical condition is called myxedema. The most severe and devastating form of hypothyroidism is seen in young children with congenital thyroid deficiency. If that condition is not corrected by supplemental therapy soon after birth, the child will suffer from cretinism, a form of irreversible growth and mental retardation. Most cases of hypothyroidism are readily treated by oral administration of synthetic thyroid hormone.

 Infancy onset Persists throughout life Severe mental retardation

Hyperthyroidism
Hyperthyroidism results from secretion of thyroid hormones. In humans the most common form of hyperthyroidism is Graves disease, an immune disease in which autoantibodies bind to and activate the thyroid-stimulating hormone receptor, leading to continual stimulation of thyroid hormone synthesis. Another interesting, but rare cause of hyperthyroidism is so-called hamburger thyrotoxicosis. Common signs of hyperthyroidism are basically the opposite of those seen in hypothyroidism, and include nervousness, insomnia, high heart rate, eye disease and anxiety. Graves disease is commonly treated with anti-thyroid drugs, which suppress synthesis of thyroid hormones primarily by interfering with iodination of thyroglobulin by thyroid peroxidase.

Hyperthyroidism

Adrenal Gland
The two adrenal glands are located immediately anterior to the kidneys, encased in a connective tissue capsule and usually partially buried in an island of fat. Like the kidneys, the adrenal glands lie beneath the peritoneum. Sectioned mammalian adrenal gland reveals two distinct regions: An inner medulla An outer cortex

 The inner medulla, which is a source of the catecholamines epinephrine and norepinephrine. The chromaffin cell is the principle cell type.The adrenal medulla consists of masses of neurons that are part of the sympathetic branch of the autonomic nervous system. Instead of releasing their neurotransmitters at a synapse, these neurons release them into the blood. Thus, although part of the nervous system, the adrenal medulla functions as an endocrine gland. The outer cortex, which secretes several classes of steroid hormones (glucocorticoids, mineralocorticoids and androgens). Cortex consists of three concentric zones of cells that differ in the major steroid hormones they secrete.

Adrenal Medulla Hormones

Cells in the adrenal medulla synthesize and secrete epinephrine and norepinephrine. The ratio of these two catecholamines differs: in humans 80% of the catecholamine output is epinephrine. Following release into blood, these hormones bind adrenergic receptors on target cells, where they induce essentially the same effects as direct sympathetic nervous stimulation.

Synthesis and Secretion of Catecholamines

Secretion of these hormones is stimulated by
acetylcholine release from preganglionic sympathetic fibers innervating the medulla. Many types of "stresses" stimulate such secretion, including exercise, hypoglycemia and trauma. Following secretion into blood, the catecholamines are carried in the circulation by albumin.

Biosinteza

 Adrenergic receptors are typical examples of seven-pass transmembrane proteins that are coupled to G proteins which stimulate or inhibit intracellular signaling pathways (membrane-intracellular mechanism). Complex physiologic responses result from adrenal medulla stimulation because there are multiple receptor types which are differentially expressed in different tissues and cells. The alpha and beta adrenergic receptors were defined:
Receptor Effectively Binds Effect of Ligand Binding

Adrenergic Receptors and Mechanism of Action

Alpha1

Epinephrine, Norepinphrine

Increased free calcium

Alpha2

Epinephrine, Norepinphrine

Decreased cyclic AMP

Beta1

Epinephrine, Norepinphrine

Increased cyclic AMP

Beta2

Epinephrine

Increased cyclic AMP

Effects of Medulla Hormones

Release of adrenaline and noradrenaline is triggered by nervous stimulation in response to physical or mental stress. Common stimuli for secretion of adrenomedullary hormones include exercise, hypoglycemia, hemorrhage and emotional distress. Circulating epinephrine and norepinephrine released from the adrenal medulla have the same effects on target organs as direct stimulation by sympathetic nerves, although their effect is longer lasting.

A major effects mediated by epinephrine and norepinephrine are:

Hyperglycemia Stimulation of glycogen breakdown in skeletal muscle to provide glucose for energy production Stimulation of lipolysis in fat cells: this provides fatty acids for energy production in many tissues and aids in conservation of reserves of blood glucose. Increased metabolic rate: oxygen consumption and heat production increase throughout the body in response to epinephrine. Increased rate and force of contraction of the heart muscle: this is predominantly an effect of epinephrine acting through beta receptors. Constriction of blood vessels: norepinephrine, in particular, causes widespread vasoconstriction, resulting in increased resistance and hence arterial

A major effects mediated by epinephrine and norepinephrine are:

Dilation of bronchioles: assists in pulmonary ventilation. Dilation of the pupils: particularly important in situations where you are surrounded by velociraptors under conditions of low ambient light. Inhibition of certain "non-essential" processes: an example is inhibition of gastrointestinal secretion and motor activity. clotting time of the blood is reduced; increased ACTH secretion from the anterior lobe of the pituitary. All of these effects prepare the body to take immediate and vigorous action.

Adrenal Steroids

Class of Steroid

Region of adrenal gland

Major Representative

Effects

Glomerulosa Mineralocorticoids Aldosterone Na+, K+ and water homeostasis

Glucocorticoids

Fasciculata Reticularis

Cortisol

Glucose homeostasis and many others

Androgens

Fasciculata Reticularis

Testosterone

 Steroid hormones are hydrophobic and must be carried in the blood bound to a serum protein: Glucocorticoids are transported by transcortin corticosteroid-binding globulin; Mineralocorticoids are transported by plasma albumin.

The cytosolic-nuclear mechanism of steroid hormones action

. Like all steroid hormones, cortisol and aldosterone bind to their respective receptor (a protein present in the cytoplasm and/or nucleus of "target" cells), and the resulting hormone-receptor complex binds to a hormone response element in DNA to modulate transcription of responsive genes.

Mineralocorticoids
The major target of aldosterone is the distal tubule of the kidney, where it stimulates exchange of sodium and potassium. Three primary physiologic effects of aldosterone result: Increased resorption of sodium (Na+). Increased resorption of water. This is an osmotic effect directly related to increased resorption of sodium. This helps maintain normal blood pressure. Increased renal excretion of potassium (K+).

Control of Aldosterone Secretion

Small increases in blood levels of potassium strongly stimulate aldosterone secretion. Angiotensin II: Activation of the renin-angiotensin system as a result of decreased renal blood flow (usually due to decreased vascular volume) results in release of angiotensin II, which stimulates aldosterone secretion. a drop in the level of sodium ions in the blood; ACTH (adrenocorticotropic hormone)

Glucocorticoids
The glucocorticoids get their name from their effect of raising the level of blood glucose. One way they do this is by stimulating gluconeogenesis in the liver: the conversion of fat and protein into intermediate metabolites, that are ultimately converted into glucose. Cortisol and the other glucocorticoids also have a potent anti-inflammatory effect on the body. They depress the immune response, especially cellmediated immune responses.

Effects on Metabolism
Glucocorticoids stimulate processes that serve to increase and maintain normal concentrations of glucose in blood. These effects include: Stimulation of gluconeogenesis, particularly in the liver: This pathway results in the synthesis of glucose from non-hexose substrates such as amino acids and lipids. Mobilization of amino acids from extrahepatic tissues: These serve as substrates for gluconeogenesis. Inhibition of glucose uptake in muscle and adipose tissue: A mechanism to conserve glucose. Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy in tissues like muscle, and the released glycerol provide another substrate for gluconeogenesis.

Effects on Inflammation and Immune Function

Glucocorticoids have potent antiinflammatory and immunosuppressive properties. As a consequence, glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis or dermatitis, and as adjunction therapy for conditions such as autoimmune diseases.

Control of Cortisol Secretion

Cortisol and other glucocorticoids are secreted in response to a single stimulator: adrenocorticotropic hormone (ACTH). ACTH is itself secreted under control of the hypothalamic peptide corticotropinreleasing hormone (CRH). Virtually any type of physical or mental stress results in elevation of cortisol concentrations in blood due to enhanced secretion of CRH in the hypothalamus. Cortisol secretion is suppressed by classical negative feedback loops. The combination of positive and negative control on CRH secretion results in pulsatile secretion of cortisol. Typically, pulse amplitude and frequency are highest in the morning and lowest at night.

Hyperadrenocorticism
Hyperadrenocorticism or Cushings disease. Excessive levels of glucocorticoids are seen in two situations Excessive endogenous production of cortisol Administration of glucocorticoids for theraputic purposes. Cushing's disease has widespread effects on metabolism and organ function. A diverse set of clinical manifestations accompany this disorder, including hypertension, apparent obesity, muscle wasting, thin skin, and metabolic aberrations such as diabetes.

 HyperAdrenalism Primarily the Glucocorticoids

Hypoadrenocorticism
Insufficient production of cortisol, often accompanied by an aldosterone deficiency, is called hypoadrenocorticism or Addison's disease Most commonly, this disease is a result of infectious disease (e.g. tuberculosis in humans) or autoimmune destruction of the adrenal cortex. As with Cushing's disease, numerous diverse clinical signs accompany Addison's disease, including cardiovascular disease, lethargy, diarrhea, and weakness. Aldosterone deficiency can be acutely life threatening due to disorders of electrolyte balance and cardiac function.

 Low adrenal activity Gonocorticoid appear normal Increased pigmentation due to increased ACTH

Sex Hormones

 Classic Sex Hormones: Gonad and Adrenal Estrogen Progesterone Dihydrotestosterone Testosterone

 Follicles Estrogen Progesterone

Mature Testis Semeniferous Tubules, Interstitial cells Testosterone Estrogen Inhibin