Endocrine module

Endocrinology

Branch of biology and medicine dealing with the endocrine system , its disease and its specific secretion known as

hormones.

Hormones – organic biologically active

compounds of different chemical nature that

are produced by the endocrine glands, enter

directly into blood and accomplish humoral

regulation of the metabolism of compounds and

functions on the organism level.

Hormonoids (tissue hormones) – compounds

that are produced not in glands but in different

tissues and regulate metabolic processes on the

local level, but some of them (serotonin,

acetylcholine) enters blood and regulate

processes on the organism level.

Specific stimulus for hormones

secretion is:

-nervous impulse

-concentration of the certain

compound in blood passing through

the endocrine gland

1. Hypothalamus2. Pituitary3. Epiphysis4. Thymus5. Thyroid gland6. Parathyroid glands7. Langergans’ islands of pancreas8. Epinephrine glands9. Sex glands

Endocrine glands:

Fate of hormones in the organism

•Are secreted directly into the blood

•Peptide and protein hormones are secreted

by exocytosis

•Steroid (lipophilic) hormones continuously

penetrate the membrane (they are not

accumulated in cells, their concentration in

blood is determined by the speed of

synthesis)

Transport of hormones in blood

Protein and peptide nature – in free state

Steroid hormones and hormones of thyroid gland –

bound with alpha-globulins or albumins

Catecholamines – in free state or bound with albumins,

sulphates or glucuronic acid

Reach the target organs

Cells have the specific receptors to certain hormone

PITUITARY GLAND

The pituitary gland(master gland) is about the size of a pea (0.5 grams).

It lies at the base of the skull in a bony cavity of the sphenoid bone (referred to as

the sella turcica)

CELLS OF THE ANTERIOR PITUITARY

• On the basis of histological and functional characters, two major types of the cells are found in the anterior pituitary gland:

Chromophobes: Histological structure that does not stain readily, appear pale under the microscope.

Chromophills (Acidophills & Basophills).

• A = Basophils

• B & C= Chromophobes

• D = Acidophils

Acidophills include furthertwo types of cells

• Somatotropes

– Responsible for the secretion of Growth hormone.

• Lactotropes.

– Secrete Prolactin.

Basophills are further subdivided into three types On the basis of

their secretions• Corticotropes.

–Responsible for the secretion of ACTH.

• Thyrotropes.

–The secretion of TSH.

• Gonadotropes.

–The secretion of FSH & LH.

Hormones of the anterior pituitary

• Somatotropin (GH).

• Corticotrophin (ACTH).

• Thyrotropin (TSH).

• Gonadotropins:

Follicle stimulating hormone (FSH).

Leutinizing hormone (LH).

• Prolactin.

Structure of the hormones of the anterior pituitary

• Polypeptide chainProlaction (198 Amino Acids)Growth hormone (191 Amino Acids)ACTH (39 Amino Acids)

o Glycoproteins (Having an alpha and beta chain)

FSH (Alpha: 89 Beta:115) LH (Alpha: 89 Beta:115)TSH (Alpha: 89 Beta:112)

Structural similarities

• GROWTH HORMONE AND PROLACTIN BELONG TO THE SAME FAMILY OF HORMONES.

Homology in Amino Acid structure

Act through the tyrosine kinase receptor system

Linked to growth

Growth Hormone(GH; Somatotropin)

• The major hormone regulating growth in the body is growth hormone(GH;somatotropin).

• Actions of Growth Hormone:

- increases skeletal growth

- increases muscular growth

- increases amino acid uptake and protein synthesis

- increased use of lipids for energy

- decreased storage of carbohydrates

Growth hormone

• Released under the influence of hypothalamic Growth Hormone Releasing Hormone (GHRH).

• Inhibited by the hypothalamic hormone Somatostatin.

• Growth hormone is released in a pulsatilefashion

BIOCHEMICAL FUNCTIONS OF GROWTH HORMONE

• Growth hormones performs its functions on the cells in two ways

Acts directly on the tissues

Acts on the liver to release somatomedians(proteins) which then act on the tissues.

• Clinical levels of growth hormone can be more specifically tested by somatomedians because

Greater half life(20 hours)

Growth hormone release is pulsatile

• Growth hormone has both catabolic and anabolic functions.

• Anabolic functions: Proteins

• Catabolic Functions: Lipids

Endocrine secretion of pancreas

• The pancreas, in addition to it's digestive functions secrets two important hormones insulin and Glucagon that are crucial for normal regulation of glucose ,lipids and protein metabolism ,although the pancreas secrets other hormones ,somatostatin, and pancreatic polypeptide .

The Endocrine Pancreas

Islets of Langerhans

• 1 million islets

• 1-2% of the pancreatic mass

• Beta (β) cells produce insulin

• Alpha (α) cells produce glucagon

• Delta (δ) cells produce somatostatin

• F cells produce pancreatic polypeptide

• Hormone of nutrient abundance

• A protein hormone consisting of two amino acid chains linked by disulfide bonds

• Synthesized as part of proinsulin (86 AA) and then excised by enzymes, releasing functional insulin (51 AA) and C peptide (29 AA).

Insulin

1- Large polypeptide 51 AA (MW 6000)

2- Tow chains linked by disulfide bonds.

A chain (21 AA)

B chain (30 AA)

3 disulfide bonds.

Insulin Structure

Physiologic anatomy of the pancreas

• The pancreas is composed of two major typestissues :1- the acini which secrets digestive juices into the duodenum

2- the islets of Langerhans ,which secrete insulin and Glucagon directly into the blood

The islets contain three major types of cells :alpha ,beta and delta cells , the alpha cells secrete glucagon hormone. And delta cells secrete somatostatin

The beta cells ,constituting about 60 percent of all cells of the islets , and secrete insulin.

insulin inhibits Glucagon secretion,and somatostatin inhibits the secretion of both insulin and Glucagon .

Insulin and it’s metabolic effects

• insulin has profound effects on :

• carbohydrate metabolism

• fat metabolism

• protein metabolism

Factors and conditions that increase and decrease insulin secretion

decrease insulin secretion Increase insulin secretion

-Decrease blood glucose

-fasting

-somatostatin

-Alfa-adrenergic activity

-increase blood glucose

-increase blood free fatty acid

-increase blood amino acid

-gastrointestinal hormones

(gastrin, choleccystokinin

secretin, gastric inhibitory

peptide)

-glucagon, growth hormone,

cortisol.

-parasympathetic stimulation

-insulin resistance ;obesity

• A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent

• Produced by α cells in the pancreas

• Its major target is the liver, where it promotes:

– Glycogenolysis – the breakdown of glycogen to glucose

– Gluconeogenesis – synthesis of glucose from lactic acid and noncarbohydrates

– Release of glucose to the blood from liver cells

Glucagon

• A serious disorder of carbohydrate metabolism

• Results from hyposecretion or hypoactivity of insulin

• The three cardinal signs of DM are:

–Polyuria – huge urine output

–Polydipsia – excessive thirst

–Polyphagia – excessive hunger and food consumption

Diabetes Mellitus (DM)

Glucagon and it’s functions

• Glucagon ,a hormone secreted by the alpha cells of the

islets of Langerhans ,when the blood glucose

concentration falls. has several functions that are

diametrically opposed to those of insulin .Most

important of these functions is to increase the blood

glucose concentration ,an effect that is exactly the

opposite that of insulin

• Like insulin ,glucagon is a large polypeptide .it has a

molecular weight of 3485 and is composed of a chain of

29 amino acids

• glucagon is also called the hyperglycemic hormone.

Diabetes mellitus

• Is a syndrome of impaired carbohydrate ,fat, and protein metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissue to insulin

• There are two types of diabetes mellitus

1-type 1 diabetes also called insulin –dependent diabetes mellitus (IDDM) is caused by lack of insulin secretion

2-type 2 diabetes mellitus also called non-insulin-dependent diabetes mellitus (NIDDM) is caused by decrease sensitivity of target tissue to the metabolic effects of insulin (also called insulin resistance )

Adrenal (Suprarenal) Glands

Comprised of two parts –each with separate functions

outer adrenal cortex &

inner adrenal medulla

(“suprarenal” means on top of the kidney)

Adrenal Cortical Steroids

• Mineralocorticoids

– eg. aldosterone

– Controls ion transport in the kidney function

– Regulates expression of a Na channel

– Important for water reabsorption

• Glucocorticoids

– eg. cortisol

– Important for metabolism esp. glucose

– Activate enzymes (in liver) that increase glucose production

– blood glucose

Steroid Hormones• Steroid hormones: produced in the

adrenal cortex, testis, ovary, andsome peripheral tissues (adiposetissue, the brain!)

• All steroid hormones share a typical(but not identical) ring structure.

Steroid hormones

All steroid hormones are derived fromcholesterol and differ only in the ringstructure and side chains attached to it.

All steroid hormones are lipid soluble

Types of Steroid hormones

• Glucocorticoids; cortisol is the major representative in most mammals

• Mineralocorticoids; aldosterone being most prominent

• Androgens such as testosterone

• Estrogens, including estradiol and estrone

• Progestogens (also known a progestins) such as progesterone

Cortisol, the important glucocorticoid

• It is essential for life

• Helps the body deal with stressful situations within minutes– Physical: trauma, surgery, exercise

– Psychological: anxiety, depression, crowding

– Physiological: fasting, hypoglycemia, fever, infection

• Regulates or supports a variety of important cardiovascular, metabolic, immunologic, and homeostatic functions including water balance

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• Keeps blood glucose levels high enough to support brain’s activity

– Forces other body cells to switch to fats and amino acids as energy sources

• Catabolic: break down protein

• Redirects circulating lymphocytes to lymphoid and peripheral tissues where pathogens usually are

In large quantities, depresses immune and inflammatory response

Aldosterone, the main mineralocorticoid

• Secreted by adrenal cortex in response to a decline in either blood volume or blood pressure (e.g. severe hemorrhage)– Is terminal hormone in renin-angiotensin

mechanism

• Prompts distal and collecting tubules in kidney to reabsorb more sodium– Water passively follows

– Blood volume thus increases

Functions of Steroid Hormones

• Steroid hormones play important roles in:

- carbohydrate regulation (glucocorticoids)

- mineral balance (mineralocorticoids)

- reproductive functions (gonadal steroids)

• Steroids also play roles in inflammatory responses, stress responses, bone metabolism, cardiovascular fitness, behavior, cognition, and mood.

Steroid hormone synthesis

•The cholesterol precursor comes from cholesterol synthesized within the cell from acetate, from cholesterol ester stores in intracellular lipid droplets or from uptake of cholesterol-containing low density lipoproteins.

•Lipoproteins taken up from plasma are most important when steroidogenic cells are chronically stimulated.

Functions of Hormones Derived from Cholesterol

Product Functions

Progesterone prepares uterus lining for

implantation of ovum

Glucocorticoids (cortisol)

(produced in adrenal cortex)

(catabolic steroid)

promote gluconeogenesis;

favor breakdown of fat and

protein (fuel mobilization);

anti-inflammatory

Mineralocorticoids

(aldosterone) (produced in

adrenal glands)

maintains blood volume and

blood pressure by increasing

sodium reabsorption by kidney

Androgens (strongest = testosterone)

(produced in testes primarily but weak

androgens in adrenal cortex) (anabolic

steroid)

development of male

secondary sex

characteristics; prevents

bone resorption

Estrogen

(produced in ovaries primarily but also

in adipose cells of males and females)

development of female

secondary sex

characteristics; prevents

bone resorption

Vitamin D (not a steroid hormone)

(produced in the skin in response to

UV light and processed to active form

in kidney)

intestinal calcium

absorption; promotes

bone formation; prevents

phosphate loss by

kidneys

Product Functions

Functions of Hormones Derived from Cholesterol

Cortisol: Role in Diseases and Medication

• Use as immunosuppressant

– Hyperimmune reactions (bee stings)

– Serious side effects

• Hypercortisolism (Cushing's syndrome)

– Tumors (pituitary or adrenal)

– Iatrogenic (physician caused)

• Hypocortisolism (Addison's disease)

Adverse Effects

1. Complications during chronic uses

1) Cushing’s syndromes body obesity, rounded face, increased fat

around the neck, thinning arms & legs, acne, hirsutism, edema,

hypokalemia, hypertension, diabetes.

2) Inducement or aggravation of infections

3) Complications of digestive system or aggravation of peptic ulcer,

pancreatitis, sebaceous hepatitis appeared occasionally

4) Complications of cardiovascular system

hypertension, atherosclerosis.

5) Osteoporosis, sweeny and wound healing delay

6) Other complications

anoia, teratogenesis

2. Withdraw

1) Iatrogenic adrenal insufficiency

2) Original disease relapse or aggravation

Thyroid Hormone

• The thyroid hormones, triiodothyronine (T3) and its prohormone, thyroxine (T4), are tyrosine-based hormones produced by the thyroid gland that are primarily responsible for regulation of metabolism.

Biosynthesis of T3 & T4

• T3 & T4 are synthesized from tyrosine amino acid by the help of thyroglobulin

• Biosynthesis covers the following steps

1. Uptake of iodine

2. Formation of active iodine

3. synthesis of T3 & T4

Goiter• Any abnormal increase in size of thyroid gland is

goiter• Enlargement is mostly to compensate ↓ thyroid

hormones & ↑ TSH• This is primarily due to a failure in the

autoregulation of T3 & T4 synthesis• May be caused by deficiency or excess of iodine• Goitrogenic substances: thiocyanates, nitrates &

percholates and drugs like thiourea, thiouracil, thiocarbamide etc.

• Simple endemic goiter: due to iodine deficiency in diet. Mostly found in those geographical regions where iodine is less in soil & water