dr.may lecture 15

ENDOCRINOLOGY

Dr Maie Al-Bader

Dept. of Physiology

Ext: 6355

E-mail: [email protected]

Dr. Maie Al-Bader - Endocrinology 2013 1

ENDOCRINOLOGY

• The main function of the endocrine system is to maintain

the homeostasis of the internal environment

• Hormone: chemical messengers secreted by cells of

endocrine glands (ductless glands) and tissues that

regulate the activity of other cells in the body.


Endocrine Glands that Function

Primarily to Secrete Hormones 1. Pituitary gland: ADH (vasopressin), oxytocin &

trophic hormones

2. Thyroid gland: thyroxine, tri-iodothyronine &

calcitonin

3. Parathyroid gland: parathyroid hormone

4. Adrenal gland: cortisol, aldosterone,

epinephrine & sex steroids

5. Pancreas: insulin and glucagon

6. Ovaries & testicles: androgens, estrogens &

progesterone

7. Pineal gland: melatonin

8. Thymus gland: thymosine


Other Organs which Function

Secondarily as Endocrine Glands

1. Heart: atrial natriuretic peptide (ANP)

2. Kidney: erythropoietin

3. Liver: somatomedin (IGF)

4. Skin: vitamin D3

5. Gastrointestinal tract: gastrin, CCK and VIP

6. Adipose tissue: leptin

7. Hypothalamus: releasing and inhibiting hormones


Mechanism of Hormone Action


Functional categories of hormones based on the location of their

receptor proteins and mechanisms of action:

a. Hormones that bind to nuclear receptor proteins e.g. steroid

and thyroid hormones (what would be the characteristics of such

hormones?)

b. Hormones that use second messengers e.g. protein and

peptide hormones (what would be the characteristics of such hormones?)

Hormones that Bind to

Nuclear Receptor Proteins Steroids

Lipohilic steroid hormones are

bound to carrier proteins in

plasma. They then dissociate

from these proteins in order to

pass through the lipid

component of the target cell

membrane and enter target cell

where their receptor proteins

are located

Secreted by: adrenal cortex,

testes and ovaries

Location of receptors: in

cytoplasm or nucleus of the

target cell


Thyroid Hormones

Very similar to steroids in size; being non-polar; and very water-insoluble; carried

mainly by thyroxine-binding globulin (TBG; T4 more than T3)

Secreted by: thyroid gland

Location of receptor proteins: are in the nucleus of target cells


Hormones that Use Second

Messengers Catecholamines (epinephrine and

norepinephrine), polypeptides and

glycoproteins cannot pass the lipid

bilayer of the cell membrane and

thus mediate their effects through

second messengers

Secreted by: all glands EXCEPT

adrenal cortex, gonads and

thyroid

Location of receptors: outer

surface of the membrane

Effects of hormone-receptor

interaction: stimulates production

of intracellular second messenger

including c-AMP, c-GMP,

phospholipase C, Ca2+ and

tyrosine kinase


Pituitary Gland (Hypophysis)

The pituitary gland is divided into two lobes:

1. Anterior hypophysis (adenohypophysis)

2. Posterior pituitary or neurohypophysis (neural part of the pituitary; pars

nervosa)


Posterior Pituitary Hormones

Posterior pituitary secretes only two hormones which are:

Produced by the hypothalamus

Stored in the posterior pituitary


Antidiuretic hormone (ADH)

• Also known as arginine vasopressin (AVP)

• It stimulates retention of water by the kidneys

Oxytocin

In females:

• It stimulates the contraction of the uterus during labour (required for

parturition; childbirth)

• It stimulates milk-ejection reflex in a lactating woman, i.e., contractions of

the mammary gland alveoli and ducts


Control of ADH & Oxytocin Secretion by Neuro-Endocrine Reflex


Anterior Pituitary Hormones

Secreted by pars distalis of adenohypophysis

They include:

Thyroid-stimulating hormone (TSH)

Adrenocorticotropic hormone (ACTH)

Follicle-stimulating hormone (FSH)

Luteinizing hormone (LH)

Prolactin

Growth hormone (GH) or somatotropin


Hyposecretion of growth hormone:

During childhood pituitary dwarfism (with normal body proportions)

During adulthood Simmonds’ disease

Hypersecretion of growth hormone:

During childhood gigantism

During adulthood acromegaly (no further growth BUT person’s

appearance changes as a result of thickening of bones, growth of soft

tissues as in face, hands and feet)


Control of Secretion of

Anterior Pituitary Hormones


1. Hypothalamic control: achieved through hormonal control 2. Feedback control by hormones secreted from target gland


STIMULATE INHIBIT

CRH: Corticotropin-releasing hormone

GnRH : Gonadotropin-releasing hormone

TRH: Thyrotropin-releasing hormone

PIH or dopamine: Prolactin-inhibiting hormone

GHRH: Growth hormone-releasing hormone

ANTERIOR PITUITARY ACTH LH & FSH TSH PRL GH

HYPOTHALAMUS CRH TRH GHRH DOPAMINE

(PIH) GnRH

1. Hypothalamic Control

2. Feedback Control Of Anterior Pituitary


Secretion of ACTH, FSH, LH and TSH is controlled by negative feedback

inhibition:

•Target gland hormones hypothalamus

•Target gland hormones anterior pituitary

•Anterior pituitary hypothalamus

• The adrenal medulla cells secrete catecholamines (epinephrine and norepinephrine;

4:1 ratio) and are innervated by sympathetic nerve fibers; activated by stress

• Once simulated the actions are

• very similar to those caused by stimulation of sympathetic nervous system,

however, they last ten times longer

• Activation of both the adrenal medulla and the sympathetic nervous system

prepares the body for greater physical performance (fight-or-flight)


Each adrenal gland consists of adrenal cortex and adrenal medulla

Adrenal Glands


Adrenal Cortex Secretes steroid hormones called corticosteroids (corticoids) including

mineralocorticoids, glucocorticoids and sex steroids


Mineralocorticoids (Aldosterone):

• Zona glomerulosa

• Secretes aldosterone which acts on the kidneys to regulate Na+ and K+

balance

Glucocorticoids (Cortisol):

• ACTH stimulates the zona fasiculata (little in zona reticularis) to secrete cortisol.

• Cortisol is a catabolic hormone that acts on the liver, muscle & adipose tissues

(to regulate carbohydrate, protein and fat metabolism) leading to an:

• serum glucose

• serum free fatty acid

• serum amino acid

Sex steroids:

• Weak androgens secreted by zona reticularis of adrenal cortex

• Supplement of sex steroids secreted by the gonads

Adrenal Cortex Secretion Abnormalities

1. Cushing's syndrome/disease:

Cause: hypersecretion of corticosteroids as a result of:

tumor of adrenal cortex (Cushing’s syndrome)

oversecretion of ACTH from anterior pituitary (Cushing’s disease)

(what are the two main differences between the syndrome and disease?)

Characterized by:

hyperglycemia

hypertension

muscular weakness

structural changes: moon face, purple abdominal striae, truncal obesity, buffalo hump and spindly arms and feet


2. Addison’s disease:

Cause: inadequate secretion of cortisol and aldosterone

Characterized by:

hypoglycemia

Na+ loss and K+ retention

dehydration

hypotension

rapid weight loss

generalized weakness

May lead to death if not treated with corticosteroids


3.Adrenogenital syndrome:

Cause: hypersecretion of adrenal sex hormones, particularly androgens

• In young children premature puberty and enlarged genitals

• In mature women growth of beard


Thyroid Glands

• Secretes

• thyroxine (T4)

• triiodothryonine (T3)

• calcitonin


Production and Storage of Thyroid Hormones

Target organ: almost all body organs

• Actions:

• stimulates protein synthesis

• promotes proper skeleton growth and development

• promotes maturation of the CNS

• its level in the blood determines the BMR (the minimum rate of caloric expenditure by the body)


Hypothyroidism


1. Iodine-deficiency (endemic goitre): form of hypothyroidism, caused by the lack

of adequate iodine in the diet

2. Cretinism: newborn infants born in areas of low iodide intake and endemic

goitre. Symptoms include : mental retardation, short stature, puffy face and

hands, deaf mutism etc.


3. Infantile hypothyroidism: occurs during childhood. Symptoms include: retarded

growth, abnormal bone development, low IQ, general lethargy and low body

temp

4. Hashimoto thyroiditis: form of hypothyroidism, characterized by a goitre, high

concentrations of antibodies, which are directed against thyroglobulin and

thyroid peroxidase. The progressive destruction of thyroid follicular tissue results

in hypothyroidism

5. Myxoedema: hypothyroidism in adulthood. Symptoms include: edema, low basal

metabolic rate, low body temperature, cold intolerance, lethargy and weight gain

tendency

http://www.usc.edu/hsc/dental/PTHL312abc/312c/25/IMGs/049big.html

http://www.usc.edu/hsc/dental/PTHL312abc/312c/25/IMGs/050big.html

Hyperthyroidism

Graves’ Disease

(Toxic Goitre)

• It is an autoimmune disease caused by antibodies that act like TSH causing

the growth of the thyroid associated with hypersecretion of thyroxine

• Clinical symptoms include:

• BMR

• heart rate

• weight loss

• excessive sweating

• heat intolerance

• exophthalamus (bulging of the eyes; because of edema in tissues of eye

socket)


Regulation of Calcium and Phosphate

Ca2+ and phosphate concentration in plasma is affected by:

• Bone resorption and absorption

• Intestinal absorption

• Urinary excretion

Regulation of plasma calcium and phosphate BY:

• Parathyroid hormone

• Calcitonin

• Calcitriol (1,25-dihydroxyvitamin D3)


Parathyroid Hormone (PTH)

• PTH is secreted by the parathyroid glands (usually 4) whenever the plasma

concentration of Ca2+ begins to fall

• PTH promotes a rise in blood calcium levels by acting on:

• Bones: stimulating bone resorption

• Kidneys: reabsorbtion of Ca2+ from glomerular filtrate and inhibiting reabsorption

of phosphate

• Intestine (indirect) : promoting the formation of 1,25-dihydroxyvitamin D3 by

stimulating 1a-hydroxylase in the kidney


Calcitriol

(1,25-dihydroxyvitamin D3)

• Production starts in the skin where Vitamin D3 is produced from precursor molecule 7-

dehydrocholesterol under the influence of sunlight

• Actions:

• Activity stimulated by PTH

• Helps to raise plasma concentration of calcium and phosphate by stimulating:

• Intestinal absorption of calcium and phosphate (main function)

• Resorption of bones

• Renal reabsorption of calcium and phosphate


Calcitonin

• Calcium lowering hormone

• Secreted by the parafollicular cell in

the thyroid gland

• It antagonizes the hypercalcemic

effect of calcitriol and PTH

• Is stimulated by high plasma Ca2+

and phosphate levels and acts to

lower Ca2+ levels by:

• inhibiting bone resorption

• stimulating the urinary excretion

of Ca2+ and phosphate by

inhibiting their reabsorption by the

kidneys


Osteoporosis

• Osteoporosis is characterized by low bone mass (due to the reduced deposition of

collagen as well as mineral). It occurs when bone resorption exceeds formation

• The bones become fragile & susceptible to fracturing (mainly hip, spine and wrist)

• Weight-bearing exercise builds denser, stronger bones (age 25 to 30). Weight-

lifting, jogging, hiking, stair-climbing, step aerobics, dancing, racquet sports, and

other activities that require your muscles to work against gravity.


Pancreas

The pancreas consists of an endocrine and an exocrine portion.

The exocrine portion is important for production of both bicarbonate and digestive enzymes

The endocrine portion of the pancreas consists of pancreatic islets (islets of Langerhans)

There are 2 types of cells in the islets of Langerhans:

alpha cells: secrete glucagon

beta cells: secrete insulin


Abnormalities – Diabetes Mellitus

• DIABETES MELLITUS is characterized by:

• Fasting hyperglycemia

• Glucose in the urine

• Type I diabetes (also known as juvenile-onset diabetes or insulin-dependent

diabetes mellitus [IDDM]). It occurs:

• in 10% of cases

• when there is lack of insulin secretion as a result of destruction of the beta

cells

• Type II diabetes (also known as maturity-onset diabetes or insulin independent

diabetes mellitus [NIDDM]). It occurs:

• in 90% of cases of diabetes

• patients are usually overweight

• there is a larger amount of insulin secretion, however, decreased tissue

sensitivity to insulin


Long Term Complications of Diabetes Mellitus


dr.may lecture 15

Health & Medicine

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