dr.may lecture 15

Dr. Maie Al-Bader - Endocrinology 2013 1

ENDOCRINOLOGY
Dr Maie Al-Bader
Dept. of Physiology
Ext: 6355
E-mail: albader@hsc.edu.kw


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


1. Hypothalamic Control

DOPAMINE
GHRH TRH (PIH) GnRH CRH HYPOTHALAMUS

ANTERIOR
GH TSH PRL LH & FSH ACTH PITUITARY

CRH: Corticotropin-releasing hormone
GnRH : Gonadotropin-releasing hormone
TRH: Thyrotropin-releasing hormone
PIH or dopamine: Prolactin-inhibiting hormone
GHRH: Growth hormone-releasing hormone STIMULATE

INHIBIT


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


Adrenal Glands

Each adrenal gland consists of adrenal cortex and adrenal medulla

• 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)


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


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

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