Endocrine

• Life Essential Glands:

1. Anterior Lobe of Pituitary
(Adenohypophysis) → ACTH
2. Adrenal Cortex → Cortisol
3. Parathyroid Gland → PTH

• Hormone Signalling Types:

1. Endocrine: enter blood to act on
distant target cells.
2. Paracrine: act on neighbouring
cells.
3. Autocrine: act on same cells that
produce it.

• Chemical Structure of Hormones:

Characteristic Amino Acid Derivatives Cholesterol Derivatives Fatty Acid Derivatives

Solubility Water Soluble Lipid Soluble
Receptor Site Cell Membrane Cytoplasm or Nucleus
Transport Independent - Conjugated Free Form (Active)
- Protein Bound (Inactive, Storage)
Catabolism Site Kidney Liver
Half Life Less than Glycoproteins More than Glycoproteins
Hormonal Mechanism of 1. Bind to cell 1. Enter cell and bind to cytoplasmic receptor.
Action membrane receptor 2. Formation of hormone/receptor complex
2. Generate 2nd 3. Complex enters nucleus and binds to specific
messenger DNA sites.
3. 2nd messenger alters 4. Gene expression
physiology of cell.
Examples Catecholamines Steroid Hormones: Prostaglandins
Melanin - Aldosterone
Thyroid Hormones - Cortisol
- Adrenal Androgen
- Sex Hormones
Secosteroid Hormone:
- Vitamin D

▪ NOTE: Thyroid hormones are derived from tyrosine (an amino acid) but are lipid soluble so
they have intracellular receptors.

1|By Mohammed E ljack from Core of Medial Physiology

• Gland Control (Hypothalamo-pituitary Axis):
▪ Environment, Nutrition, Ions → Hypothalamus (Releasing / Inhibitory Hormones → Pituitary
(Trophic / Tropic Hormones) → Gland
▪ Glands not controlled by Hypothalamo-pituitary axis:
1. Parathyroid Gland
2. Pancreas
3. Adrenal Medulla
- These glands are controlled by: Environment, Nutrition, Ions (Humoral) factors.

• Feedback Mechanism Types:

Characteristic Negative Feedback Positive Feedback

Used By Most hormones 1. Oxytocin
2. Angiotensin 2
3. LH just before ovulation

• Cell membrane receptors are integral proteins, they have three domains:
1. Extracellular Domain (N-Terminal): Bind hormone.
2. Transmembrane Domain: Anchor receptor to domain.
3. Intracellular Domain (C-Terminal): Help form 2nd messengers.

• Pituitary Gland

Characteristics Posterior Lobe (Neurohypophysis) Anterior Lobe (Adenohypophysis)

Function Stores and releases hormones that were Synthesis and secretion of hormones.
synthesized by the hypothalamus by the
help of pituicytes.
Neuroendocrine Hormones are received by axons from Hormones are received by portal
Relationship hypothalamus. (Neural) blood vessels.
Hormones ADH, Oxytocin 1. Trophic Hormones:
- TSH (Thyrotropin)
- ACTH (Corticotropin)
- FSH & LH (Gonadotropin)
2. GH
3. Prolactin
Cells Modified astrocytes (pituicytes) Acidophils (40%): GH & Prolactin
Basophils (10%): FSH, LH, TSH, ACTH
Chromophobes (50%): Inactive
Note

▪ NOTE: Tropic hormones increase cellularity, vascularity and secretion of the affected glands.

2|By Mohammed E ljack from Core of Medial Physiology

• Peptide Hormones 2nd Messengers:

2nd Messenger Hormones Mechanism

cAMP 1. Hormones ending in -H, 1. Hormone bind activate G-Protein
except GnRH, TRH, GH 2. G-Protein activate adenylate cyclase
(e.g, ADH) 3. Adenylate cyclase forms cAMP from ATP
2. Calcitonin 4. cAMP activates protein kinase A
3. Glucagon 5. Protein kinase A phosphorylates other proteins / enzyme
4. Catecholamine 6. Effect takes place.
IP3 1. GnRH 1. Hormone bind activate G-Protein
DAG 2. TRH 2. G-Protein activates phospholipase C
Calcium 3. Catecholamine 3. Phospholipase C hydrolyses PIP2 (4,5) into two:
4. Angiotensin 2 IP3 (1,4,5) DAG (Diacylglycerol)
5. ADH 4. Triggers release of Ca from 4. Activates protein
sarcoplasmic reticulum. kinase C
5. Ca bind to calmodulin.
6. Calmodulin activates
calmodulin-dependent
kinase.
cGMP 1. ANP 1. Hormone bind causes receptor changes.
2. Local Hormones: 2. Activation of guanylyl cyclase which forms cGMP
- Nitric Oxide 3. cGMP activates cGMP-dependent protein kinase &
- Histamine Protein Kinase A
4. Effect takes place.
Tyrosine 1. GH 1. Hormone bind causes receptor changes.
Kinase 2. Oxytocin 2. Intracellular domain becomes tyrosine kinase.
3. Prolactin 3. Tyrosine kinase phosphorylates itself / other proteins
(GO PIE) 4. Insulin 4. Effect takes place.
5. Erythropoietin

3|By Mohammed E ljack from Core of Medial Physiology

• TIP: Anything released by Pituitary, Pancreas, or Parathyroid is PROTEIN.

• Hormones of Anterior Pituitary:

Hormone Control Effect Stimulus Inhibitor
GH GHRH Anabolic: Physical: Physical:
GHIH ↑ Growth 1. Sleep (Non-REM) 1. Sleep (REM)
(Somatostatin) ↑ Protein 2. Stress Chemical / Hormonal:
↓ Urea & AA 3. Exercise 2. FFA
Ketogenic: 4. Fasting, Starvation. 3. GH (-ve feedback)
↑ FFA in Plasma Chemical / Hormonal: 4. Cortisol
↑ FFA Utilization 5. Ghrelin 5. Medroxyprogesterone
Diabetogenic: 6. Glucagon, Estrogen, (Progestin)
↑ CHO in Plasma Androgen. Electrolytes:
↓ Insulin Effects 7. L-Dopa. 6. I.V Glucose
Activate Vit D: 8. α adrenergic &
↑ Ca++ Absorb agonists
↑ PO4 Absorb 9. Protein Intake
Kidney Keeps: 10. 2-Deoxyglucose
↑ Na Electrolytes:
↑K 11. Hypoglycaemia
Lactogenic

▪ Important Notes:
▪ Somatomedins:
- Insulin-like Growth Factor 1 (Somatomedin C)
- Insulin-like Growth Factor 2

Growth Hormone
Change Before Puberty After Puberty
Increase Gigantism Acromegaly
Decrease Dwarfism Minor Metabolic Abnormalities & Increased
Sensitivity to Insulin

4|By Mohammed E ljack from Core of Medial Physiology

 Hormone Control Effect Stimulus Inhibitor
PRL PRLRH 1. Mammary Gland Physical: Chemical / Hormonal:
PRLIH Growth (During 1. Nipple Stimulation 1. L-dopa
(Dopamine) pregnancy) 2. Lactation 2. Dopamine Agonist
2. Milk Production 3. Sleep (Bromocriptine)
(After delivery) 4. Stress
3. Antigonadotropin 5. Exercise
Chemical / Hormonal:
6. TRH &
Hypothyroidism
7. Dopamine
Antagonist
(Phenothiazine)
Electrolytes:
8. Hypoglycaemia
NOTE
• Released by anterior pituitary, endometrium & placenta
• PRLIH is more dominant.
• Structurally similar to hCS & GH

PRL Excess (PITUITARY TUMORS) PRL Deficiency

1. Infertility
2. Amenorrhea
3. Impotence
4. Osteoporosis in females (low Estrogen)
5. Galactorrhoea

5|By Mohammed E ljack from Core of Medial Physiology

 Hormone Control Effect Stimulus Inhibitor
ACTH CRH 1. Trophic effect on Physical:
adrenal cortex 1. Stress
(except zona 2. Exercise
glomerulosa, in 3. Fear
low levels) 4. Cold Exposure
2. Increases 5. Fear
responsiveness Chemical / Hormonal:
of adrenal cortex 6. TRH &
3. Skin Hypothyroidism
Pigmentation 7. Dopamine
Antagonist
(Phenothiazine)
Electrolytes:
8. Hypoglycaemia
NOTE
• 75% Diurnal Rhythm (regulated by suprachiasmatic nuclei of hypothalamus)
• Stress stimulates median eminence of hypothalamus to increase CRH by PVN, then CRH stimulates
ACTH secretion.

ACTH Excess ACTH Deficiency

Pituitary Tumors ↑ACTH Pituitary Tumors ↓ACTH
(Secondary Cushing’s Synd.) (Secondary Addison’s Disease
Lung Tumors ↑ACTH Adrenal Problems
(Ectopic Cushing’s Syndrome) ↑Cortisol → ↓ ACTH
Adrenal Problems ↓Cortisol (Primary Cushing’s Synd.)
(Primary Addison’s Disease)

• NOTE:
- High Cortisol / ACTH → Cushing’s
- Low Cortisol / ACTH → Addison’s

6|By Mohammed E ljack from Core of Medial Physiology

• Regulation of Calcium & Phosphate:

Characteristic Calcium Phosphate

Normal Total Body Amount 1100 g (99% bone, 1% soft tissue 500 – 800 g (85 – 90% in
& plasma) skeleton)
Plasma Amount 9 – 10.5 mg/dL 12 mg/dL
Affected By 1. Protein Amount Inverse with Calcium
2. Electrolytes (Low K = Low Ca)
3. pH (Acidosis → ↑ Ionized Ca)
Hormonal Effect By
Intestinal Absorption 30 – 80%
Site Duodenum (Best), Ileum Duodenum
Kidney Reabsorption 60% 85 – 90% (Decreased by PTH)
Site PCT, Ascending LOH, DCT PCT
Absorption Mechanism Active Transport (by Vitamin D)
Passive Diffusion

Absorption Increasing Factors Absorption Decreasing Factors

1. Vitamin D 1. Phosphate, Oxalate (In plants)
2. Protein Diet 2. Caffeine
3. Fats (Low bile salts)
4. High intestinal pH (due to gastrectomy)

• Bone Cells:
Osteoblast Osteoclast
Function Bone Formation: Bone Resorption:
- Lay down osteoid, and - Break down osteoid and
release enzyme involved in release calcium from bone to
bone mineralization. plasma.
Enzyme Alkaline Phosphatase
Calcium Mobilization Calcium from plasma to bone Calcium from bone matrix to
matrix plasma
Stimulus 1. Vitamin D 1. PTH
2. GH 2. Vitamin D
3. Thyroid Hormones
4. Sex Hormones
Inhibitors 1. Calcitonin
2. Bisphosphonates
NOTE:
• Estrogen hastens epiphyseal plate closure.
• Growth hormone increases bone growth by somatomedins.
• Detoxification is a function of bone.
• Bone conduction increases hearing ability.

7|By Mohammed E ljack from Core of Medial Physiology

Characteristics Osteoporosis Osteopetrosis Rickets & Paget’s Disease
Osteomalacia
Bone ↓ Bone Matrix ↑ Bone Matrix ↓ Bone Matrix Deformed Bone
Cell Activity OC > OB OB > OC ↓ OB (Soft Bones) ↑ OC → ↓ OB
Cause Hyperparathyroidism Genetic Defective Vit D Deficiency Excessive bone
Cushing Syndrome Osteoclasts Low Ca Diet resorption
Low Estrogen followed by
irregular bone
formation.
Note Deformities appear Calcitonin
in legs, ribs, wrists Bisphosphonates
and skull.

NOTE: Rickets and Osteomalacia people can have osteoporosis.

PTH Vitamin D Calcitonin

Intestine Absorption ↑ Ca ↑ Ca
(Indirect by Vitamin D) ↑ PO4
Kidney Reabsorption ↑ Ca (DCT, CD) ↑ Ca ↓ Ca
↓ PO4 (PCT) ↑ PO4 ↓ PO4
Bone ↑ Resorption ↑ Formation ↓ Resorption
NET PLASMA EFFECT ↑ Ca ↑ Ca ↓ Ca
↓ PO4 ↑ PO4 ↓ PO4

1ry Hyper PTH 2ndry Hyper PTH 3ry Hyper PTH

Caused by Parathyroid Tumor Chronic Hypocalcaemia Prolonged
Lung Tumor (Chronic Renal Failure, Hypocalcaemia 2ndry to
Rickets / Vit D) 2ndry hyper PTH
Complication Hypercalcemia 3ry Hyper PTH Autonomous Release of
Hypophosphatemia PTH
Kidney Filtered Load ↑ Calciuria Renal failure means that ↑ Calciuria
↑ Phosphaturia calcium and other ↑ Phosphaturia
things will not be
reabsorbed.

Latent Tetany Overt Tetany

Threshold Not reached, but more Reached
excitability.
Calcium Levels Low Very Low
Tetany Signs (Carpal Spasms, Don’t appear, because threshold Appears.
Muscle Spasms, Laryngeal wasn’t reached, but it can be
Spasms) shown by chvosteck & trousseau

8|By Mohammed E ljack from Core of Medial Physiology

• Effects of Insulin
Rapid (seconds) Intermediate (minutes) Delayed (hours)
Increases entry of: 1. ↑ Glycogenesis Increases mRNA for enzymes
- Glucose (GLUT-4 muscles and 2. ↑ Lipogenesis involved in anabolism = increases
fat) 3. ↑ Protein Synthesis growth.
- Amino Acids 4. ↓ Gluconeogenesis
- Potassium (↑ Na/K Pump) 5. Activate Lipoprotein Lipase
6. Inhibit HS-L
NOTE:
• Cells that don’t need insulin to get glucose:
- Brain
- Kidney
- Intestine
- RBCS

9|By Mohammed E ljack from Core of Medial Physiology

RBC Formation is controlled by:
1. Normal bone growth
2. Certain hematopoietic growth factors (IL3, 6, 11)
3. Certain hormones (erythropoietin, thyroxin)
4. Certain nutrients (iron, folic acid, bit 12, vit c)

Mention three hormones and their effect in regulation of blood pressure:

1. ADH → Causes formation of aquaporin 2 on the distal nephron for water retention ↑BP
2. Aldosterone → Causes salt and water retention in distal nephron ↑BP
3. Epinephrine → Causes vasoconstriction of blood vessels ↑BP

Define auto regulation and mention the physiological theories that explain it:
- It’s the ability of the organ to control it’s blood flow and pressure in avoidance of organ damange.
- Theories:
1. Myogenic Theory
2. Metabolites Theory

10 | B y M o h a m m e d E l j a c k f r o m C o r e o f M e d i a l P h y s i o l o g y
11 | B y M o h a m m e d E l j a c k f r o m C o r e o f M e d i a l P h y s i o l o g y
12 | B y M o h a m m e d E l j a c k f r o m C o r e o f M e d i a l P h y s i o l o g y