CH0576: The Biology of Disease-Dr Richard N. Ranson

Endocrine Disorders 1.

Goiter

Historical Perspectives 1: the first endocrine experiment

A. A. Berthold 1849 – Concluded that testes secreted something that

conditioned blood

Historical Perspectives 2: “Sexual Rejuvenation”

Hormone replacement therapy

1889- Charles Brown-Sequard Extract of Testes dissolved in H2O

Steroid Hormones Lipid

Soluble

Placebo effect

Intuitive observations

Basic definitions:

Endocrinology: • Hormones• Receptors

• Signalling pathways

• Diseases/pathophysiology

Hormone: (hormon = to excite or get moving):

• Molecule secreted from endocrine cells that regulates activity of target cells

Location of Endocrine

Glands

Young, T-Cells

Other hormone secreting cells located in:

• Kidneys• Stomach e.g. Gastrin• Liver• Small Intestine• Heart e.g. ANP• Skin• Adipose Tissue• Placenta e.g. Progesterone

Leptin

Leptin

Decreased Appetite signal

Hormone synthesis:

Fig 7.3-Silverthorn

Catecholamine, Peptide and thyroid hormones

Enzyme

Post-translational modification

C-peptideUsed as measure of insulin production

Hormone release - Local or circulating.

Effects: Mins to hrs Rapid inactivation● Example Local Hormone NO (Nitric Oxide) – Blood Vessel

endothelial cells

● Acts on Smooth muscle – Vasodilatation

● Viagra enhances NO effects – Role in penile erection

Fig 18.2 Tortora & Derrickson

Importance of receptors:For hormone to be active ‘Target cell’ must express

specific receptor

Hormone excess Homeostasis Hormone deficient

Down-regulation Up-regulation

Receptor Blocking

E.g. RU486 (mifepristone) – Induces Abortion

Blocks progesterone receptorsPrevents uterine conditions

embryo nurturing

Hyperinsulinemia - diabetes

Types of Hormones 1: Water Soluble hormones

Norepinephrine

Amines Peptides & Proteins Eicosanoids

Adrenal medulla

Pineal Gland

All Cell Types Except RBC

Local HormonesVarious effects

e.g. vasodilatation

Vasopressin

Posterior Pituitary

Urine Output

Insulin

Pancreas

Increased Glucose uptake

Blood Glucose

Types of Hormones 2: Lipid Soluble Hormones

Testosterone Steroid Hormones

Nitric Oxide - Endothelial Cells

Testes, Adrenal Cortex

Thyroid HormonesThyroid Gland

Progesterone, Oestrogen (Ovaries)

HRT-Oral administration-cross intestinal lining

Transport of Hormones in BloodWater soluble circulate in blood plasma in ‘free’ form

Lipid Soluble bound to transport proteins (synthesized in liver)

● Makes lipid hormones ‘water soluble’

● Increases half life of hormone by protecting from enzyme degradation

● 0.1-10% hormone is unbound – “Free fraction” – leaves blood to react with cells

Mechanisms of Hormone Action 1. Steroid and thyroid hormone receptors

Fig 7.7 From Silverthorn

Mechanisms of Hormone action 2; Water soluble hormones

NE, ACTH, FSH, LH etc.

Activates Protein Kinases

Fig 9.1. E.N. Marieb.

The Major Endocrine Organs in adults 1 The Pituitary Gland 1.

Posterior

Fig 20-8 McCance

The Major Endocrine Organs 1 The Pituitary Gland 2- Pituitary-hypothalamo relationship

Anterior Posterior

. CRH, GnRH

The Major endocrine glands 2. The Pineal gland

Decreased Light

Melanopsin

Melatonin

Circulation

BrainstemBody target

cells

Metabolic rate

Promotes Sleep

Pinealocytes

Antioxidant?

The Major endocrine glands 3. : The thyroid gland

Colloid

Iodine

TYr

T3, triiodothyronineT4, thyroxine

Lack of Iodine in Diet (seafood) results in goiter

Stimulate metabolic rateIncrease protein synthesis etc.

The Major endocrine glands 4. : The Parathyroid gland 1.

The Major endocrine glands 4. : The Parathyroid gland 2.

PTH

The Major endocrine glands 5. : The Pancreas

The Major endocrine glands 5. : The Pancreas cont…

Raises Blood Glucose

Lowers Blood Glucose

Paracrine-inhibits glucagon & Insulin

Pathophysiology- Diabetes Mellitus

Inhibits SOM, gallbladder contraction

The Major endocrine glands 6. : The Adrenal gland 1

The Major endocrine glands 6. : The Adrenal gland 2

Promotes GluconeogenesisAnti-inflammatory

Immunosuppressive (transplants)

Metabolism

Adr, NA

Stress & Exercise

● Increased HR

● Increased CO

● Blood to Muscles

● Dilate Airways

Cortisol

The Major endocrine glands 7. : The Gonads

Ovary

TestisInhibin – Inhibits FSH from Anterior Pituitary (negative feedback)

Estrogens & Progesterone

Relaxin

Testosterone

Dilates uterine cervix

● Stimulates testis descent

● Regulates spermatogenesis

● Male 20 Sex Characteristics

● Menstrual Cycle● Maintain pregnancy & Prep Mammary glands● Female 20 Sex Characteristics

ReferencesHadley, M.C. & Levine J.E. (2007). Endocrinology. 6th Edit, Pearson International.

McCance, K. L. & Huether, S. E. (2006). Pathophysiology. (The Biologic Basis for Disease in Adults and Children). 5th Edit. Elsevier Mosby.

Marieb, E. N. (2009) Essentials of Human Anatomy & Physiology. 9th Edit, Pearson International

Purves, D et al (2008). Neuroscience. 4th Edit. Sinauer.

Tortora G. J. & Derrickson B.(2006). Principles of Anatomy and Physiology. 11th Edit, Wiley.

Unglaub Silverthorn D. (2007) Human Physiology (An integrated approach), 4th Edit, Pearson International.