Endocrinology

What are hormones?

Chemical messengers released from one tissue which produce a specific, receptor-mediated change in another tissue

What do hormones do?

Involved in:

• Development - Proliferation, growth, and differentiation

• Metabolism - Energy storage, metabolic rate and temperature

• Reproduction - Sexual maturation & behaviour, pregnancy & lactation

• Fluid homeostasis - Water balance, salt levels, blood volume, pressure

What are the endocrine glands?

• Brain

• Pituitary

• Thyroid

• Thymus

• Adrenal

• Pancreas

• Kidney

• Testes

• Uterus

 

What tissues have an endocrine function?

• Kidney - erythropoietin (EP)

• Heart - atrial natriuretic peptide (ANP)

• Gut - gastrin, secretin

• Adipocytes - leptin, adiponectin (fat cells)

• Pancreas - insulin

What are the 4 different functions tissues can have?

What are the 3 major chemical classes of hormones?

• Amines

  • Tyrosine, l-dopa, dopamine, noraepinephrine, epinephrine

• Peptides and proteins

• Steroids

Describe peptide hormones

• Synthesised from AAs

• Processed in several stages

• N-terminal signal sequence cleavage in ER

• Glycosylation in ER

• Cleavage of pro-hormone by endopeptidases in cell

• Prolactin

• ACTH

• Vasopressin

• Oxytocin

Describe steroid hormones

• Grouped by the receptor that they bind to 

• Glucocorticoids - cortisol (metabolism)

• Mineralocorticoids - aldosterone (salt balance)

• Androgens - testosterone (sex determination)

• Oestrogens - oestradiol (sex determination)

• Progestogens – progesterone (pregnancy)

What is the synthesis pathwa for hormones?

Cholesterol → Pregnenolone → Progesterone → all other hormones

Where are hormone receptors?

• Levels are normally low

• They can be inside the cell or on the cell membrane

  1. Thyroid and steroid hormone receptors

  2. Polypeptide and protein receptors

Cell membrane receptor

Steroid-hormones receptor mechanism (estrogen/thyroid)

What is up and down regulation?

Up regulation - increase in the number of receptors for a hormone

Down regulation - decrease in the number of receptors for a hormone 

What factors alter the rate of hormone secretion?

• Ions/nutrients

• NTs

• Tropic hormones

  • Hormones that stimulate endocrine glands to secrete

Neural control of hormones

HPA-axis (T hormone) feedback mechanism

What is the hypothalamus and its role in the endocrine system?

Made of neurones called nuclei or areas

• As an endocrine organ that controls the anterior pituitary (AP; major function)

• Via nerve fibres that innervate the posterior pituitary (PP)

• Via autonomic innervations of more distant glands (adrenal medulla, pineal, kidney parathyroid, pancreatic islets)

What does the hypothalamus regulate?

• Blood pressure

• Temperature

• Fluid and electrolyte balance

• Body weight

• Sleep

What connections does the pituitar gland (hypophysis) have?

• Direct - neuronal connection (posterior)

• Indirect - portal blood vessels (anterior)

What can the hormones from the anterior pituitary act on?

• Adrenal function

• Thyroid function

• Gonadal function

• Water balance (kidneys)

• Lactation

• Metabolism

How does the pituitary gland get its blood supply?

• The AP receives blood after it has been through the hypothalamus

• The blood drains into the hypothalamic-hypophysial portal system and runs down the infundibulum and releases into the AP

  • Hormones from hypophysis can enter anterior pituitary

• Hormones secreted by the pituitary are then taken away into the venous return

• The posterior lobe has a separate blood supply and drainage

  • Small # that go: pp → ap → h

What are the main hypophysiotropic hormones?

What is corticotropin releasing hormone?

• Highly conserved, 41 amino acid peptide

• Stimulates secretion of ACTH (adrenocorticotropic hormone) and LPH (lipotropin)

• The pre-curser molecule for these (any many others) is Proopiomelanocortin (POMC)

• CRH secreting neurons have bodies in PVN

• CRH is secreted in pulsatile bursts, especially in early morning

• Physical, emotional or chemical stress (stimulation from higher brain centres)

What is thyrotropin releasing hormone?

• Highly conserved, 3 amino acid peptide

• TRH secreted from neurons in the dorsomedial region of hypothalamus

• Stimulates secretion of TSH (thyroid stimulating hormone) from cells in the anterior pituitary known as thyotropes.

• Also stimulates Prolactin

• Secretion is regulated by higher brain centres via noradrenergic neurons.

• Pharmaceutical form is used to test pituitary response (secondary hypothyroidism)

What are the pituitary hormones?

What does vasopressin do in the kidney?

• Vasopressin binds to receptors on cells in the collecting ducts of the kidney

• Promotes reabsorption of water back into the circulation

• Without vasopressin, the collecting ducts are impermeable to water, and it flows out as urine

What are different endocrine disorders and diseases?

Endocrine disorders:

• Excess secretion of a hormone

• Deficient secretion of a hormone

• Failure to respond to a hormone

  • Usually due to absence or malfunction of a receptor

Endocrine diseases:

• Diabetes mellitus - insulin deficiency or insensitivity

• Thyroid disease (too little or too much)

• Infertility (hypothalamic, pituitary, gonadal)

• Obesity (leptin)

Control systems involving the hypothalamus and pituitary

Endocrine axes

How much fatty acids get released in the thyroid?

Synthesis of thyroid hormones

What are the different structures of the thyroid gland?

What is hypothyroidism?

• Primary defect of the gland

• Causes by iodine deficiency

• Symptoms: feeling cold, wait gain, lethargy, cardiac effects

• Autoimmune- Hashimoto’s disease, Graves’ disease

How is hypothyroidism treated?

• Drugs that block T3/T4 production

• Radioactive iodine

• Thyroidectomy