HPA Axis Flashcards
What are the 3 classifications of hormones?
- Polypeptide (protein and peptides)- water soluble
- Amine (derived from amino acids)- water soluble
- Steroids hormones- lipid soluble
Negative vs positive feedback on the HPA
What are the lobes of the hypothalamus?
Hypothalamus: Located in the brain just below the thalamus
Anterior lobe (Adenohypophysis) – protrusion of ectoderm from roof of mouth (Rathke’s pouch)
Posterior lobe (Neurohypophysis)- Neuroectoderm
What are the divisions of the pituitary gland?
Anterior- synthesises and stores hormones
Posterior- doesnt synthesise but stores and releases them
What are the hormones in the anterior pituitary?
✓ Growth hormone (GH) secreted by somatotrophs (20%)
✓ Thyroid-stimulating hormone (TSH) or thyrotropin by thyrotrophs (5%)
✓ Adrenocorticotropic hormone (ACTH) by corticotrophs (15%)
✓ Follicle-stimulating hormone (FSH)
✓ Luteinizing hormone (LH)
✓ Prolactin (PRL) secreted by Lactotrophs (15%)
What are the hormones stored in the posterior pituitary?
✓ The posterior lobe of the pituitary secretes ADH and oxytocin. Both ADH and oxytocin are neuropeptides synthesized in cell bodies of hypothalamic neurons and secreted from nerve terminals in the posterior pituitary
What are the actions of the hypothalamus hormones on the pituitary ones (TRH, PIF, CRH, GHRH, GH-RIH, GnRH)
What is GH, what are the actions and how does it exert them?
✓ Secretion is favored by sleep, stress and young age; decreased secretion in old age and obesity
✓ GH secretion released in pulsatile pattern
GH has 2 major actions
✓ Growth of skeletal and soft tissues and
✓ Metabolic on carbohydrate, lipid and protein metabolism.
GH hormone exerts its actions by 2 ways
✓ Indirect through another hormone called, insulin-like growth factor-1 (IGF-1)/ somatomedins
✓ Direct through GH-receptors in target tissue
What is prolactin and what are its actions?
▪ PRL is a peptide hormone secreted by the lactotrophs.
▪ PRL is predominantly inhibited by hypothalamic Dopamine (also known as prolactin inhibiting hormone, PIH) in both males and females
▪ Serum level is very low in both men and women.
▪ PRL level increases only during pregnancy and breast feeding in women.
➢ Actions of Prolactin on target tissue
• Main function is breast development and milk production (lactogenesis), but not ejection of milk
• PRL suppresses sexual drive in both sex.
• In the ovary, PRL causes anovulation.
How is oxytocin synthesised and released and what are the actions?
❖ Synthesis and release of oxytocin
Oxytocin is synthesized mainly by paraventricular nucleus in the
hypothalamus. It is stored and released by the posterior pituitary
❖ Action of oxytocin
✓ Myoepithelial cells of the mammary gland—- Milk ejection
✓ Smooth muscles of the uterus (Myometrium)—- Expulsion of fetus and placenta. Both are positive feedback mechanism
How is ADH synthesised and released and what are the actions?
❖ Synthesis and release of ADH
ADH is synthesized mainly by the supraoptic (SO) nuclei of the hypothalamus, it is stored and released by the posterior pituitary
❖ Actions of ADH
✓ ADH increases the water permeability of principal cells in the late distal tubule and collecting duct.
✓ ADH also acts via V1 receptors in the vascular smooth muscles to cause contractions
What is the role of the gonadotropins?
✓ Follicle stimulating hormone (FSH) and Luteinizing hormone (LH) are secreted by gonadotropic cells of anterior pituitary
✓ FSH stimulate production of gametes (eggs or sperms)
✓ LH promotes production of gonadal hormones
-In female——mature follicles of egg, trigger ovulation and release of estrogen and progesterone
✓ -In male —— stimulate production of testosterone
✓ Sex hormones have a key role in bone metabolism
• GnRH secretion is pulsatile
• HPA affected by environmental factors such as stress, exercise, weight loss
• Deregulation of HPA leads to menopause in female
• HPA activity in ♂ decreases over time
Hyper vs hyposecretion
➢ Hypersecretion
- Hormone secreting tumors (Adenoma or Carcinoma)
- Hyperplasia
- Autoimmune stimulation
- Ectopically produced peptide hormone (ACTH, ADH)
➢ Hyposecretion
- Autoimmune disease
- Tumors
- Infection
- Hemorrhage
What are disease associates with growth hormone deficiency?
✓ Pituitary dwarfism
▪ Impaired GH secretion by the anterior pituitary (pituitary dwarf)
▪ These children show decreased rate of growth and short stature, but normal brain development and intellectuality
▪ These patients have decreased plasma GH and IGF-1
✓ Laron dwarfism
▪ Defective GH receptors in the target tissue. This is called Laron dwarfism, a type of GH insensitivity syndrome.
▪ These patients have decreased plasma IGF-1 but elevated plasma GH
✓ Growth hormone deficiency in adults
▪ If the GH deficiency occurs after the fusion of epiphyses of long bones (after the age of about 20), height is not affected. These patients develop increased body fat, reduced muscle mass, fatigue and decreased physical fitness
What are the disease associated with excess growth hormone?
Gigantism- is the pituitary disorder characterized by excess growth of the body. Excess GH secretion before the fusion of the. epiphyseal plates of the long bones. Rapid increase in height and weight. Other features are: Large hands and feet, coarsening of the facial features with frontal bossing and prognathism (projection of the jaw), headaches, and excessive sweating. May be because of a tumor in the anterior pituitary that hyper-secretes GH
Acromegaly- Excess GH secretion after the fusion of the epiphyseal
plates (in adults). Excessive skeletal, soft tissue and internal organ growths. Acral bony overgrowth results in frontal bossing, increased hand and foot size, mandibular enlargement with prognathism (projection of the jaw), and frontal bossing. Other features: Headaches, ↑BP, excessive sweating and ↑blood glucose. Treatment is somatostatin analogues (Lanreotide/Octreotide/Pasireotide)
What are the causes, symptoms and treatment of diabetes insipidus?
What are the causes, symptoms and treatment of increased ADH disorders?
What is the function of the adrenal cortex hormones?
What is the HPA axis?
What is the result of abnormal secretion of cortisol?
Wha are the investigations and treatment of Cushing syndrome?
Medical
Adrenal enzyme inhibitor
- Metyrapone; 11β-OH Inhibitor
- Ketoconazole (anti-fungal drug); P450 enzyme inhibitor
- Mitotane; inhibits side chain cleavage + direct toxic effect
Surgical
Trans sphenoidal surgery
Bilateral adrenalectomy
Radiotherapy
What is addisons disease? Symptoms and treatment.
