Introduction to endocrinology

• Different chemical classes of hormones: Peptides, Amino acid derivatives, Lipid/Steroids
• Hormones are chemical messengers secreted directly into the bloodstream and act slowly on distant organs and tissues
• Endocrine glands secrete substances into the bloodstream, while exocrine glands release products to ducts
• Cells communicate through substances recognized by other cells, including growth factors, prostaglandins, and inflammatory substances
• Neuronal transmission is a fast response with short-term effects
• Endocrine function involves circulating hormones that diffuse into capillaries and are transported via the bloodstream to target cells
• Hormones alter cell activity by stimulating selective receptors or inhibiting cell function
• Missions of the endocrine system include maintaining homeostasis and regulating various body activities
• Endocrine system regulates growth, development, reproduction, digestion, blood pressure, metabolism, and more
• Main endocrine disorders: Diabetes, Thyroid disorders
• Hormones stimulate or inhibit cell function, maintain ion levels, stimulate cell division, and affect programmed cell death
• Some hormones affect many different cell types in the body, while others have specific effects on target tissues
• Endocrine cells release hormones in response to selective stimuli and stop secretion when the body's need is satisfied
• Hormone secretion can be triggered by other hormones, neurotransmitters, follow circadian rhythms, or be commanded by the central nervous system
• Some hormones are released in short pulses and triggered by neurohormones synthesized by the brain
• Some endocrine secretions are partly commanded by the central nervous system, and hormones can be synthesised by both the CNS and peripheral organs
• Different chemical classes of hormones: Peptides, Amino acid derivatives, Lipid derivatives
• Peptides are stored in dense granules, while steroids are not stored but synthesized and released upon hormonal stimulation
• Tyrosine derivatives include hormones like adrenaline, noradrenaline, thyroxine (T4), and triiodothyronine (T3)
• Steroids are synthesized from cholesterol and include glucocorticoids, mineralocorticoids, sex steroids, and more
• • Maturation process can be complex, with preprohormone peptides as precursors of different active peptides
  • Examples:
  • Insulin is part of a larger precursor (proinsulin) cleaved into insulin and peptide C
  • Oxytocin and vasopressin are synthesised by neurones and part of larger precursors cleaved into different biologically active fragments
  • POMC (proopiomelanocortin) is a precursor of ACTH and other active peptides
  • Proglucagon can be processed into glucagon or glucagon-like peptides
• Peptide hormones:

  • Synthesised primarily as pro-hormone
  • Stored in dense granules and released in a Ca++ - dependent process
  • Circulate free in the blood
  • Sensitive to peptidase
  • Short half-life (minutes to hours)
  • Interact with membrane receptors on target cells
  • First synthesised as a preprohormone with NH2 signal sequence in the endoplasmic reticulum
  • Packaging in the Golgi of the prohormone, cleavage of signal sequences, possible further cleavages and glycosylation
  • Final cleavage of the prohormone in dense granules
• Steroids and thyroid hormones:

  • Lipophilic
  • Carried in the plasma by globulins, sometimes very specific (e.g., thyroid hormone binding protein, sex hormone binding protein)
  • Only a fraction of the hormone is free in the plasma
  • Longer half-life correlated with the % of binding with globulin
  • Advantages of plasma protein binding:
  • Long-lasting effects developing progressively
  • Additional pool of the hormone directly available
  • Prevention of abrupt fluctuations in hormonal secretion
  • Second protection against wastage
  • Receptors for hormones:
• • Peptide hormones and catecholamines stimulate receptors on the plasma membrane of target cells
  • Steroids and thyroid hormones can cross the cell membrane and stimulate intracellular receptors (cytoplasm/nucleus)
• Giantism


  Acromegaly (drug: octeotride)
• Pit dwarfism


  Growth retard (GH anal.)
• Gonads


  • Stage of menstrual cycle
  • Precocious puberty
  • GnRH agonists* (desensitisation process, puberty blocker)
• Mammary gland


  • Hyperprolactinemia
  • Oligo/amenorrhea
  • galactorrhoea
  • Infertility, gynecomastia
• Thyroid gland


  • Cold exposure
  • Exercise
  • hypothyroidism
  • Lactation (decrease)
  • goitre
• SIADH (Syndrome of inappropriate antidiuretic hormone secretion)

  hyponatremia associated with heart failure condition, or common ADR in aged patients treated with SSRI and patients treated with neuroleptics
• SIADH can be caused by MDMA (life threating), some cancer associated with oversecretion of ADH from tumour
• The majority of gynecomastia cases are due to drugs already known for causing this side effect (bicalutamide, dutasteride, flutamide, finasteride and the association furosemide/spironolactone).
• Thin arms and legs, due to effect of cortisol on protein catabolism. Cortisol promotes protein degradation (in healthy conditions, cortisol is important to maintain normal protein turnover).
• Hypertension


  Due to effect of cortisol on blood pressure, cortisol can also acts on aldosterone receptors stimulating water and sodium retention and increased blood pressure via this way, but most likely, in Cushing, there is a strong effect of cortisol on its own receptors, cortisol enhance adrenaline synthesis which may also increase BP.
• Hyperglycaemia


  Cortisol stimulates synthesis of new glucose (neoglucogenesis, mainly in liver) from lipolysis and proteolysis products. Cortisol antagonises effect of insulin (cortisol is a diabetogenic hormone), Cushing's patients are prone to diabetes. Polyury and polyphagia are often associated symptoms of Cushing's, like in diabetic patients.
• Abdominal obesity (plethoric)


  Abnormal distribution of fat, cortisol stimulates lipolysis, leading to redistribution of fat in the body and abnormal fat deposition in central areas. High lipidemia is likely to cause cardiovascular complications
• Buffalo hump and moon face


  Mainly caused by an excess of fat deposit near the collar bone areas and around base of the skull.
• Edema


  Water retention, likely due to mineralocorticoid activity of cortisol (also causing hypertension in Cushing patients). Sodium and water retention leads to increased hydrostatic capillary pressure which causes increased leakage of fluid through capillaries all over the body.
• Stria


  Mainly due to decreased collagen synthesis in part due to accelerated catabolism of proteins. The skin becomes thinner and capillaries more fragile. There is an increased tendency of bruises and rupture of capillaries which leads purplish striae on the abdominal wall. In addition, tissue healing is very slow due to decrease in inflammatory process associated with a decrease in collagen synthesis.
• Backache and bone problem

  Excess of cortisol decreases collagen in bones (collagen is an essential component of the bone matrix) which makes them brittle and results in pathological fractures. Fractures in spine causes backache as bony fragments impinge upon nerves and spinal cord.