Hormones are secreted by specialized endocrine glands/tissues.
- Endocrine: ductless, and secreted straight into the blood
- Exocrine: with ducts
It then acts on target organs to produce certain functions, and is important for the balance in the body (homeostasis). Many hormones are released in a pulsatile fashion (in it’s own timing, not all the time).
Here are the major endocrine glands with it’s hormones:
|Hypothalamus||TRH, CRH, GHRH, GHIH, GnRH, PIF|
|Ant Pituitary||HH, TSH, ACTH, Prolactin, FSH, LH|
|Post Pituitary||Oxytocin, ADH|
|Thyroid||T3, T4, Calcitonin|
|Adrenal Cortex||Cortisol, Aldosterone|
|Adrenal Medulla||Epinephrine, Norepinephrine|
|Placenta||HCG, Human Somatomammotropin, Oestrogen, Progesterone|
|Kidney||Renin, Erythropoeitin, 1,25-Dihydroxycholecalciferol|
|Small Intestine||Secretin, CCK|
These hormones are produced either from Amino Acids (proteins) / Lipid Precursors (Cholesterol/Steroids)
- Amino acid derivatives: thyroxine, serotonin
- Peptides: Insulin, TSH, TRH, Vasopressin, Somatostatin, gonadotrophin
- Steroids: Cortisol, sex hormones (testosterone, oestrogens, progesterone)
What’s the difference between these 2? Peptide hormones can be big/small (monopeptide – polypeptide) and are water soluble, so it can move freely in blood. However, steroids are derived from cholesterol, which are insoluble in water (as well as thyroid hormones) therefore, it requires carrier proteins to be transported in blood.
There are 4 main functions of the hormones:
- Growth & Development
- Reproduction (both male & female have receptors for both male & female hormones)
- Production, Utilization, Energy Storage
- Maintain internal environment of the body
Sexual dimorphism controls the reproductive functions of the human body, this being the difference in the amount and pattern of secretions of the sexual hormones). Therefore, boys can grow into man, and girls can grow into ladies.
So how does this hormone act on our body?
A hormone will act on target tissues. Imagine it as a homing missile. When the hormone reaches the target tissues, it either acts on the plasma membrane of the cells (peptide hormones and epinephrine) or in the cytosol/nucles (steroid, thryroid hormones, active vit D3, retinoic acid). It is very specific in that sense.
The component that receives the hormone is called a receptor, a protein. When the hormone binds into the receptor’s active site, a series of mechanism takes place which at last produces the intended action. However, the interaction is swift and reversible, so there will be a rapid onset (quick action) and then the action will be terminated (not permanent). The hormones secreted is very very little (in pico/nanomole concentrations) therefore, the receptor affinity must be high, meaning the receptor must be willing to accept the hormone. When the hormone is needed badly, the receptor is up-regulated (increase) or vice versa – down-regulated.
When the hormone binds to the receptor (ligand interaction), the receptor will undergo conformational changes (change shape), which activates G-protein in the cell (which can be stimulatory, Gs, or inhibitory, Gi). Assuming that it is stimulatory, it will cause phosphorylation of GDP to convert to GTP which will bind to the effector (enzyme adenylyl cyclase) coverting ATP to cAMP. cAMP will activate Protein Kinase A which inturn will lead to phosphorylation of intracellular mediators called second messengers (relay message from the hormone) producing intracellular effects.
|E, NE, Glucagon, LH, FSH, TSH, Calcitonin, PTH, ADH||Cyclic AMP|
|Insulin, GH, PRL, Oxytocin, Erythropoietin, Growth factors||Receptor Tyrosine Kinase|
|E, NE, Angiotensin II, ADH, GRH, TRH||Calcium/ Phosphoinositides|
|ANP, NO||Cyclic GMP|
Ca2+ (usually stored in ER) regulates a very large no. of physiologic processes, 2nd messengers act on ER and releases the endoplasmic Ca2+ (now cytoplasmic in the cytoplasm). Or it obtains straight from the extracellular fluid (outside cell) by influx.
However there are some hormone receptors who are themselves protein kinases, known as tyrosine kinase. Therefore, when bound to hormone, it iself phosphorylates intracellular mediators/enzymes producing actions. An example of a hormone whose receptor is a TK is Insulin.
Besides extracellular receptors that activates the 2nd messenger cascade and phosphorylation to produce actions, there are also intracellular receptors composed to a single polypeptide with 3 domains :
1) amino-terminus (activating/stimulating transcription by interacting with other component of the transcriptional machinery)
2) DNA-binding domain (bind receptor to specific sequences of DNA)
3) Carboxy-terminus/ligand-binding domain (binds to hormone).
Such receptors are an example of receptors of steroid & thyroid hormones.
Since intracellular receptors are in the cell which is bounded by the phospholipid bilayer, hormones have different mechanisms to enter the cell. Steroids are cholesterol derivatives, therefore it is a lipid and will be able enter thru the cell membrane by simple diffusion. Thyroid hormones however enter the cell thru facilitated diffusion.
As usual, when a hormone binds to the receptor, the receptor undergo conformational changes when activated, therefore it becomes competent to bind to DNA stimulating transcription. Small amounts of hormone will bring about major physiologic effect.
Therefore, it is important to have a control/ feedback mechanism to control these actions. Most hormones when in high amounts will bring about a negative feedback, only certain hormones like LH and Oxytocin encourages positive feedback.
Besides the amount of hormone, hormones are also controlled and secreted in bursts, such as during sleep,following a diurnal cycle, aging and stages of development.
Growth hormone: High during strenuous exercise and 1st few hours of deep sleep.
ACTH & Cortisol: High during last few hours before waking up, uptil several hours after waking up.
FSH & LH: Following the normal menstrual cycle.
Hormones can be measured using immunoassays (usually double sandwich ELISA), where monoclonal antibodies will bind to specific epitopes on the hormone, producing a formation of a colored fluorescent product. The amount of these fluorescent products will then be measured using optical methods such as: spectrophotometer, flurometer, luminometer, or radiochemical assays.
As we know different hormones are released in different timings, therefore it is best to determine the optimum time to get a blood sample, or by serial measurements.
In Summary, the endocrine system depends on hormone-receptor interaction by 2 types of receptors: extracellular and intracellular. Extracellular will require a cascade of 2nd messengers to relay it’s message inside the cell, however intracellular directly binds to DNA to produce it’s intended actions.