72. Classification of hormones, dynamics of the ligand - receptor interaction, the feed-back mechanism Flashcards
Feed-back
Classical “feed-back”
- The essence of a classical feedback mechanism is that enhanced levels of hormones produced by glands inhibit central facilitation.
- Feedback mechanisms can be classified as long feedback (peripheral gland - hypothalamus), short feedback (peripheral gland - pituitary gland) or ultra-short feedback (hypothalamus and pituitary gland)..
- We use the thyroid hormones to demonstrate the classical regulatory pathway:
- Changes of the environment elicits the synthesis of hypothalamic-hypophyseal (HT-HP) trop hormones (TRH and TSH) which will stimulate hormone synthesis of the peripheral target gland (thyroid gland).
- The increased thyroid hormone level has a negative influence on its own synthesis and also decreases the activity of the HT-HP system.
Thyroid feed-back
Classification of hormones
Lipophilic hormones:
- Easily pass plasma membrane
- Act intracellularly
- Carrier proteins
- directly act on the nucleus (except for lipid-soluble eicosanoids).
Hydrophilic hormones:
- Exert their effects on surface receptors
- No carrier proteins
- action is manifested through second messenger molecules.
Classification of hormones (table)
Table legends:
– BP = binding protein
– T1/2 = half life (in plasma)
– The intracellular mediator is the receptor-hormone complex, which, in most cases, passes across the nuclear envelope and exerts its effects by stimulation or inhibition of gene expression
– The IC signaling is mediated by IC “second messengers”, e.g.: cAMP, cGMP, calcium ions, diacylglycerol (DAG), inositol trisphosphate (IP3), etc.
ones : group 1 and group 2
Scatchard analysis
designed to measure the properties of receptor - ligand interaction.
two important parameters can be estimated:
the total amount of binding sites
the strength (affinity) of binding formed
The technique is based on the administration of a small amounts of ligands to the receptor-containing sample. Binding of the labeled hormone is measured. Then, step by step in different sets of experiments, an increasing amount of non-labeled ligand is given to the sample.
The stronger the ligand - receptor connection is, the more non-labeled hormone is required to displace the radioactive hormone from the receptor.
Two characteristic values:
Bmax, the number of the total binding sites.
Kd, the dissociation constant of the binding site
Regulation of receptor number
Cells are able to regulate the strength of the biological response to a hormonal signal appearing in the circulation or in tissues. The basis of the regulation is the ability of the cell to vary the number of the signal receiving receptors according to the actual needs of the cell.
- Long lasting exogenous hormone treatment can result in completely abolished response in tissues, which gave the correct biological answers previously. The cause of the phenomenon is the termination of the synthesis and expression of specific receptors, as a consequence of the long lasting administration of the particular hormone. The phenomenon is referred to as “down-regulation”. The number of receptors decrease.
- The cell might need the hormone-evoked biological response even when hormone concentration is low. In this case, the cell synthesizes and expresses a fairly high amount of receptors specific to the particular hormone, thus, obtains amplified response in spite of the constant (low) plasma level of the hormone. The phenomenon is referred to as “up-regulation”.
ligand-receptor interaction
- interaction between a molecule (usually of an extracellular origin) and a protein on or within a target cell. One type of ligand-receptor interaction can be between steroid hormones and their cytoplasmic or nuclear receptors. Another can be between secreted polypeptide ligands and transmembrane receptors.
