steroid hormones Flashcards
signal transduction
biochemical mechanism to transmit extracellular signals across the plasma membrane into the cell
involved in communication of cells and the environment
external signal > functional response
how do steroid hormones regulate gene expression?
by entering cells, binding to intracellular receptors and forming a hormone-receptor complex which directly interacts with DNA to control the transcription of target genes by altering mRNA and protein synthesis
steroid hormone structure
cholesterol backbone
lipophilic
diffuse freely through the plasma membrane
lipid function
steroid hormones
hydrophobic so they are high affinity stereospecific ligands that bind to hydrophobic pockets in receptor proteins
steroid hormones
summary
cholesterol derived ligands for intracellular receptor proteins which mediate hormone signals by altering the expression of specific genes
have a critical role in;
* cell development
* reproductive biology
* organismal physiology
steroid hormone: mechanism of action
exit endocrine cells
diffuse across membrane
bind to carrier proteins
bind to hormone receptor in cytoplasm
translocate to the nucleus
interact with a DNA binding protein or response element as a transcription factor
changes in gene expression
categories of steroid hormones
glucocorticoids - regulation of glucose metabolism
progesterone - menstrual cycle, development of mammary tissue
mineralcocorticoids - salt and water balance e.g. aldosterone
androgens - regulate development and maintanence of male characteristics e.g. testosterone
estrogens - development and regulation of the female reproductive system e.g. estradiol
nuclear receptor signalling
the cell-specific physiological responses controlled by nuclear receptors are governed by three parameters;
- cell specific expression of nuclear receptors
- localised bio-availability of the hormone
- differential accessibility of target gene DNA sequences in chromatin to nuclear receptor binding
nuclear receptor mechanism of action
binding of lipophilic first messenger to ligand binding domain in the cytoplasm or nucleus to activate nucelar receptors by conformational change resulting in the loss of inhibitory proteins
hormone-receptor complex binds directly or indirectly to hormone regulatory elements in the DNA
co-regulatory proteins are recruited to alter transcription rates through acetylation or deacetylation of histones in chromatin which alters accessibility of DNA for transcription
glucocorticoid receptor (GR)
steroid hormones
binding of a glucocorticoid induces a conformational change, causing the receptor to dissociate from protein chaperones, and a homodimer is formed. the receptor translocates to the nucleus and binds to specific glucocorticoid response elements in the promoter or enhancer regions of target genes
glucocorticoid anti-inflammatory response
inhibition of pro-inflammatory cytokines
suppression of immune cell activation
potent anti-inflammatory drugs that treat asthma