Стероид гормондарының рецепторлары: түрлері мен әрекет ету механизмі

Group of protein families
Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days. The best studied steroid hormone receptors are members of the nuclear receptor subfamily 3 (NR3) that include receptors for estrogen (group NR3A) and 3 ketosteroids (group NR3C). In addition to nuclear receptors, several G protein coupled receptors and ion channels act as cell surface receptors for certain steroid hormones. A steroid hormone receptor is a protein molecule located either within the cell cytoplasm or nucleus that specifically binds to steroid hormones, such as estrogen, progesterone, and testosterone, leading to the activation or suppression of gene expression and subsequent cellular responses. This interaction is crucial for mediating the physiological effects of steroid hormones in various tissues and organs of the body.

Depending on their mechanism of action and subcellular distribution, nuclear receptors may be classified into at least two classes. Nuclear receptors that bind steroid hormones are all classified as type I receptors. Only type I receptors have a heat shock protein (HSP) associated with the inactive receptor that will be released when the receptor interacts with the ligand. Type I receptors may be found in homodimer or heterodimer forms. Type II nuclear receptors have no HSP, and in contrast to the classical type I receptor are located in the cell nucleus. Free (that is, unbound) steroids enter the cell cytoplasm and interact with their receptor. In this process heat shock protein is dissociated, and the activated receptor ligand complex is translocated into the nucleus. It is also related to EAATs. After binding to the ligand (steroid hormone), steroid receptors often form dimers. In the nucleus, the complex acts as a transcription factor, augmenting or suppressing transcription particular genes by its action on DNA. Type II receptors are located in the nucleus. Thus, their ligands pass through the cell membrane and cytoplasm and enter the nucleus where they activate the receptor without release of HSP. The activated receptor interacts with the hormone response element and the transcription process is initiated as with type I receptors.

The cell membrane aldosterone receptor has shown to increase the activity of the basolateral Na/K ATPase, ENaC sodium channels and ROMK potassium channels of the principal cell in the distal tubule and cortical collecting duct of nephrons (as well as in the large bowel and possibly in sweat glands). There is some evidence that certain steroid hormone receptors can extend through lipid bilayer membranes at the surface of cells and might be able to interact with hormones that remain outside cells. Steroid hormone receptors can also function outside the nucleus and couple to cytoplasmic signal transduction proteins such as PI3k and Akt kinase.

GPCR linked proteins most likely interact with steroid hormones through an amino acid consensus sequence traditionally thought of as a cholesterol recognition and interaction site. About a third of Class A GPCRs contain this sequence. The steroid hormones themselves are different enough from one another that they do not all affect all of the GPCR linked proteins; however, the similarities between the steroid hormones and between the receptors make plausible the argument that each receptor may respond to multiple steroid hormones or that each hormone could affect multiple receptors. This is contrary to the traditional model of having a unique receptor for each unique ligand. At least four different GPCR linked proteins are known to respond to steroid hormones. G Protein Coupled Receptor 30 (GPR30) binds estrogen, Membrane Progestin Receptor (mPR) binds progesterone, G Protein Coupled Receptor Family C Group 6 Member A (GPRC6A) binds androgens, and Thyroid Hormone and Trace Amine Associated Receptor 1 (TAAR1) binds Thyroid hormone (though not technically steroid hormones, thyroid hormones can be grouped here because their receptors belong to the nuclear receptor superfamily). As an example of the effects of these GPCR linked proteins consider GPR30. GPR30 binds estrogen, and upon binding estrogen this pathway activates adenylyl cyclase and epidermal growth factor receptor. It results in vasodilation, renoprotection, mammary gland development, etc.

Neuroactive steroids bind to and modulate the activity of several ion channels including the GABAA, NMDA, and sigma receptors. The steroid progesterone has been found to modulate the activity of CatSper (cation channels of sperm) voltage gated Ca2+ channels. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs (chemotaxis).

Sex hormone binding globulin (SHBG) is thought to mainly function as a transporter and reservoir for the estradiol and testosterone sex hormones. However it has also been demonstrated that SHBG can bind to a cell surface receptor (SHBG R). The SHBG R has not been completely characterized. A subset of steroids are able to bind to the SHBG/SHBG R complex resulting in an activation of adenylyl cyclase and synthesis of the cAMP second messenger. Hence the SHBG/SHBG R complex appears to act as a transmembrane steroid receptor that is capable of transmitting signals to the interior of cells.