Hormone receptor

A hormone receptor mediates the effect of the respective hormone, to the respective cell. Since hormones through the bloodstream to reach all tissues, the function of a hormone but should be restricted to certain tissues, the tissue-specific expression of the hormone receptor plays an important role in the endocrine events. Most hormones have a receptor, however, there are certain hormones such as up to five somatostatin receptors, which are found in various combinations on different target cells and trigger signal, different switches.

• 4.1 Books
• 4.2 Notes and references

Membrane receptor types

There are several hormone receptor types, which differ significantly in their structure, the placement in the cell and in the effects provoked by them:

Heptahelical transmembrane receptors

In these receptors, the protein chain penetrates through the cell membrane seven times. Arise because between the membrane passes both on the outside of the cell and in the cell grinding the polypeptide chain. The outer loops with the N -terminal residue form the binding site for the particular hormone, however, the inner loops coupled to GTP -binding proteins, namely G- proteins. Almost all peptide hormones, as well as the glycoprotein hormones, but also bind catecholamines such heptahelical transmembrane receptors. This kind of receptors is not limited to hormones, but includes, for example, rhodopsin receptors, measuring the light pulses, this receptor; In addition, receptors for neurotransmitters such as serotonin or glutamate belong to these receptors.

The receptor - hormone - formation on the outside of the cell G- proteins are bound to the cell membrane inside and activated. These activated G proteins, various intracellular signaling cascades turn:

• Formation of cGMP by activation of guanylyl cyclase
• Activation of phospholipase and thus release of diacylglycerol and inositol trisphosphate, phosphorylcholine, also of arachidonic acid and thus release of prostaglandin and thromboxane formation
• Activation of sphingomyelinase and formation of ceramides and phosphorylcholine

CAMP, cGMP, diacylglycerol, inositol triphosphate, etc. are intracellular messengers that trigger other signals in the cells. Since hormones were designated as the primary messengers that were minted for these substances the term Secondary Messengers.

Hormone receptors with tyrosine kinase activity

The insulin receptor is a receptor with tyrosine kinase activity (see receptor tyrosine kinase; RTK). It consists of two alpha and two beta chains and is the prototype of class II RTK. In addition, there are single-chain hormone as RTK receptors for PDGF, VEGF or CSF -1, which belong to the class V of the RTK. The receptors for the insulin-like growth factors (IGF- R) also belong to the class II - RTK.

Hormone receptors with serine / threonine kinase activity

These include the receptors for activin and inhibin (ACV -R and INH -R) and the receptors for transforming growth factor - receptor (TGF- R). Binding of inhibin to the INH -R leads to serine phosphorylation of Smad5, which thus binds after migration to the nucleus to gene promoters and stimulates protein synthesis.

Membrane-bound guanylate cyclases

The receptors for hormones of crabs belonging to the family of the crustacean hyperglycemic hormone ( CHH ) and molt inhibitory hormone ( MIH ) belong, are membrane-bound guanylate cyclases that trigger intracellular by increasing cGMP signaling.

Membrane receptors without kinase activity

The prototype of this receptor family, the receptor for granulocyte colony -stimulating factor (G- CSF). Hormones such as leptin, prolactin and growth hormone ( somatotropin ) bind to receptors of this receptor family.

The receptors themselves are not enzymatically active. After the binding of two hormones at each receptor aggregate the two receptors. This binding site is created for a STAT protein. This then takes over the signaling.

Intracellular nuclear receptors

Receptors for thyroid hormone ( triiodothyronine ) for steroid hormones and for vitamin D3 for retinoic acid and bile acids are intracellular receptors, which are located in the nucleus. For the hormones have to diffuse into the nucleus. For active transport into the nucleus, there is no indication. By binding, for example, two testosterone molecules that each has androgen receptors can dimerize and pair as transcription factors directly to characteristic DNA - binding motifs. This leads to gene activation.

While for membrane receptors, the presence of the receptor on the cell surface can cause the binding of the hormone, seem to have to diffuse the hormones in all cells at the intracellular nuclear receptors in order to induce in the few cells that then the nuclear receptor actually have signals. Such flooding with steroids or thyroid hormone could explain the delayed responses to these hormones policy. On the other hand, it is possible, as the steroid is bound in the blood in the steroid -binding globulin ( SBG), that receptor -expressing cell, the dissociation of the steroid / SBG complex solely by triggering that through binding of the steroid to the receptor, the current hormone concentration is lowered.

Hormone receptors and gene defects

• Therapy resistance despite hormone replacement:

If the formation of a hormone is disrupted by a mutation in hormone gene therapy with synthetic hormones can help alleviate the failures in many cases today. Conversely, if the receptor gene has a defect, replacement therapy is not successful, since the externally supplied hormone on the defective receptors can lead to no activity. This type of therapy resistance can not be overcome at the time.

• Trigger of prostate cancer

The androgen receptor gene contains a CAG repeat, in which the nucleotide sequence occurs repeatedly and generates an oligo- glutamate in the androgen receptor portion. In prostate cancer patients, it was found that this repeat fewer repetitions than in healthy subjects.