Hormone receptors

A hormone receptor mediates the effect of the respective hormone on the respective cell. Since hormones can reach all tissues via the bloodstream, but the function of a hormone should be restricted to certain tissues, the tissue-specific expression of the hormone receptor plays an important role in endocrine processes. Most hormones have a receptor , but there are certain hormones such as B. Somatostatin has up to five receptors, which are found in different combinations on the different target cells and which also trigger different signal transmissions.

Membrane receptor types

There are different types of hormone receptors that differ significantly in terms of their structure, their placement in the cell and the effects they trigger:

Heptahelical transmembrane receptors

With these receptors, the protein chain penetrates the cell membrane seven times. This creates loops of the polypeptide chain between the membrane passages both on the outside of the cell and in the cell. The outer loops with the N-terminal residue form the binding site for the respective hormone, while the inner loops couple to GTP-binding proteins, namely G-proteins . Almost all peptide hormones, as well as glycoprotein hormones, but also catecholamines bind to such heptahelical transmembrane receptors. This type of receptor is not just limited to hormones, but includes e.g. B. also the rhodopsin receptors, which measure light pulses, to this type of receptor; Receptors for neurotransmitters such as serotonin or glutamate also belong to these receptors.

Through the formation of receptor hormones on the outside of the cell, G proteins are bound and activated on the inside of the cell membrane. These activated G proteins can switch on various intracellular signal cascades:

Formation of cAMP through activation of adenylyl cyclase
Formation of cGMP through activation of guanylyl cyclase
Activation of phospholipase and thereby the release of diacylglycerol and inositol trisphosphate , phosphorylcholine , also of arachidonic acid and thus triggering of prostaglandin and thromboxane formation
Activation of sphingomyelinase and formation of ceramides and phosphorylcholine

cAMP, cGMP, diacylglycerin, inositol trisphosphate, etc. are intracellular messenger substances that trigger further signals in the cells. Since hormones were called the primary messenger substances, the term secondary messenger substances was coined for these substances .

Hormone receptors with tyrosine kinase activity

The insulin receptor is a receptor with tyrosine kinase activity (compare receptor tyrosine kinase ; RTK). It consists of two alpha and two beta chains and is considered a prototype of class II of the RTK. There are also single-chain hormone RTKs such as the receptors for PDGF , VEGF or CSF-1 , which belong to class V of RTKs. 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 the transforming growth factor receptor (TGF-R). Binding of inhibin to the INH-R leads to serine phosphorylation of SMAD 5, which after migrating into the cell nucleus binds to gene promoters and stimulates protein synthesis.

Membrane-bound guanylate cyclases

The receptors for hormones from crustaceans, which belong to the family of crustacean hyperglycemic hormones (CHH) and molting-inhibiting hormones (MIH), are membrane-bound guanylate cyclases that trigger signaling intracellularly by increasing cGMP.

Membrane receptors without kinase activity

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

The receptors themselves are not enzymatically active. After two hormones bind to one receptor each, the two receptors aggregate. This creates a binding site for a STAT protein . This then takes over the signal switching.

Intracellular nuclear receptors

The receptors for the thyroid hormone ( triiodothyronine ), for the steroid hormones and for vitamin D3 , for retinoic acids and for bile acids are intracellular receptors that are located in the cell nucleus. To do this, the hormones have to diffuse into the core. There is no evidence of active transport into the cell nucleus. By binding z. B. two testosterone molecules to one androgen receptor each can dimerize the receptors and, as transcription factors, couple them directly to characteristic DNA binding motifs. This leads to gene activation.

While with membrane receptors the presence of the receptor on the cell surface can trigger the binding of the hormone, with intracellular nuclear receptors the hormones seem to have to diffuse into all cells in order to be able to trigger signals in the few cells that actually have the nuclear receptor. Such a flood of steroids or thyroid hormones could possibly explain the delayed responses to these hormones. On the other hand, since steroids are bound to steroid-binding globulin (SBG) in the blood , the receptor-expressing cell triggers the dissociation of the steroid / SBG complex solely by the fact that the current hormone concentration is achieved by binding of steroid to the receptor is humiliated.

Hormone receptors and gene defects

Therapy resistance despite hormone substitution:

If the production of a hormone is disturbed by a mutation in the hormone gene, therapy with synthetically produced hormones can help alleviate the failures in many cases. If, on the other hand, the receptor gene is defective, substitution therapy is unsuccessful, since the hormone supplied from the outside cannot trigger any activity on the defective receptor. This type of resistance to therapy cannot currently be overcome.

Prostate cancer trigger

The androgen receptor gene contains a CAG repeat in which the nucleotide sequence occurs repeatedly and which creates an oligo-glutamine segment in the androgen receptor. It has been found in prostate cancer patients that this repeat has fewer repetitions than in healthy people.

literature

Books

P. Reed Larsen et al .: Williams Textbook of Endocrinology. 10th edition. Saunders, Philadelphia, PA 2003, ISBN 0-7216-9184-6 .
Bernhard Kleine, Winfried Rossmanith: Hormones and the endocrine system. Springer Verlag, 2007, ISBN 978-3-540-37702-3 . (Chapter 5: hormone receptors)

Individual evidence

↑ P. Ferro, MG Catalano, R. Dell'Eva et al .: The androgen receptor CAG repeat: a modifier of carcinogenesis? In: Mol Cell Endocrinol. 193 (1-2), Jul 31, 2002, pp. 109-120. PMID 12161010 .
↑ M. Zitzmann, E. Nieschlag: The CAG repeat polymorphism within the androgen receptor gene and maleness. In: Int J Androl. 26 (2) Apr. 2003, pp. 76-83. PMID 12641825 .

[1] P. Ferro, MG Catalano, R. Dell'Eva et al .: The androgen receptor CAG repeat: a modifier of carcinogenesis? In: Mol Cell Endocrinol. 193 (1-2), Jul 31, 2002, pp. 109-120. PMID 12161010 .

[2] M. Zitzmann, E. Nieschlag: The CAG repeat polymorphism within the androgen receptor gene and maleness. In: Int J Androl. 26 (2) Apr. 2003, pp. 76-83. PMID 12641825 .