Overview

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.

There are two types of endocrine receptors: cell surface receptors and intracellular receptors. Cell surface receptors work similarly to other membrane bound receptors. Hormones, the ligand, bind to a hormone specific G-protein coupled receptor. This initiates conformational changes in the receptor, releasing a subunit of the G-protein. The protein activates second messengers which internalize the message by triggering signaling cascades and transcription factors.

Many hormones work through cell surface receptors, including epinephrine, norepinephrine, insulin, prostaglandins, prolactin, and growth hormones.

Steroid hormones, like testosterone, estrogen, and progesterone, transmit signals using intracellular receptors. These hormones are small hydrophobic molecules so they move directly past the outer cell membrane. Once inside, and if that cell is a target cell, the hormone binds to its receptor. Binding creates a conformational change in the receptor which activates its potential as a transcription factor. Once activated, the receptor or hormone-receptor complex promote or suppress gene expression.

The intracellular hormone receptors are a large superfamily of receptors but they all have a similar single polypeptide chain with three distinct domains. The N-terminus is the active transcription factor domain. The middle contains a DNA binding domain specific for the gene of interest. And the hormone binds to a domain at the C-terminus.

Procedure

Endocrine signaling occurs when cells located in different organs need to communicate, such as when the pituitary gland communicates with the kidneys. When this happens, hormones, the signaling ligands, use the bloodstream to reach their target cells.

For example, the pituitary gland signals the kidneys to reabsorb water from urine, by releasing the hormone arginine vasopressin, or AVP, into the blood. When blood is filtered in the kidneys, AVP binds to its G protein-coupled receptor, AVPR2, on targeted renal cells.

Upon activation by the hormone, the G protein subunits decouple from the receptor, and activate adenylate cyclase, to make the second messenger, cyclic AMP. Cyclic AMP activates the intracellular signaling cascade involving protein kinase A, or PKA.

PKA has two functions. First, it phosphorylates the aquaporin channel, APQ2, held in reserve in cytoplasmic vesicles. This action brings the vesicle, and the channels, to the cell membrane, allowing the flow of water back into the renal cells. 

Secondly, PKA phosphorylates CREB in the nucleus, causing it to bind to the aquaporin 2 gene, and start its transcription and then translation for new aquaporin channels.

Thus, endocrine signaling is a crucial step in osmoregulation, and other functions where remote cell groups must communicate.