wed, April 4.... classes of hormones and peptide secretion

defining endocrinology: is the study of the chemical coordination of bodily functions. In this case we are specifically talking about hormones.
Hormone: a chemical, non-nutrient substance. (glucose does not count as a hormone) And is effective at very low concentrations (on the order of 10^-10 or -12). it is released and then causes a reaction in a target cell.

Actions of hormones:
Substance is made one place in the body, and travels in the blood to a distance target cell.
and/or
Substances that have paracrin actions. (is released from one cell and acts on a target cell that is very near by)
and/or
autocrin action. (cell releases a hormone, and that acts upon the cell that made it).

Many hormones act in all three ways. If it is secreted by a neuron in the brain, it is called a neurotransmitter.

The cells or organs that produce hormones are called endocrin cells or endocrin organs. Endocrin organs include the pituitary gland, the thyroid gland, the adrenal gland, the parathyroid gland, the ovaries, and the testes, and the pancreas. Other organs also make hormones, such as the GI tract, but are not the 'classical' organs, and we only really want to focus on the classical ones.

We are going to cover a number of different hormones in this class, and you want to be able discuss intelligently and draw the chemical structure of the hormones. You need to be able to draw the entire biosynthetic pathways of these hormones. And be able to discuss where they are synth'd, and what regulates their production, explain what each ones does, and how it does it (mechanism of action).

Hormones regulate all different kinds of bodily function, and some are required for regulation of reproduction, or homeostasis, or normal development, or normal growth, or normal use as substrates such as fats and proteins from your diet. Nearly all cases, every hormone does a laundry list of actions. And every process you can think of is controlled/regulated by more than one hormone.

Let's look at glands...

Endocrin gland and exocrin gland.... a gland is something that secretes a product. Secretion refers to sythesizing, and then releasing it. glands are epithelial cells that secrete something, and there are two types: exocrin and endocrin. they look different, so look them up. The exocrin gland looks similar to a pore shape, and its product actually exits to the outside of the body (sweat, saliva, tears). There is a duct between the gland, and the 'outside'. In the case of an endocrin gland, it starts out LOOKING like an exocrin gland early in development, but as it developes the connection to the outside closes off, and there is no longer a connection. Instead the endocrin cells secrete their products into the extracellular fluid and that product then diffuses into capillaries that are very close by. One of the characteristics of an endocrin gland, they are super vascularized, highly profused, and they need to be to be able secrete into the circulation. ECF: extracellular fluid.

Different chemical classes of hormones:
If you look at the hormones we are dealing with this quarter, they fall into 3 basic types of structures. It is important to know what type of compound it is for several reasons, such as predicting its mech of action, or the time response, or how long it hangs out in the circulation. So this is very important to know for each chemical. Most hormones are peptides and proteins. If you look at their composition, the smallest ones are 3 AAs, up to 200 AA, but even up to 20K, or 30K sometimes. If you ever have to guess what type it is, it is probably a peptide or a protein, because that is the most prevalent. The second type is an Amine. It is made from an AA. all the ones we are talking about are made from Tyrosine. Amine examples:T3 is a product of the thyroid gland, epinephrine, norepinephrine is nor-adrenal produced by the adrenal medula, dopamine is structurally similar to ep/norep, and is a product of the CNS. Each one has an amino group, and that is why they are called an Amine. The third class is Steroids: 5 basic classes of steriods, all derived from cholesterol and they are all products of interrelated biosynthetic pathways.
estrogens (estrodial)
progestins (progesterone)
androgens (testosterone)
?aldosterone? (meteralo-corticoids?) (regulate sodium and potasium balance in the body)
glucocorticoids (cortisol) (carbohydrate metabolism)(important in stress response)

If you look at the structures of these, and if you know anything about cholesterol, you know they are these are substances are highly lipid soluable, and poorly water soluble, and that will impact how they work. They have different functional groups, but superficially they look very similar. But they are not interchangable. If you give testerone to a woman she starts to grow facial hair.

Now we move onto the other side of the handout. If you have taken cell bio it is a repeat. if you look at the synthesis of peptide or proteins (peptides are a shorter protein) (greater than ~100 is a protein). so it is better to call them all peptides, but if it is short you can't call it a protein.

the hydrophobic segment is called a signal or leader sequence, its purpose is to direct the peptide into a secretory pathway in a cell. In order for them to be secreted under normal conditions, they have to be synth'd with this signal peptide. the function of the sig pep is taht it directs the peptide chain into the ER, and from there into the golgi, and into membrane bound vesicles, and secreted from the cell. How that is done is on the handout.

Going through the diagram:
The translation of the peptide starts in the cytoplasm on the free rhybosomes (they are not attached to anything), the amino terminal is synth'd first so that the sig sequence is the first to emerge after translation starts. once the sig peptide emerges from the translation machineray, it is recognized by a signal recognition particle, in the cytoplasm, which binds to it, and translation stops. the sig rec particle ribosomal complex binds to the docking protein or signal recognition particle receptor protein in the membrane of the ER. this attaches the ribosome to the outside of the ER, and with lots of ribosomes attached is called the rough ER. we have a ribosome with the beginning peptide attached to the outside of the ER, the receptor for the signal recognition particle is oriented in a way that when a complex binds to it, the peptide ends up physically rotated over a translocator pore in the membrane. the ribosome and the peptide bind to the translocator pore. the sig-rec-part leaves and the ribosome is now stuck there, and translation starts again, but it is now forced into the inside of the ER. as translation is continuing, the signal peptide is cleaved from the rest of the peptide. you now have a completely translated peptide free insdie the ER, because the sig peptide has been cleared away. from there, the peptide is destined to be glycosolated, phosphorylated, sulfated, that happens in the ER, and the material is moved to the golgi and packaged into secretory granules, (membrane bound granules that contain lots of high density of wahtever protein is packaged in them. these secretory vesicles hang out in the cyotplasm for hours or days until there is a signal to release them. your product concentrations in cytoplasm increase the factor release signal and causes exocytosis of the vesicles, and the contents of the vesicles are spewed int the extracellular fluid and into a capillary.

situations for hormones is more complicated than that.
terminology:
peptide chains with carboxyl term, or amino terminal, signal sequence peptide,
the whole thing would be called a 'pre-hormone', an example is: pre-prolactin. we won't see pre-hormone in the blood because it is always cleaved in the ER before it is released. there are also pro hormones: an example of a pro-peptide is a poly peptid ( aa chain) with the pre part, and then there is the rest of the peptide chain, and parts that are pro parts are AA sequence that do not have any biological activity, H is the hormone, and the whole thing is called a pre-pro-hormone. the pro hormone is packaged into secretory vesicles and then as they mature specific enzymes in the vesicles hydrolyze the bonds between the hormone and the pro sequences. what is released are the actual hormones, plus pro-sequences. they pro-seq are not bio active. the pro seq are eventually degraded. if there is a huge amount of hormones released you might find some pro seqs around, but not normally. why go to all this trouble? the function they serve is allow biosynth for hormones that are under 100 AA in length, that would otherwise be too short. it makes sure the nacient peptide has time to be routed into the ER. It gives a buffer time for translation to make sure it gets fed into the ER before the hormone is produced.