How is it that humans and animals maintain quite constant blood concentrations of glucose throughout their lives despite

wildly varying frequencies of meals?

If your blood glucose concentration drops much below 1 mg per ml, your neurons will begin to misbehave, leading ultimately to coma and death. Yet skipping breakfast is rarely life threatening.

!he answer is that a battery of chemical messengers hormones are secreted into blood in response to rises and falls in blood glucose concentration and stimulate metabolic pathways that pull glucose concentrations back into the normal range.

"ndocrinology is the study of chemical communication systems that provide the means to control a huge number of physiologic processes. components of endocrine system# transmitters, signals and receivers that are called, respectively, hormone producing cells, hormones and receptors.

!wo systems control all physiologic processes#

!wo systems control all physiologic processes#

!he nervous system

e$erts point to point control through nerves, similar to sending messages by conventional telephone. %ervous control is electrical in nature and fast. broadcasts its hormonal messages to essentially all cells by secretion into blood and e$tracellular fluid. &ike a radio broadcast, it requires a receiver to get the message in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.

!he endocrine system

'istinct endocrine organs are scattered throughout the body

In addition to the classical endocrine organs, many other cells in the body secrete hormones. (yocytes in the atria of the heart and scattered epithelial cells in the stomach and small intestine are e$amples of what is sometimes called the )diffuse) endocrine system. If the term hormone is defined broadly to include all secreted chemical messengers, then virtually all cells can be considered part of the endocrine system.

*hat e$actly are hormones and how are they different from )non hormones)?

Hormones are chemical messengers secreted into blood or e$tracellular fluid by one cell that affect the functioning of other cells.

+ctions of Hormones

three actions are defined#

Hormone +ction

Endocrine action: the hormone is distributed in blood and binds to distant target cells. Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood. Autocrine action: the hormone acts on the same cell that produced it.

!wo important terms are used to refer to molecules that bind to the hormone binding sites of receptors# +gonists

+ntagonists

!wo important terms are used to refer to molecules that bind to the hormone binding sites of receptors#

+gonists

are molecules that bind the receptor and induce all the post receptor events that lead to a biologic effect. In other words, they act like the )normal) hormone, although perhaps more or less potently. %atural hormones are themselves agonists and, in many cases, more than one distinct hormone binds to the same receptor. ,or a given receptor, different agonists can have dramatically different potencies.

!wo important terms are used to refer to molecules that bind to the hormone binding sites of receptors#

Antagonists

are molecules that bind the receptor and block binding of the agonist, but fail to trigger intracellular signalling events. +ntagonists are like certain types of bureaucrats they don-t themselves perform useful work, but block the activities of those that do have the capacity to contribute. Hormone antagonists are widely used as drugs.

How are hormones named?

are often named for the first physiologic effect observed or for their ma.or site of synthesis

/hemistry of the Hormones

hormones are categori0ed into four structural groups#

1 2eptides and proteins 1 3teroids 1 +mino acid derivatives 1 ,atty acid derivatives "icosanoids

2eptides and 2roteins

2eptide and protein hormones

products of translation. vary considerably in si0e and post translational modifications, ranging from peptides as short as three amino acids to large, multisubunit glycoproteins.

3ynthesis of peptides and proteins

2reprohormones "4

2rohormone "4

5olgi +pparatus

cytoplasmic compartment of endocrine cell

secretion

!hey can be secreted by one of two pathways#

Regulated secretion# !he cell stores hormone in secretory granules and releases them in )bursts) when stimulated. !his is the most commonly used pathway and allows cells to secrete a large amount of hormone over a short period of time. Constitutive secretion: !he cell does not store hormone, but secretes it from secretory vesicles as it is synthesi0ed.

3teroids

derivatives of cholesterol. "$amples# se$ steroids such as testosterone and adrenal steroids such as cortisol.

2regnenolone is formed on the inner membrane of mitochondria then shuttled back and forth between mitochondrion and the endoplasmic reticulum for further en0ymatic transformations involved in synthesis of derivative steroid hormones.

!ypically, endocrinologists classify steroid hormones into five groups of molecules, based primarily on the receptor to which they bind#

5lucocorticoids6 cortisol is the ma.or representative in most mammals (ineralocorticoids6 aldosterone being most prominent +ndrogens such as testosterone "strogens, including estrodiol and estrone 2rogestogens 7also known a progestins8 such as progesterone

+mino +cid 'erivatives

!here are two groups of hormones derived from the amino acid tyrosine#

!hyroid hormones are basically a )double) tyrosine with the critical incorporation of 9 or : iodine atoms. /atecholamines include epinephrine and norepinephrine, which are used as both hormones and neurotransmitters.

3ynthesis

,atty +cid 'erivatives "icosanoids

"icosanoids are a large group of molecules derived from polyunsaturated fatty acids. !he principal groups of hormones of this class are prostaglandins, prostacyclins, leukotrienes and thrombo$anes.

synthesis

+rachadonic acid is the most abundant precursor for these hormones. 3tores of arachadonic acid are present in membrane lipids and released through the action of various lipases. !he specific eicosanoids synthesi0ed by a cell are dictated by the battery of processing en0ymes e$pressed in that cell. !hese hormones are rapidly inactivated by being metaboli0ed, and are typically active for only a few seconds.

How 'o Hormones /hange !heir !arget /ells?

!here are two fundamental mechanisms by which such changes occur#

+ctivation of en0ymes and other dynamic molecules

change in membrane permeability

(odulation of gene e$pression#

Hormone receptors

large proteins locations#

in or on the surface of cell membrane in the cell cytoplasm in the nucleus

(echanism of action

second messenger mechanism action of steroids to cause protein synthesis action of thyroid hormones in the cell nucleus

3teroid Hormone action

thyroid hormones

3econd (essenger mechanism of Hormone action

/yclic +(2# "pinephrine and norepinephrine, glucagon, luteini0ing hormone, follicle stimulating hormone, thyroid stimulating hormone, calcitonin, parathyroid hormone, antidiuretic hormone 2rotein kinase activity# Insulin, growth hormone, prolactin, o$ytocin, erythropoietin, several growth factors /alcium and;or phosphoinositides "pinephrine and norepinephrine, angiotensin II, antidiuretic hormone, gonadotropin releasing hormone, thyroid releasing hormone. /yclic 5(2 +trial naturetic hormone, nitric o$ide

/ontrol of "ndocrine +ction

/ontrol of "ndocrine +ction

%egative feedback is seen when the output of a pathway inhibits inputs to the pathway