1-The Endocrine System (1)

8/3/2019 1-The Endocrine System (1)

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1- THE ENDOCRINESYSTEM

Prof. Dr. Maha Gamal


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The Endocrine System

The Endocrine glands:They are ductless glands which secrete hormones into the interstitial spaces,

from where they are absorbed and pass directly to the blood to be distributed

to near or distant tissues to exert their function.

Hormones:Definition:

They are specific chemical substances secreted by the endocrine glands in

small amounts to affect nearby or distant target cells, i.e. They are chemical

messengers.

Chemical nature:

Hormones are classified according to their chemical nature into:

a- Protein and polypeptide hormones: They include hypothalamic, pituitary,pancreatic and parathyroid hormones.

b- Steroid hormones: They are derived from cholesterol. They include

adrenocortical, gonadal hormones and vitamin D (cholecalciferol).

c-Tyrosine derivatives: They include thyroid and adrenal medullary hormones.


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The Endocrine System (cont.)Forms in the blood:

a- Free: 1- Not carried by plasma proteins, 2- Can bind directly to theirreceptors (active) and 3- Small in size, so can be filtered in urine.

b- Protein-bound : 1- Carried by plasma proteins, 2- Cannot bind directly toreceptors (inactive), and 3- Large in size so cannot be filtered in urine. Theyrepresent a reservoir for the hormone in blood.

Hormone receptors:

Hormones act on the cells which contain their receptors i.e. target cells. Thesereceptors are present in the cell membrane, nucleus or in the cytoplasm.

The receptors are characterized by: They are protein in nature, specific, and

dynamic. They are not static cell components but their number either

increases or decreases according to various physiological conditions. This

leads to the regulation of receptors and thus regulation of the hormone action.This regulation occurs by two ways:

1- Down-regulation of receptors: chronic high level of the hormone in the bloodleads to decrease in the total number of the target cell receptors.

2- Up-regulation of receptors: chronic low level of the hormone in the blood

leads to increase in the total number of target cell receptors.


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Mechanisms of Hormone action

(Signal transduction pathways)

The binding of the hormone (first messenger) with its specific receptorcauses a conformational change in the receptor leading to its activation which

is the initial step in the cell response to the messenger. The sequence of

events between the receptor activation and the cell responses are diverse and

termed signal transduction pathways.

There are two major signal transduction pathways:

1- Pathways initiated by intracellular receptors:

It is the mechanism initiated by receptors located in the cytoplasm or nucleus.

The hormones acting by this mechanism are the steroid and thyroid

hormones. These hormones are lipid soluble and can pass through the cell

membrane.The steps of this pathway:

1- The hormone diffuses across the cell membrane of the target cells (step 1)

and binds to the receptor. Binding to the receptor causes a conformational


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Mechanisms of Hormone action (cont.)

1- Pathways initiated by

intracellular receptors (cont.):2- The activation of the receptor (H-R

complex) exposes a DNA-binding domain

on the receptor (step 2).

3- In the nucleus, the DNA-binding domain

interacts with specific DNA. Thustranscription is initiated (step 3) and

results in the production of new mRNA.

4- mRNA move out of the nucleus to the

cytoplasm to be translated (step 4) and

results in the production of specificproteins (step 5) that produce physiologic

actions (step 6) and can alter cell activity.

5- This process is slow because it is due to

synthesis of new proteins.


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2- Pathways initiated from cell membranereceptors:

In this mechanism the hormone (first messenger) binds to a

surface membrane receptor. The active H-R complex affects the

cell activity through the release of intracellular chemicalmessenger (second messenger) via activation of G protein.

This mechanism is rapid and transient because it involves

activation of already formed proteins.

The hormones acting by this mechanism are the: 1- Protein andpolypeptide hormones. 2- Adrenal medullary hormones.

The cell membrane pathways include:


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Mechanisms of Hormone action (cont.)2- Pathways initiated from cell membrane

receptors (cont.):A- Adenylate cyclase pathway: 1- activation of the receptor by the bindingof the hormone allows the receptor to activate its associated G protein.

2- The active G protein activates adenylate cyclase enzyme whichchanges ATP to cAMP. 3- cAMP (2nd messenger) activates cAMPdependent protein kinase (protein kinase A) which phosphorylates otherproteins (e.g. enzymes) and changes their activity thus producing cell

responses.


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Mechanisms of Hormone action (cont.)2- Pathways initiated from cell

membrane receptors (cont.):B- The calcium-calmodulin pathway:1- The hormone binds to the receptor in the cell

membrane (step1) activating it.

2- The H-R complex activates G protein. Active

G protein has 2 actions: it opens cellmembrane Ca2+ channels and it releases

Ca2+ from endoplasmic reticulum (step 2).

3- Together, these 2 actions produce an

increase in intracellular [Ca2+]. (step 3)

4- The Ca2+ (2nd messenger) binds tocalmodulin changing its shape (step 4).

5- Ca2+-calmodulin complex activates protein

kinases which phosphorylate proteins (e.g.

enzymes) and alter their activity thus

producing physiologic actions.


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2- Pathways initiated from cell membrane receptors (cont.):

C- Membrane phospholipids pathway:

1- The hormone binds to a receptor in the cell membrane (step1) thus

activating it.

2- The active hormone-receptor complex activates G protein (step 2).

3- The active G protein activates membrane bound phospholipase C (step 3).

4- Phospholipase C liberates diacylglycerol and inositol triphosphates (IP3)

from membrane phospholipids (?) (step 4).

5- Ip3 mobilizes Ca2+ from endoplasmic reticulum (step 5). This calcium can

bind calmodulin like the previous mechanism. Or

6- Together, Ca2+ and diacylglycerol activate protein kinase C (step 6).

7- Protein kinase C phosphorylates proteins (step 7) and produces

physiologic actions.


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C- Membrane Phospholipids pathway:


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Mechanism of action of different hormones

ANP= atrial natriuretic peptide cGMP= cyclic guanosine monophosphate

EDRF = endothelium-derived relaxing factor

HCG = human chorionic gonadotropin IGF-1 = insulin-like growth factor-1

PTH = parathyroid hormone


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Regulation of Hormone Secretion The hormone secretion is regulated by many factors:

1. Nervous control: external and internal stimuli affect hormonesecretion either directly or by the secretion of releasing orinhibitory hormones from the hypothalamus.

2. Feedback control: The level of the hormone in blood affectsthe endocrine gland from which it is secreted either stimulatingor inhibiting it.It is of 2 types:

1- Negative feedback (most common) : If the hormone level islow it stimulates its corresponding gland to increase the rate ofhormone secretion. And if the hormone level is high it inhibitsthe gland decreasing the rate of hormone secretion. Thus itmaintains the level of the hormone constant.

2- Positive feedback (less common): If the hormone level is highit stimulates the gland to produce more hormone.


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The Pituitary Gland (Hypophysis Cerebri)It is a small gland which lies in a small cavity at the base of the skull.

It is divided into 2 lobes:

1-The anterior lobe (Adenohypophysis):Which secretes the following 5 hormones:

1- Growth hormone (GH).

2- Prolactin hormone (PRL).

And the tropic hormones which stimulate the secretion of the hormones ofother glands. They include:

3- Thyroid stimulating hormone (TSH).

4- Gonado-tropic hormones (FSH & LH).

5- Adrenocorticotropic hormone (ACTH). It is derived from the large molecule

proopiomelanocortin. Proopiomelanocortin (POMC) is the precursor for ACTH,- lipotropin and - endorphin in the human anterior pituitary. ACTH has a

melanocyte-stimulating hormone (MSH) activity (?).

2-The posterior lobe (Neurohypophysis):which secretes: 1- Antidiuretic hormone (ADH).

2- Oxytocin hormone.


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The Pituitary Gland

1-The Endocrine System (1)

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