BCH 313 Hormones

Question 1

What is a hormone?

Answer 1

A hormone is a chemical messenger, secreted in trace amounts by one type of tissue and carried by the blood to a target tissue elsewhere in the body to stimulate a specific biochemical or physiological activity.

Hormones are produced by special cells or glands such as adrenals, ovaries, parathyroids, pituitary, testes and thyroid. These glands secrete their hormones directly into the bloodstream and are known as endocrine glands.

Question 2

Characteristics of hormones

Answer 2

1) They have strict specificity of biological action therefore replacement is impossible.

2) They have high biological activity i.e. small quantity is usually needed for action.

3) They have remote action i.e. action is usually at a distance.

Question 3

What are glands?

Answer 3

Glands are individual cells or groups of cells that secrete substances. The glands that secrete hormones, spill these chemicals directly into the bloodstream and are called endocrine or ductless glands.

Glands that secrete other substances such as digestive enzymes or sweat, route their secretions to specific destinations by means of ducts. They are called exocrine glands. For example, digestive enzyme pancreatic amylase flows directly from the pancreas to the small intestine and goes nowhere else.

Question 4

The messages of the endocrine hormones are varied but can be grouped into four categories:

Answer 4

Regulation: Hormone control the internal environment of the body by regulating the secretion and excretion of various chemicals in the blood such as salts and acids.

Response: Hormones help the body respond to changes in the environment and cope with physical and psychological stress.

Reproduction: Hormones control the female reproductive cycle and other reproductive processes essential to conception and birth, and control the development of sex cells, the reproductive organs and secondary sexual characteristics in both sexes.

Growth and development: Hormones are essential for the proper growth and development of the body from conception to adulthood.

Question 4

Discuss the action if a hormone

Answer 4

Once molecules of hormones are released into the bloodsream, they travel throughout the body. Although, hormone molecules may pass billions of cells. Specific hormones only affect specific cells called target cells. Hormones recognize target cells because they bind to receptor molecules embedded within the cell membrane or located within the cytoplasm of the cell. The binding of a hormone molecule activates a chain of events in the target cell that results in the effect of the hormone being expressed.

Question 4

Hormones can be classified according to:

Answer 4

• Chemical structure
• Mechanism of hormone action.

Question 5

Classification Based on Chemical Structure

Answer 5

Peptide hormones
Steroid hormones
amine hormones or amino acid derivatives

Question 6

Describe peptide hormones

Answer 6

Peptide hormones:
These are water soluble and may have 3 to over 200 amino acid residues, e.g. hormones of the hypothalamus and pituitary. As well as insulin and glucagon of the pancreas.

Unable to pass through the cell membrane, peptide hormones bind to receptor molecules embedded in the cell membrane of target cells. The binding of hormone to the receptor triggers an increase in that cell’s production of second messenger.

A second messager triggers enzymes that cause the cell to alter its functioning in response to the hormone. Example is prolactin that stimulates the cells of the mammary gland to produce milk. Target cells go into action catalyzing reactions that produce the components of mother’s milk.

Other types of hormone responses include the secretion of the substances from target cells and the closing or opening of certain doors within target cell membranes. Cyclic adenosine monophosphate (cyclic AMP), a cousin of ATP, acts as a second messenger to many cells.

Question 7

Describe a Steroid hormones

Answer 7

Steroid hormones:
These are fat soluble (lipophilic) and all are derivatives of cholesterol. For example:
*Adrenal cortical hormones
* Androgen (male sex hormones)
* Estrogens (female sex hormornes).

Steriod hormones being lipid soluble, pass freely through the lipid bilayer of the cell membrane. Once inside a cell, these hormones bind to receptor molecules located within the cytoplasm of target cells. Together the hormone-receptor complex moves into the nucleus of the cell, causing the cell hereditary material or DNA to trigger the production of certain proteins. In response to the sex hormones estrogen or testoterone, for example, the protein produced are those involved in such processes as the development and maintenance of female or male sexual characteristics.

Question 8

Describe Amine hormones or amino acid derivatives

Answer 8

These are small, water soluble compounds containing amino groups. For example:

• Adrenaline of the adrenal medulla
• Thyroid hormones.

Question 9

Classification Based on Mechanism of Hormone Action (this classification is based on location of the hormone receptors)
Hormones can be classified according to mechanism of hormone action to:

Answer 9

1. Group I hormones
2. Group II hormones

Question 10

Describe Group 1 hormones

Answer 10

The hormones of Group I are lipophilic which readily pass through the lipophilic plasma membrane of the target cells and interacts with receptors which are located intracellularly in either the cytosol or the nucleus. The hormones that have intracellular receptors are given in Table 1.

• The receptors for the different steroid hormones are found mainly in the cytoplasm and the receptors for the thyroid hormones are found in the nucleus.

Question 11

Describe Group 2

Answer 11

The hormones of group II are water-soluble peptides and amine (except T3 and T4) hormones (Table 1) which do not penetrate lipophilic cell membrane readily. The receptors for such hormones are located on the outer surface of the target cell (cell surface receptors).

• Nerve impulses received by the hypothalamus cause it to send specific hormones to the pituitary gland, stimulating (or inhibiting) the release of different tropic hormones.
• The anterior pituitary hormones in turn can stimulate other endocrine glands to secrete their characteristic hormones, which in turn, stimulate specific target tissues

Question 12

Describe mechansim of hormone action

Answer 12

MECHANISM OF HORMONE ACTION

The first step of hormone action is binding of hormone to specific receptors of the target cell. Hormone-receptor complex activates the receptor itself and the activated receptor initiates the hormonal effects. Hormonal receptors are large proteins, which are highly specific for a single hormone. Due to this specificity, a particular hormone will act on a particular tissue.

Question 13

MECHANISM OF HORMONE ACTION AT CYTOSOLIC OR NUCLEAR LEVEL

Answer 13

• Several hormones, e.g. steroid hormones (adrenal and gonadal) and thyroid hormones bind with receptors inside the cell rather than in the cell membrane. Because these hormones are lipid soluble, they readily cross the cell membrane and interact with receptors in the cytoplasm or nucleus.
• The receptors for the steroid hormones are found mainly in the cytoplasm and the receptors for the thyroid hormones are found in the nucleus.
• The hormone receptor complex is assumed to be the intracellular messenger for these (Group I) hormones.
• The activated hormone receptor complex undergoes conformational change which then binds with a specific regulatory (promoter) sequence of DNA called the hormone response element (HRE) which activates transcription of specific genes and formation of mRNA.
• These mRNA get translated into proteins. Newly formed proteins in the cell controls the cellular metabolic functions.

Question 13

CELL MEMBRANE RECEPTOR MECHANISM OF HORMONE ACTION

Answer 13

• The receptors for group II hormones are located on the outer surface of the target cell because these hormones are water soluble which do not penetrate lipophilic cell membrane.
• Hormones that bind to surface receptors of the cells communicate their action through intermediary molecules called second messenger (the hormone itself is the first messenger).
• On binding of the hormone to the receptor, a conformational change occurs in the receptor, that causes activation of the G-protein (GTP-binding protein). This results from the exchange of GDP to GTP on the α-subunit. G-protein is a group of three subunits α, β, γ. In absence of the hormone the G-protein is in an inactive form. Inactive G-protein is bound to GDP (Figure 3).
• Activation of G-protein by hormone leads to dissociation of α-subunit (to which GTP is bound) from β, γ subunits of the G-protein.
• The dissociated α-subunit with bound GTP interacts with other intracellular signaling enzymes such as adenylate cyclase or phospholipase-C which generates second messenger. Interaction of α-subunit with adenylate cyclase generates c-AMP as a second messenger and interaction with phospholipase C generates inositol triphosphate (IP3) and diacylglycerol (DAG) as a second messenger from phosphatidylinositol. These second messengers serve as mediators of the hormone action.

Question 14

Describe c-AMP Second Messenger

Answer 14

c-AMP derived from ATP through the action of adenylate cyclase is the second messenger for many hormones, e.g. epinephrine, glucagon, calcitonin, PTH, etc.

c-AMP then activates c-AMP dependent protein kinase, which phosphorylates specific proteins (enzymes) in the cell. Phosphorylation alters activities of these enzymes, some are activated (e.g. glycogen phosphorylase) while some are inactivated (e.g. glycogen synthase).

Question 15

Describe Phosphatidylinositol/calcium second messenger

Answer 15

Phosphatidylinositol/calcium second messenger

• Certain hormone-receptor interaction result in the activation of the enzyme phospholipase C through a specific G-protein.
• Phospholipase C enzyme catalyzes the breakdown of phospholipids in cell membrane especially phosphatidylinositol bisphosphate (PIP2) into two different second messenger products:

Inositol triphosphate (IP3)

2. Diacylglycerol (DAG).

• The IP3 liberates stored intracellular calcium ions from mitochondria and endoplasmic reticulum.
• The calcium in turn acts as a third messenger which influences a variety of biochemical processes through the mediation of calmodulin (calcium-binding messenger protein).
• DAG, the other second messenger, activates the enzyme protein kinase C (PKC), which then alter physiological processes. The hormones thyrotropin releasing hormone (TRH) gastrain, cholecystokinin act through this second messenger.