ECDA

August 2009

STEROIDS

AND HORMONES

STEROIDS AND HORMONES Steroids and hormones are alicyclic

compounds, all of which are derivatives of a fused tetracyclic ring system, the cyclopentanoperhydrophenanthrene ring.

These tetracyclic hydrocarbons are much more common in eukaryotes than in prokaryotes.

STEROIDS AND HORMONES The most important and most prominent

compound under this classification is cholesterol.

Cholesterol is an important component of many eukaryotic cell membranes.

Cholesterol is also the precursor of two major classes of steroids: the steroid hormones and the bile acids.

Cholesterol is a 27-carbon sterol

STEROIDS AND HORMONES

STEROIDS AND HORMONES Bile acids are the primary degradation

products of cholesterol. They are made in the liver, stored in the

gallbladder, and secreted into the small intestine

Beginning in the duodenum, they aid in the solubilization of dietary lipids, thereby facilitating their digestion by intestinal lipases.

Dietary Lipid Digestion

STEROIDS AND HORMONES Steroid hormones play a key role in the

regulation of metabolism In general, steroids exert their action and effect

changes in the cell by mediating DNA/RNA synthesis.

○ When the steroid hormone binds at receptor sites in cell membrane, both the hormone and receptor enter the cell.

○ The mobile receptor breaks up and returns to the membrane as soon as the hormone binds to cytoplasmic receptors which allow it to enter the nucleus and affect synthesis of some proteins.

STEROIDS AND HORMONES Examples of steroid hormones derived

from cholesterol are important sex hormones such as testosterone, estrogen, and progesterone

Some steroid hormones serve as regulatory substances of metabolism. These are aldosterone (mineralocorticoid) and cortisol (glucocorticoid).

SEX HORMONES

PROGESTERONE

Precursor of other steroids

Prepares uterus for implantation of an egg

Prevents ovulation during pregnancy

SEX HORMONES

ESTROGEN

Responsible for sexual development in the female

Promotes and maintains female sex characteristics

SEX HORMONES

TESTOSTERONE

Promotes male sexual development

Promotes and maintains male sex qualities

METABOLIC HORMONES

ALDOSTERONE

Synthesized in the adrenal glands

Increases retention of Na ions by the renal tubules

METABOLIC HORMONES

CORTISOL

Synthesized in the adrenal glands

Promotes gluconeogenesis

Suppresses inflammatory reactions

ANABOLIC STEROIDS Also called anabolic-

androgenic steroids (AAS)

Are a class of steroid hormones related to testosterone

They increase protein synthesis within cells which results in the buildup of cellular tissues, especially muscles

ANABOLIC STEROIDS Anabolic-androgenic steroids have two

different but overlapping, types of effects:ANABOLIC

○ Promotes anabolism or cell growthIncreases appetite, stimulation of bone marrow, increase

production of RBCs, increased protein synthesis, etc.

ANDROGENIC○ Affect the development and maintenance of

masculine characteristicsIncreased libido, growth of penis and clitoris, impaired

sperm production, sebaceous gland production, etc.

ANABOLIC STEROIDS AAS have many adverse

effects: Raises blood pressure especially

in those that are pre-hypertensives

Increases risk for cardiovascular disease

Increase in acne occurrence Can cause massive liver damage Can cause testicular atrophy Increase in body hairs Increased frequency and

duration of erections

ANABOLIC STEROIDS

EICOSANOIDS

EICOSANOIDS

Eicosanoids are a diverse group of hormones, most of which are derivatives of arachidonic acid (20:4Δ5,8,11,14)

Most prominent among the group is a series of cyclopentanoic acids known as prostaglandins (PG)

Closely related to PG are thromboxanes (TXA2), also are eicosanoids

EICOSANOIDS Prostaglandins were initially isolated from the

seminal fluid and were therefore thought to be produced by the prostate glands. However, more studies have shown that these substances are present in various tissues in the body

Different prostaglandins exist in the body: PGE2, PGF2, PGG2, PGH2, PGI2, etc.

○ PG stands for “prostaglandin”○ The 3rd letter refers to a particular structure○ The subscript 2 notes the number of double bonds

EICOSANOIDS

Initial steps for the synthesis of PGs and TXA2

are the oxidation and cyclization of arachidonic acid to yield the PGG2 and PGH2

PROSTAGLANDINS

PGE2

In human adipose cells causes 15-fold increase in the concentration of cyclic AMP or cAMP, an energy containing molecule used in membrane transport reactions

It is also observed to cause dilatation of blood vessels

PROSTAGLANDINS

PGF2

PGF2 has a physiological function opposite PGE2, that is it constricts blood vessels

PROSTAGLANDINS

PGH2

The precursor of various prostaglandins and tromboxanes

Formation of this PG from PGG2 is catalyzed by the peroxidase component of the enzyme

PROSTAGLANDINS

PGI2

Derived from PGH2 with enzyme PGI2 synthase

Synthesized in endothelial cells that line blood vessels (arterial walls)

Inhibits platelet aggregation by binding to a receptor on the plasma membrane of platelets

EICOSANOIDS

TXA2

Derived from PGH2 with enzyme TXA2 synthase

Has opposite effects of PGI2: it causes platelet aggregation leading to formation of blood clots (major cause of coronary artery disease)

Aspirin (Aspilet) can inhibit platelet thromboxane formation

Aspirin activates cyclooxygenase by acetylation of a serine at or near the active site of the enzyme.

Possible actions of PGI2 and TXA2 in blood clotting and thrombosis.

QUESTIONS?