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

 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 growth Increases appetite, stimulation of bone marrow, increase production of RBCs, increased protein synthesis, etc. ANDROGENIC ○ Affect the development and maintenance of masculine characteristics Increased 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 are a diverse group of hormones, most of which are derivatives of arachidonic acid (20:4Δ 5,8,11,14 )  Most prominent among the group is a series of cyclopentanoic acids known as prostaglandins (PG)  Closely related to PG are thromboxanes (TXA 2 ), 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: PGE 2, PGF 2, PGG 2, PGH 2, PGI 2, etc. ○ PG stands for “prostaglandin” ○ The 3 rd letter refers to a particular structure ○ The subscript 2 notes the number of double bonds

EICOSANOIDS  Initial steps for the synthesis of PGs and TXA 2 are the oxidation and cyclization of arachidonic acid to yield the PGG 2 and PGH 2

PROSTAGLANDINS PGE 2  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 PGF 2  PGF 2 has a physiological function opposite PGE 2, that is it constricts blood vessels

PROSTAGLANDINS PGH 2  The precursor of various prostaglandins and tromboxanes  Formation of this PG from PGG 2 is catalyzed by the peroxidase component of the enzyme

PROSTAGLANDINS PGI 2  Derived from PGH 2 with enzyme PGI 2 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 TXA 2  Derived from PGH 2 with enzyme TXA 2 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?