Steroid HormonesSteroid Hormones

HO

Cholesterol Starting material

Steroid Sex HormonesSteroid Sex Hormones• Androgens:Androgens: male sex hormones

• synthesized in the testes• responsible for the development of male secondary sex characteristics

AndrosteroneTestosteroneO

OH

H3C

H3C H3C

H3C

O

HO

Steroid HormonesSteroid Hormones• Among the synthetic anabolic steroids are:

O

H3C

H3C

MethandienoneO

CH3

H3CH3C

OHOH

CH3

MethenoloneO

H3C

H3CO

4-Androstene-3,17-dione

Prohormones, see p.515 Chemical Connections 20G

Why are these hormones of interest?

Do steroids really work? i.e. improve muscle mass

and performance? . . .

A resounding Yes . . .

AndrosteroneTestosteroneO

OH

H3C

H3C H3C

H3C

O

HO

Steroid Sex HormonesSteroid Sex Hormones• Estrogens:Estrogens: female sex hormones

• synthesized in the ovaries from progesterone testosterone . . . (aromatization) estradiol

• responsible for the development of female secondary sex characteristics and control of the menstrual cycle

Steroid Sex HormonesSteroid Sex Hormones

• Progesterone-like analogs are used in oral contraceptives: they Make the body think it is Pregnant at all times. . .

preventing folicle stimulation and ovulation. . .

A woman's monthly cycle w/o the pill (Blue and Red solid lines)

A woman's monthly cycle on the pill (Blue and Red dashed lines)

Prevents egg from staying implanted . . Gets released. . .

•Steady stream of Progesterone required for implantation and development of oocyte

Other pills block Progesterone

all together. . .e.g. RU- 486

Progesterone

Steroid HormonesSteroid Hormones• Adrenocorticoid hormonesAdrenocorticoid hormones

• synthesized in the adrenal cortex.• regulate metabolism of carbohydrates.• decrease inflammation.• involved in the reaction to stress.

Bile SaltsBile Salts• Bile saltsBile salts, the oxidation products of cholesterol.• synthesized in the liver, stored in the gallbladder, and secreted into the intestine where they emulsify dietary fats and aid in their absorption and digestion

HO

H3C

CH3

H3C

OH

HO NH

O

HO

H3C

CH3

H3C

OH

HO NH

O

SO32-

Glycocholate(from glycine)

Taurocholate(from taurine)

COO-

Other Classes Lipids: Other Classes Lipids: - - ProstaglandinsProstaglandins- - ThromboxanesThromboxanes - Leukotrienes - Leukotrienes

• Prostaglandins:Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid. COOH

2

3

4

5

67

89

2011

1213

1415

1617

1819

1

10

ProstaglandinsProstaglandins• Not stored in tissues - synthesized from membrane-bound

20-carbon polyunsaturated fatty acids in response to specific physiological triggers.

• One such polyunsaturated fatty acid is arachidonic acid.

COOH

Arachidonic acid1514

89

11 12

6 5

ProstaglandinsProstaglandins

15

9 9

11 11

Arachidonic acid

PGF2PGE2

PGG2

Aspirin and other NSAIDs inhibit this enzyme

15

9

11

9

11

15

OOH

COOHO

O

OH

COOH

O

HO

COOH

OH

COOH

2O2

15

cyclooxygenase (COX)

HO

HO

COX EnzymesCOX Enzymes• The COX (cyclooxygenase) enzyme occurs in two forms:

• 1. COX-1 catalyzes the normal physiological production of prostaglandins.

• 2. COX-2 is responsible for the production of prostaglandins in inflammation.

• Tissue is injured or damaged, special inflammatory cells invade the injured tissue and interact with resident cells, e.g. smooth muscle cells or skin.

• This interaction activates COX-2 and prostaglandins are synthesized.

Aspirin helps relieve this anti-inflammatory responseBy inhibiting the production of prostaglandins . . .

ThromboxanesThromboxanes• Thromboxanes are also derived from arachidonic acid.• Thromboxane A2 induces platelet aggregation and vasoconstriction.

• Aspirin and other NSAIDs inhibit the synthesis of thromboxanes by inhibiting the COX enzyme.

O

OOH

COOH

Thromboxane A2

189

11 201512

10

Challenge QuestionsChallenge Questions

How Does Aspirin prevent strokes caused by blood clots in the brain?

NOTE: Doctors recommend 81mg/ day for people at risk for Heart Attack or stroke. . .

LeukotrienesLeukotrienes• Leukotrienes are also synthesized from arachidonic acid.• They occur mainly in leukocytes.• They produce muscle contractions, especially in the lungs and thereby can cause asthma-like attacks.

• In this regard, they are 100 times more potent than histamine.

• Several recently-developed anti-asthma drugs inhibit the synthesis of leukotrienes.OH OH

COOH

Leukotriene B4

1512

20