Steroids Lecture 4

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SteroidsLecture 4

• Synthesis and metabolism of steroidal hormones

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Synthesis of testosterone
1) Removal of most of side chain (C27 down
to C21) 2) 17?-Hydroxylation 3) Removal of rest
of side chain (C21 down to C19) 4)
Reduction of 17-oxo to 17?-OH 5) Oxidation of
3?-OH to 3-oxo Isomerisation of double bond
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Synthesis of testosterone

• Dont learn the names and structures of all the
  intermediates!
• Would expect you to appreciate
• Synthesis of steroid hormones is usually
  multi-step.
• There may be a variety of routes from
  cholesterol to the finished hormone.
• Hormone syntheses usually involve
• Introduction of new -OH groups
• Removal of carbons
• Interconversions of -OH and O groups
• Moving double bonds

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?4 and ?5 Pathways
Textbooks often emphasise the ?4
route. Synthesis of testosterone within the
testes is actually mainly via the ?5 route.
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Metabolism of steroid hormones

• Mainly in the liver
• Biological inactivation
• Increased water solubility - renal and biliary
  excretion
• Increased molecular weight - biliary
• excretion

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Metabolism of steroid hormones

• Reduction of keto hydroxyl
• Oxidation of hydroxyl keto
• Reduction of double bond single
• (mainly at C 4)
• Removal of side chain
• Conjugation with sulphate or glucuronide
• (Mainly responsible for increased water
  solubility and molecular weight)

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Four metabolites from a single steroid (e.g.
testosterone)1) Reduction of 4-double bond
A
B
O
5?
5?
A
B
A
B
O
O
H
H
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Four metabolites from a single steroid (e.g.
testosterone)2) Reduction of 3-keto
A
B
O
3?
3?
A
B
A
B
HO
HO
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Four metabolites from a single steroid (e.g.
testosterone)3) Oxidation of 17?-hydroxyl
OH
O
D
D
C
C
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Four products from testosterone

• 3?-hydroxy-5?-androstan-17-one
• 3?-hydroxy-5?-androstan-17-one
• 3?-hydroxy-5?-androstan-17-one
• 3?-hydroxy-5?-androstan-17-one
• Excreted as sulphate and glucuronide conjugates

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Terms with which you should be familiar

• D4 and D5 pathways

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What you should be able to do

• Describe in outline the biosynthesis of
  testosterone
• List significant consequences of the metabolism
  of steroidal hormones
• Provide examples of the chemical changes that
  occur during the metabolism of steroidal hormones
• Describe why the metabolism of a single
  steroidal hormone may give rise to a variety of
  metabolites