Androgens in Health and Disease.pdf - E Library

Chapter 1/Testosterone Synthesis, Transport, and Metabolism 17
5-androstane-17-one). These products are excreted in the urine and bile. Although
these hydroxylations occur primarily in the liver, activity is also found in other tissues,
including the kidney, adipose, brain, and prostate. The finding that the formation of
hydroxylated steroids is under developmental and hormonal control and is influenced
by drugs and by environmental factors raises the possibility that metabolism influences
the action of testosterone in certain target cells. Moreover, the hydroxylated
products of testosterone may themselves have a biological function and could play a
role in disease processes.
Testosterone and its hydroxylated metabolites are also conjugated at the 3 or 17
position by glucuronyltransferases and sulfotransferases to produce water-soluble conjugates
that are readily excreted in the urine and bile. Finally, a small fraction (2%) of
the circulating testosterone is excreted unchanged in the urine.
SUMMARY
Molecular methods have exponentially increased our understanding of how testosterone
is synthesized and secreted by Leydig cells. Yet, these mechanisms remain far from
clear. Stimulation of StAR synthesis by LH acutely increases steroid production, but
how cholesterol is transported from lipid droplets to P450scc in the inner mitochondrial
membrane is not yet known. The importance of pulses of LH to this process also remains
uncertain. Local control mechanisms are complex. Leydig cells synthesize many proteins
that are not steroidogenic enzymes, most of which have not been identified or
sequenced, and their physiological actions remain to be established. Finally, the function
of SHBG remains controversial, and our understanding of the tissue-specific metabolism
of testosterone is rudimentary. However, there is a wealth of information that
provides a basis for understanding testosterone deficiency and justifies androgenreplacement
therapies.
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