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TESTOSTERONE: AN OVERVIEW OF BIOSYNTHESIS, TRANSPORT, METABOLISM
AND NONGENOMIC ACTIONS.
Rommerts, F.F.G.
Dept. of Internal Medicine, Erasmus Medical Centre, Rotterdam, PO
Box 1738 3000 DR, Rotterdam, The Netherlands
Testosterone, the major andropause hormone, is produced by steroidogenesis
in the lowest endocrine gland, the testis. Steroidogenesis
is the cleavage of the carbon chain of cholesterol
inside the mitochondria with formation of the biologically
inactive steroid pregnenolone as the end product.
Specific enzymes in the endoplasmic reticulum of the
Leydig cells form a metabolic network to catalyse
the transformation of pregnenolone into biologically
active testosterone. LH regulates the transport of
cholesterol to the inside of the mitochondria (short-term
regulation of steroidogenesis) as well as the profile
and activities of the pregnenolone-metabolising enzymes
(long-term regulation of steroidogenesis). The physiological
role of specific paracrine factors for regulation
of Leydig cell steroidogenesis is less clear than
the role of LH. For extra-cellular and intra-cellular
transport of cholesterol, specific transport systems
are required. In contrast, androgens diffuse through
tissues without specific transport systems and, as
a result, all cells in the body "see" roughly the
same concentration of unbound testosterone. In target
cells, transformations of testosterone into more active
ligands can take place when the rate of inactivation
is low. The response of target cells depends on the
occupancy of the receptors that in turn depends on
the intracellular concentration of unbound active
androgens. In addition to genomic effects of androgens
through the nuclear receptor, androgens can also stimulate
non-genomic effects through interactions with receptors
in the cell membrane. Disturbances in the biosynthesis
of androgens through enzyme defects or in the actions
of androgen are often the cause of abnormal sexual
differentiation. Testicular functions are relatively
resistant to ageing.
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