Physiology of Androgen
Disorders brought about
by excess action of androgen include gynopathy, hypertrichosis,
acne, amenorrhea in females, prostatic hypertrophy,
prostatic carcinoma, and baldness in men. PCO (polycystic
ovary syndrome) and excess androgen seem to result
in many symptoms in Caucasians, but may not in Japanese.
In women, androgen is produced in the adrenals and
ovaries;. in men, in the adrenals and testes. Finally,
a receptor in a cell is activated through a process
of testosterone to reach DHT (dehydrotestosterone)
which is last active substance. There are DHEA (dehydroepiandrosterone),
DHEAS (dehydroepiandrosterone sulfate), AD (androstenedione),
and T (testosterone) present in blood. T is converted
into DHT by 5arufa-reductase.
Androgen is actively produced in a woman's
ovaries, but production in the ovary seems to be strongly
influenced by LH, insulin, and IGF-1. Androgen made
in the ovaries is mainly AD and T, and there is also
a great deal of DHEA, DHEAS, and AD present.
Metabolism mainly takes place in the
liver, but there are 2 other routes as well. One is
aromatization in muscle and adipose tissue.
When done in this way, AD and T are converted into E1 (estrone)
and E2 (estradiol). Another way is T is converted into DHT
by 5 arufa-reductase. There are two kinds in 5 arufa-reductase,
type1 is mainly in the skin and the sebaceous gland. Type
2 is mainly in the prostrate gland and skin of the external
T and DHT strongly connect to SHBG (sex
hormone binding protein) and albumin in the bloodstream.
It is known that SHBG increases in hypothyroidism,
hepatopathy, alcoholics, or estrogenic administration.
When SHBG increases, Free T decreases, action of T attenuates,
and metabolism and excretion of T slows. On the other hand,
it is known that SHBG increases in obesity, hyperinsulinism
blood disease and androgen administration. The difference
between DHEAS, DHEA and AD and the half life of blood is
that the half-life of DHEAS is long, its circadian rhythm
of 1 day is short, and it connects mainly with albumin in
Total T or free T is used
for the measurement of androgen in blood T, but physiological
T does not really correspond to either of them. Part
of T binds to SHBG in blood, and it is not physiologically
active. Free T is physiologically active, and usually
measured by ELISA. Free T has a correlation of a certain
degree to bioavailable T, but it is said that there
is only around a 1/20 of real bioavailable T (Vermeulen).
There is T which is bound to albumin in blood flow,
but only a part of albumin-bound T is said to be bioavailable.
T[nM/L] *100/ SHBG[nM/L] is used as FAI (free androgen
index) to simply calculate the value of bioavailable
Extra attention is needed in pregnant
women in which albumin rises (five or six times for
example), though even if the level gets high androgen
symptoms usually do not appear. In addition, there
is a possibility of accidental SHBG combination with
estradiol when estradiol levels are very high.
Total T = free T + albumin-T+SHBG-T,
usually albumin-T is around 22 times that of free T,
SHBG-T 30-100 times (there is a sex difference which
depends on level of SHBG: in adult males there is a
lot, and in women, a little. There is a report that
says around 2% of total T is free T, 68% weakly bound
with albumin is bioavailable T, and the remaining 30%
is strongly bound to SHBG and assumed to be non-bioavailable.