Physiology of Androgen

Kotaro Yoshimura

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 genitalia.

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 the bloodstream.

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 T.
　

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.