Hormone Action

Testosterone

Testosterone is an androgenic hormone that promotes the normal development and maintenance of male sex and reproductive organs. Testosterone levels (i) facilitate spermatogenesis and promote the maturation of sperm, (ii) influence sexual desire and related behaviours, (iii) stimulate metabolic processes such as protein synthesis and muscle growth, (iv) facilitate the development of male secondary sexual characteristics such as bone mass, musculature, fat distribution, and hair patterns, and (v) aid in the maintenance of the male reproductive tract.

Testosterone production is regulated by a complex chain of signals referred to as the hypothalamic-pituitary-gonadal axis. Gonadotropin-releasing hormone (GnRH) is secreted by the hypothalamus in pulses and travels to the anterior pituitary via the hypophyseal portal system. The anterior pituitary gland then releases leutenizing hormone (LH) which in turn stimulates the production of testosterone by the interstitial Leydig cells in the testes. A negative-feedback loop controls the level of testosterone production - above-normal levels of testosterone in the circulation inhibits GnRH secretion by the hypothalamus which causes a reduction in LH secretion and lowers testosterone levels.

Testosterone is transported in plasma while bound to one of two types of plasma proteins: (i) sex hormone-binding globulin (SHBG) transports roughly two-thirds of circulating testosterone, and (ii) albumins bind the remaining one-third save for a very small percentage (< 2%) that remains free in the circulation to bind with androgen receptors. As a steroid, testosterone enters target cells by diffusing across cell membranes and binds to an intracellular receptor. The hormone-receptor complex then binds to DNA and promotes gene transcription. In some target cells, testosterone is converted into dihydrotestosterone (DHT) which can bind to the same receptors targeted by testosterone. Certain tissues, including those of the external genitalia and the prostate gland, are more responsive to DHT than to testosterone.

Testosterone production increases markedly at puberty and declines naturally after age 50. Insufficient testosterone production and secretion may result from damage or disease of the hypothalamus, pituitary, or testicles and can lead to developmental abnormalities of muscle, bone, and genitalia. Testosterone deficiency in males has been linked to cryptorchidism (failure of testicles to descend into scrotum), hypogonadism (enlargement of breast tissue), erectile dysfunction, diminished libido, depression, and osteoporosis. Recent studies have shown that some environmental chemicals act like anti-androgens by binding with the androgen receptor and blocking testosterone and DHT from binding and exerting their effects.