By Dr Ananya Mandal, MD
Testosterone is the principle male sex hormones in mammals, birds and other vertebrates. The effects of the hormone are exerted in two main ways:
Testosterone can activate the androgen receptor itself or after conversion to 5α-dihydrotestosterone (DHT) by the enzyme 5α-reductase.
Testosterone can also be converted into the sex hormone estradiol (by the enzyme aromatase), the most important of the estrogens in reproductive function and bone health in females.
Synthesis, transport and action
Once synthesised, testosterone is secreted into the blood and carried to target cells in the male reproductive organs. Most of the testosterone is transported bound to a specific plasma protein called sex hormone binding globulin (SHBG). The remainder is termed free testosterone.
It is free testosterone that can be converted into DHT but it cannot be converted by aromatase into estradiol.
Both DHT and testosterone can bind to the androgen receptor but DHT binds with a greater affinity than unbound or unchanged testosterone.
Once bound to the androgen receptor, DHT or testosterone forms a complex that undergoes a structural change. This complex then moves into the nucleus of the cell and binds to specific nucleotide sequences of DNA which are termed hormone response elements.
This binding of the complex to the elements brings about changes in the transcription of various proteins mediated by specific genes, which produces the androgenic effects of the cells.
Testosterone plays an important role in the growth and development of the primary male reproductive tissues and organs such as the testes and prostate.
A deficiency in the enzyme 5-alpha reductase (that forms DHT from testosterone), reduces the androgenic effects responsible for male development before birth and during puberty.
The shortage of DHT prevents proper formation of the male sex organs and babies are often born with genitalia that appear either female, neither male or female (ambiguous genitalia) or the genitalia may be predominantly male but the penis particularly small and a urethral opening may be present.
Testosterone also promotes the secondary sexual characteristics in males during puberty such as increased muscle mass, increased bone mass, deepening of the voice and the growth of facial, armpit, chest and pubic hair. Adequate testosterone levels are also protective against several conditions such as osteoporosis.
The pituitary gland secretes the hormones luteinizing hormone (LH) and follicle stimulating hormone (FSH) which regulate the number of Leydig cells and their secretion of testosterone. LH controls the amount of 17-β hydroxysteroid dehydrogenase enzyme produced and since this enzyme mediates the rate-limiting step of testosterone synthesis, its inhibition can prevent the synthesis of testosterone.
Reviewed by Sally Robertson, BSc