Testosterone secretion occurs within the Leydig cells located within the interstitial compartment of the male testes, between the seminiferous tubules. It is synthesized from cholesterol with the participation of some cytochrome P-450 enzymes such as 17-hydroxylase and 17,20 lyase. Some additional testosterone synthesis occurs in the adrenal cortex’s zona reticularis; the quantity produced from the cortex is relatively insignificant in men, but in women, it contributes to a large proportion of the circulating testosterone.
Testosterone occurs at three major stages of life in the typical male, namely:
- A transient increase during the first trimester of intrauterine life.
- A transient perinatal surge during early neonatal life.
- Continual increase after puberty until the third or fourth decade of life when testosterone levels begin to gradually decrease.
Testosterone synthesis is regulated by the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. The released GnRH then stimulates the release of luteinizing hormone (LH) from the brain’s pituitary gland. The LH that is released then triggers the synthesis of testosterone from the Leydig cells in the testes. Testosterone also has a negative feedback effect on GnRH and LH’s release from then hypothalamus and pituitary glands respectively.
After its synthesis, testosterone is further metabolized before it can exert its effects in the body; there are two major pathways by which this may occur. In the first metabolic pathway, synthesized testosterone is converted into dihydrotestosterone through the action of the enzyme 5-alpha reductase; DHT then binds to and activates androgen receptors in organs such as the prostate, muscles, and skin where it exerts its effects. In the second pathway, the enzyme aromatase converts testosterone into estradiol; estradiol binds with estrogen receptors and exerts its effects on the brain and bone. In both pathways, binding to the androgen receptors causes dissociation of heat shock proteins that are bound to the receptors. This dissociation allows for the translocation into the nucleus, as well as phosphorylation, interaction, and modification of the DNA at the target genes. Once this occurs, the transcription activities that result in the synthesis of the relevant proteins then takes place.