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Function

DHT plays a critical function in the sexual development of males, beginning early in prenatal life. The role of DHT differs as males progress through the different stages of development; it has various impacts on their physiology during childhood, puberty, and even throughout adult life.

Prenatal

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During sexual development, various embryological structures develop under the influence of multiple genes and hormones. A specific and unique environment of hormones results in male or female differentiation of structures. In males, testosterone, anti-Mullerian hormone (AMH), and DHT act in concert to inhibit female differentiation and promote the development of the male phenotype. DHT is essential for the formation of the male external genitalia. The testicular Leydig cells produce testosterone under the influence of placental human chorionic gonadotropin by around day 60 of prenatal development.

The fetal pituitary’s luteinizing hormone (LH) takes over testosterone production by roughly week 16. The peripheral 5-alpha-reductase type 2 converts circulating fetal testosterone to DHT, responsible for proper male differentiation of the urogenital sinus, the genital tubercle, the urogenital fold, and labio-scrotal folds. This activity leads to the formation of the penis, scrotum, and prostate.

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DHT and insulin-like factor 3 (INSL3) help stimulate the gubernacular growth required for testicular descent. The absence of DHT may lead to ambiguous male external genitalia and undescended testis. Sex steroids accumulate from the testicular production of testosterone in the male fetus and the placental production of estrogen in both sexes, causing negative feedback on the fetal pituitary, which helps control gonadotropin levels in the womb.

Childhood

After birth, the loss of placental estrogen removes negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, resulting in a transient increase in activity in both sexes for the first few months of life. This promotes a rise in testosterone levels and DHT in males. The negative feedback on the HPG axis recovers by six months of age, and the levels of sex hormones remain low until adrenarche.

Adrenarche typically occurs around six years of age in both sexes. The adrenal gland develops a new layer, the zona reticularis. This layer of the adrenal gland produces androgens, including testosterone, which increases systemic testosterone, developing sebaceous and apocrine glands and contributing to minor acne and body odor. Testosterone production continues to grow as the zona reticularis continues to mature. There is enough peripheral conversion of testosterone into DHT by age 10 to result in pubic hair development. These events of adrenarche are distinct from puberty though they often coincide.

Puberty

An increase in the HPG axis activity characterizes puberty’s onset. Hypothalamic secretion of gonadotropin-releasing hormone (GnRH) increases, stimulating pituitary LH secretion, which increases testosterone production from the testes. The increase in systemic testosterone is associated with a significant conversion to DHT in its target tissues. This DHT promotes further growth and maturation of the penis and scrotum.[2]

DHT is also the primary androgen responsible for facial hair, body hair, pubic hair, and prostate growth. The circulating level of DHT in the blood is only 10% of the circulating testosterone level. However, due to its isolated production in peripheral tissues, the DHT level can be as much as ten times greater than testosterone.[2]

Adult

DHT does not play a significant role in the normal physiology of adults. The most notable effects are prostate enlargement and male pattern hair loss as they age.[7]

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