What is the Function of DHT?
Written by Ben Bunting: BA, PGCert. (Sport & Exercise Nutrition) // British Army Physical Training Instructor // S&C Coach.
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DHT, or dihydrotestosterone, is a hormone that plays a crucial role in the development and functioning of the human body.
While it is primarily known for its impact on hair loss and prostate health, its functions go far beyond that. In this article, we will delve into the fascinating world of DHT and explore the various ways it influences our overall well-being.
From regulating sexual function to promoting muscle growth and bone density, DHT is involved in a wide range of physiological processes.
Understanding how this hormone functions can help us comprehend the underlying mechanisms of certain conditions, such as androgenetic alopecia and benign prostatic hyperplasia.
What is (Dihydrotestosterone) DHT?
DHT is an essential male hormone until puberty. After that, it's considered an etiology of certain diseases.
This hormone has a dual function that places it both in the field of basic science and medicine.
This activity will outline the basic biochemistry, the physiological functions of the hormone at different stages of its development, and the role it plays in certain pathological conditions.
Androgens, also known as endogenous steroids, are endogenous hormones. They contain dehydroepiandrosterone (DHEA), androstenedione, testosterone, and dihydrotestosterone (DHT).
DHT is the strongest androgen and it is a pure androgen because it does not convert to estrogen. DHT is primarily formed in the peripheral tissues of your body where it has its effects.
DHT is essential for the development of sexuality in males. DHT plays a major role in sexual differentiation during embryonic life.
DHT is a hormone that promotes hair growth in the body, face, and pubic areas.
The hormone does not appear to have any significance in the normal female physiology.
The mutations that cause dramatic loss of DHT among females have only minor effects on the normal physiology. In this activity, the various functions of DHT in each pathology are highlighted.
A deficiency of DHT or excess DHT can lead to specific diseases.
It is important to identify and treat these pathologies in order for males to develop and function properly.
A hormone deficiency is a serious issue as it can affect the fetal sexual differentiation, leading to a series of developmental problems that only become apparent during puberty.
DHT is more potent than other androgens due to its high affinity for the androgen receptor and its slow dissociation.
The enzyme 3-alpha-hydroxysteroid dehydrogenase, present in the DHT target tissues and the liver, is responsible for the metabolism of DHT. The inactive metabolites are excreted through the urine.
The Role of DHT in the Body
DHT is essential for the development of sexuality in males. It begins early in pregnancy.
DHT has different effects on males' physiology as they progress through their development. It can have a variety of impacts during childhood, puberty and even adulthood.
Prenatal
During the sexual development of an embryo, different structures are formed under the influence multiple genes and hormonal influences. The male or female differentiation is a result of a unique and specific environment of hormones.
The combination of testosterone, antimullerian hormone (AMH), DHT, and other male hormones inhibits female differentiation, and promotes the development and maturation of the male phenotype.
DHT is necessary for the development of male external genitalia. By day 60, the testicular Leydig cell produces testosterone under influence of human chorionic gonadtropin in placenta.
By approximately week 16, the fetal pituitary’s luteinizing (LH) hormone takes over testosterone production.
This enzyme converts the circulating testosterone into DHT. DHT is responsible for the proper differentiation of male urogenital structures, such as the urogenital, genital, and labioscrotal folds. This activity is responsible for the formation of penis, the scrotum and the prostate.
DHT and Insulin-like Factor 3 (INSL3) stimulate gubernacular development required for testicular decension. Absence of DHT can lead to undescended testis and ambiguous external genitalia in males.
Sex steroids are produced by the production of testicular testosterone in the male foetus, and placental estrogen in both genders. This causes a negative feedback to the pituitary gland, which controls the gonadotropin level 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.
It also promotes an increase in DHT and testosterone in males. By six months, the HPG axis is no longer negatively impacted. The levels of sex-hormones are low until the adrenarche.
Adrenarche usually occurs between the ages of six and twelve years in both genders. The adrenal gland forms a new layer called the zona reticularis.
This layer of adrenal gland produces androgens including testosterone. It increases systemic testosterone and develops sebaceous, apocrine and apocrine ducts.
As the zona reticularis matures, testosterone production increases. By age 10, there is sufficient peripheral conversion of DHT into testosterone to cause pubic hair growth. The onset of adrenarche is distinct from puberty, even though they may coincide.
Adolescents
The onset of puberty is marked by an increase in HPG axis activation. Hypothalamic secretion of gonadotropin-releasing hormone (GnRH) increases, stimulating pituitary LH secretion, which increases testosterone production from the testes.
This DHT promotes further growth and maturation of the penis and scrotum. This DHT stimulates the growth and maturation in the penis and sacrum.
DHT is the main androgen that causes facial hair, body and pubic hair as well as prostate growth.
DHT can be ten times more potent than testosterone due to its isolated production in peripheral tissues. DHT can be ten times more potent than testosterone due to the isolated production of DHT in peripheral tissues.
Adulthood
DHT is not a major factor in the normal physiology of adults. As men age, the most noticeable effects are an enlarged prostate and male pattern hair loss.
Functions of DHT in Hair Loss
Male androgenic hair loss is also known as male pattern baldness. This type of alopecia causes hair to fall out on the frontal and top part of the scalp. It is progressive. The pathophysiology behind androgenic hair loss is due to increased DHT activity.
[14] Patients with an enzyme deficiency have a lower risk of developing male androgenic hair loss.
Finasteride is an oral 5-alpha reductase inhibitor that can be used to slow down or reverse the hair loss. About 99% of participants in two large randomized-controlled trials showed a reduction or reversal in hair loss. [15] Topical minoxidil is the other first-line treatment for MAA.
The Relationship Between DHT and Prostate Health
The prostate produces large amounts of DHT, a potent hormone. This local DHT induces regular activity, but can also cause prostate hypertrophy or hyperplasia. Over 50% of men older than 50 years have BPH. [12]
Increased prostate growth can cause symptoms like difficulty urinating or sexual dysfunction.
BPH is treated primarily with alpha-1-adrenergic receptor antagonists. Finasteride or dutasteride may be indicated in certain patients. These drugs reduce the size of the prostate and alleviate symptoms associated with BPH. [11]
Prostate Cancer
DHT activity is also increased in prostate cancer. All three isoforms (5-alpha reductase) are upregulated. These gene mutations cause uncontrolled proliferation, and inhibit apoptosis. They are linked to DHT pathways. [13] Mutations in the androgen-receptor also play a role in prostate cancer.
Although several clinical trials have shown a decrease in prostate tumor incidence, the rate of high-grade cancers has increased in patients who are taking these drugs.
The Role of DHT and Polycystic Ovarian Syndrome (PCOS)
DHT was thought to play a minor part in the regulation of normal female physiology. Recent gene expression studies on humans have revealed potential implications for DHT in the PCOS pathophysiology.
In a study that compared the gene expression profiles of PCOS patients' ovaries with those of control groups, it was found that PCOS patients have a higher level of genes involved in the biosynthesis of DHT via the backdoor pathway.
DHT causes an increase in weight, fat and serum cholesterol in mice with PCOS.
The administration of prenatal DHT to experimental female mice did not cause penile formation.
The Effects of DHT on Muscle Development
It has been concluded in a 2001 double-blind study that 3-month treatment with transdermal DHT at a relatively higher dose shows stable pharmacological characteristics with consistent negative feedback on the pituitary and testicular axis, reduced body fat, but minimal effects on muscle mass, strength or function.
In older men, the absence of an increase in prostate volume or PSA as well as a change in lipids and vascular reactivity supported its short-term safety.
Results from a study based on the mouse model showed that high levels circulating dihydrotestosterone improve power and speed, but decrease endurance in isolated muscles of fast and slow twitch in both males and women.
DHT on Bone Health
In a 1996 study looking at bone formation in rats, DHT increased skeletal weight by increasing bone formation and growth.
This was accompanied by an increase in total body mass. DHT was more effective on cortical bones and partly mitigated estrogen's suppressive effects on female bone growth and development.
A 2022 study, DHT was associated with a significantly lower hip fracture risk in a group older men who did not suffer from cardiovascular disease.
DHT for Androgenic Deficiencies
Testosterone can be used to treat androgen-deficiency conditions such as male hypogonadism and androgen deficiencies caused by severe illness, aging and infancy.
DHT is also proposed as a therapy for androgen deficiencies as it's pure androgen that doesn't convert to estrogen.
DHT's reported, and paradoxically mild effects on prostate growth may be an advantage over testosterone.
The decreased effect of DHT on human prostate glands may be a result of the lower intraprostatic levels of estradiol.
How to Treat Excessive DHT Levels
5-alpha reductase inhibiters help treat conditions that have excessive DHT activity.
This includes benign prostatic hyperplasia, prostate cancer and androgenic hair loss (male pattern hairloss).
These drugs reduce tissue DHT by inhibiting 5-alpha reductase. Finasteride is the most commonly prescribed drug.
Finasteride only inhibits 5-alpha reductase type 2 while dutasteride also inhibits both the type 1 and type 2 isoforms. The drugs are generally well tolerated but they can reduce libido or sexual function.
Conclusion
Dihydrotestosterone is responsible for the external virilisation in males at embryological development.
5-alpha reductase converts DHEA, testosterone and androstenedione to DHT. DHT is the cause of external mascularisation in males.
It is an endogenous androgen hormone that plays a major role in the growth and repair the prostate, production of sebum and the composition of body hair.
This enzyme catalyzes DHT formation from testosterone. It is found in many tissues, including the prostate, epididymides and seminal vesicles. This enzyme is responsible for the reduction of the C4-5 dual bond in testosterone.
DHT may also be synthesized from progesterone and 17a-hydroxyprogesterone via the androgen backdoor pathway in the absence of testosterone. DHT is a much more potent agonist of androgen receptors (AR) than testosterone.
Deficiency of DHT leads to ambiguous genitalia for males. Females have little importance for the concentrations that circulate.
