DHT. But what is DHT?
DHT stands for Dihydrotestosterone, also known as Androstanolone (5α–Androstan–17β–ol–3–one) or 17β–hydroxy–5α–Androstan–3–one, the biologically active metabolite of testosterone.
Testosterone is the most important androgenic steroid hormone, produced mainly in the Leydig cells, and secondarily by the adrenal gland (1 to 5%) (Gauchez & Leban, 2012). Gonadoliberin-releasing hormone (GnRH) is released by specialised neurons of the hypothalamus, and stimulates luteinizing hormone (also known as lutropin, lutrophin or Interstitial Cell Stimulating Hormone) produced in the pituitary gland. LH then stimulates the secretion of testosterone, a natural androgen or testoid.
Under the catalyse reaction of the SRD5A (both types I and II) enzymes (5-α-reductase) - occurring into the prostate gland, testicles (in men), the ovaries (in women), the skin, the hair and adrenal glands - 10% of the produced testosterone is metabolized into dihydrotestosterone.
At least, that's what we thought.
In 2008, Mostaghel et al. discovered new pathways (“backdoor” and “intracrine reverse”) in which DHT can be synthesized from 17-hydroxypregnenolone and 17-hydroxyprogesterone and 5α-androstane-3α, 17-β-diol via the intracrine reverse synthesis pathway (1).
How does androstanolone work?
DHT specifically recognizes androgen receptor NR3C4 (nuclear receptor subfamily 3, group C, member 4) and shows a higher potency compared to its analog.
In fact, dihydrotestosterone demonstrates:
ü an affinity to androgen receptor four times greater than that of testosterone (2)
ü a rate of dissociation from the NR3C4 three times slower than testosterone (3)
ü an amplification of the androgenic signal by its more efficient conversion to the DNA-binding state (4), increasing the so called “transformation” process.
Once the androstanolone binds to its NR3C4, the confirmation change of the androgen receptor results in an alteration in net charge and allows the receptor-hormone complex to bind to DNA and regulate the gene expression.
DHT is involved, among other things, in the male differentiation of the external genitalia during embryonic development. In men, the DHT level fluctuates considerably during the course of life. For example, high concentrations are observed at birth or at the beginning of puberty, when testosterone levels also rise. In women, blood DHT levels normally remain very low throughout life.
What is the normal blood concentration of 5α-dihydrotestosterone?
The DHT test is generally recommended when there are clinical signs of hirsutism (increased body, facial and pubic hair growth) or amenorrhoea (stopping of menstrual periods) in women. In men, androstanolone is a marker for pseudohermaphrodism conditions (due to 5α–reductase deficiency), male pattern baldness (MPB), and benign prostatic hyperplasia (BPH).
Dihydrotestosterone concentration is determined by analysis of a blood sample. The reference values, about one-tenth that of total serum testosterone concentrations, are as follows:
- between 0.14 and 1.02 nanograms per millilitre (ng/ml) in healthy men (5, 6, 7),
- between 0.06 and 0.30 ng/ml in healthy women.
In these mentioned studies, LC-MS-MS technique has been considered as state of the art method compared to DHT immuno-assays. In fact, LC-MS-MS offer detection limits in the pg range for hormones, and seems to be particularly good fit to measure steroid metabolites when analyzed compounds differ by only the substitution of a carbonyl or hydroxyl group.
Nevertheless the disadvantages of LC–MS–MS remain: higher operational cost, more limited sample throughput, and no possibility to visualize dihydrotestosterone antigen presence in cells and tissues.
At SYnAbs, we have so decided to offer a unique solution for immuno-fluorescence, immuno-histochemistry and ELISA assays, by developing a monoclonal antibody of higher specificity and affinity. Immunizing guinea pigs (Cavia porcellus), a species well known for high affinity antibody, SYnAbs achieved to generate anti-DHT monoclonal antibodies that don’t cross-react with free testosterone and that offer a sensitivity of 0,04 ng/ml (40 pg/ml)! An unprecedented outcome in the history of antibody generation against steroid compounds! Let’s meet with our GP-DHT-1!
(1) Mostaghel EA , Nelson PS. Intracrine androgen metabolism in prostate cancer progression: mechanisms of castration resistance and therapeutic implications. Best Pract Res Clin Endocrinol Metab. 2008;22(2):243–258.s
(2) Gao W , Bohl CE, Dalton JT. Chemistry and structural biology of androgen receptor. Chem Rev. 2005;105(9):3352–3370.
(3) Wilson EM , French FS. Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate. J Biol Chem. 1976;251(18):5620–5629.
(4) Kovacs WJ, Griffin JE, Weaver DD, Carlson BR, Wilson JD. A mutation that causes lability of the androgen receptor under conditions that normally promote transformation to the DNA-binding state. J Clin Invest. 1984;73(4):1095-1104. doi:10.1172/JCI111295
(5) Shiraishi S , Lee PW, Leung A, Goh VH, Swerdloff RS, Wang C. Simultaneous measurement of serum testosterone and dihydrotestosterone by liquid chromatography-tandem mass spectrometry. Clin Chem. 2008;54(11):1855–1863.
(6) Handelsman DJ , Yeap B, Flicker L, Martin S, Wittert GA, Ly LP. Age-specific population centiles for androgen status in men. Eur J Endocrinol. 2015;173(6):809–817.
(7) Yeap BB , Alfonso H, Chubb SA, Handelsman DJ, Hankey GJ, Norman PE, Flicker L. Reference ranges and determinants of testosterone, dihydrotestosterone, and estradiol levels measured using liquid chromatography-tandem mass spectrometry in a population-based cohort of older men. J Clin Endocrinol Metab. 2012;97(11):4030–4039.