La nandrolone est un anabolisant norstéroïde de synthèse aux propriétés androgéniques connues. À l'aube de la Coupe du Monde 1998, la polémique concernant la possibilité d'une synthése endogène de nandrolone à des taux supérieurs à ceux pris en compte par le Comité international olympique (CIO), n'a été entretenue que par l'expression publique du manque de rigueur de certains ≪ scientifiques ≫. Nous montrerons ici pourquoi elle a fait ≪ long feu ≫. Ces substances sont des intermédiaires biochimiques obligatoires dans l'aromatisation des androgènes. Dans les années 1990, la chromatographie gazeuse couplée à la spectrométrie de masse a permis d'abaisser le seuil de détection de ces substances à 1 pg/mL voire moins ce qui rend possible la quantification de taux infimes de métabolites endogènes qui n'ont rien à voir avec les taux élevés rapportés lors des contrôles antidopage de 1997–1998. Nous ferons le point sur la biologie de la nandrolone et des norstéroïdes. Face au grave problème de santé publique que représente la prise abusive d'anabolisants à doses pharmacologiques, la rigueur scientifique des contrôles, dans le cadre du suivi médical des sportifs, est justifiée et confortée. Norsteroids are xenobiotics with androgenic and anabolic properties known since as far back as the 1930s. In 1998, an active polemic took place over the possibilities of an endogenous production of nandrolone over the IOC's recommended limit, after the detection of a number of nandrolone-positive cases in famous French athletes. This, however, only reflected either commercial interests or the poor state of scientific knowledge on these substances within sports bodies. We will try and summarize here the state of the scientific knowledge to date. Paradoxically, norsteroids are not only xenobiotics but also obligatory intermediaries in the biological synthesis of estrogens from androgens in all species, man included. This important point will be addressed. Since the 1990s, high-resolution mass spectrometry permits a detection limit of 1 pg/mL, or less, reproducibly. However, notwithstanding the particular technical difficulties attached, the very small endogenous levels detected have nothing in common with the high levels reported in doping controls in 1997–1998. In view of the well-documented noxious effects repeatedly observed after anabolic steroid intake, the confirmed procedure for reporting norsteroid abuse in sports is most important.

Le dopage par les androgènes est l’utilisation de substances dérivées ou apparentées à la testostérone à des fins d’amélioration de la performance sportive. Toute prise d’androgène est illégale de par la Loi du 28 Juin 89 relative au sport. Il n’existe pas, pour cette classe de substances, de justification thérapeutique possible. Le Comité Médical d’Éthique a confirmé cette décision légale en 1993.

The nuclear matrix (NM) is a salt and nuclease-resistant nuclear substructure. It is associated with active DNA transcription and has been shown to contain acceptor sites for steroid receptors in a number of specific target tissues. We have investigated the presence of acceptor sites for the androgen receptor (AR) in the NM of human newborn foreskin. The NM was prepared from the 800 g pellet by successive treatments with detergent, DNase and high salt extraction. It contained 13 ± 7% of total proteins and 10 ± 6% of total DNA. After extensive washing, the NM spheres were incubated in the presence of cytosol and [3H]methyltrienolone ± 200-fold excess of unlabeled steroid. Maximal binding of the AR to NM was reached in 30 min and decreased slightly thereafter to reach an equilibrium which was maintained for 18 h. Binding was saturable. In the absence of AR, the steroid did not bind to NM. When Scatohard analysis was performed on cytosol previously incubated with NM, cytosolic binding capacity significantly decreased relative to preincubation values (3.6 ± 1.9 to 1.3 ± 1.2 fmol/mg protein, P < 0.05, n = 6). In contrast, apparent binding affinity was not changed. 0.8 mg of NM protein could bind AR from 2.4 mg of cytosol protein. In conclusion, NM from human foreskin binds the AR with high affinity. This binding is rapid and is maintained for at least 18 h. This is consistent with a potential role of NM in the mechanism of action of androgens in their target tissues.

Urinary testosterone and 3 alpha-androstanediol (3 alpha diol G) glucuronides together with plasma testosterone, 5 alpha-dihydrotestosterone (DHT), and delta 4-androstenedione (delta 4) were measured in 43 normal young men (18-36 yr old), 23 elderly men without clinically evident prostatic pathology (54-89 yr old), 68 elderly men with benign prostatic hyperplasia (BPH group; 54-91 yr old), and 26 elderly men with well differentiated cancer of the prostate (K group; 63-97 yr old). Plasma testosterone decreased slightly with age in all 3 elderly groups (from 591 to 438, 479, and 444 ng/100 ml, respectively). Plasma DHT, on the contrary, was significantly (P less than 0.01) higher in the BPH group than in the other three groups (68 vs. 30, 37, and 32 ng/100 ml, respectively). Plasma delta 4 was significantly lower (P less than 0.01) in the elderly K group than in all other groups (59 vs. 109, 83, and 78 ng/100 ml, respectively). Urinary testosterone glucuronide decreased with age in all 3 elderly groups (from 109 to 55, 38, and 44 micrograms/24 h, respectively) as a result of decreased androgen production rates with age. All 3 elderly groups also had decreased urinary 3 alpha diol G, from 194 to 123, 55, and 118 micrograms/24 h, respectively. The group of elderly patients with BPH had the lowest mean urinary 3 alpha diol G excretion together with the highest mean plasma DHT. This low urinary 3 alpha diol G excretion, which reflects a decrease in both androgen production and DHT metabolism, suggests a decrease in 3 alpha-hydroxysteroid dehydrogenase activity, which, in turn, could explain the increased DHT availability and tissue retention in most target organs. Moreover, the extent of these modifications in androgen metabolism specific to the BPH condition raises the question of an overall alteration of androgen metabolism in patients with BPH which could be the cause of the disease.

We have measured the total (cytosolic plus nuclear) androgen binding capacity of pubic skin fibroblasts from nine patients with hirsutism of various origin. Confluent intact cell monolayers were incubated with increasing concentrations (0.05-2 nM) of [3H]dihydrotestosterone ([3H]DHT) with or without a 200-fold excess of unlabeled DHT. The androgen binding capacities (mean +/- SD) were similar in normal men (411 +/- 171 fmol/mg DNA), women (310 +/- 103 fmol/mg DNA), and hirsute patients (313 +/- 141 fmol/mg DNA) regardless of the plasma androgen levels. In contrast, the 5 alpha-reductase level in pubic skin fibroblasts (mean +/- SD) was, as previously described, higher in hirsute women (3.3 +/- 2.6 fmol/micrograms DNA . h) than in normal women (1.1 +/- 0.6 fmol/microgram DNA . h; P less than 0.05). We conclude from these data that: 1) increased androgen binding capacity cannot be held responsible for hypersensitivity to androgens in hirsutism; 2) the androgen receptor is not regulated by androgens in human skin, as similar levels are observed in men, women, and hirsute patients; 3) this contrasts with 5 alpha-reductase activity and emphasizes the importance of this enzyme as an amplifier of androgen action in areas where it is stimulated by androgens, such as pubic skin.

Estradiol and progesterone receptors (ER and PR) were studied in 46 breast fibroadenomas obtained at different periods of the menstrual cycle (n = 38) or from patients under combined estrogen-progestagen contraceptive (n = 4) or substitutive progestagen treatment for progesterone insufficiency (n = 4). Cytosolic and nuclear ER (ERc and ERn) increased throughout the follicular phase and were at their maximal level in the preovulatory phase. They decreased during the luteal phase. PR levels were high in the follicular phase, especially in the cytosol (PRc). PRc then decreased while nuclear progesterone receptor (PRn) increased at the beginning of the luteal phase. Thereafter, PRc and PRn decreased and remained low during the luteal phase. PRc and PRn levels in fibroadenomas from patients under estrogen-progestagen therapy were similar to those found during the luteal phase of untreated patients. In patients receiving a substitutive progestagen treatment to correct progesterone insufficiency, PRn was markedly higher than PRc. The existence of ER and PR in breast fibroadenomas and the variations in their levels during the menstrual cycle or under hormonal treatment provide valuable information on the hormone dependency of breast fibroadenoma.