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Nandrolone treatment decreases the level of rat kidney alpha(1B)-adrenoceptors.

Abuse of anabolic androgenic steroids (AAS) is associated with serious side effects, such as hypertension and fluid retention. Renal alpha(1)- and alpha(2)-adrenoceptors are implicated in the regulation of blood pressure and fluid balance. In the present study, the levels of renal alpha(1A)-, alpha(1B)-, alpha(2A)- and alpha(2B)-adrenoceptors, and spleen alpha(1B)-adrenoceptors, were quantified in tissue membranes from rats treated with the AAS nandrolone decanoate (15 mg/kg) for 14 days. The radioligands used were [(3)H]-prazosin and [(3)H]-RX821002. The nandrolone treatment caused a 50% reduction of kidney alpha(1B)-adrenoceptors (from 15 fmol/mg protein in control rats to 6.5 fmol/mg protein in treated rats). In contrast, the levels of kidney alpha(1A)-, alpha(2A)- and alpha(2B)-, and spleen alpha(1B)-adrenoceptors were unaffected. These results raise the possibility that a decreased level of kidney alpha(1B)-adrenoceptors may cause some of the effects observed on blood pressure and fluid balance in heavy abuse of AAS.

Adrenergic alpha-1 Receptor Antagonists↗

Comparison of the receptor binding properties of nandrolone and testosterone under in vitro and in vivo conditions.

Previous in vitro binding studies with androgen receptors in rat seminal vesicles (Toth M. and Zakar T., J. steroid Biochem. 17 (1982) 653-660) have shown that the difference in the effects of nandrolone (N) and testosterone (T) is caused by the fact that 5 alpha-reduction increases the affinity of T and decreases the affinity of N. We confirmed this result using androgen receptors in rat prostate and intact human MCF-7 cells. We also analysed the receptor binding properties of N, T, dihydronandrolone (DHN) and dihydrotestosterone (DHT) in vivo following a combined 2-h infusion of a physiological dose of [3H]T and the same dose of [3H]N in castrated male rats, which permitted a direct comparison of the accumulation of [3H]N, [3H]T, [3H]DHN and [3H]DHT in different sub-cellular fractions of various tissues. There was a considerable accumulation of radioactivity in the liver, but no retention of active compounds. In the prostate there was a preferential retention of [3H]DHT over [3H] DHN in the receptor fractions whereas in thymus, spleen and muscular tissues [3H]N and [3H]T were retained in equal amounts. The kidney showed a preferential retention of [3H]N over [3H]T. The present results explain the relatively strong effect of nandrolone compared to that of testosterone on target tissues devoid of 5 alpha-reductase activity (e.g. muscular tissue) compared to its relatively weak effect on tissues with a relatively high 5 alpha-reductase content (e.g. prostate).

Animals↗

Study of the metabolism of testosterone, nandrolone and estradiol in cattle.

The current metabolism study was undertaken to identify key analytes in urine, plasma and bile following testosterone, nandrolone and estradiol administrations to cull cows, heifers and steers. This information will be used to develop confirmatory analysis procedures. In the present study, mixtures (1:1) of testosterone, nandrolone or estradiol and their deuterium labelled analogues were administered to cull cows, heifers and steers. Two analogues of deuterium labelled testosterone were synthesised and administered, to facilitate identification of metabolites. Following administration, urine, plasma and bile samples were collected and subjected to solid phase extraction. The extracts were derivatised and analysed by GC-MS. The major analytes derived from the administered steroids were identified on the basis of the twin ion peaks produced for their non-labelled and deuterium labelled analogues and their stereochemistries determined by comparison of retention times with appropriate reference standards. Using suitable internal markers, excretion profiles for the major analytes in urine and plasma have been determined and levels in isolated bile samples estimated. This work is on-going, and this paper is a summary of some of the studies completed to date.

Animals↗

Anabolic steroid (nandrolone) treatment during adolescence decreases the number of glucocorticoid and estrogen receptors in adult female rats.

The density of thymic glucocorticoid receptors and the density of uterus estrogen receptors (I) decreased significantly in adult female Wistar rats following nandrolone treatment at the age of six and seven weeks. There was no significant alteration of thymic glucocorticoid receptor density in males. Affinity of glucocorticoid and estrogen receptors did not differ from the controls significantly. The results demonstrate that the receptors of immature cells can be imprinted in adolescence similarly to those in the perinatal period and chemical substances capable of binding to the immature receptors can result in prolonged alteration of their binding character. This phenomenon should be taken into consideration especially in the case of nandrolone administration which can be used as a doping substance.

Animals↗

The diffusion of nandrolone through hydrated human cadaver skin.

Effective diffusion constants have been determined for the permeation of nandrolone through whole and stripped human abdominal cadaver skin in vitro. From the values obtained, the diffusion constant for nandrolone in the stratum corneum has been inferred. The experimental approach used yields reproducible results for skin samples taken from a single individual. There is also a surprising degree of uniformity in the values obtained for skin from different individuals.

Cadaver↗

The effect of intracutaneous injections of micronized crystalline suspensions of nandrolone phenyl-propionate in the skin of female hairless hamsters.

Single intracutaneous injections of micronized crystalline suspensions of nandrolone phenylpro-pionate have been shown to induce local thickening of the epidermis of female hairless hamsters, accompanied by a marked increase in sebaceous gland volume over a period of 7 days. It is known that certain materials, when injected intracutaneously, may produce a diffuse inflammatory response in the dermis which in turn causes hyperplasia in the adjacent epidermis. The response observed in the present case, however, is clearly specific to nandrolone phenylpropionate, and cannot be attributed to an inflammatory response of the dermis to intracutaneously injected crystalline material.

Animals↗

Effects of nandrolone phenylpropionate in the horse: (3) skeletal muscle composition in the exercising animal.

The effect of 11 weekly injections of nandrolone phenylpropionate (400 mg) on some skeletal muscle parameters was investigated in 6 Thoroughbred geldings undergoing training. Three muscles were sampled, the middle gluteal, the biceps femoris and the semitendinosus. Training alone produced increases in the percentage of fast twitch high oxidative fibres (FTH), glycogen content and the activities of citrate synthase, 3-hydroxyacl CoA dehydrogenase and cytochrome oxidase. In contrast the training programme did not alter water content, total protein content, the activities of lactate dehydrogenase, phosphofructokinase of beta glucuronidase, fibre area ratios or the number of capillaries per unit fibre area. Nandrolone phenylpropionate given in conjunction with the training programme only resulted in changes in 2 of these parameters. There was no increase in the percentage of FTH fibres in the biceps femoris with anaerobic training and the fibre area ratio increased significantly in this muscle.

Anabolic Agents↗

Anabolic and androgenic activities, in rat, of some nandrolone and androstanolone esters.

The anabolic and androgenic activities of the formate to undecanoate esters of nandrolone and formate to valerate esters of androstanolone, after intramuscular injection, have been determined in rat. The response to a given dose was measured as cumulative weight (the area under the plot of weight of indicator organ against time). Levator anus muscle was used to assess anabolic activity, and the sum of the cumulative weight for prostate and seminal vesicles for androgenic activity. Log dose-log cumulative weights plots were parallel, and biological activities were expressed as the cumulative weight corresponding to a 2 muM dose, calculated from the regression lines. Anabolic-androgenic ratios for both series were calculated and were found to be minimum in the region of the propionate and butyrate. The anabolic-androgenic ratios of the nandrolone esters continued to increase after the minimum, as the series ascended. This method is believed to give a reliable assessment of anabolic and androgenic activities of steroid esters.

Anabolic Agents↗

The diffusion of nandrolone through occluded and non-occluded human skin.

Diffusion constants have been measured for nandrolone in human cadaver skin in vitro under conditions which approximate to both the occluded and non-occluded topical therapeutic situation. The results suggest that occlusion affects the diffusion parameters only marginally, if at all, but appears to reduce the ability of the stratum corneum to "irreversibly" bind a fraction of the applied dose. Studies of nandrolone diffusion in freshly excised human epidermis yield similar results to those from measurements on cadaver skin, and it has also been found that epidermal samples excised from non-involved sites of human psoriatic patients behave under these conditions in essentially the same way as normal epidermis.

Cadaver↗

Body mass reduction markedly improves muscle performance and body composition in obese females aged 61-75 years: comparison between the effects exerted by energy-restricted diet plus moderate aerobic-strength training alone or associated with rGH or nandrolone undecanoate.

OBJECTIVE: To investigate the effectiveness of a body mass reduction programme entailing diet caloric restriction and moderate physical activity with or without supplementary treatment with recombinant (r) GH or steroids to improve body composition and muscle performance in severely obese women aged 61-75 years. METHODS: Twenty women were randomly assigned to one of three groups: body mass reduction alone; body mass reduction plus rGH; body mass reduction plus nandrolone undecanoate. Body composition, isotonic muscle strength and anaerobic power output during jumping were determined before and after the 3-week period. RESULTS: Whatever the experimental group considered, body mass (P<0.01), body mass index (P<0.05) and fat mass (P<0.05) decreased significantly, whereas muscle strength and power increased significantly (P<0.05) after the intervention. CONCLUSION: Small body mass reductions after 3 weeks of energy-restricted diet combined with moderate aerobic and strength exercise are associated with significant improvements in upper and lower limb muscle strength and power and reduction of fat mass in severely obese women aged 61-75 years. Although the association of rGH or nandrolone undecanoate does not appear to exert additional effects on body composition and muscle performance attained by body mass reduction alone, further additional studies with larger study groups, different dosages and more prolonged periods are required for definitive conclusions to be drawn.

Aged↗

[Effects of nandrolone phenylpropionate on the expression level of pro alpha 1 (I) collagen after burn in rats].

OBJECTIVE: To explore the effects of nandrolone phenylpropionate (NP) on the expression level of pro alpha 1 (I) collagen after burn in rats and the possible mechanism involved in the process. METHODS: Thirty-two Wistar rats with a deep second-degree scald injury and 20% of total body surface area were randomly divided into two groups to receive either 5 mg/kg NP(NP group) or normal saline (control group) every other day. We analyzed the mean integrated optical density(mIOD) of androgen receptor (AR) to determine the distribution and expression of AR in fibroblasts by immunohistochemistry, and measured expression level of pro alpha 1 (I) collagen mRNA by quantitative fluorescent RT-PCR to find the relation between expressions of AR and pro alpha 1 (I) collagen mRNA. The total specimens were obtained from the scalded rats after 4, 7, 14 and 21 of after burn. RESULTS: The expression of pro alpha 1 (I) collagen mRNA in NP group was significantly higher than that in control group on the 7th, 14th and 21st days(P < 0.05), but there was no significant difference on the 4th day. The density of AR in fibroblasts had significant difference (P < 0.05) between the two groups after 4, 7, 14 and 21 days. A positive relationship existed between the expression of pro alpha 1 (I) collagen mRNA and quantity of AR in fibroblasts(r = 0.836). CONCLUSION: The nandrolone phenylpropionate increased the expression of pro alpha 1 (I) collagen mRNA and enhanced the density of AR in fibroblasts. The higher expression of pro alpha 1 (I) collagen mRNA had a relation with the change of quantity of AR in fibroblasts.

Animals↗

[The effects of nandrolone phenylpropionate on androgen receptor of liver and sexual glands in burned rats].

OBJECTIVE: To assess the effects of nandrolone phenylpropionate (NP) on androgen receptor (AR) of liver and sexual glands in burned rats for supporting the clinical application of anabolic steroids. METHODS: Thirty-two Wistar rats with a deep second-degree cutaneous burn of 20% total body surface area were randomly divided into two groups to receive either 5 mg/kg NP (NP group) or normal saline as placebo (control group) every other day. The mean integrated optical density (mIOD) of androgen receptor (AR) in liver, testis, ovary tissues were measured by immunohistochemistry ENVISION and LSAB respectively on the 4th, 7th, 14th and 21st days after scalding. RESULTS: The density of AR in liver tissue in NP group was higher than that in control group (P < 0.05). The density of AR in testis and ovary tissues showed no significant difference between NP group and control group at every time-point (P > 0.05). The side-effect of NP at this dose level on sexual glands seemed limited. CONCLUSION: Nandrolone phenylpropionate up-regulated the density of AR in liver tissue, whereas it had no significant effects on the density of AR in testis and ovary tissues. NP was used with safety at this dose level in rats.

Animals↗

[Effect of nandrolone phenylpropionate on expression of hepatic albumin-mRNA and androgen receptor in burned rats].

OBJECTIVE: To study the mechanism of nandrolone phenylpropionate (NP) on hepatic albumin mRNA and androgen receptor(AR) in burned rats. METHODS: Thirty-two Wistar rats with a deep second-degree cutaneous burn of 20% total body surface area were randomly divided into two groups: NP group (experimental group, 5 mg/kg NP) and normal saline as control group every other day. The expression copy quantity of albumin-mRNA and mean integrated absorbency(mIA) of AR in liver tissue were measured by quantitative fluorescent RT-PCR and immunohistochemistry respectively on the 4th, 7th, 14th and 21st days of post-burned. RESULTS: The expression levels of albumin-mRNA and AR in liver tissue in NP group were much higher than those in control group. The albumin-mRNA and AR expression increased significantly (P < 0.05) after 7 and 14 days, while the expression had no significant difference between NP group and control group on the 4th day. A positive correlation occurred between the expression level of albumin-mRNA and the quantity of AR in liver tissue(r = 0.936, P < 0.05). CONCLUSION: Nandrolone phenylpropionate up-regulated respectively the expression of albumin-mRNA and the density of AR in liver tissue.

Albumins↗

[Effect of nandrolone phenylpropionate on hepatic albumin mRNA and granulational alpha 1(I) procollagen mRNA in burned rats].

OBJECTIVE: To assess the mechanism for the effect of nandrolone phenypropionate (NP) on hepatic albumin mRNA and granulational alpha 1(I) procollagen mRNA in burned rats with the aim to underpin the clinical application of anabolic steroids. METHODS: Thirty-two Wistar rats with a deep second-degree cutaneous burn of 20% total body surface area were randomly divided into two groups to receive either 5 mg/kg NP (NP group) or normal saline as placebo(control group) every other day. The expression copy quantities of albumin-mRNA in liver tissue and alpha 1 (I) procollagen mRNA in granulation wound were measured by quantitative fluorescent RT-PCR respectively on the post-burned days 4, 7, 14 and 21. RESULTS: The expression levels of albumin-mRNA and alpha 1 (I) procollagen mRNA in NP group were much higher than those in control group. The 7th and 14th days were the periods in which the albumin-mRNA and alpha 1 (I) procollagen mRNA expression had been increasing obviously (P < 0.01). CONCLUSION: Nandrolone phenylpropionate could effectively up-regulate the expression of albumin-mRNA in liver tissue and the alpha 1 (I) procollagen mRNA in granulation wound.

Albumins↗

[Effects of nandrolone phenylpropionate on fibroblasts after injury in rats].

OBJECTIVE: To explore the effects of nandrolone phenylpropionate (NP) on fibroblasts after injury in rats. METHODS: Thirty-two Wistar rats with a deep second-degree scald injury and 20% total body surface area were randomly divided into two groups to receive either 5 mg/kg NP (NP group) or normal saline as placebo (control group) every other day. Integrated optical density (IOD) of androgen receptor (AR) and mRNA expression level of alpha1 (I) procollagen were measured by immunohistochemistry and quantitive fluorescent RT-PCR individually on the post-burn days 4, 7, 14 and 21. Fibroblasts were isolated from granulation tissue of a Wistar rat and were cultured in RPMI1640 with the addition of NP at different concentrations. Cell viability of fibroblasts was measured by MTT test, and the proliferative index, by flow cytometry (FCM). RESULTS: (1) Compared with the A value of the concurrent control group, higher A values were seen in NP groups containing different concentrations of NP, and significant difference of proliferative index was observed in NP group, P<0.05. (2) The expression of alpha1 (I) procollagen mRNA in NP groups was much higher than that in control groups. A significant difference between the two groups was noted on the post-burn days 7, 14 and 21, P<0.05, but no difference was seen on day 4. (3) The density of AR on fibroblasts in NP group was higher than that in control group at each time point. And a positive correlation between the expression of alpha1 (I) procollagen mRNA and the quantity of AR on fibroblasats was confirmed (r = 0.836). CONCLUSION: Nandrolone phenylpropionate could promote fibroblast replication, increase the mRNA level of alpha1 (I) procollagen and enhance the density of AR on fibroblasts.

Anabolic Agents↗

Analysis of nandrolone esters in oily injections by reversed-phase high-performance liquid chromatography.

A specific liquid chromatographic (HPLC) procedure is presented for the analysis of nandrolone esters (phenylpropionate, decanoate and undecanoate) in commercial oily injections. The analysis was carried out under isocratic, reversed-phase (RP8 column) conditions using a UV detector (240 nm). The system discriminates between nandrolone alcohol, a potential impurity, and its esters and permits the quantitation of trace benzaldehyde derived from the oxidative degradation of benzyl alcohol. The proposed HPLC method was found to be more specific and accurate than the pharmacopoeial spectrophotometric assay procedure (isoniazid reagent). The interference of benzaldehyde with the isoniazid method was also investigated.

Journal Article↗

Hormonal treatment of advanced breast cancer. A randomized trial of tamoxifen versus nandrolone decanoate.

The response to tamoxifen (TAM) (10 mg to 20 mg twice orally) was compared with the response to nandrolone decanoate (NAN) (50 mg every second week or 100 mg every third week intramuscularly) in this randomized study in previously untreated women with advanced breast cancer. Patients were postmenopausal or postmenopause was induced with irradiation therapy. The two treatment groups were highly similar in different patient characteristics. Of 67 evaluable patients treated with TAM, ten (15%) had a complete or partial remission, 28 (42%) had stabilized disease and 29 (43%) had progressive disease. In the 60 patients treated with NAN, the figures were ten (17%), 22 (37%) and 28 (47%) respectively. The response rates did not differ significantly. Tam was as good as NAN in osseous metastases. Four of 34 patients responded to TAM and three of 38 patients responded to NAN. NAN had a tendency for better response in the treatment of visceral metastases. Six (43%) of 14 patients responded to NAN while only three (14%) of 21 responded to TAM (P = 0.11). The median duration of remission was 24 months in the TAM arm and 17 months in NAN (insignificant). As second line treatment, NAN after TAM gave one complete remission and three partial remissions, but none responded to TAM after NAN. The side-effects of both drugs were rare and mild. These data indicate that TAM and NAN are comparable in the treatment of advanced breast cancer.

Breast Neoplasms↗

Successful treatment of severe refractory aplastic anemia with 3-beta etiocholanolone and nandrolone decanoate.

A patient with aplastic anemia, who had been unresponsive to androgens, antithymocyte globulin, high-dose methylprednisolone, and cyclosporine, responded to treatment with 3-beta-etiocholanolone, nandrolone decanoate, and prednisolone acetate. Six months following initiation of therapy, she became red cell and platelet transfusion independent with neutrophils persistently over 1,000/microliters. A sustained partial remission has persisted for over 2 years. This observation suggests that a combined hematostimulatory approach may be of benefit, even in patients with long-standing refractory aplasia.

Anemia, Aplastic↗