Methyltestosterone Research Articles

Sex hormones affect the production of recombinant Factor IX in CHO and HEK-293 cell lines

Recombinant human Factor IX (rFIX) was cloned in a mammalian expression vector and transfected into CHO and HEK-293. Treatment with 10(-9) M methyl testosterone increased rFIX production by 30-50% in CHO and HEK clones. However, 10(-9) M 17beta-oestradiol increased production of rFIX by ~50% in CHO-F7 clone and decreased production by 48% and 37% in CHO-F8 and HEK-F2-6, respectively. Progesterone treatment inhibited rFIX production in both cell lines. Production of rFIX can thus be increased by sex hormone treatment and therefore used to enhance biotechnological production in mammalian cells.

Using the Protein Chip to Screen Agonists and Antagonists of the Androgen Receptor

Based on its important physical and pathological function, the androgen receptor (AR) is regarded as a significant drug target. In this report, the authors describe a novel strategy of protein chip technology to screen agonists and antagonists of AR. First, the AR ligand binding domain (AR-LBD) was expressed in Escherichia coli, purified, and then immobilized on a silane-polysaccharide surface of a protein chip. Second, the affinities of methyltestosterone (MT) and fluorescent-labeled testosterone for the AR-LBD protein chip were determined. Third, a converse strategy of the protein chip was tested to evaluate its reliability as a drug screening method. Fourth, a 10,067-compound library was screened to find new ligands of AR. From the results, the K(d) of testosterone and the IC(50) of MT are consistent with the literature (0.61 vs. 0.49 nM 2.88 vs. 3.90 nM, respectively). The Z' factor of the high-throughput screening (HTS) method was 0.76, which meets the requirement of drug screening (>0.4). Finally, 3 active ligands of AR were identified with their IC( 50) values of 3.63, 2.19, and 1.71 microM, respectively. In summary, the novel strategy of the AR-LBD protein chip was suitable for HTS at the molecular level.

The effects of methyltestosterone on the sexual development and reproduction of adult medaka ( Oryzias latipes)

We examined the effects of methyltestosterone (MT) on the reproduction of medaka ( Oryzias latipes). Six mating pairs of medaka were exposed for 3 weeks to MT at the measured concentrations of 22.5, 46.8, 88.1, 188, and 380 ng/L. The fecundity and fertility of paired medaka were significantly decreased in the 46.8, 88.1, 188, and 380 ng/L MT groups compared with those of controls. The gonadosomatic indices of female fish exposed to ≥46.8 ng/L were increased significantly. Gonadal histology showed degeneration of oocytes in the ovaries of fish in all MT treatment groups. Hepatic vitellogenin concentrations were significantly decreased in female fish treated with MT at 188 and 380 ng/L, and the hatchability and survival rate of the offspring were decreased in all MT treatment groups. These results clearly demonstrate that MT at ≥46.8 ng/L inhibited gonadal development and adversely affected the reproduction of medaka.

Exposure of the eggs to 17α-methyl testosterone reduced hatching success and growth and elicited teratogenic effects in postembryonic life stages of crayfish

Testosterone is regularly found in the tissues of decapod crustaceans. Although this vertebrate-type sex hormone is not the principal factor of sex differentiation in crustaceans, it was shown to be capable of acting on the reproductive organs of shrimps and crabs. In the present study I have exposed developing eggs and stage 5 juveniles of the parthenogenetic all female marbled crayfish to 17α-methyl testosterone in order to test whether in freshwater crayfish sex can be changed from female to male by this androgen. MT did not elicit sex change, neither when administered during embryonic development nor during juvenile stage 5, the main period of proliferation of the oocytes. However, exposure to 100 μg/L MT from 64% to 84% embryonic development resulted in prolonged embryonic development, reduced hatching success, reduced growth of the juveniles, and severe malformations of the appendages in the juveniles. The marbled crayfish is recommended to be considered for toxicity tests due to its easy culture in the laboratory and its genotypical uniformity.

P.1.c.006 Effect of the ghrelin agonist, CP-464709, on Atlantis watermaze performance

Recent research on the impact of testosterone (T) on female sexual function has yielded inconsistent results, and few studies have used physiological measures of genital arousal.This study examined the effects of an acute dose of methyltestosterone (MT) on physiological (genital) and subjective sexual response in postmenopausal women.Vaginal pulse amplitude (VPA) and self-reported sexual response.Randomized, double-blind, crossover, placebo-controlled trial of 5 mg MT, consisting of two separate 8-hour visits. Participants were 10 postmenopausal women without sexual dysfunction. Participants viewed both neutral and erotic video segments during five post-dose trials while their genital and subjective responses were monitored.The Wilcoxon signed rank test indicated a significant difference in VPA between the T (M = 0.018, SD = 0.018) and placebo (M = 0.016, SD = 0.017) conditions at 4.5 hours post-dose (P = 0.03). Higher difference scores were noted for 80% of subjects during the T condition at 4.5 hours, in contrast with only 50% of subjects responding to T at the other four time points. No differences were found on VPA relative change scores or subjective sexual arousal scores. When summed across all five time points, genital and subjective measures were correlated regardless of medication condition (0.62 and 0.60 for self-reported physical and mental sexual arousal scores, respectively).These findings in postmenopausal women combined with those of two previous investigations in premenopausal women demonstrate a probable acute-dose time delay for genital sexual effects of exogenous T with no change in self-reported sexual arousal. Further investigation is needed to determine whether acute dosing of T has a consistent and predictable impact on genital arousal that has promise for the treatment of any subgroup of women with sexual disorders. Heard-Davison A, Heiman JR, and Kuffel S. Genital and subjective measurement of the time course effects of an acute dose of testosterone vs. placebo in postmenopausal women. J Sex Med 2007;4:209–217.

Exposure to TBT increases accumulation of lipids and alters fatty acid homeostasis in the ramshorn snail Marisa cornuarietis

Recent studies have shown that organotin compounds affect lipid homeostasis in vertebrates, probably through interaction with RXR and/or PPARγ receptors. Molluscs are sensitive species to the toxic effects of tributyltin (TBT), particularly to masculinization, and TBT has been recently shown to bind to molluscs RXR. Thus, we hypothesized that exposure to TBT could affect lipid homeostasis in the ramshorn snail Marisa cornuarietis. For comparative purposes, the synthetic androgen methyl-testosterone (MT) was included in the study due to its masculinization effects, but its lack of binding to the RXR receptor. M. cornuarietis was exposed to different concentrations of TBT (30, 125, 500 ng/L as Sn) and MT (30, 300 ng/L) for 100 days. Females exposed to 500 ng/L TBT showed increased percentage of lipids and increased levels of fatty acids in the digestive gland/gonad complex (2- to 3-fold). In addition, fatty acid profiles were altered in both males and females exposed to 125 and 500 ng/L TBT. These effects were not observed in females exposed to MT. Overall, this work suggest that TBT acts as a potent inducer of lipid and fatty acid accumulation in M. cornuarietis as shown in vertebrate studies earlier, and that sex differences in sensitivity do exist.

Diploid sperm produced by artificially sex‐reversed Clone loaches

Clone loaches reproduce unisexually in a wild population of Hokkaido Island, Japan. These clone loaches produce genetically identical unreduced eggs which develop to diploid individuals without any genetic contribution of sperm donors. In the present study, sex reversal of clone loaches was attempted and the reproductive potential of resultant clone males was examined. Clone loaches administered 0.5 ppm of 17-alpha methyltestosterone (MT) for 30 days from 1 month after hatching differentiated into physiological males. These sex-reversed clone males produced fertile spermatozoa with a diploid DNA content. Diploid spermatozoa had significantly larger heads than normal haploid sperm, but had a normal shape showing a head, mid-piece, and tail. The motility of diploid spermatozoa was low after ambient water was added. Concentration of diploid spermatozoa per unit of sperm was lower than that of control haploid spermatozoa. Microsatellite genotyping revealed that triploid progeny from the cross between a normal diploid female and a sex-reversed clone male had two alleles specific to the diploid clone male and one allele of the mother loach. These results indicated that the sex-reversed clone males produced fertile diploid spermatozoa genetically identical to the clone lineage.

Prosobranch snails as test organisms for the assessment of endocrine active chemicals––an overview and a guideline proposal for a reproduction test with the freshwater mudsnail Potamopyrgus antipodarum

Recently, prosobranch snails have been recommended as promising candidates for test organisms for the assessment of endocrine active chemicals. Three prosobranch snail species, the freshwater mudsnail Potamopyrgus antipodarum, the freshwater ramshorn snail Marisa cornuarietis, and the marine netted whelk Nassarius reticulatus are portrayed and their respective biotests are presented together with results of laboratory experiments and biological effect monitoring surveys in the field. All characterized species are highly sensitive toward xeno-androgens [triphenyltin (TPT), tributyltin (TBT), methyltestosterone (MT) and fenarimol (FEN)], and xeno-estrogens [bisphenol A (BPA), octylphenol (OP), ethinylestradiol], and show effects at environmentally relevant, rather low concentrations in laboratory experiments. For exposure to the xeno-androgen TPT, EC(10) values range between 15.9 and 29.0 ng as Sn/L (sediment 0.03 mug as Sn/kg), for TBT, EC(10) values are found between 3.42 and 37.8 ng as Sn/L (sediment 2.98 microg as Sn/kg) and effect concentrations for FEN are calculated as 18.6 ng/L (EC(10)) and 0.19 microg/kg (EC(50) sediment; EC(10) not calculable). Exposure to xeno-estrogens yielded EC(10 )values of 13.9 ng/L (0.19 microg/kg) for BPA, a NOEC of <1 microg/L (EC(10) of 0.004 microg/kg) for OP and a NOEC of 1 ng/l (EC(10) sediment of 2.2 microg/kg) for ethinylestradiol. Responses to androgens comprised the development of imposex and the reduction of fertility or embryo production, effects of estrogens included the stimulation of egg production and embryo production, and the increased weight of glands. Also, biological effect monitoring studies with P. antipodarum and N. reticulatus in several rivers or estuarine areas revealed the capacity of the biotests to detect an androgenic or estrogenic potential of sediment samples. A comparison of the three test species with regard to sensitivity and practical aspects in routine application favors the freshwater mudsnail P. antipodarum for a standardized procedure, and this reproduction test will be introduced into the OECD guideline program for standardization in the near future.

Endocrine disruption in aquatic pulmonate molluscs: few evidences, many challenges

As compared to other groups of aquatic gastropods, documented examples of endocrine disruption in pulmonates are rather limited. This is quite surprising because the endocrine control of physiological functions has been extensively studied in these animals. In the model-species Lymnaea stagnalis, the neurohormonal regulation of reproduction has been thoroughly investigated, and the primary structure of several peptides and receptors involved in endocrine processes has been established. However, the use of this knowledge has been fairly limited in the context of ecotoxicology, to investigate the effects of endocrine-disrupting chemicals. The present review summarizes the main and more recent findings on the neuroendocrine control of reproduction in aquatic pulmonate snails (Basommatophora). It then comprehensively describes selected in vivo laboratory and semi-field studies which provide evidence for possible endocrine disrupting effects of estrogenic and androgenic test compounds [e.g., ethynylestradiol, methyltestosterone (MT)], and of environmental contaminants [e.g., cadmium (Cd), tributyltin (TBT), and nonylphenol (NP), pesticides]. Finally, challenging perspectives for future research are discussed.

Genital and Subjective Measurement of the Time Course Effects of an Acute Dose of Testosterone vs. Placebo in Postmenopausal Women

Recent research on the impact of testosterone (T) on female sexual function has yielded inconsistent results, and few studies have used physiological measures of genital arousal. This study examined the effects of an acute dose of methyltestosterone (MT) on physiological (genital) and subjective sexual response in postmenopausal women. Vaginal pulse amplitude (VPA) and self-reported sexual response. Randomized, double-blind, crossover, placebo-controlled trial of 5 mg MT, consisting of two separate 8-hour visits. Participants were 10 postmenopausal women without sexual dysfunction. Participants viewed both neutral and erotic video segments during five post-dose trials while their genital and subjective responses were monitored. The Wilcoxon signed rank test indicated a significant difference in VPA between the T (M = 0.018, SD = 0.018) and placebo (M = 0.016, SD = 0.017) conditions at 4.5 hours post-dose (P = 0.03). Higher difference scores were noted for 80% of subjects during the T condition at 4.5 hours, in contrast with only 50% of subjects responding to T at the other four time points. No differences were found on VPA relative change scores or subjective sexual arousal scores. When summed across all five time points, genital and subjective measures were correlated regardless of medication condition (0.62 and 0.60 for self-reported physical and mental sexual arousal scores, respectively). These findings in postmenopausal women combined with those of two previous investigations in premenopausal women demonstrate a probable acute-dose time delay for genital sexual effects of exogenous T with no change in self-reported sexual arousal. Further investigation is needed to determine whether acute dosing of T has a consistent and predictable impact on genital arousal that has promise for the treatment of any subgroup of women with sexual disorders.

Effect of 17α-Methyltestosterone Hormone Manipulation in Various Water Temperatures on Sex Ratio of Guppy (Poecilia reticulata Peters)

&lt;p&gt;This study was conducted to determine percentage of male progeny of guppy (&lt;em&gt;Poecila reticulata&lt;/em&gt; Peters) broodstock immersed in water containing various dose of 17α-Methyltestosterone (MT) and different temperature. Immersion of broodstock was carried out at 10&lt;sup&gt;th&lt;/sup&gt; day after spawning. Dosage of MT used was 0, 0.5 and 1 mg per liter of water, while the water temperature was 27, 30 and 33&lt;sup&gt;o&lt;/sup&gt;C, for 24 hours immersion. The result of study showed that the combination of hormone treatment 1mg/L and temperature 27&lt;sup&gt;o&lt;/sup&gt;C produced higher percentage of male progeny (92.7%). Increasing water temperature in combination with dose of hormone treatment can reduce percentage of male progeny.&lt;/p&gt; &lt;p&gt;Keywords: guppy, &lt;em&gt;Poecilia reticulata&lt;/em&gt;, 17α-Methyltestosterone, temperature, sex reversal, monosex&lt;/p&gt; &lt;p&gt; &lt;/p&gt; &lt;p&gt;ABSTRAK&lt;/p&gt; &lt;p&gt;Penelitian ini dilakukan untuk mengetahui nisbah kelamin jantan keturunan induk ikan gapi (&lt;em&gt;Poecila reticulata&lt;/em&gt; Peters) yang telah direndam hormon 17α-Metiltestosteron (MT) dengan berbagai tingkatan dosis yang dikombinasikan dengan temperatur air yang berbeda-beda. Perendaman induk dilakukan pada hari kesepuluh setelah pemijahan. Dosis hormon yang digunakan adalah 0, 0,5 dan 1 mg/L air, sementara suhu air perendaman adalah 27&lt;sup&gt;o&lt;/sup&gt;C, 30&lt;sup&gt;o&lt;/sup&gt;C dan 33&lt;sup&gt;o&lt;/sup&gt;C, dengan lama perendaman 24 jam. Hasil penelitian menunjukkan bahwa kombinasi perlakuan hormon 1 mg/L dengan temperatur 27ºC menghasilkan rataan persentase ikan gapi kelamin jantan tertinggi yaitu 92,7%. Peningkatan temperatur yang dikombinasikan dengan dosis hormon ternyata mengakibatkan penurunan persentase anak berkelamin jantan.&lt;/p&gt; &lt;p&gt;Kata kunci: ikan gapi, &lt;em&gt;Poecilia retiulata&lt;/em&gt;, 17α-Metiltestosteron, temperatur, seks reversal, monoseks&lt;/p&gt;

Molecular cloning, expression and phylogenetic analyses of parvalbumin in tilapia, Oreochromis mossambicus

The gene expression of parvalbumin (Pvalb), a high-affinity calcium-binding protein and the major fish allergen, was significantly increased in the tilapia fry treated with methyltestosterone (MT) as examined using a subtractive hybridization assay. Using the real-time quantitative PCR, we further confirmed the increased Pvalb expression in the MT-treated tilapia fry. The 568 base pairs (bp) tilapia Pvalb (tPvalb) cDNA clone was fully sequenced and found to contain a coding region of 330 bp, which encodes a 108 amino acids protein with a molecular weight of 11,370.5 and an calculated isoelectric point of 4.56. The predicted secondary structure of tPvalb is comprised of seven alpha helices. It contains two characteristic EF-hand calcium-binding motifs, one PKC and five casein kinase II consensus phosphorylation sites. The tPvalb is highly homologous to the selected fish Pvalbs at a similarity ranging from 53% to 80%. The phylogenetic tree analysis showed that the tPvalb is closest to the Scomber japonicus Pvalb. The tPvalb was found to express in the heart, muscle, gill, kidney, brain and ovary of adult fish by RT-PCR analysis. In situ hybridization also revealed that the tPvalb was highly expressed in the hypothalamus and sarcoplasmic reticulum. A tPvalb glutathione S-transferase (GST) fusion protein was generated and digested by thrombin to remove the GST moiety. Further Western analysis showed that the tPvalb protein was cross-reacted to an anti-rat Pvalb antibody. Those results suggest that Pvalb is evolutionally conserved in tilapia.

Determination of the androgenic potency of whole effluents using mosquitofish and trout bioassays

This study combined bioassay-derived and direct chemical analysis of steroidal compounds in pulp and paper and municipal sewage effluent in order to determine the cause of masculinization of female mosquitofish. The bioassays used in this study consisted of androgen and estrogen receptor binding, and aromatase inhibition using tissues from rainbow trout. This study observed no masculinization of female mosquitofish from a pulp and paper mill effluent that was previously observed to cause this effect. Mosquitofish sampled from the receiving environment of the same mill verified that masculinization was not occurring in the wild. The municipal sewage effluent also had no masculinizing effect. In vitro bioassays indicated significant sources of both androgens and estrogens in the effluents tested with sewage effluent having both the highest estradiol (41 ng/L) and testosterone (182 ng/L) equivalent concentration. These results could not be attributed to any particular compounds measured in the effluents. Two compounds implicated in the masculinization of mosquitofish by pulp and paper effluent, androstenedione and androstadienedione required relatively large (10–100 μg/L) waterborne concentrations to elicit a masculinizing effect and neither of these compounds are likely to occur at levels this high in the natural environment. The potent aromatase inhibitor, 4-hydroxyandrostenedione also did not cause masculinization at 100 μg/L indicating that masculinization did not occur through this mechanism. The mammalian anti-androgen, cyproterone acetate was only partially effective in mosquitofish and reduced the severity of masculinization in the presence of methyl testosterone. While neither effluent masculinized mosquitofish, there was a significant reduction of in vitro ovarian steroid production with the most severe effects observed with the sewage effluent. Overall, this study found the disappearance of a masculinizing effect that had been previously observed; concluded that based on 21 days aqueous exposures androstenedione and androstadienedione are not likely candidates for mosquitofish masculinization, and showed that masculinization and in vitro steroid production are unrelated biological endpoints.

Anabolic androgenic steroid abuse and mood disorder: a case report

Current data suggest that the use of anabolic androgenic steroids (AAS) has become quite common among athletes, bodybuilders, as well as adolescents and young adults who want to increase their muscle mass for aesthetic or athletic reasons. Commonly used anabolic steroids are the oral 17α alkyl derivatives of testosterone (methyl testosterone, oxymetholone, oxandrolone, stanozolol) and the intramuscular 17β-esterified agents such as nandrolone decaonate, nandrolone phenpropionate, testosterone cypionate and testosterone propionate (Blue and Lombardo, 1999). The abuse of AAS has been associated with various psychiatric manifestations: sleep disorders, anxiety, labile mood, mania, depression, irritability, aggression, violence, suicidal and homicidal ideation and behaviour, psychosis, confusion and delirium. Long-term abuse may lead to the development of a dependence syndrome and associated withdrawal symptoms on attempted discontinuation (Hall et al., 2005; NIDA, 2006).

The benefits of androgens combined with hormone replacement therapy regarding to patients with postmenopausal sexual symptoms

Objective To evaluate the benefits and risks of hormone replacement therapy (HRT) combined with methyltestosterone (MT) in postmenopausal women with sexual dysfunction. Design This study was a randomized, double-blind, placebo-controlled and crossover trial. Eighty-five women using HRT were divided into four treatment groups: GI–HRT plus placebo for 4 months; GII–HRT plus MT 2.5 mg/day for 4 months; GIII–HRT plus placebo for 2 months and then replaced with HRT plus MT 2.5 mg/day for 2 months; GIV–HRT plus MT 2.5 mg/day and then replaced with HRT plus placebo for 2 months. Blood was collected at baseline, after 2 months (T1) and 4 months (T2) of treatment for hormone determinations of estradiol, FSH, total and free testosterone, GOT, GPT, glucose, total and fractions of cholesterol and triglycerides. All participants answered clinical questions and a validated questionnaire of modified McCoy's sex scale. Results The association of HRT with MT 2.5 mg/day did not significantly change liver enzymes or increase cardiovascular risk factors. The patients of GII, GIIII and GIV when using MT presented amelioration of sex symptoms, mainly satisfaction and desire ( p < 0.01); however, GIII at T1 (1.3 ± 0.3) presented similar problem score results as compared to GIII at T2 (1.5 ± 0.6). Conclusion All data suggest that combined HRT-androgen therapy may be beneficial for postmenopausal women receiving HRT who continue to complain of sexual difficulties or for postmenopausal women with sexual complaints who are not undergoing estrogen therapy.

Central effects of the anabolic steroid 17α methyltestosterone in female anxiety

The androgen 17α-methyltestosterone (17α-meT) is one of the most commonly abused anabolic androgenic steroids (AAS). We assessed the impact of 17α-meT after bilateral infusion into the dorsomedial hypothalamus (DMH) in female anxiety. A paradoxical effect in Vogel conflict test (VCT) behavior was noted: while AAS infusion induced an increase in the latency to display the appetitive reaction of the task, it also increased the number of punished responses. No changes in elevated plus maze (EPM) behavior were noted. However, AAS infusion induced an increase in social interactions. Changes in social interactions were mimicked by muscimol infusion and counteracted by co-infusion of AAS plus the GABA A receptor (GABA A-R) antagonist GABAzine. A reduction of systolic blood pressure was registered after AAS infusion in the DMH. No changes in fluid intake or locomotor behaviors were noted. We conclude that the AAS 17α-meT modulates distinct anxiety domains in females through a fast-acting mechanism.

Sexual dimorphism in esterified steroid levels in the gastropod Marisa cornuarietis: The effect of xenoandrogenic compounds

Molluscs can conjugate a variety of steroids to form fatty acid esters. In this work, the freshwater ramshorn snail Marisa cornuarietis was used to investigate sex differences in endogenous levels of esterified steroids. Testosterone and estradiol were mainly found in the esterified form in the digestive gland/gonad complex of M. cornuarietis, and males had higher levels of esterified steroids than females (4–10-fold). Additionally, the ability of several xenobiotics, namely tributyltin (TBT), methyltestosterone (MT) and fenarimol (FEN) to interfere with the esterification of testosterone and estradiol was investigated. All three compounds induced imposex – appearance of male sexual characteristics in females. Exposure to TBT led to a decrease in both esterified testosterone (60–85%) and estradiol (16–53%) in females after 100 days exposure, but had no effect on males. Exposure to FEN and MT did not alter levels of esterified steroids in males or in females, although exposed females developed imposex after 150 days exposure. The decrease in esterified steroids by TBT could not be directly linked with a decrease in microsomal acyl-CoA:testosterone acyltransferase (ATAT) activity, which catalyzes the esterification of steroids. In fact, ATAT activity was marginally induced in organisms exposed to TBT for 50 days (1.3-fold), and significantly induced in males and females exposed to MT for 50 days (1.8- and 1.5-fold, respectively), whereas no effect on ATAT activity was observed after 150 days exposure.

Testosterone Therapy for Postmenopausal Women: Efficacy and Safety

The treatment of postmenopausal women with a variety of androgen formulations is increasing, despite the lack of clear guidelines regarding the diagnosis of androgen insufficiency. This review summarizes evidence on the efficacy and safety of adding testosterone to hormone therapy in postmenopausal women. Fair to good evidence exists that the use of testosterone in combination with hormone therapy has both benefits and risks. The benefits are an improvement in sexual function with various regimens of testosterone use (good evidence), an improved sense of well-being with transdermal testosterone (fair evidence), and a reduction in triglyceride levels with methyl testosterone (fair evidence). The most consistent risk is a reduction in high-density lipoprotein (HDL) cholesterol, particularly with methyl testosterone (good evidence). There has been insufficient reporting of other side effects; hence, testosterone therapy should be used with caution. The use of testosterone may be justified in specific clinical circumstances and should be limited to short-term use; long-term studies are not available. Close surveillance for HDL cholesterol and other side effects is necessary.

Investigation, Treatment, and Monitoring of Late‐Onset Hypogonadism in Males: ISA, ISSAM, and EAU Recommendations

Demographic data clearly demonstrate that the percentage of the population in the older age group is increasing. Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. Cross-sectional and longitudinal data indicate that the testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adult (age 20–30 years) men (1–4). The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment of hypogonadal men on multiple target organs and the recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. This has been comprehensively reviewed and summarized by the Institute of Medicine in ‘Testosterone and Aging: Clinical Research Directions’ (5). Long-term data on the effects of testosterone treatment in the older population are limited mainly to effects on body composition and bone mass (6–11). Key questions of the effects of testosterone on patient reported outcomes and functional benefits that may retard physical or mental frailty of the elderly or improve the quality of life are not yet available. Specific risk data on the prostate and cardiovascular systems are needed.

Effects of the model androgen methyltestosterone on vitellogenin in male and female eelpout, Zoarces viviparus (L)

In the present experiment male and female eelpout, Zoarces viviparus were exposed to different doses of the model androgen 17alpha-methyltestosterone (MT) and the effects on the plasma level of vitellogenin and the gonadosomatic index were investigated. In females exposed to different doses of MT (nominal concentrations 10, 25, 50, 100 and 500 ng/L) in the ambient seawater, the concentrations of the circulating yolk-precursor protein vitellogenin (vtg) were shown to decrease in all groups but only significantly in the MT-100 group when compared to controls. No significant effects could be observed on the GSI during early vitellogenesis (April/May). Males exposed to E2 under flow through conditions during 10 days showed an induced synthesis of vtg as depicted by a high level of circulating vtg. When the estrogen-exposed males were subsequently exposed to different doses of MT only, during another 10 days, the levels of vtg decreased significantly in three of the MT-treated groups when compared with the level of vtg in plasma of the estrogen-treated group after the first 10 days. The gonadosomatic index was observed to decrease by the estradiol-treatment but to increase in a dose-dependent manner in the MT-exposed groups, indicating that MT had the capacity to override the effect of the preceding exposure to estradiol-17beta.