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PubMed1980

Role of testosterone and of its metabolites in regulating gonadotrophin secretion in the Japanese quail.

In the Japanese quail gonadal steroids can depress plasma levels of LH and FSH. Since it is now accepted that testosterone metabolites may be metabolized to the tissue-active forms of the hormone, the in-vitro tissue incubation has been combined with steroid replaement therapy in vivo to investigate the physiological roles of various testosterone metabolites as inhibitory feedback agents on gonadtorophin secretion in quail. After the incubation of quail pituitary glands for 3 h with labelled testosterone four metabolites could be identified; androst-4-ene-3,17-dione, 5 beta-dihydrotestosterone (5 beta-DHT), 5 beta-androstane-3 alpha, 17 beta-diol and 5 alpha-DHT. No 5 alpha-androstane-3 alpha, 17 beta-diol was found. Quantitatively, androstenedione was the major metabolite and converison of testosterone to 5 beta-metabolites was significantly greater than to 5 alpha-androgens. Hypothalamic and hyperstriatal tissues converted testosterone than to 5 alpha-androgens. Hypothalamic and hyperstriatal tissues converted testosterone to androstendione, 5 beta-DHT and 5 beta-androstane-3 alpha, 17 beta-diol but not to 5 alpha-DHT or 5 alpha-androstane-3 alpha, 17 beta-diol. Gonadotrophin secretion was studied in castrated quail after chronic s.c. implantation of steroid-containing silicone elastomer capsules or acute injection i.m. of steroid in ethanol: saline. Irrespecive of the route of administration seven androgens, listed in descending order of potency, reduced the increased levels of plasma LH: testosterone: 5 alpha-DHT; androstenedione; 5 alpha-androstane-3, 17-dione; 5 alpha-androstane-3 alpha, 17 beta-diol; 5 alpha-androstan-3 alpha-ol-17-one; 5 alpha-androstan-3 beta-ol-17-one. No changes in levels of plasma LH were observed after the administration of 5 beta-DHT, 5 alpha-androstane-3 beta,17 beta-diol, 5 beta-androstante-3 alpha, 17 beta-diol, 5 beta-androstane-3, 17-dione, androst-5-ene-3 beta, 17 beta-diol or androst-5-en-3 beta-ol-17-one. Testosterone and oestradiol-17 beta were effective in inhibiting secretion of both LH and FSH in young photostimulated quail and completely blocked testicular growth: 5 alpha-DHT inhibited only the release of LH and testicular growth was unaffected.

Androgens↗

PubMed1981

Steroidal interactions in the regulation of maternal behaviour in virgin female rats: effects of testosterone, dihydrotestosterone, oestradiol, progesterone and the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione.

The effects of exposure to concentrations of androgens, oestradiol (OE2) and progesterone similar to those found during pregnancy on the induction of maternal behaviour were investigated in female rats. In the first experiment the effects of testosterone and dihydrotestosterone (DHT) administered in combination with progesterone (using silicone elastomer capsules) on the induction of behavioural responsiveness towards young (crouching, retrieval and grouping of pups) were measured in ovariectomized virgin rats. Hormonally treated animals were exposed to testosterone or DHT from day 1 of treatment to the end of behavioural testing, while progesterone was administered for 10 days (days 3-13). Testing for maternal responsiveness began on day 14 and lasted until day 23. Significant reductions in latencies to show individual aspects of and complete maternal behaviour were found only in animals treated with a combination of testosterone and progesterone (range of mean latencies for showing one aspect of, to complete, maternal behaviour = 1.0-1.4 days). The mean latencies of the other hormonally treated animals ranged from 5 to 6 days and were similar to those of non-hormonally treated control rats. The second experiment examined the possibility that stimulation of maternal behaviour in animals given testosterone and progesterone resulted from the aromatization of testosterone to OE2. Ovariectomized virgin rats were implanted with capsules containing testosterone and other with the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD) on day 1, and with progesterone capsules on day 3. Progesterone capsules were removed on day 13 and behavioural testing commenced on day 14. Treatment with testosterone and progesterone failed to stimulate maternal behaviour in rats treated with ATD. In a third study ovariectomized virgin rats were implanted with OE2 on day 1 and progesterone on day 3. The progesterone implants were removed on day 13 and testing began on day 14. Significant reductions in latencies to show all aspects of maternal behaviour were found in these rats. In a final study progesterone capsules remained in OE2- and progesterone-treated rats from day 3 until the completion of behavioural testing. The presence of progesterone implants throughout the test period (days 14-23) blocked the rapid onset of maternal responsiveness induced by removal of progesterone on day 13 shown in rats treated with OE2 plus progesterone in experiment 3. These data suggest that during gestation testosterone, through its conversion to OE2, synergizes with progesterone to help stimulate the development of the capacity of the female animal to respond maternally to young, a capacity unmasked by withdrawal of progesterone before parturition.

Androstatrienes↗

PubMed1988

Effects of an aromatase inhibitor on testosterone-induced inhibition of thymus growth in immature female rats.

The hypothesis was tested that the inhibitory action of testosterone on thymus growth is mediated by its metabolism to oestradiol. Immature female rats were given s.c. implants of silicone elastomer tubing containing 5 or 20 mg testosterone alone, or together with 25 or 50 mg of an aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD). Some rats received implants containing 5 mg oestradiol or 5 mg dihydrotestosterone (DHT). After 14 days the thymus was removed and weighed. Body weight gain was similar in animals treated with empty implants, or 5 mg testosterone or DHT, or with ATD alone. The combination of testosterone and ATD significantly increased body weight gain, and oestradiol significantly decreased it. Thymus growth was inhibited by both doses of testosterone and by oestradiol, but not by DHT. ATD alone did not inhibit thymus growth, nor did the lower dose of ATD inhibit the action of testosterone. The higher dose of ATD did, however, significantly reduce the inhibitory action of testosterone on the thymus. The inhibitory action of testosterone on the growing thymus may be due, at least in part, to its conversion to oestradiol.

Androstatrienes↗

PubMed1989

Differential effects of FSH and testosterone on the maintenance of spermatogenesis in the adult hypophysectomized rat.

In order to clarify further the role of FSH in the maintenance of spermatogenesis, adult rats were treated with purified human FSH (2 X 5 IU/day per rat), testosterone (1.5 cm silicone elastomer implant) or a combination of both hormones for 2 weeks following hypophysectomy. After hypophysectomy alone, no elongate spermatids were observed and the numbers of pachytene spermatocytes and round spermatids observed were reduced when compared with untreated controls. Testosterone supplementation alone qualitatively maintained the formation of elongate spermatids in most seminiferous tubules, whilst in FSH-treated rats increased numbers of round spermatids and pachytene spermatocytes were observed when compared with hypophysectomized animals. Formation of elongate spermatids, however, did not occur under FSH treatment alone. A combination of FSH and testosterone treatment maintained spermatogenesis in an almost quantitative fashion. Numbers of pachytene spermatocytes and round spermatids were maintained at about 80% of levels seen in intact control animals. Treatment with FSH or testosterone alone maintained testis weights at significantly higher levels than those seen in hypophysectomized controls (FSH, 0.79 +/- 0.05 g; testosterone, 0.81 +/- 0.07 g; hypophysectomized, 0.50 +/- 0.04 g). Animals treated with FSH and testosterone showed testis weights 20% below control values (1.22 +/- 0.05 vs 1.51 +/- 0.06 g; P less than 0.05). No increases in intratesticular or intratubular androgen concentrations or in testosterone: dihydrotestosterone ratios were observed in any of the hormone-treated groups when compared with hypophysectomized controls. In all hypophysectomized animals testicular androgen concentrations were reduced to less than 5% of control values. The results obtained in this study suggest that FSH is involved in the maintenance of spermatogenesis in the adult rat and that the effects of FSH are not mediated through changes in intratesticular androgens. Low levels of testosterone in combination with FSH can almost quantitatively maintain spermatogenesis in adult rats.

Androgens↗

PubMed1989

Effect of a single injection of human chorionic gonadotrophin on testosterone levels in testicular interstitial fluid, and in testicular and peripheral venous blood in adult rats.

We have used a push pull cannula to collect interstitial fluid from the testes of anaesthetized rats at various times after a single injection of human chorionic gonadotrophin (hCG; 50 IU), and compared the levels of testosterone in this fluid with the levels in testicular and peripheral venous blood collected at the same times. Following hCG injection, significant increases in testosterone concentrations were observed in all fluids with notable peaks occurring in interstitial fluid at 2, 8 and 24 h, in testicular venous blood at 2, 8 and 30 h, and in peripheral venous blood at 2, 8, 24 and 72 h. The results demonstrate for the first time that changes in testosterone concentrations in interstitial fluid can be different from those in testicular venous blood. In addition, when testosterone levels in interstitial fluid were compared with levels in testicular venous blood at each time-point, the results suggested that the partitioning of testosterone between these two compartments can be regulated. Furthermore, the changes in both interstitial fluid and testicular venous blood levels of testosterone do not always parallel those in peripheral venous blood, suggesting that changes in testicular blood flow and peripheral clearance rates of testosterone may also be important in the control of circulating testosterone concentrations.

Animals↗

PubMed1991

Effect of administration of human chorionic gonadotrophin on criteria used to assess testosterone administration in athletes.

Abnormal ratios of testosterone to epitestosterone (T/E) and testosterone to LH (T/LH) in the urine of male athletes are indicative of testosterone administration. The T/E ratio has been adopted by the International Olympic Committee as the sole criterion used in the detection of testosterone administration. An athlete is usually considered to have failed a drug test if the urinary T/E ratio is greater than 6. Human chorionic gonadotrophin (hCG) has been used by some male athletes to stimulate testicular secretion of testosterone. The purpose of this investigation was to examine whether the urinary T/E ratio can remain unaffected by administration of hCG to normal adult males. Administration of hCG resulted in large increases in serum testosterone concentrations and urinary T/LH ratios but small changes in urinary T/E ratios of two subjects (maximum T/E values observed were 0.8 and 1.2 respectively). These observations suggest that the urinary T/LH ratio is a valuable indicator of hCG as well as of testosterone administration. This study is the first to measure urinary T/LH ratios using the technique of gas chromatography-mass spectrometry for quantification of testosterone, and highly specific monoclonal antibodies for the measurement of LH. An ultrafiltration method is proposed as part of a confirmatory procedure to be adopted in the measurement of urinary gonadotrophins for drug control in sport.

Chorionic Gonadotropin↗

PubMed1994

Regulation of oxytocin production by purified adult rat Leydig cells in vitro: effects of LH, testosterone and lipoproteins.

The aim of the present study was to determine whether LH stimulates oxytocin production by adult rat Leydig cells directly or indirectly via testosterone. Purified adult rat Leydig cells were cultured in the presence or absence of 0.1 ng/ml LH or 1, 10 or 100 ng/ml testosterone for 22 h. Culture medium was collected at 2-hourly intervals and assayed for oxytocin and testosterone. In the presence of LH, Leydig cells produced significantly higher levels of both testosterone (basal production 1.4 +/- 0.13 ng, LH-stimulated 4.1 +/- 0.13 ng/10(6) cells per 2 h) and oxytocin (basal production 8.3 +/- 1.2 pg, LH-stimulated 20.2 +/- 1.3 pg/10(6) cells per 2 h). Testosterone also stimulated oxytocin secretion. However, the increase was smaller compared with that seen with LH and was not found to be dose-dependent. Furthermore, testosterone production was only significantly increased by LH during the first 10 h of the 22-h culture period whereas LH stimulated oxytocin production throughout the whole culture period. To further determine the effect of LH on oxytocin production, cultures were performed in the presence of LH and/or 400 microM aminoglutethimide. In the presence of aminoglutethimide both the basal and LH-stimulated production of testosterone was significantly reduced. However, in the same cultures aminoglutethimide did not alter either the basal or LH-stimulated production of oxytocin. These data show that LH does not act via testosterone to stimulate oxytocin production and therefore acts directly or by some alternative indirect mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglutethimide↗

PubMed2001

Proof of the effect of testosterone on skeletal muscle.

In spite of the widespread abuse of androgenic steroids by athletes and recreational body-builders, the effects of these agents on athletic performance and physical function remain poorly understood. Experimentally induced androgen deficiency is associated with a loss of fat-free mass; conversely, physiologic testosterone replacement of healthy, androgen-deficient men increases fat-free mass and muscle protein synthesis. Testosterone supplementation of HIV-infected men with low testosterone levels and of older men with normally low testosterone concentrations also increases muscle mass. However, we do not know whether physiologic testosterone replacement can improve physical function and health-related quality of life, and reduce the risk of falls and disability in older men or those with chronic illness. Testosterone increases maximal voluntary strength in a dose-dependent manner and thus might improve performance in power-lifting events. However, testosterone has not been shown to improve performance in endurance events. The mechanisms by which testosterone increases muscle mass are not known, but probably involve alterations in the expression of multiple muscle growth regulators.

Adult↗

PubMed2005

Capacitative calcium entry in testosterone-induced intracellular calcium oscillations in myotubes.

Ca2+ oscillations are one of the most important signals within the cell. The mechanism for generation of Ca2+ oscillations is still not yet fully elucidated. We studied the role of capacitative Ca2+ entry (CCE) on intracellular Ca2+ oscillations induced by testosterone at the single-cell level in primary myotubes. Testosterone (100 nM) rapidly induced an intracellular Ca2+ rise, accompanied by Ca2+ oscillations in a majority of myotubes. Spectral analysis of the Ca2+ oscillations revealed a periodicity of 20.3 +/- 1.8 s (frequency of 49.3 +/- 4.4 mHz). In Ca(2+)-free medium, an increase in intracellular Ca2+ was still observed, but no oscillations. Neither nifedipine nor ryanodine affected the testosterone-induced Ca2+ response. This intracellular Ca2+ release was previously shown in myotubes to be dependent on inositol-1,4,5-trisphosphate (IP3). Intracellular Ca2+ store depletion in Ca(2+)-free medium, using a sarcoplasmic/endoplasmic reticulum calcium ATPase-pump inhibitor, followed by re-addition of extracellular Ca2+, gave a fast rise in intracellular Ca2+, indicating that CCE was present in these myotubes. Application of either testosterone or albumin-bound testosterone induced Ca2+ release and led to CCE after re-addition of Ca2+ to Ca(2+)-free extracellular medium. The CCE blockers 2-aminoethyl diphenylborate and La3+, as well as perturbation of the cytoskeleton by cytochalasin D, inhibited testosterone-induced Ca2+ oscillations and CCE. The steady increase in Ca2+ induced by testosterone was not, however, affected by either La3+ or cytochalasin D. These results demonstrate testosterone-induced Ca2+ oscillations in myotubes, mediated by the interplay of IP3-sensitive Ca2+ stores and Ca2+ influx through CCE.

Animals↗

PubMed2004

Testosterone and luteinizing hormone responses to naloxone help predict sexual performance in rams.

The first objective of this study was to determine whether LH and testosterone respond differently to a naloxone injection in relation to varying sexual performance in rams. If differences occurred, the second objective was to determine whether differences would predict variation in sexual performance. From a group of 1.5- to 3-yr-old rams, 20 sexually active and 39 sexually inactive rams were selected based on previously observed sexual behavior with estrual ewes. Each ram was exposed to three estrual ewes for 18 30-min sexual performance tests, and those found to be inactive were given two 30-min sexual partner preference tests. The final distribution was 28 sexually active, 22 inactive, and nine male-oriented rams. Rams were treated with 1.5 mg of naloxone/kg BW in December of Year 1 and again with either 0.75 or 1.5 mg of naloxone/kg BW in November of Year 2. Plasma concentrations of LH and testosterone were evaluated with mixed model analyses for repeated measures separately for each year to coincide with logistic procedures for modeling the probability that rams were sexually active. For Year 1, a sexual activity x age x time interaction for LH after naloxone was observed (P < 0.03). For testosterone, there was a sexual activity x time interaction (P < 0.03), with a similar, early increase for sexually active female-and male-oriented rams compared with a delayed, minimal increase for inactive rams. For Year 2, when all rams were over 2.5 yr of age, a sexual activity x time interaction for both LH and testosterone (P < 0.02) seemed more related to an earlier increase of both hormones for sexually active rams than the increase observed for inactive rams. In addition, sexually active rams had a greater increase in testosterone than inactive rams. No significant difference was observed between 0.75 and 1.50 mg of naloxone/kg BW. Testosterone and LH were used as explanatory variables and sexual activity was used as the response variable in logistic procedures. In Year 1, greatest prediction accuracy was 73.5% using testosterone at 60 min after naloxone injection. In Year 2, the greatest prediction accuracy was 85% using LH at 15 min multiplied by testosterone at 60 min after naloxone. Test repeatability for both years on the same rams was 76%. In conclusion, pattern and magnitude of naloxone-induced changes in endocrine function may facilitate identification of sexually active and inactive rams during the breeding season. Prediction accuracy of the naloxone-based test was 69 to 85%.

Animals↗

PubMed2004

Effect of divergent selection for testosterone production on testicular morphology and daily sperm production in boars.

The objective of this study was to characterize correlated responses in testicular morphology and daily sperm production to divergent selection for testosterone production. Duroc boars from high and low lines (HTL and LTL, respectively) divergently selected over 10 generations for testosterone production in response to a GnRH challenge followed by random selection were used. Testicular tissues were sampled from all available males of generation 20 (HTL, n = 46; and LTL, n = 13). Volume densities for Leydig cells, seminiferous tubules, and Sertoli cells were estimated along with sperm production. The HTL boars had greater volume densities of Leydig cells than did LTL (P < 0.01). Volume density of seminiferous tubules tended to differ between lines (P < 0.07), but Sertoli cell volume densities did not differ (P < 0.27). Sperm production traits, adjusted for age, did not differ significantly between lines. Body, testicular, and epididymal weights were recorded for boars from HTL (n = 82) and LTL (n = 44) from generations 20 and 21. After adjustment for BW, average paired testicular weights for HTL and LTL were 417 and 457 g (P < 0.01), respectively. Epididymal weights, adjusted for BW, were heavier for HTL (P < 0.01) than for LTL. To demonstrate that the selection lines still differed for testosterone production, lines were evaluated in generation 21. Endogenous testosterone production of the HTL (n = 54) and LTL (n = 44) testosterone production line averaged 49.0 ng/mL and 27.8 ng/mL (P < 0.01), respectively. Plasma FSH concentrations did not differ between lines (P < 0.30). Selection for testosterone production in response to a GnRH challenge was an effective method of changing testosterone concentrations, testicular size, epididymal weight, and volume density of Leydig cells. However, daily sperm production per gram of testes was unchanged. Based on the results of this study, selection for testosterone production is not recommended as a method of increasing sperm production in pigs.

Animals↗

PubMed1980

Testosterone influences on growth, performance, carcass characteristics and composition of young market lambs.

Ram lambs, wethers and wethers implanted with Silastic capsules containing crystalline testosterone were placed on test at 14.9 +/- 1.1 kg and evaluated for differences in growth, performance, carcass characteristics and composition. Silastic implants that were able to maintain physiological concentrations of serum testosterone provided appropriate replacement therapy in wethers. Growth rate, efficiency of feed utilization and carcass yield of intact ram lambs and testosterone-implanted wethers were superior to the corresponding traits of wethers. Wethers had greater backfat thickness and percentage kidney and pelvic fat, and their carcasses graded higher than those of ram lambs or wethers implanted with a high dosage of testosterone. Empty body composition was significantly affected by treatment. Thus, intact rams contained more water and protein but less fat and gross energy than wethers. Testosterone-implanted wethers were intermediate in composition. Carcass water and protein were not significantly affected by treatment; however, carcass fat and gross energy were highest for wethers and lowest for intact rams. The relationship between testosterone and carcass fat and energy was dose dependent; i.e., decreased fat and energy were associated with increased serum testosterone. In conclusion, testosterone appears to be the principal testicular hormone responsible for the superior performance and preferred carcass traits characteristic of young market rams.

Animals↗

PubMed1984

In vitro testosterone secretion by testicular tissue from young bulls and the effects of chronic and acute exposure to estradiol-17 beta.

The possibility that estradiol-17 beta may directly influence testicular steroidogenesis in bulls was investigated in vitro. Testicular tissues were incubated for 4 h and regression coefficients (b, ng X ml-1 X h-1) based on the increase in testosterone in the medium were used to describe testosterone secretion rates. In the first experiment, testicular tissues from control bulls and bulls chronically implanted with estradiol were incubated in the absence (basal conditions) or presence of 10 mIU/ml human chorionic gonadotropin (hCG). Under basal conditions, testosterone secretion rates were similar for tissues from control (b = 24.1 +/- 6.0) and implanted (b = 34.7 +/- 6.0) bulls. Testosterone secretion rates were increased approximately fourfold during incubation with hCG; tissues from implanted animals secreted testosterone at a higher rate (P less than .05) than control tissues (b = 120.7 +/- 6.0 vs 81.6 +/- 6.0). In a second experiment, testicular tissues were obtained from control bulls and incubated both with and without hCG (10 mIU/ml) and with and without estradiol (concentrations ranging from 3.7 nM to 37 microM). In this experiment, basal secretion rate (b = 12.6 +/- 3.6) was increased threefold during incubation with hCG (b = 37.8 +/- 3.6). Estradiol failed to inhibit hCG-stimulated testosterone secretion when bovine testicular tissue was incubated with 0, 3.7 and 370 nM estradiol. In contrast, 37 microM estradiol suppressed (P less than .05) testosterone secretion, perhaps reflecting a pharmacologic effect. The results suggest that neither chronic nor acute exposure to estradiol directly affects testosterone secretion by the bovine testis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Active immunization of prepubertal boars against testosterone: testicular and endocrine responses at 14 months of age.

Thirteen crossbred boars were immunized at 1 mo of age against either testosterone-3-oxime-equine serum albumin (treated boars) or equine serum albumin (control boars) to test the hypothesis that active immunization against testosterone stimulates testicular growth and development in the prepubertal boar. All boars were injected with the appropriate antigen at 2, 3, 4, 5 and 6 mo of age and were slaughtered at 14 mo of age. Active immunization against testosterone resulted in an increase (P less than .05) in tritiated-testosterone binding by plasma within 60 d after the primary immunization; the degree of binding decreased by 6 mo but remained elevated (P less than .05) relative to controls through 12 mo of age. There was no effect of treatment on body weights through 12 mo of age. Concentrations of testosterone in plasma were higher (P less than .05) in testosterone-immunized boars than in controls; this increase was likely due to antibody binding rather than increased testosterone secretion because (1) concentrations of androgen in testicular parenchyma at slaughter were not altered by treatment and (2) plasma concentrations of estrogens were generally not affected by treatment. Concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were markedly suppressed in testosterone-immunized boars during the time when concentrations of these gonadotropins were high in control boars (greater than 3 mo of age). In spite of suppression of average LH and FSH concentrations, testicular weights, daily sperm production rates and seminal characteristics were similar for the two groups of boars at slaughter. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Effect of testosterone propionate on performance and carcass characteristics of heifers and cows.

Two experiments were conducted to evaluate the effect of testosterone on growth and composition of cattle. In the first experiment, crossbred yearling heifers (n = 48) were assigned to four treatments: 1) control (no implant), 2) Synovex-H implants on d 1 and 84, 3) one testosterone propionate implant administered on d 1 and a second on d 84 and 4) two testosterone propionate implants administered on d 1. Heifers were fed a high-energy diet for the 157-d study. Implanting with the high-testosterone treatment improved (P less than .05) daily gain and feed efficiency compared with the other treatments. Marbling score was reduced (P less than .05) with the high-testosterone treatment. In Exp. 2, mature cows (n = 36) were assigned to one of three feeding periods (0, 42, or 84 d) with the cows fed 42 or 84 d subdivided into two groups (implanted with testosterone propionate or nonimplanted control). Cows were fed a high-energy diet and slaughtered at the end of each feeding period. Testosterone did not influence (P greater than .05) feedlot performance. Increased time on feed reduced (P less than .01) daily gain (live weight basis) and feed efficiency but did not influence feed intake. Testosterone treatment had little influence on the fat and moisture contents of the carcass soft tissue or on the palatability characteristics of loin steaks. Time on feed increased lean muscle mass and carcass fat (P less than .05). Sensory traits were improved at 42 d on feed (P less than .05), but no further sensory improvement was observed at 84 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Association of serum-free-testosterone level with hand preference in right-handed young females.

The relationship between the degree of right-hand preference and serum free-testosterone level was studied in right-handed female subjects, who were 17-19 years old. It was assumed that free testosterone levels in serum of young female subjects would reflect the perinatal testosterone levels. Hand preference was assessed by the Edinburgh Handedness Inventory (Geschwind score, GS) and Waterloo Handedness Questionnaire (Waterloo score, WS). The degree of the right-hand preference linearly and significantly increased as the serum free-testosterone level increased in the moderately right-handed (GS = < 70) subjects. There was only a marginally significant negative linear correlation between these parameters in the strongly right-handed subjects (GS > 70). These results only partly supported the testosterone hypothesis of cerebral lateralization that testosterone would slow the growth of the left cerebral hemisphere, reducing the degree of right hand preference. The results also suggested a trophic effect of testosterone especially on the left cerebral cortex in females. Activational effects of testosterone may also contribute to an increase in the degree of right-hand preference in right-handed young females.

Adolescent↗

PubMed1983

Oral testosterone load related to liver function in men with alcoholic liver cirrhosis.

The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely with galactose elimination capacity (r = 0.54; P less than 0.001), serum albumin (r = -0.53; P less than 0.001), plasma factor II + VII + X (r = 0.62; P less than 0.001), indocyanine green clearance (r = -0.71; P less than 0.001), and hepatic blood flow (r = -0.61; P less than 0.01) and correlated directly with wedged-to-free hepatic vein pressure (r = +0.54; P less than 0.01). The increase of testosterone after the load did not correlate significantly with sex hormone-binding globulin (r = +0.35; P greater than 0.05). It is concluded that the hepatic extraction of testosterone is significantly decreased in patients with alcoholic cirrhosis. This decrease seems to be due to decreased liver function, decreasing hepatic blood flow, and increased portosystemic shunting. Oral testosterone loading may therefore be of prognostic significance in patients with alcoholic liver cirrhosis.

Administration, Oral↗

PubMed1992

Testosterone regulation of sex differences in fetal lung development.

Fetal lung development, in particular surfactant synthesis, exhibits a sexual dimorphism. Dihydrotestosterone (DHT) has been shown to delay fetal pulmonary surfactant production, but the potential role for testosterone is unknown. Both testosterone and DHT are potent masculinizing hormones, yet in some instances, an end organ specificity for DHT is present. We hypothesized that the delay in fetal lung surfactant production is dependent upon DHT such that inhibition of the synthesis of DHT from the precursor hormone testosterone would eliminate the sex difference by allowing the male fetus to produce surfactant at the female level. We tested this hypothesis using 17 beta-N,N-diethylcarbamoyl-4-aza-4-methyl-5-alpha-androstane-3-one (4-MA), a potent inhibitor of the enzyme 5 alpha-reductase, which converts testosterone into DHT. First, studies were performed in vivo. 4-MA (20 mg/kg/day) or an equivalent volume of vehicle was injected into pregnant rabbits from Day 12 through Day 26 of gestation. On Day 26, the fetuses were delivered, the lungs were lavaged, and fetal sex was noted. Treatment with 4-MA resulted in a lack of any male-female difference in the anogenital distance and no DHT was detected in the serum of any treated fetus. Phosphatidylcholine (PC), saturated phosphatidylcholine (SPC), and sphingomyelin (S) were measured in the lung lavage, and were expressed as the ratios of PC to sphingomyelin (PC:S) and SPC to sphingomyelin (SPC:S). Sex differences in the PC to sphingomyelin ratio of 4-MA-treated fetuses (female PC:S ratio, 1.43 +/- 0.14; male PC:S ratio, 1.00 +/- 0.13 [mean +/- SE]; P = 0.04) and in the SPC:S ratio of the 4-MA-treated group (female SPC:S ratio, 0.68 +/- 0.10; male SPC:S ratio, 0.35 +/- 0.10; P = 0.03) were present after treatment with 4-MA. The effect of testosterone and of 4-MA on fibroblast pneumonocyte factor (FPF) production was studied in vitro. Fetal rat lung fibroblasts were cultured to confluence with either no added androgen, DHT, testosterone, or testosterone plus 4-MA, and conditioned media for FPF were prepared. Conditioned media were added to fetal Type II cell cultures and FPF activity was measured as the degree of stimulation of the incorporation of [3H] choline into SPC. The conversion of radiolabeled testosterone to DHT by the fibroblasts was inhibited by 4-MA (10(-5) M). Conditioned media from untreated female fibroblasts stimulated with cortisol exhibited significant FPF activity ([3H]choline incorporation into SPC, 140 +/- 17% of control).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗