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PubMed1989

Changes in the testicular binding of luteinizing hormone and plasma testosterone concentrations in the Djungarian hamster subjected to different photoperiods and temperatures and effects of long-term testosterone treatment on the binding.

The effects of artificial photoperiod, temperature, and long-term testosterone treatment on testicular luteinizing hormone (LH) binding were studied in adult male Djungarian hamsters. In hamsters transferred to long-day (LD; 16 hr light, 8 hr dark) photoperiod 8 weeks after adaptation in short-day (SD; 8 hr light, 16 hr dark) photoperiod of 25 degrees C, testicular growth was associated with an increase in the total LH binding per two testes and a decrease in LH binding per unit testicular weight. Plasma testosterone levels reached a peak 47 days after transfer to LD and tended to decrease thereafter, while the testes continued growing. In contrast, when hamsters reared under LD conditions at 25 degrees C for 12 weeks were transferred to SD, testicular regression was associated with a decrease in plasma testosterone and the total LH binding per two testes and an increase in LH binding per unit testicular weight. A significant decrease in LH binding per unit weight compared to SD controls was observed in those hamsters exposed to SD with continuous testosterone treatment. The testosterone treatment tended to induce decrease in the total LH binding. Scatchard plot analyses of the binding suggested that changes in LH binding were due to changes in the number of binding sites. When sexually mature male hamsters were subjected for 8 weeks to two different ambient temperatures (7 degrees C and 25 degrees C) and photoperiods (LD and SD), the difference between the two temperature groups was statistically not significant regarding the weights of testes, epididymides, and prostates; plasma testosterone levels; and LH binding in either LD or SD group. These results suggest that photoperiod is a more important environmental factor than temperature for the regulation of testicular activity and LH receptors and that testosterone reduces the number of LH receptors per unit testicular weight in adult male Djungarian hamsters.

Animals↗

PubMed1979

Separation and determination of testosterone and testosterone esters in selected pharmaceutical formulations.

A rapid quantitative procedure is presented for the separation of testosterone esters from their hydrolysis products through the use of the acetonitrile-infusorial earth column. The method was applied to testosterone cypionate, testosterone enanthate, and testosterone propionate. Recovery and replication of reference standard testosterone and its three esters through the proposed method ranged from 99.1 to 100.3%, and the percent relative standard deviation ranged from 0.6 to 1.0%. Two samples can be separated into testosterone and testosterone ester fractions in about 1.5 hr. The analyses of 20 injectable and one buccal tablet formulations made by 12 different manufacturers are reported.

Drug Stability↗

PubMed1989

Effects of serum testosterone level with buserelin on the activities of drug and testosterone hydroxylase and on the content of a male-specific form of cytochrome P-450 in male rats.

The effects of administration of buserelin, a synthetic agonist of lutenizing hormone-releasing hormone (LH-RH), on the content of P-450-male, a male specific form of cytochrome P-450, and the activities of drug and testosterone hydroxylases were examined in liver microsomes of male rats. Administration of buserelin resulted in a decrease in the serum level of testosterone in a dose-dependent manner. Similar decreases were seen in the activities of aminopyrine N-demethylase, 7-propoxycoumarin O-depropylase and testosterone 2 alpha- and 16 alpha-hydroxylases, but not in the activity of aniline p-hydroxylase. Thus, correlations were observed between the serum level of testosterone and the activities of drug and testosterone hydroxylases except for aniline p-hydroxylase. These results indicate that the drug and testosterone hydroxylases are affected sensitively and sequentially by the changes in the testosterone levels in the body.

Aminopyrine N-Demethylase↗

PubMed1987

Direct assay for testosterone in saliva: relationship with a direct serum free testosterone assay.

A direct non-extraction radioimmunoassay for salivary testosterone is described using a modified commercial kit procedure that is in use for total serum testosterone (T). Serum free testosterone was also measured by direct radioimmunoassay. A significant correlation (r = 0.83, p less than 0.01, n = 194) was obtained between salivary and serum free testosterone in matched serum and saliva samples over a wide range of concentrations. Within- and between-batch precision for the salivary testosterone method was 11% and 18%, respectively at a concentration of 170 pmol/l. Recovery of added T was 89% +/- 15% (mean +/- 2 SD) dilution of high samples showed parallelism. Salivary testosterone measured by direct radioimmunoassay offers a simple cheaper alternative to serum free testosterone measurement with the additional advantages of a stress-free non-invasive sampling procedure.

Adult↗

PubMed1997

Serum LH concentrations in hypogonadal men during transdermal testosterone replacement through scrotal skin: further evidence that ageing enhances testosterone negative feedback. The Testoderm Study Group.

OBJECTIVE: The present study was designed to explore further the mechanism for the decline in androgen production as men age by studying the influence of ageing on testosterone negative feedback control of gonadotrophin secretion. DESIGN: Circulating testosterone, dihydrotestosterone, oestradiol, SHBG and LH concentrations were measured during long-term treatment of men with primary hypogonadism using transdermal testosterone via scrotal skin. PATIENTS: Results were compared in 12 hypogonadal men below age 40 years (34 +/- 1.1 years; mean +/- SEM), 13 middle-aged men, aged 51 +/- 2.2 years, and 10 men age 64 years or older (68 +/- 1.4 years). RESULTS: During the course of therapy, circulating LH levels were suppressed 48% (F = -2.42, P = 0.018) from 19.6 +/- 6.0 IU/I at baseline to 10 +/- 7.7 IU/I during month 15 in elderly men. By contrast, LH levels were unchanged (F = 0.31; P = 0.97) in young men (20.3 +/- 7.4 IU/I at baseline and 17.7 +/- 14.9 IU/I during treatment month 15). Intermediate results were observed in middle-aged men in whom LH levels declined slightly (F = 1.34; P = 0.24). Transdermal testosterone treatment produced similar circulating testosterone levels (F = 1.49; P = 0.24) and oestradiol levels (F = 0.60; P = 0.42) in elderly and young men. Mean plasma DHT levels were approximately 20% higher (F = 9.91; P = 0.01) during treatment in elderly men overall mean values of 8.03 +/- 0.37 nmol/l) than in young men (6.68 +/- 0.08 nmol/l). When total DHT was adjusted for higher plasma SHBG levels in elderly men, the free DHT index during treatment was similar (F = 0.23; P = 0.64) in both groups. CONCLUSIONS: These data provide further evidence that the set point for androgen negative feedback control of gonadotrophin accretion in men is altered by ageing. Taken together with previous findings, these results provide a potential explanation for the unchanged or slightly increased plasma LH levels and reduced testosterone production characteristic of elderly men. Accordingly, ageing-associated Leydig cell insufficiency leads to a decline in testosterone production, but circulating LH levels do not rise appropriately because the set-point for negative feedback is decreased.

Administration, Cutaneous↗

PubMed2001

Structural insights into steroid hormone binding: the crystal structure of a recombinant anti-testosterone Fab fragment in free and testosterone-bound forms.

The monoclonal anti-testosterone antibody (3-C(4)F(5)) has a relatively high affinity (3 x 10(8) m(-1)) with an overall good specificity profile. However, the earlier characterized binding properties have shown that both the affinity and specificity of this antibody must be improved if it is intended for use in clinical immunoassays. In this paper, the crystal structures of the recombinant anti-testosterone (3-C(4)F(5)) Fab fragment have been determined in the testosterone-bound and free form at resolutions of 2.60 and 2.72 A, respectively. The high affinity binding of the (3-C(4)F(5)) Fab is mainly determined by shape complementarity between the protein and testosterone. Only one direct hydrogen bond is formed between the hydroxyl group of the testosterone D-ring and the main-chain oxygen of Gly100(J)H. The testosterone is deeply bound in a hydrophobic pocket, and the close shape complementarity is mainly formed by the third complementarity-determining regions (CDR) of the heavy and light chain. Comparison of the bound structure with the free structure indicates conformational changes in the protein upon testosterone binding. The conformational changes of the side chains of two residues Glu95H and Tyr99H in the CDR-H3 are particularly essential for the binding. Interesting similarities in the binding of different steroids were also observed upon comparison of the available structures of anti-steroid antibodies.

Amino Acid Sequence↗

PubMed2003

Testosterone metabolism, dose-response relationships and receptor polymorphisms: selected pharmacological/toxicological considerations on benefits versus risks of testosterone therapy in men.

In this review selected toxicological problems related to testosterone therapy in hypogonadal men are discussed. Applying "classical" pharmacological/toxicological findings (e.g. animal studies on short- and long-term toxicity) to clinical situations is not very helpful. Molecular biological knowledge and especially evaluation of epidemiological studies, as well as intervention studies, on testosterone therapy in hypogonadal men are more useful. Potential risks include overdosage for lifestyle reasons, e.g. excessive muscle building and reduction of visceral obesity, when erythrocytosis occurs concomitantly. Modern galenic formulations of testosterone administration (e.g. transdermal gel, suitable testosterone esters for intramuscular application and newer oral preparations) avoid supraphysiological serum concentrations, therefore significantly reducing the toxicological risk. A hypothetical model of the toxicological risks of testosterone therapy is given that is based on the influence of testosterone metabolism (aromatization vs. reduction) of the respective parameter/target chosen. Finally, the great influence of polymorphisms of the androgen receptor on the assessment of toxicological risk and on the individualization of androgen therapy is shown. Already existing national, continental and international guidelines or recommendations for the testosterone therapy should be harmonized.

Dose-Response Relationship, Drug↗

PubMed1988

Effects of local heating of the testes on the concentration of testosterone in jugular and testicular venous blood of rats and on testosterone production in vitro.

Heating both testes of rats to between 39 degrees C and 41 degrees C for 30 min was apparently without effect 21 days later, but heating to between 41.5 degrees C and 43 degrees C for 30 min resulted in a significant drop in testis weight accompanied by significant rises in the serum levels of LH and FSH. There were no changes in serum testosterone concentration in the peripheral circulation although there were increases in the concentration in testicular venous blood. The ability of the heated testis to secrete testosterone in vivo in response to maximal stimulation by hCG was reduced, as judged by testosterone levels in peripheral blood, while there was a supranormal increase in testosterone levels in testicular venous blood. Maximally stimulated testosterone production in vitro by the heated testis was supranormal whereas the basal production of testosterone per testis was not different from control values. Therefore, it appears that the testosterone produced by Leydig cells from heated testes may not be secreted as effectively as in normal testes.

Animals↗

PubMed2004

Are published normal ranges of serum testosterone too high? Results of a cross-sectional survey of serum testosterone and luteinizing hormone in healthy men.

OBJECTIVE: To derive normal ranges of serum testosterone and luteinizing hormone (LH) concentrations in healthy men, and thus evaluate whether testosterone replacement therapy is prescribed inappropriately. SUBJECTS AND METHOD: The study comprised 266 healthy male volunteers (aged 18-75 years) who were defined as healthy by strict eligibility criteria. Subjects had a body mass index (BMI) of 18.6-32.2 kg/m2, smoked 0-10 cigarettes/day, and had an alcohol intake 0-40 units/week (one unit = 8 g ethanol). We measured serum testosterone and LH concentrations in the morning (08.00-09.00 hours) and evening (20.00-21.00 hours). RESULTS: Morning normal ranges of testosterone for men aged < or = 40 years were 10.07-38.76 nmol/L (2.90-11.18 microg/L), and for men age > or = 40 years, 7.41-24.13 (2.14-6.96); the respective evening normal ranges were 6.69-31.51 (1.93-9.09) and 6.46-21.93 (1.86-6.33). Both morning and evening serum testosterone declined significantly with increasing age and BMI. LH was significantly higher in the morning than in the evening, but did not vary between the age groups or with BMI. The calculated normal ranges of LH were 0.9-7.0 IU/L (morning) and 0.7-6.8 IU/L (evening). CONCLUSIONS: The lower limit of normal for serum testosterone was 3-4 nmol/L (0.86-1.15 microg/L) lower than that of published ranges. The results have important implications for the diagnosis of hypogonadism and use of testosterone replacement therapy.

Adolescent↗

PubMed2005

Comparison of the steady-state pharmacokinetics, metabolism, and variability of a transdermal testosterone patch versus a transdermal testosterone gel in hypogonadal men.

AIM: To compare the pharmacokinetics (PK), metabolism, intra- and inter-subject variability of a permeation-enhanced testosterone patch versus a topical testosterone gel. METHODS: 28 hypogonadal men were treated with a testosterone patch (5 mg/day applied at 2200 h) and a 1% testosterone gel (5 g/day applied at 0800 h; nominal delivery 5 mg/day), each for 14 days, in an open-label crossover design. PK profiles of total testosterone (TT) and calculated free testosterone (cFT) were measured on day 7 and day 14 of each treatment, with patches or gel applied to the abdomen; dihydrotestosterone (DHT) and estradiol (E2) profiles were measured on day 14. The time-average (Cavg), maximum (Cmax), time of maximum (Tmax) and minimum concentrations (Cmin) were derived from each profile. The intra- and inter-subject coefficients of variation (CVintra and CVinter) of the TT and cFT parameters were computed by ANOVA. RESULTS: Nightly applications of the patch produced a mean TT profile that mimicked the circadian pattern of healthy men. Morning applications of the gel produced a flatter mean profile; though individual subjects exhibited significant peaks at variable times. For TT, the mean and 90% confidence intervals of the patch/gel ratio of Cavg (1.030; 0.936-1.133; P > 0.05) and Cmax (1.086; 0.974-1.211; P > 0.05) met the criteria for bioequivalence. Cmin was lower for the patch. DHT levels and DHT/T ratios were 2 to 3-fold higher for the gel (P < 0.0001). E2 levels and E2/T ratios were comparable. CVintra and CVinter for Tmax approached 100% for the gel and were 23% and 42%, respectively, for the patch (P < 0.0001). Other variability parameters were generally comparable. Both products were well tolerated, and the patches adhered well. CONCLUSIONS: These findings reflect the different mechanisms of transdermal absorption from the patch and gel and provide new considerations for selecting testosterone replacement therapies in hypogonadal men.

Administration, Cutaneous↗

PubMed2006

Subjective sexual response to testosterone replacement therapy based on initial serum levels of total testosterone.

INTRODUCTION: Testosterone replacement therapy (TRT) has been shown to be beneficial for men with hypogonadism. However, it is unknown how well hypogonadal men respond to TRT based on the severity of testosterone deficiency. AIM: To determine subjective sexual response rates to TRT based on initial serum testosterone values, with particular interest in men with "low-normal" levels of total testosterone (TT). MAIN OUTCOME MEASURES: Subjective responses to TRT in the domains of erectile dysfunction, libido, orgasm, and morning erections. METHODS: A retrospective study was performed of 211 men with sexual symptoms of hypogonadism who underwent TRT. All men had either low values of TT (<300 ng/dL) or free testosterone (FT) (<1.5 ng/dL). The cohort was divided into three groups based on initial TT levels: Group 1: 0-200 ng/dL (N = 26; 12.3%); Group 2: 201-300 ng/dL (N = 64; 30.3%); Group 3: 301 ng/dL or greater (N = 121; 57.3%). Improvement in erectile function was determined prior to addition of any other treatment (e.g., phosphodiesterase type 5 inhibitors). The mean follow-up was 9 months (range 3-36 months). RESULTS: The mean age was 55.2 years. Testosterone gel was used in approximately two-thirds of each group. Improvement in libido was reported in 61.5%, 96.6%, and 29.8% for Groups 1, 2, and 3, respectively (P < 0.001). Improvement in erectile function was noted in 46.2%, 45.3%, and 73.6% for Groups 1, 2, and 3, respectively (P < 0.001). At time of last follow-up, the percentage of men continuing with TRT was 73.1%, 57.8%, and 58.7% for Groups 1, 2, and 3, respectively (P = nonsignificant). CONCLUSIONS: These preliminary data suggest that men with sexual symptoms of hypogonadism respond well to TRT across a wide range of initial TT values, including men with low-normal TT levels. These men may have low bioavailable levels of testosterone that are not reflected in TT values.

Adult↗

PubMed1978

Serum-testosterone during oral administration of testosterone in hypogonadal men and transsexual women.

Testosterone tablets of crystal size 2-5 micrometer were administered orally for 10 dags to 3 human subjects with low endogenous serum testosterone (se-T) levels. Fifty mg testosterone increased se-T slightly, while one daily dose of 200 mg maintained the se-T level within normal range for men for more than 12h. No cumulative effect was seen. Seven further subjects with low androgen production ingested 100 or 200 mg testosterone of crystal size 125-400 micrometer. Blood samples were taken frequently during the 24 h period following administration of the testosterone and se-T levels determined. Testosterone levels in serum increased in 6 patients and was maintained within the normal male range for 5-7 h. In one subject a slight but significant increase in se-T was observed although the level did not reach the normal male range. Although it has been shown that it is possible to use orally administered testosterone to maintain se-T levels in the normal male range, the convenience to the patient must be balanced against the cost and possible side effects of the large doses required.

Administration, Oral↗

PubMed1999

Testosterone and andropause: the feasibility of testosterone replacement therapy in elderly men.

Andropause, a syndrome in aging men, consists of physical, sexual, and psychologic symptoms that include weakness, fatigue, reduced muscle and bone mass, impaired hematopoiesis, oligospermia, sexual dysfunction, depression, anxiety, irritability, insomnia, memory impairment, and reduced cognitive function. Free testosterone levels begin to decline at a rate of 1% per year after age 40 years. It is estimated that 20% of men aged 60-80 years have levels below the lower limit of normal. Although the causal relationship between declining testosterone levels and development of andropause symptoms is not firmly established, administration of testosterone to this population resulted in improvements in many areas. Most studies to date focused on physical benefits of testosterone replacement and failed to assess psychologic symptoms rigorously. Preliminary data suggest that therapy may benefit elderly men with new-onset depression. Testosterone administration is not without problems, the most worrisome being the potential for increased prostate cancer risk. Despite this concern, a limited number of studies administered the hormone weekly for up to 2 years, with only mild increases in prostate-specific antigen over control values. Currently, insufficient evidence, primarily regarding psychologic safety and efficacy, exists to warrant general administration of testosterone to elderly hypogonadal men. Further clinical investigations of this therapy in men with low testosterone levels and andropause symptoms are justified and necessary.

Aged↗

PubMed1986

Comparison of methods for determination of testosterone and non-protein bound testosterone in men with alcoholic liver disease.

The serum concentrations of testosterone and of non-protein bound testosterone were determined in 28 men with alcoholic liver disease having normal to decreased serum albumin concentrations and normal to raised SHBG concentrations. Serum testosterone concentrations determined with two radioimmunoassays using different purification procedures and antibody batches did not differ significantly and correlated significantly (r=0.91; p less than 0.001). The median serum concentration of non-protein bound testosterone was 0.265 nmol/l (range 0.068-0.495 nmol/l) when determined by equilibrium dialysis and 0.232 nmol/l (range 0.042-0.610 nmol/l) when calculated according to the law of mass action. This difference is insignificant. The concentrations of non-protein bound testosterone determined by the two methods correlated significantly (r=0.83; p less than 0.001). In the calculation of non-protein bound testosterone, the actual serum albumin concentration can be replaced by a fixed albumin concentration (r=0.99; p less than 0.001). Further, in these patients the serum concentration of non-protein bound testosterone can be expressed by the testosterone/SHBG ratio (r=0.97; p less than 0.001).

Dialysis↗

PubMed2000

Oral testosterone administration detected by testosterone glucuronidation measured in blood spots dried on filter paper.

BACKGROUND: Blood sampling is not a common practice for sports drug testing. Our aim was to investigate whether dried blood spots on filter paper could be an alternative to plasma samples for monitoring steroid profiles in dope testing. METHODS: We collected dried blood spots and plasma from six healthy Caucasian subjects after an oral 120-mg dose of testosterone undecanoate (TU). Nonconjugated testosterone, testosterone glucuronide (TG), androsterone glucuronide (AG), and etiocholanolone glucuronide (EtG) were measured by gas chromatography-mass spectrometry in both matrices. 17alpha-Hydroxyprogesterone (17alphaOHP) and luteinizing hormone (LH) also were measured in the plasma samples. For comparison, similar measurements were done on samples obtained from the same subjects given 25 mg of testosterone propionate (TP) plus 110 mg of testosterone enanthate (TE) intramuscularly after a wash-out period. RESULTS: After oral TU intake, TG, AG, and EtG increased sharply, whereas nonconjugated testosterone did not change significantly. Results on dried blood spots correlated well with those on plasma. The TG/testosterone ratio in blood or plasma was verified to be a sensitive and specific marker (significantly increased for up to 8 h after intake; P <0.05) for oral TU intake but not for intramuscular administration of TP plus TE. Little suppression of plasma LH and 17alphaOHP was observed after a single oral dose of TU. One subject did not show a significant increase of blood TG after oral TU intake. CONCLUSIONS: The measurement of glucuronide conjugates in blood and plasma samples is relevant for sports drug testing when analyzing the steroid profile. Dried blood spots collected on filter paper are a suitable alternative to plasma for detecting testosterone abuse.

Administration, Oral↗

PubMed1989

Testosterone replacement with transdermal therapeutic systems. Physiological serum testosterone and elevated dihydrotestosterone levels.

Testosterone was administered transdermally to hypogonadal men under three protocols. In the first protocol, it was shown that peak levels of testosterone were achieved three to eight hours after scrotal application of a transdermal therapeutic system containing 5, 10, or 15 mg of testosterone, and values at 22 hours were greater than 60% of peak values. In the second protocol, patients were treated with 10-mg systems for four weeks followed by 15-mg systems for eight weeks. Serum samples were obtained three to five hours after application of the transdermal therapeutic system. Testosterone increased from a pretreatment level (mean +/- SE) of 1.5 +/- 0.4 nmol/L to 15.2 +/- 3.4 nmol/L at four weeks, 18.6 +/- 3.3 nmol/L at eight weeks, and 17.3 +/- 2.8 nmol/L at 12 weeks. The serum testosterone/dihydrotestosterone (DHT) ratio fell from 4.53 to 2.47 at four weeks and was similar at eight and 12 weeks, reflecting a greater rise in DHT with this route of treatment (normal testosterone/DHT ratio, 9/1 to 12/1). Eight patients were treated with the 15-mg systems for an additional year. Seven of the eight were compliant and maintained serum testosterone levels (at six time points from two to 12 months [mean +/- SE] ) ranging from 11.5 +/- 1.2 to 44.9 +/- 2.4 nmol/L. It was possible to achieve physiological serum levels of testosterone by transdermal administration of testosterone in two thirds of our hypogonadal men.

Administration, Cutaneous↗

PubMed1995

Castration decreases thrombocytopoiesis and testosterone restores platelet production in castrated BALB/c mice: evidence that testosterone acts on a bipotential hematopoietic precursor cell.

BALB/c male mice have higher platelet counts than female mice of the same strain. To test the hypothesis that testosterone influences platelet production, we evaluated indices of both red blood cell and platelet production in intact male BALB/c mice, in male mice 4 weeks after castration, and in castrated mice administered maintenance doses of testosterone as testosterone propionate. As predicted, castration resulted in decreased hematocrit and body weight in BALB/c mice. Body weights and hematocrits returned to noncastrated levels after 2 and 7 days, respectively, of administration of testosterone. Total circulating red blood cell mass and total circulating red blood cell count were both decreased by castration and were returned to control (noncastrated) levels after 2 days of testosterone therapy. Reticulocyte counts were not changed by castration, but they increased above counts of uncastrated and castrated control mice after 3 days of testosterone administration. White blood cell (WBC) numbers were unaffected by castration or testosterone administration. Additionally, platelet count (956 vs 834 x 10(3)/microliters), platelet size (3.87 vs 3.75 microns3), sulfur 35 incorporation into platelets (6.36 vs 4.87 x 10(-3)%), mean megakaryocyte ploidy (17.43N vs 16.89N), total circulating platelet mass (TCPM) (490 vs 379 x 10(8) microns3), and total circulating platelet count (TCPC) (131 vs 103 x 10(7)) were significantly (p < 0.05) decreased in castrated mice as compared with intact control mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Intratesticular factors and testosterone secretion. Effect of treatments that alter the level of testosterone within the testis.

The authors recently have reported the presence of a nongonadotropic polypeptide factor in rat testicular interstitial fluid that can exert marked stimulatory effects on Leydig cell testosterone production. To assess the potential physiologic significance of this factor, its effective levels in rat interstitial fluid have been investigated in response to treatments that either markedly reduce interstitial fluid testosterone concentrations (anti-LH treatment; transient or chronic experimental cryptorchidism; destruction of Leydig cells with ethane dimethanesulphonate) or that significantly elevate testosterone levels in interstitial fluid by injection of hCG. The possible relationship between this factor and changes in testicular weight, serum LH and FSH, and interstitial fluid volume also were monitored. When testosterone levels in interstitial fluid were decreased by 75 to 99% either acutely (5-72 hours) or chronically (20-75 days), there was an accompanying increase (P less than 0.001) in the levels of the interstitial fluid factor(s), as determined by the ability of charcoal-stripped interstitial fluid from individual rats to enhance hCG-stimulated testosterone production by Percoll-purified Leydig cells in vitro. Anti-LH treatment increased the levels of the interstitial fluid factor(s) over the ensuing 5 to 48 hours. In abdominal testes from rats made unilaterally or bilaterally cryptorchid for 20 or 55 days, a decrease in interstitial fluid testosterone levels was associated with increased levels of the interstitial fluid factor(s). The same inverse relationship was found 72 hours after treatment with ethane dimethanesulphonate in which Leydig cells had disappeared from the testis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗