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Biomedical subjects

I Cooper

Publications and source records attributed to I Cooper.

At least 19 recordsLinked to original sources
PubMed1992

High dose chemotherapy and autologous bone marrow transplantation in advanced Hodgkin's disease.

OBJECTIVE: To present the use of high dose chemotherapy with autologous bone marrow transplantation as salvage therapy for advanced Hodgkin's disease in Australia. DESIGN: A prospective open study for patients whose disease was resistant to conventional treatment. SETTING: The bone marrow transplantation units of four Australian tertiary hospitals. PATIENTS: Seventeen patients (median age 30 years) entered and completed the study. The stage of the disease at initial diagnosis was I or II (seven patients), III (seven patients) and IV (three patients). Histological types were lymphocyte predominant (one), nodular sclerosis (12), mixed cellularity (three) and unknown (one). Therapy before consideration for transplantation included radiotherapy (13), mustine, vincristine, procarbazine and prednisone (MOPP--17 patients) or doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD--13 patients) and other chemotherapy regimens (five). The median interval from diagnosis to transplantation was 29 months (range, 9-178 months). The patient's disease was classified as sensitive (nine) or resistant (eight) to treatment, depending on the response to the most recent course of chemotherapy. INTERVENTIONS: Morphologically normal autologous bone marrow was harvested and cryopreserved. The conditioning regimen given was cyclophosphamide, carmustine and etoposide (14) or busulphan and cyclophosphamide (three). The marrow was then infused. MAIN OUTCOME MEASURES: Remission (complete or partial), disease-free survival and overall survival. RESULTS: Over all, 10 of 17 patients (59%) entered or remained in complete remission and four of 17 (24%) achieved partial remission. The overall actuarial survival at 30 months was 70%. Eight of the nine patients with treatment-sensitive disease (89%) remain disease-free at a median of 22 months (range, 18-29 months) after transplantation. Two of the eight patients with resistant disease (25%) are disease-free at 20 and 28 months. There was one procedure-related death from haemorrhage and four disease-related deaths at six, seven, eight and 13 months after transplantation. CONCLUSION: Autologous bone marrow transplantation may provide an effective salvage therapy in advanced Hodgkin's disease, particularly for patients with treatment-sensitive disease and a low tumour burden.

Adult↗
PubMed1991

201Tl scintigraphy in the assessment of patients with multi-vessel coronary disease undergoing angioplasty who have previously had a coronary bypass graft operation.

Percutaneous transluminal coronary angioplasty (PTCA) has an important therapeutic role in the treatment of coronary artery disease. The purpose of this study was to investigate the role of 201Tl scintigraphy in symptomatic patients with multi-vessel coronary artery disease undergoing angioplasty who had previously undergone coronary graft operations. 201Tl imaging was carried out in 12 patients prior to PTCA, 6 weeks and 6 months to 1 year post-PTCA. Prior to PTCA, 201Tl imaging correctly identified the site of the dominant lesion in all patients in correlation with the catheter results. Six weeks post-PTCA, seven cases who had angiographically successful angioplasty showed persistent defects on 201Tl imaging. In five of these cases, follow-up catheter showed that re-stenosis had occurred. Six months to 1 year post-PTCA, 201Tl imaging was found to have good correlation (11 out of 12 patients) with the catheter results. The results suggest that 201Tl imaging is useful in the management of patients with multi-vessel disease undergoing angioplasty.

Aged↗
PubMed1990

Sequential karyotypes in non-Hodgkin lymphoma: their nature and significance.

The examination of sequential karyotypes in hematologic disorders has demonstrated that karyotypic changes are often associated with concurrent changes in clinical behavior. Acquired abnormalities that recur among different patients may also suggest genomic areas important to tumor progression. We therefore examined sequential karyotypes in 21 patients with non-Hodgkin lymphoma (NHL). Sixteen of the 21 karyotypes demonstrated changes, including the majority of 6 small lymphocytic, 11 follicular, and 4 intermediate and high-grade diffuse lymphomas. The t(14;18)(q32;q21) occurred in ten initial karyotypes was retained in all cases. The band most frequently affected by newly acquired abnormalities was 14q32 (n = 5); chromosomes 1 and 2 (n = 5, each), and the 17p arm (n = 4) were also commonly affected. The acquired deletion of all or part of 17p appeared to be associated with a poor prognosis. Histologic transformation and karyotypic change did not correlate. This study of sequential karyotypes in NHL 1) confirms the primary importance of the t(14;18), 2) suggests that the 14q32 band is involved frequently in both primary and secondary cytogenetic events, and 3) suggests other genomic regions of potential significance to progression.

Adult↗
PubMed1990

Cytogenetic analysis of 147 cases of non-Hodgkin's lymphoma: non-random chromosomal abnormalities and histological correlations.

A prospective cytogenetic study of patients with non-Hodgkin's lymphoma (NHL) presenting to one institution was commenced in 1983 as part of a larger study including histology, immunophenotyping, cytokinetics and survival. 175 patients were studied over 5 years and G-banded karyotypes were successfully obtained in 147. Chromosome abnormalities were detected in 135 cases (92%) with the commonest abnormality being t(14;18)(q32;q21) in 69 cases. Other non-random translocations were much less frequent, i.e. t(11;14) in seven cases and t(8;14) in four cases. Other specific structural changes included partial deletions of 6q (breakpoints ranging within q13-q23), 3q (breakpoints ranging within q21-q27), 1q and 10q22. Chromosome regions highlighted as being frequently involved in structural abnormalities were 11q13-q25, 1p22-p36, 3q21-q27 and 6q13-q23. Several specific recurring breakpoints were identified and these included 14q32, 18q21, 1p36 and 6q21. Frequently occurring numerical abnormalities were gains of chromosomes 3, 7, X and 12. Correlation with histological type showed, as expected, that t(14;18) was present in 89% of follicular lymphoma but also occurred in 30% of diffuse lymphoma. Abnormalities of 11q were correlated with the diffuse histologies as a group, whereas both numerical and structural abnormalities of chromosome 3 correlated with the diffuse large cell lymphoma (DLCL) subtype, and t(11;14) with diffuse small cleaved cell lymphoma (DSCCL). Although not statistically significant, abnormalities of 6q occurred twice as frequently in DLCL than in any other variety. However, several other commonly occurring abnormalities, such as extra copies of chromosomes 7, X, 12 and most of the structural abnormalities of 1p, did not correlate with any histological type. Therefore this large cytogenetic study has confirmed some previously reported correlations between specific chromosome abnormalities and histological subtypes of non-Hodgkin's lymphoma and has also identified some new correlations which may prove useful in the investigation of the biological basis of the disease.

Chromosome Aberrations↗
PubMed1989

Role of angioplasty in patients with previous coronary artery bypass surgery.

Fifty-nine patients with previous coronary artery bypass surgery (CABG) underwent coronary artery or vein graft angioplasty following a recurrence of symptoms, 141 lesions were attempted in 70 procedures. The overall angiographic success rate was 77%. Some angiographic success was achieved in 83% of patients. Complications included myocardial infarction in three (4.3%), death in one (1.4%), and iliac artery thrombosis in one (1.4%). No patients were referred for urgent surgery. Twenty-eight patients have undergone repeat coronary arteriography after 7.5 +/- 2.6 months (mean +/- SD), and 31% of lesions have recurred. Fifty-eight percent of patients without recurrence at follow-up continue to have improved symptoms. Treadmill exercise time was significantly prolonged in patients in whom all attempted lesions had been successfully dilated and in those in whom only some lesions were dilated. Our experience suggests that approximately 29% of patients with recurrence of angina following CABG may be suitable for angioplasty.

Adult↗
PubMed1988

Immunoglobulin allotypes Gm and Km in hematologic malignancies.

Immunoglobulin allotypes of the Gm and Km systems have been compared in patients with various forms of hematologic malignancies and healthy controls of the same ethnographic background. These comparisons found an increased frequency of the haplotype Gm and a decreased frequency of Gm in patients with Hodgkin's disease; a decreased frequency of Gm in diffuse, large-cell lymphoma patients; a decreased frequency of Gm and an increased frequency of Gm in acute myeloid leukemia patients; a decreased frequency of Gm in chronic myeloid leukemia patients, and an increased frequency of the phenotype Km(1+) in chronic lymphocytic leukemia patients. These results support previous suggestions of the involvement of immunoglobulin allotypes in the susceptibility to some forms of human hematologic malignancy.

Gene Frequency↗
PubMed1988

Transient platelet and HLA antibody formation in multitransfused patients with malignancy.

Fifty-nine patients receiving platelet transfusions for bone marrow failure secondary to malignancy were screened at regular intervals for the presence of antibodies to human leucocyte (HLA) and platelet specific antigens. HLA antibodies occurred in 19 patients, 10 of whom also developed platelet specific antibodies. The HLA antibodies disappeared in 10 of 15 patients followed for periods of 2-14 months. In two patients this occurred whilst still receiving platelet transfusions. Antibody reappeared in only two of six patients subsequently transfused. Antibodies to platelet specific antigens were detected in 28 patients. They were transient, often appeared in association with infection, and in 50% of cases tested demonstrated autoantibody activity. There was no association with antibiotic drug therapy, or PFA/EDTA-dependent cryptantigens. Platelet recovery at 1 h or 20 h post transfusion was not significantly reduced in the presence of platelet specific antibodies. These findings have important implications for the selection of platelet donors for alloimmunized recipients.

Antibodies↗
PubMed1988

Re-evaluation of the intratesticular level of testosterone required for quantitative maintenance of spermatogenesis in the rat.

The amount of testosterone required for quantitative maintenance of spermatogenesis has been re-evaluated using techniques aimed at minimizing the synthesis of testosterone after removal of the testis. Adult male rats were treated with ethane dimethane-sulphonate (EDS) to destroy the Leydig cells, and were supplemented with 25, 5 or 1 mg testosterone esters by injection every 3 days for 21 days. Serum hormone levels, testicular morphology and spermatogenesis were assessed and the intratesticular levels of testosterone compared in testes either removed under ether anaesthesia and placed in liquid nitrogen (right testis) or removed after collection of blood and placed in ice (left testis). Data for testosterone-supplemented rats were compared with those for control rats and rats treated with EDS alone. All doses of testosterone suppressed LH and FSH levels in serum to within the hypophysectomized range, and Leydig cell regeneration in EDS-treated rats was prevented completely. Treatment of EDS-injected rats with 25 or 5 mg testosterone maintained testicular weight, the number of germ cells and the diameter of seminiferous tubules at stage VII within or above the control range, although there was a significant increase in the number of degenerating pachytene spermatocytes at stage VII with 5 but not 25 mg testosterone; none of these parameters was maintained at control levels by a dose of 1 mg testosterone. Levels of testosterone in testosterone-supplemented rats differed little between testes collected in ice and liquid nitrogen, but in controls and rats treated with EDS alone, testosterone levels were overestimated by 75 and 27% respectively when comparing testes collected in ice with those collected in liquid nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Factors affecting the secretion of immunoactive inhibin into testicular interstitial fluid in rats.

Immunoreactive inhibin was measured in testicular interstitial fluid (IF) from rats during sexual maturation or after impairment of spermatogenesis induced by ethane dimethanesulphonate (EDS), unilateral cryptorchidism or local heating (43 degrees C, 30 min) of the testes, to ascertain its usefulness as a marker of changing Sertoli cell function. Cultures of isolated seminiferous tubules were also studied. Inhibin was measured by a radioimmunoassay directed towards the first 26 amino acids of the N-terminus of the alpha-subunit, and the results confirmed for selected pools of IF by in-vitro bioassay using dispersed ovine pituitary cells. During puberty, IF levels of immunoactive inhibin fell by more than 90% (P less than 0.001) between 30 and 60 days of age, a decrease paralleled by the levels of androgen-binding protein (ABP), another Sertoli cell product secreted into IF. These changes also paralleled, but preceded, the fall (60%; P less than 0.001) in serum levels of FSH between 40 and 70 days, while the serum and IF levels of testosterone increased more than two-fold over this period. When adult rats were injected with EDS to destroy the Leydig cells, testosterone levels in IF and serum were undetectable at 3 and 7 days after treatment, were just detectable at 14 days and thereafter returned slowly towards normal by 42 days. The initial androgen withdrawal following EDS treatment caused a progressive reduction in testicular weight up to 21 days and this was accompanied by a significant increase in the serum levels of FSH and a two- to threefold increase in the IF levels of immunoactive inhibin (and also of ABP). Serum FSH and IF levels of immunoactive inhibin returned to within the normal range by 42 days when testosterone levels had normalized. In contrast, in two other experimental situations in which a marked decrease in testicular weight coupled with an increase in IF levels of ABP occurs, different results for the IF levels of immunoactive inhibin were obtained. Thus, in rats exposed to local heating of the testes, IF levels of immunoactive inhibin remained unchanged from control values at 21-40 days after treatment, a finding confirmed by bioassay results. In rats made unilaterally cryptorchid for 10 months, levels of immunoactive inhibin in IF were reduced by 60% (P less than 0.01) in the abdominal compared with the contralateral scrotal testis.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1987

Relationship between the exposure of Leydig cells to factor(s) present in testicular interstitial fluid and changes in their capacity to secrete testosterone during culture or after hCG-induced desensitization.

This study has evaluated whether the decrease in capacity of Leydig cells to secrete testosterone that occurs during culture or after desensitization with hCG in vivo, is a consequence of the removal of a stimulatory factor(s) in testicular interstitial fluid (IF) to which Leydig cells are normally exposed. When Percoll-purified rat Leydig cells were cultured for 3 days in vitro, there was a progressive reduction in their ability to respond to hCG in terms of either testosterone or progesterone production. In contrast, culture of the cells in the presence of 10% charcoal-stripped IF maintained responsiveness to hCG either partially or completely. This effect was attributable to a factor(s) in IF with a molecular weight of greater than 30 kDa; a comparable fraction from serum had little or no effect. Crude Leydig cells from rats injected 24 h previously with 50 IU hCG showed a 70% reduction in their testosterone response to hCG in vitro and, compared to controls, increased testosterone production poorly in response to increasing concentrations of IF. However, progesterone secretion was increased considerably in response to IF. As in controls, fractionation of crude Leydig cells from hCG-desensitized rats on Percoll gradients resulted in three bands of Leydig cells, except that the yields of band 2 and 3 cells (containing about 40 and 85% Leydig cells, respectively) were reduced by 75% and 90%, respectively, with the majority of Leydig cells remaining in band 1 (which comprises poorly responsive cells). Band 2 and 3 cells from hCG-desensitized rats were not greatly different to cells from control rats in terms of their testosterone response to hCG +/- IF, although they produced considerably more progesterone. It is concluded that the reduced capacity of Leydig cells to secrete testosterone during culture may be attributable to some extent to the removal of a factor(s) in IF to which the cells are normally exposed. In contrast, the reduced in vivo exposure of Leydig cells to such factors, as occurs after hCG injection, cannot explain the poor testosterone response of these cells when they are isolated and cultured.

Animals↗
PubMed1987

Comparison of the effects on purified Leydig cells of four hormones (oxytocin, vasopressin, opiates and LHRH) with suggested paracrine roles in the testis.

Four hormones have been identified by various authors as possible paracrine regulators of testicular Leydig cells. The aim of this study was to evaluate their effects on purified adult rat Leydig cells under various conditions in vitro, and then to assess whether comparable effects occurred in vivo. In agreement with previous findings, an LHRH agonist (LHRH-A) exerted clear-cut effects on testosterone secretion by Leydig cells both in vitro and in vivo. On its own, LHRH-A stimulated testosterone production by Leydig cells for up to 24 h in culture but inhibited testosterone production stimulated by human chorionic gonadotrophin (hCG) between 24 and 72 h of culture. In-vivo, unilateral intratesticular injection of adult rats with 1 ng LHRH-A resulted 5 h later in a significant increase in testosterone concentrations in testicular interstitial fluid (IF). Vasopressin exerted effects in vitro which were similar to those of LHRH-A. On its own, vasopressin stimulated testosterone production for up to 5 h of culture, but not thereafter, while in the presence of hCG, vasopressin inhibited testosterone production beyond 24 h of culture. The initial stimulatory effect of vasopressin on testosterone production occurred with concentrations of 1 nmol/l and higher, but the magnitude of stimulation (threefold or less) was considerably less than that induced by LHRH-A (ninefold) over the same time period. In contrast to LHRH-A, unilateral intratesticular injection of vasopressin in high doses (20 and 2 ng) had no effect on IF testosterone levels 5 h later.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Intratesticular factors and testosterone secretion: the effect of treatment with ethane dimethanesulphonate (EDS) and the induction of seminiferous tubule damage.

The role of seminiferous tubule dysfunction in regulating the levels of a factor (or factors) in testicular interstitial fluid (IF) which stimulates Leydig cell testosterone secretion in vitro, was assessed by injecting rats with the Leydig cell toxin, EDS. Within 72 h of treatment EDS destroyed the Leydig cells and concomitantly reduced IF testosterone to undetectable levels. This was associated with nearly a 2-fold increase (P less than 0.001) in levels of the IF-factor(s) as judged by the enhancement of hCG-stimulated testosterone production (= IF bioactivity). By 3 weeks, and thereafter up to 10 weeks post-EDS, Leydig cells regenerated within the testis, and testosterone levels returned to control values, but IF-bioactivity remained significantly increased. The latter was associated with seminiferous tubule dysfunction as indicated initially by testicular morphology, raised serum levels of FSH and reduced testicular weight. For animals with normal testosterone levels, there was a significant negative correlation (r = -0.57, N = 46; P less than 0.001) between testicular weight and IF bioactivity. A similar increase in IF bioactivity in the presence of normal testosterone levels was observed in rats in which patchy severe seminiferous tubule damage had been induced by short-term cryptorchidism. It is concluded that, in addition to testosterone, seminiferous tubule function may dictate the intratesticular levels of the testosterone-stimulating factor(s) in IF.

Animals↗
PubMed1986

Intratesticular factors and testosterone secretion: the role of luteinizing hormone in relation to changes during puberty and experimental cryptorchidism.

Testicular interstitial fluid (IF) from the rat contains a nongonadotropic polypeptide factor (or factors) which can enhance human CG (hCG)-stimulated testosterone production by Percoll-purified Leydig cells in vitro. The potential importance of this factor has been investigated by measuring its effective levels in testicular IF from individual rats during sexual maturation or after the induction of unilateral cryptorchidism (UCD). In both situations, the effect of modulating LH drive to the testis was also assessed. In abdominal testes from UCD rats, levels of the IF factor were nearly doubled (P less than 0.001) when compared to levels in the contralateral scrotal testis; this was associated with more than an 85% reduction in IF testosterone levels. Further lowering of testosterone levels by the injection of an antiserum to LH beta, raised levels of the IF factor by 30-40% (P less than 0.01) in both scrotal and abdominal testes. Conversely, raising of testosterone levels by injection of hCG caused more than a 90% reduction (P less than 0.001) in levels of the IF factor in both scrotal and abdominal testes. During sexual maturation, levels of the IF factor doubled (P less than 0.01) between 30 and 40 days of age, remained high until 70 days of age, and then decreased to the lower levels found in adult rats. High pubertal levels of the IF factor were associated with the most rapid phase of testicular growth and with a steady increase in the IF levels of testosterone. Injection of pubertal or adult rats with antiserum to ovine LH (oLH) reduced testosterone levels by approximately 85% and doubled (P less than 0.01) levels of the IF factor(s) in both groups. It is concluded that levels of the IF-factor are influenced: by testosterone levels and/or LH drive and by the maturational and/or functional status of the testis. These results also suggest that changing levels of the IF factor may be of physiological significance during puberty.

Animals↗
PubMed1984

Increase in Leydig cell responsiveness in the unilaterally cryptorchid rat testis and its relationship to the intratesticular levels of testosterone.

Adult rats were made unilaterally cryptorchid (UCD) and 6-7 weeks later Leydig cells were isolated from the scrotal and abdominal testes and their capacity to secrete testosterone in vitro was compared. Basal testosterone production by Leydig cells from the abdominal testes of UCD rats was lowered, compared with cells from the contralateral scrotal testes, whilst their responsiveness to both human chorionic gonadotrophin and an LH releasing hormone agonist was enhanced two- to threefold (P less than 0.001) compared both with cells from the contralateral scrotal testes and with cells isolated from untreated rats of the same age. In the UCD rats, concentrations of testosterone in testicular interstitial fluid (IF) were reduced (P less than 0.001) by 70-90% in abdominal, compared with scrotal, testes. A similar reduction was evident in the levels of testosterone in spermatic venous blood, and both this decrease and that in IF levels of testosterone varied according to the degree of testicular involution. The ontogeny of the above changes was investigated. After induction of unilateral cryptorchidism, the weight of the abdominal compared with the scrotal testis declined slowly, such that by day 5 there was only a 25% reduction in weight compared with a 70% reduction by day 40. In contrast, the levels of testosterone in IF from abdominal testes declined rapidly, such that by day 5 an 80% reduction was attained, compared with scrotal testes, with little further change by day 40.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Factors determining whether the direct effects of an LHRH agonist on Leydig cell function in vivo are stimulatory or inhibitory.

The influence of (1) repeated exposure to LHRH agonist and (2) concomitant exposure to various levels of LH or hCG, on the direct testicular effects of LHRH agonist have been investigated in hypophysectomized and intact rats. In the latter, LHRH agonist was injected intratesticularly into the right testis whilst the left testis was injected with vehicle, and the level of testosterone in interstitial fluid (IF) from left and right testes was compared 2-4 h later. In hypophysectomized rats, a single injection of 50-1000 ng LHRH agonist raised (P less than 0.001) serum levels of testosterone 2 h later to within the normal range (1-8 ng/ml) for intact rats of comparable age. Subsequent daily injections of LHRH agonist elicited progressively smaller responses and by day 5 no response was evident, this decline being unrelated to the increase in time after hypophysectomy. Comparable changes were observed in hypophysectomized rats pretreated with an LH antiserum. Daily injection of hypophysectomized rats with 10 IU hCG for 6 days raised serum levels of testosterone to supraphysiological levels on each day, whilst concomitant injection of LHRH agonist (1 microgram) decreased (P less than 0.001) this response at all times, an effect that became progressively more pronounced. In contrast, daily treatment with 1 microgram ovine LH raised serum levels of testosterone to within the physiological range, and concomitant treatment with LHRH agonist (50 ng) had either no effect (days 1-2) or significantly increased (days 4-6) the testosterone response to LH. In intact rats, a single unilateral intratesticular injection of 1 ng LHRH agonist increased the IF levels of testosterone unilaterally 3 h later, but subsequent injections on days 2 and 3 elicited progressively smaller responses. In rats given a single intratesticular injection of LHRH agonist combined with a peripheral injection of different doses of LH or hCG, the LHRH agonist induced a unilateral increase in IF levels of LH/hCG, whilst in rats treated with high doses of LH (12.5--25 micrograms) or hCG (50 IU). LHRH agonist either had no effect or significantly reduced the IF levels of testosterone unilaterally. However, LHRH agonist also had significant effects on testicular IF volume and, as this may reflect altered transport of LH and hCG to the Leydig cells, the inhibitory effects of LHRH agonist may be related to this change rather than to an effect of steroidogenesis itself.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Testicular interstitial fluid as a monitor for changes in the intratesticular environment in the rat.

The use of testicular interstitial fluid (IF) collected from the rat testis has been validated as (1) an index of the total extracellular extratubular fluid volume of the testis (which reflects the permeability of testicular capillaries) and (2) as a means of measuring changes in the interstitial hormonal environment. The former was tested by comparing the albumin 'space' with the volume of recovered IF in the same testes from control and bilaterally cryptorchid rats sampled at 0-40 h after injection of hCG. Although the volume of IF recovered was on average only 50% of the albumin 'space', both measures increased in parallel after hCG injection and were always closely correlated (P less than 0.001) over a 4- to 5-fold range. The volume of recovered IF increased with age in parallel with increase in testicular weight, and the testosterone concentration in IF paralleled changes in peripheral serum, increasing from 45 to 80 days of age and then declining. After injection of 25 micrograms bovine LH, testosterone levels in IF, spermatic venous (SV) and peripheral venous (PV) blood increased up to 10-fold by 1 h and returned to control levels over the next 11 h. Testosterone levels in IF were always considerably higher than those in SV blood, but this difference was not constant. Subcutaneous injection of rats with an LH-RH agonist resulted in parallel increases in the serum levels of LH and in the IF and PV levels of testosterone. However, at 6 h there was an 'LH-independent' secondary increase in testosterone levels which was associated with an increase in IF volume, reflecting an increase in capillary wall permeability and hence increased transport of LH into the testis.

Age Factors↗
PubMed1982

Stimulatory effect of LHRH and its agonists on Leydig cell steroidogenesis in vitro.

Short-term (4 h) incubation of collagenase-dispersed Leydig cells from adult rats in the presence of an LHRH agonist caused a 2-3-fold stimulation (P less than 0.001) of testosterone production. This effect was dose-dependent and as little as 5 x 10(-11) M LHRH agonist caused significant stimulation whilst maximal effects were achieved with 10(-9) M concentrations. Stimulation of steroidogenesis by LHRH agonist was prevented by addition of an antiserum specific for the peptide, but was exaggerated in the presence of the phosphodiesterase inhibitor MIX, suggesting the involvement of cyclic AMP in the response of the Leydig cells to the agonist. Native LHRH caused a similar degree of stimulation of testosterone secretion to LHRH agonist but concentrations 1000 times greater than those of the agonist were required to achieve this, a finding consistent with the known affinities of these 2 peptides for the Leydig cell LHRH-receptor. The addition of LHRH agonist also enhanced (P less than 0.001) testosterone secretion by adult rat Leydig cells in response to hCG or dibutyryl cyclic AMP, and this effect was still evident in the presence of maximally-stimulating concentrations of these factors. LHRH agonist also stimulated testosterone secretion by Leydig cells from immature rats, but this effect differed from that in the adult in being of smaller magnitude and being restricted to effects on basal secretion or secretion elicited by low concentrations of hCG. These results show for the first time (a) that LHRH and its agonists can exert effects on Leydig cell steroidogenesis during short-term incubation, and (b) that these effects are stimulatory, which contrasts with the inhibitory effects reported after long-term (2-3 days) exposure of Leydig cells to LHRH agonists in vivo and in vitro. The availability of this simple and rapid measure of a biological action of LHRH on the Leydig cell should enable its precise mode of action to be determined, and should throw light on the physiological role of endogenously produced testicular 'LHRH'.

1-Methyl-3-isobutylxanthine↗