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S Maddocks

Publications and source records attributed to S Maddocks.

At least 37 records · Page 2Linked to original sources
PubMed1990

Regulation of the testis.

The testicular cells are regulated by factors produced locally in the testis. These factors include peptide growth factors, pro-opiomelanocortin derivatives, neuropeptides and steroids. Several agents able to affect steroido- and spermatogenesis can also affect leukocytes and many of the testis-regulating factors are produced by immune cells, suggesting that testicular cells and leukocytes may interact. In the present article, the effects of various testicular cell and leukocyte produced factors on steroido- and spermatogenesis are reviewed. The possibility that leukocytes may produce substances able to affect the testicular functions suggests that inhibition of immune system activation in the testis may be important also for reasons other than protection of autoantigenic germ cells from an autoimmune attack.

Androgens↗
PubMed1990

The effects of sexual maturation and altered steroid synthesis on the production and route of secretion of inhibin-alpha from the rat testis.

This study has determined the route of secretion of inhibin-alpha into blood by the rat testis during sexual maturation, and in adult animals in which Leydig cell steroidogenesis was stimulated with human CG (hCG) or suppressed with aminoglutethimide. In each rat, inhibin-alpha levels were measured in samples of testicular (TV), spermatic (SV), and peripheral (PV) venous blood plasma, and in testicular interstitial fluid (IF). The IF and TV plasma reflect inhibin-alpha secretion via the base of the Sertoli cell while that secreted via the apex of the Sertoli cell (which is resorbed from the rete testis) was determined from the difference between SV and TV levels of inhibin-alpha. During sexual maturation, inhibin-alpha levels in IF and all plasma samples declined from maximal values at 28 days of age to minimal values at 100 days of age, in contrast to testosterone levels which showed the reverse pattern. There was a major change with age in the route of secretion of inhibin-alpha from the testis into blood. In immature (28-35 days) rats, most inhibin-alpha (58-65%) leaving the testis in blood was derived from that secreted via the base of the Sertoli cell with a relatively small contribution (35-42%) from apically-secreted inhibin-alpha. However, the latter made a progressively increasing contribution between 45 and 100 days of age (adults) and in adult rats the vast majority of inhibin-alpha (95%) leaving the testis in blood was derived from apically-secreted inhibin-alpha. This change was due primarily to a progressive reduction with age in the secretion of inhibin-alpha via the base of the Sertoli cell, a change which was confirmed by inhibin bioassay. Stimulation of steroidogenesis in the adult testis with hCG significantly increased inhibin-alpha and testosterone levels in IF and all plasma samples. The concomitant administration of hCG and aminoglutethimide (to block steroidogenesis) prevented the hCG-induced increase in testosterone levels, but still led to significant increases in inhibin-alpha secretion which were comparable to those seen with the use of hCG alone. The administration of aminoglutethimide (AMG) on its own did not alter the inhibin-alpha secretion profile from that seen in controls, but it did significantly reduce the levels of testosterone in all fluids. In rats treated with hCG +/- AMG there was a small change in the route of secretion of inhibin-alpha into blood, with an increased contribution (24-37%) from inhibin-alpha secreted via the base of the Sertoli cell, when compared with controls (7-16%).(ABSTRACT TRUNCATED AT 400 WORDS)

Aminoglutethimide↗
PubMed1989

Assessment of the contribution of Leydig cells to the secretion of inhibin by the rat testis.

Cultured Leydig cells secreted 1.3-4.3 ng 1-26 alpha-inhibin/10(6) cells/24 h, and although this was unaffected by human chorionic gonadotrophin (hCG), these cells could contribute to the intratesticular and blood levels of inhibin. The present study evaluated this contribution in rats in which the Leydig cells were destroyed by injection of ethane dimethane sulphonate (EDS). In these animals, inhibin levels increased in testicular interstitial fluid (IF), and in testicular (TV) and spermatic (SV) venous blood. In EDS-treated rats supplemented for 21 days with 1 or 25 mg testosterone esters to maintain full spermatogenesis and/or suppress the elevated follicle-stimulating hormone (FSH) levels and prevent Leydig cell regeneration, significant changes occurred in the levels of inhibin in IF, in TV and SV plasma and in the route of secretion of inhibin from the testis (i.e. via IF or seminiferous tubule fluid). However, none of these changes was related to the presence or absence of Leydig cells. It is concluded that Leydig cells make little contribution to the intratesticular and blood levels of inhibin in the adult rat.

Animals↗
PubMed1989

Evaluation of the relative importance of endocrine and paracrine factors in control of the levels of inhibin in testicular interstitial fluid.

This study aimed to identify the role of endocrine (FSH, LH, testosterone) or paracrine (Leydig or germ cell) factors in control of the secretion of inhibin into testicular interstitial fluid (IF). This was done by measuring inhibin and testosterone levels in IF, and serum gonadotrophin and testosterone levels in adult rats following the destruction of Leydig cells with ethane dimethane sulphonate (EDS), alone or in combination with testosterone ester (TE) supplementation at various doses initiated at various times after EDS treatment. The effect of germ cell loss (induced by local testicular heating) on its own or in combination with the above treatments was also assessed. Treatment with EDS led to major increases in the levels of inhibin in IF and of FSH and LH in serum whilst testosterone levels in IF and serum fell to undetectable levels. Supplementation with TE (1-25 mg) for 21 days from the time of EDS treatment failed to prevent the initial (+3 days) increase in IF levels of inhibin but thereafter suppressed inhibin to control levels or lower and grossly suppressed FSH and LH levels, irrespective of whether the dose of TE administered did (25 or 5 mg) or did not (1 mg) prevent major seminiferous tubule damage. Partial regeneration of Leydig cells and normalization of testosterone levels occurred in rats 21 days after treatment with EDS alone but this failed to normalize inhibin and gonadotrophin levels. When supplementation with TE (25 mg) was initiated at 3, 6 or 9 days after EDS treatment, IF levels of inhibin were normalized within 3 days and maintained thereafter in parallel with suppression of serum FSH and LH to below control levels. Seminiferous tubule damage induced by local testicular heating (43 degrees C for 30 min) led to increased IF levels of inhibin 3 and 14 days later, in parallel with increased serum levels of FSH (but not LH). Suppression of FSH to subnormal levels in heat-exposed rats by TE treatment (25 mg) restored IF inhibin to control levels or below, a change which still occurred when Leydig cells were destroyed by EDS treatment. It is concluded that secretion of inhibin via the base of the Sertoli cell into testicular IF is controlled primarily by FSH, although local factors may play a minor role. These findings have important implications regarding the possible paracrine role(s) of inhibin in IF during puberty and in the normal adult testis.

Animals↗
PubMed1989

Interstitial fluid volume in the rat testis: androgen-dependent regulation by the seminiferous tubules?

Regulation of testicular interstitial fluid (IF) volume has been investigated in adult male rats in which the Leydig cells were selectively destroyed with a single i.p. injection of ethane dimethane sulphonate (EDS). Following this treatment, some animals also received testosterone supplementation by s.c. injection every 3 days, beginning either from the time of EDS injection, or 3-12 days afterwards. The volume of IF obtained by drip collection was determined, and testosterone and gonadotrophin concentrations measured in blood and in IF. Testosterone levels in IF and serum became undetectable by 3 days after EDS treatment. IF volume was reduced by 50% (P less than 0.01) to reach a minimum level between 6 and 9 days after treatment. However, this decline was prevented in the absence of Leydig cells by supplementation with testosterone from the time of EDS injection, a treatment which also kept gonadotrophins at minimum or undetectable levels. Furthermore, the reduced IF volume seen up to 9 days after treatment with EDS alone could be restored to control levels within 3 days by a single injection of testosterone. The results obtained demonstrate that androgens, but not Leydig cells or gonadotrophins, are required for the maintenance of interstitial fluid volume in the adult rat testis. It is suggested that the seminiferous tubules may mediate this response, through an androgen-dependent mechanism.

Animals↗
PubMed1989

The route of secretion of inhibin from the rat testis.

Levels of immunoactive and bioactive inhibin were measured in venous blood collected at a point just before (testicular venous) and after (spermatic venous) its passage through the mediastinal venous plexus over the anterior pole of the rete testis, and compared with levels in peripheral venous blood and testicular interstitial fluid (IF). In 15 control rats, levels of inhibin were highest in IF (8900 +/- 432 ng/l; mean +/- SEM) and lowest in peripheral (290 +/- 32 ng/l) and testicular (288 +/- 34 ng/l) venous blood, whilst levels in spermatic venous blood (633 +/- 99 ng/l) were always higher (P less than 0.002) than the levels in testicular venous blood. The latter difference was either reduced or abolished after disruption of spermatogenesis by local heating of the testes 8, 14, or 21 days previously, and by ligation of the efferent ducts for 6 h or more, but was not affected by acute removal of the epididymis. It is concluded that inhibin secreted into seminiferous tubule fluid may be reabsorbed from the rete testis and this may be the major route by which it reaches the peripheral bloodstream in rats with normal spermatogenesis.

Animals↗
PubMed1989

Testosterone concentrations in testicular interstitial fluid collected with a push-pull cannula or by drip-collection from adult rats given testosterone or aminoglutethimide.

This study was designed to investigate the differences in testosterone concentrations measured in testicular extracellular interstitial fluid obtained with a push-pull cannula or by post-mortem drip-collection. In the first experiment, testosterone-filled silicone elastomer capsules (2-16 cm lengths) or empty 2 cm capsules were implanted s.c. in adult male rats for 1 week. Animals were then anaesthetized and interstitial fluid was collected with a push-pull cannula for 1 h from one testis in each animal. Testicular and peripheral venous blood were then sampled and supernatant fluid was collected from the dispersed cells of the same testis. The contralateral testis in each animal was removed, and postmortem interstitial fluid obtained by drip-collection for 20 h at 4 degrees C. In animals given empty capsules, testosterone concentrations in drip-collected interstitial fluid were significantly (P less than 0.01) greater than testicular and peripheral venous blood levels, testicular fluid levels, and levels in interstitial fluid calculated from push-pull cannula samples. The concentrations of testosterone calculated in interstitial fluid collected with a push-pull cannula were never significantly greater than testicular venous blood levels. In animals with testosterone-filled capsules, testosterone concentrations measured in drip-collected interstitial fluid were similar to those calculated from push pull cannulae samples, and to testicular venous blood levels. In a second experiment, a group of adult male rats was pretreated with amino-glutethimide to block steroidogenesis. Two hours later, interstitial fluid was drip-collected from the testes of these animals and from a group of vehicle-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglutethimide↗
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↗
PubMed1989

Dynamics of testosterone secretion by the rat testis: implications for measurement of the intratesticular levels of testosterone.

Testosterone concentrations have been measured in testicular interstitial fluid (IF), and in blood plasma sampled from various parts of the rat testis and spermatic cord, to assess (1) the most accurate method for determination of the intratesticular levels of testosterone, and (2) the route of secretion of testosterone from the testis. In untreated adult rats, testosterone concentrations were highest in blood collected from veins on the surface of the testis (269.50 +/- 30.63 (S.E.M.) nmol/l), but were reduced by 56% on average in blood collected from veins at the proximal end of the spermatic cord (123.06 +/- 24.75 nmol/l), and were reduced considerably in peripheral venous blood (4.55 +/- 0.55 nmol/l). Similar changes occurred in adult rats in which steroidogenesis was either stimulated (by treatment with human chorionic gonadotrophin; hCG) or inhibited (by treatment with aminoglutethimide; AMG), and in rats of various ages during sexual maturation. The reduction in testosterone levels during passage of blood from the testis up the spermatic cord is probably due mainly to dilution by incoming arterial blood which transfers to venous blood via anastomoses in the spermatic cord. Venous-arterial transfer of testosterone in the cord contributed to this in only a minor way. Concentrations of testosterone in testicular IF were always greater than testicular venous concentrations in control, developing and hCG-stimulated rats, but were comparable in rats treated with AMG to suppress Leydig cell steroidogenesis. These and other results demonstrate that the method of drip-collection of IF results in over-estimation of the actual intratesticular levels of testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Evidence for a role of the Leydig cells in control of the intratesticular secretion of inhibin.

Injection of adult male rats with human chorionic gonadotrophin (hCG) caused a dose- and time-dependent increase in the levels of immunoactive inhibin in testicular interstitial fluid (IF), which differed from the pattern of change in testosterone levels. Blockage of the hCG-induced increase in IF levels of testosterone, by administration of aminoglutethimide, only partially attenuated the increase in levels of inhibin. Inhibin levels in IF were only increased by doses of hCG which cause inflammatory changes and focal seminiferous tubule damage, but there was no association between the degree of tubule damage and inhibin levels. It is concluded that one or more luteinizing hormone (LH)-regulated, non-steroidogenic Leydig cell products may be involved in the paracrine control of inhibin secretion. These data are of clinical relevance and of potential physiological significance.

Aminoglutethimide↗
PubMed1988

The rejection of thyroid allografts in the ovine testis.

The survival of thyroid autografts and allografts in the ovine testis has been investigated. Thyroid autografts survived and concentrated iodine 4 weeks after transplantation. Healthy colloid-containing follicles were found in the graft at this time, although no response of the grafts to a thyrotropin releasing hormone (TRH) challenge could be detected and there was no detectable basal thyroxine secretion into testicular venous blood or lymph. Thyroid allografts, however, were effectively rejected within 4 weeks of transplantation and did not concentrate iodine. No healthy tissue in the allografts could be found at 4 weeks after transplantation. Thus, in contrast to rodents and related species, the ovine testis does not appear to be an immunologically privileged site. This suggests that the immune privileged status of the rodent testis is not necessarily a general mammalian characteristic.

Animals↗
PubMed1988

The composition of extracellular interstitial fluid collected with a push-pull cannula from the testes of adult rats.

1. A push-pull cannula has been used to obtain extracellular interstitial fluid from the testes of anaesthetized adult rats. 2. Assuming or having demonstrated that appropriate radioactive markers had equilibrated between the vascular and extracellular fluid compartment of the testis, the dilution of the cannula infusate by extracellular interstitial fluid of the testis has been determined. These dilutions have then been used, with the measured concentrations of sodium, potassium, protein and testosterone in the perfusate, to calculate the concentrations of these substances in undiluted extracellular interstitial fluid of the testis. 3. Sodium, potassium and protein levels in testicular interstitial fluid calculated in this way were similar to blood plasma levels. Testosterone concentrations were certainly no greater than in testicular venous blood, and may have been even less. The results with testosterone and potassium contrast with earlier results obtained with less-physiological techniques.

Animals↗
PubMed1988

Macrophages, lymphocytes and MHC II antigen in the ram and the rat testis.

Macrophages and various subtypes of lymphocytes were identified in the ram and the rat testis by using cytochemical and immunocytochemical techniques. Large and round acid phosphatase-positive cells, notably macrophages, were observed in the rat testis. These cells were absent in the ram testis. Small, elongated cells exhibiting acid phosphatase activity were observed in the testis of both species. The rat testicular interstitium contained 7.7 times as many acid phosphatase-positive cell profiles/surface area unit as did the ram testicular interstitium. T lymphocytes were only occasionally seen in the testis of rat and ram. B lymphocytes were not found in the ram. None of the cell types studies was found in the germinal epithelium.

Animals↗
PubMed1987

Effects of repeated injections of human chorionic gonadotrophin on vascular permeability, extracellular fluid volume and the flow of lymph in the testes of rats.

Testicular lymph flow, interstitial fluid volume and vascular permeability have been measured in adult male rats injected subcutaneously with hCG daily for up to 4 consecutive days. Albumin clearance was also measured in rats given two or three hCG injections at 2- or 3-day intervals, or every 2 days for 22 days. While a single dose of hCG increased vascular permeability and lymph flow within 24 h, subsequent daily injections did not produce any additional response and, in fact, values returned towards control levels. A second hCG dose 2 days after an initial dose did produce another similar increase in the clearance of albumin injected directly into the testis and, with continued injections every second day, a response was still evident after 22 days. The response to the second dose of hCG occurred at a time when down-regulation of hCG receptors on Leydig cells is reported to be maximal. These results suggest that in the testis, the vascular response to hCG does not require the normal number of luteinizing hormone (LH) receptors, although other evidence suggests that Leydig cells must somehow be involved.

Animals↗
PubMed1986

A double-blind placebo-controlled trial of progesterone vaginal suppositories in the treatment of premenstrual syndrome.

Rigorous criteria were used to select women with severe premenstrual syndrome for inclusion in an 8-month double-blind placebo-controlled clinical trial of progesterone vaginal suppositories. Following a control month without treatment, progesterone (200 mg in polyethylene glycol base) or placebo was self administered twice daily by vaginal suppository for a minimum of 12 days before the onset of menstruation for 3 months. Crossover to the opposite medication for a further 3 months was followed by a final control cycle without treatment in month 8. Physician contact was minimized throughout the study to avoid any possible positive effects of psychological support which may have confounded past investigations. Detailed self-report questionnaires were completed every 3 days for the duration of the study. Although the attrition rate was high, 20 women completed the trial and their records are analyzed here. The results of this trial indicate that the response to vaginal progesterone in these dosages is, at best, marginal and not significantly different from response with placebo use.

Adolescent↗
PubMed1985

Effect on wool growth of thyroxine replacement in thyroidectomized merino rams.

The effect on wool growth of thyroidectomy with subsequent thyroxine replacement at subnormal and supranormal levels has been investigated in Merino rams fed a restricted basal diet. Thyroidectomy without thyroxine replacement caused a greater than 60% reduction in wool growth. Provision of 30% of normal plasma thyroxine concentrations was sufficient to return wool growth to normal. Similarly, complete replacement of plasma thyroxine levels gave normal wool growth while increasing thyroxine concentrations to three times normal increased wool growth to levels slightly above normal. These results provide a possible explanation for the inability of other workers to correlate seasonal thyroxine patterns and annual wool growth variations.

Animals↗
PubMedDate not supplied

Testosterone and spermatogenesis. Identification of stage-specific, androgen-regulated proteins secreted by adult rat seminiferous tubules.

The aim of this study was to identify potential androgen-regulated proteins (ARP) that might mediate the supportive effects of testosterone on spermatogenesis. Adult rats were injected with ethane dimethane sulphonate (EDS) to destroy Leydig cells and thus induce complete testosterone withdrawal. Other EDS-treated rats were injected with 25 mg testosterone esters (TE) every 3 days to maintain quantitatively normal spermatogenesis. A timeframe for the study of androgen action on spermatogenesis was deduced from enumeration of degenerating germ cells at stage VII of the spermatogenic cycle in perfusion-fixed testes from rats in the early stages (4 to 8 days) after EDS treatment. Based on this data and changes in testicular interstitial fluid volume, long seminiferous tubule segments were isolated from control rats and from EDS-treated rats (+/- TE-supplementation) at stages II-V, VI-VIII, or IX-XII, 2 days to 6 days after EDS treatment. Seminiferous tubule segments were incubated for 22 hours with 60 microCi 35S-labelled methionine. Incorporation into newly synthesized proteins in the seminiferous tubule culture medium (= secreted proteins) or in seminiferous tubule lysates (= intracellular proteins) was determined by trichloroacetic acid-precipitation followed by analysis using two-dimensional sodium dodecylsulfate polyacrylamide gel electrophoresis. In control rats, incorporation of 35S-methionine into proteins secreted by isolated seminiferous tubules was more than twice as great at stages VI-VIII than at stages II-V or IX-XII. This doubling in methionine incorporation into stages VI-VIII secreted proteins was abolished, however, 4 days after EDS treatment (when germ cell degeneration at stage VII was only just evident). A similar change occurred 4 days after testosterone withdrawal induced by immunoneutralization of luteinizing hormone. In the latter case and after EDS treatment, TE-supplementation of rats from day 0 maintained the normal control pattern of methionine incorporation into seminiferous tubule secreted proteins, although 6 days after EDS and TE treatment, incorporation into stages VI-VIII secreted proteins was 19% lower (P less than 0.05) than in the control group. In contrast, incorporation of methionine into proteins secreted by seminiferous tubules at stages II-V and IX-XII was unaffected by EDS and TE pretreatment, as was incorporation into intracellular proteins at all stages.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen-Binding Protein↗