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Biomedical subjects

B P Setchell

Publications and source records attributed to B P Setchell.

At least 55 records · Page 3Linked to original sources
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

Development of the blood-testis barrier and changes in vascular permeability at puberty in rats.

The effectiveness of the blood-testis barrier to water-soluble substances was assessed in rats of various ages by measuring the volumes of distribution of Cr-EDTA and albumin, and estimating the proportion of the testis made up by interstitial tissue and tubular lumen by morphometric techniques on cryostat sections of frozen tissue. The interstitial tissue volume fell from 15 days to reach adult values at about 30 days of age. A lumen was present in some animals at 15 days, and it enlarged progressively to reach adult levels at about 45 days of age. The 1-h Cr-EDTA space began to fall after 25 days, and reached adult values by 33 days; in rats aged 25 and 30 days, the Cr-EDTA space was almost twice the measured interstitial tissue volume, but even in the older rats, the Cr-EDTA space remained appreciably greater than the interstitial tissue volume. The 20-h albumin space did not begin to fall until after 33 days, and had still not reached adult values in rats aged 44 days. Thus, the functional barrier to water-soluble markers develops later and more gradually than the barrier to electron-opaque markers as used by previous authors, and its appearance correlates more closely with enlargement of the tubular lumen than with formation of the inter-Sertoli cell junctions. The rate at which the albumin space approached its final value was used to calculate the vascular permeability to albumin. This rose to a maximum between 25 days and 33 days of age, and then fell again, although adult values had still not been reached by 44 days of age.

Animals↗
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↗
PubMed1988

Effects of local heating of the testis on testicular blood flow and testosterone secretion in the rat.

Exposure of one or both testes of rats to heating at 43 degrees C for 30 min resulted in a significant reduction in blood flow per testis, as measured using microspheres. The effects on the testes of unilateral and bilateral heating were similar, although the changes in FSH levels in peripheral blood were in general less marked after unilateral heating. Testicular blood flow fell, along with testicular weight, beginning at 2-4 days and reaching minimum values 14-21 days after heating. Both blood flow per testis and testicular weight were beginning to recover 35 days post-heating and blood flow per testis was normal by 56 days following heat treatment, although testicular weight was still slightly reduced at that time. Heating one or both testes to 42 degrees C produced similar but smaller responses 21 days later, whereas temperatures of 41 degrees C or lower were without effect on the parameters measured, except for some rises in serum LH and FSH. With slight reductions in blood flow, there were corresponding increases in testicular venous testosterone concentration so that testosterone secretion was unaffected. Further reductions in blood flow at 14 and 21 days after heating to 43 degrees C were not fully compensated by an increase in the concentration of testosterone in testicular venous blood, with the result that testosterone secretion fell.

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

Is embryonic mortality increased in normal female rats mated to subfertile males?

Normal female rats were mated to control males or males which were subjected to unilateral testicular heating (43 degrees C for 30 min), irradiation (500 R), efferent duct ligation, arterial ligation or castration; in all males, the contralateral ductus deferens was ligated. All treatments caused reduced fertility and eventually infertility, as judged by the percentage of females becoming pregnant; the infertility was temporary after heating and irradiation. During the periods of reduced fertility, the numbers of fetuses per pregnant female and the fetus/corpus luteum ratios were reduced. In subsequent experiments, after heating of the testis, there was not only failure of fertilization despite the presence of normal numbers of spermatozoa in the uterus, but also an increased rate of embryonic degeneration in normal females. These results provide evidence that the male, while still fertile, can affect the fecundity of the female and the rate of embryo mortality.

Animals↗
PubMed1988

Gonadotrophin secretion and ovarian responses in prepubertal heifers actively immunized against androstenedione and oestradiol-17 beta.

Groups of heifer calves received a primary immunization against androstenedione (Group A; N = 11) or oestradiol-17 beta (Group E; N = 10) at 3 months of age and booster injections on 5 occasions at 2- to 3-month intervals. Controls (Group C, N = 11) were immunized against human serum albumin alone using the same protocol. Immunity was achieved against both steroids as judged by the secondary antisteroid antibody titres in Group A (1126 +/- 261; reciprocal of titre) and Group E (10,357 +/- 4067) heifers. In Groups A and E there was a general decline in the respective peak antibody titres after successive booster injections. From 3 to 9 months of age mean plasma concentrations of LH were higher (P less than 0.05) in Group E heifers (0.89 +/- 0.08 ng/ml) than in Group C (0.46 +/- 0.03 ng/ml) and Group A (0.59 +/- 0.05 ng/ml) heifers which did not differ from one another. There were no differences between groups in plasma FSH concentrations. At 10 months of age the LH response to exogenous LHRH was of higher (P less than 0.05) amplitude for heifers in Group E (2.59 +/- 0.56 ng/ml) than for those in Groups C (0.61 +/- 0.07 ng/ml) and A (1.04 +/- 0.22 ng/ml). Elevated plasma progesterone concentrations at 5 months of age were shown by 2 heifers in Group C, 10 in Group A, and 6 in Group E. From 8 to 14 months of age a consistently higher proportion of Group A heifers exhibited elevated progesterone compared with Group C and Group E heifers. After ovarian synchronization and booster injection at 15 months of age a corpus luteum was present in 2 heifers in Group C, 7 in Group A and none in Group E. The ovaries of Group A heifers were different from those of Groups C and E and were characterized by greater numbers of 2-4 mm follicles. It is concluded that active immunization against gonadal steroids influences both LH secretion and ovarian function in prepubertal heifers. Early increases in ovarian activity in androstenedione-immunized heifers are maintained after puberty and may therefore confer some lifetime reproductive advantages.

Androstenedione↗
PubMed1988

Distribution of 5 alpha-reductase in the epididymis of the tammar wallaby (Macropus eugenii) and dependence of the epididymis on systemic testosterone and luminal fluids from the testis.

The activity of 5 alpha-reductase was much higher in the caput and corpus epididymidis than in the cauda epididymidis. Orchidectomy caused a reduction in 5 alpha-reductase activity in the caput and corpus epididymidis, and regression of the epithelium and reduction in mass of all regions of the epididymis. Subsequent testosterone therapy caused a substantial increase in amount of epithelium and overall mass of the cauda epididymidis but showed little or no increase in any of the responses measured in the caput and corpus epididymidis. We concluded that the caput and corpus epididymidis of the tammar respond to factors other than testosterone, probably some constituent in the luminal fluid, and therefore are homologous with the initial segments of the epididymis in eutherians.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1988

Increases in ovulation rate in lupin-fed ewes are initiated by increases in protein digested post-ruminally.

Parous Merino ewes were maintained outdoors in feedlots during the beginning of the spontaneous breeding season and fed a maintenance ration of wheaten hay. For 14 days, ewes in each of 4 groups (N = 40/group) were given supplements of lupin grain or formaldehyde-treated casein and/or wheat starch. These were calculated to supply equivalent amounts of protein post-ruminally and/or digestible energy. Supplementation with lupin grain significantly increased ovulation rate by 37% by increasing the proportion of ewes with two ovulations. Similar increases in ovulation rate were achieved by increasing the supply of digestible protein post-ruminally in the casein and casein + starch-supplement groups. Increasing the intake of digestible energy separately in the starch-supplement group did not increase ovulation rate. It is concluded that increases in ovulation rate in ewes fed a lupin supplement are the result of significant increases in the amount of protein digested post-ruminally.

Animals↗
PubMed1987

The enterohepatic recycling of bile choline in sheep.

1. Measurement of unesterified choline in blood samples taken from five conscious multi-cannulated sheep indicated a significant production of unesterified choline by the alimentary tract, as judged by the portal venous minus arterial difference and significant uptake by the liver, as judged from the portal venous minus hepatic venous and arterial minus hepatic venous differences. 2. A mean liver blood flow rate of 1.68 +/- 0.22 1/min for the five sheep was determined by bromosulphophthalein clearance and, combined with the differences in unesterified choline across organs, gave a production rate of free choline of 9.1 mmol/day by the alimentary tract and an uptake by the liver of 13.2 mmol/day. 3. Infusion of [methyl-3H]choline chloride into the portal vein of a sheep over 1 hr and subsequent isolation of the bile for several days showed over 70% cumulative recovery of the radioactivity in the choline moiety of bile phosphatidylcholine over a 120 hr period. 4. Subsequent infusion 17 days later of bile lipid [3H]choline via a duodenal fistula also gave approx. 70% cumulative recovery of radioactivity in the choline moiety of newly secreted bile phosphatidylcholine in 120 hr. 5. These results show a very extensive enterohepatic recirculation of bile choline in the sheep, which is in contrast to the situation in monogastric animals.

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↗
PubMed1987

Reproductive hormone secretion and testicular growth in bull calves actively immunized against testosterone and oestradiol-17 beta.

Groups of bull calves received a primary immunization against testosterone (Group T; N = 7) or oestradiol-17 beta (Group E; N = 9) at 3 months of age and booster injections on four occasions at approximately 2 month intervals. Controls (Group C, N = 7) were immunized against human serum albumin alone using the same protocol. Immunity was achieved against both steroids as judged by the secondary antisteroid antibody titres in Group T (730 +/- 231; reciprocal of titre) and Group E (12,205 +/- 4366) bulls; however, peak antibody titres generally declined with successive booster injections. Mean plasma concentrations of LH, FSH and testosterone during the period from 3 to 10 months of age were higher (P less than 0.05) in Group T bulls than in Groups C and E. Group T bulls had larger testes compared with controls from 6 months of age onwards. At castration at 14 months of age, testes of Group T bulls were heavier (P less than 0.05) than those of Groups C and E (179 +/- 13, 145 +/- 8 and 147 +/- 6 g, respectively). At 10 months of age, there were no differences among treatment groups in LH responses to LHRH, but the testosterone responses were greater (P less than 0.05) in bulls in Group T (26.2 +/- 4.9 ng/ml) and Group E (16.6 +/- 1.8 ng/ml) compared with those in Group C (6.9 +/- 0.6 ng/ml). Testosterone responses to hCG determined at 13 months of age were also greater (P less than 0.05) in Groups T and E relative to controls. At 14 months of age daily sperm production rates per bull (X 10(-9)) were higher (P less than 0.10) in Group T bulls (2.2 +/- 0.1) than those in Groups C (1.6 +/- 0.2) and E (1.6 +/- 0.1). These results indicate that early immunity against testosterone is associated with increased gonadotrophin secretion and accelerated growth of the testes in prepubertal bulls. Also, chronic immunity against testosterone or oestradiol-17 beta enhances the steroidogenic response of bull testes to gonadotrophic stimulation. If the above responses observed in young bulls are shown to be sustained, then immunity against gonadal steroids early in life may confer some reproductive advantage in mature animals.

Animals↗
PubMed1986

The increase in testicular vascular permeability induced by human chorionic gonadotrophin involves 5-hydroxytryptamine and possibly oestrogens, but not testosterone, prostaglandins, histamine or bradykinin.

Possible intermediates in the response of the rat testicular vasculature to human chorionic gonadotrophin (hCG) have been investigated. Ketanserin, an antagonist of 5-hydroxytryptamine, significantly reduced the increase in 1-h albumin space seen 20 h after hCG, as did one aromatase inhibitor (1,4,6-androstatriene-3,17-dione), but the effect of another (testolactone) did not reach significance. Aminoglutethimide, which inhibits overall steroid synthesis as well as aromatase, reduced the albumin space in both control and hCG-injected rats but the hCG response, as judged by the ratio between treated and control rats, was unaffected. Inhibitors of overall steroid synthesis (WIN 32,729), prostaglandin synthesis (meclofenamic acid or indomethacin) and angiotensin converting enzyme (captopril) and blockers of H1 and H2 histamine receptors (mepyramine, cimetidine or ranitidine) were without effect. The time course of the vascular response to hCG is quite different from the response in testosterone secretion by the testis. Considerable numbers of mast cells were found in the vicinity of the testicular artery in the testicular capsule, and these may be a source of 5-hydroxytryptamine.

Aminoglutethimide↗
PubMed1986

The movement of fluids and substances in the testis.

Three aspects of the control of movements of fluids and substances into, out of and inside the testis are discussed: the tubular barrier, the interstitial extracellular fluid and the testicular blood vessels. The functional basis for the tubular barrier is twofold; there are significant differences in the concentration of many substances inside and outside the tubules and marker substances enter or leave the tubular fluid at widely different rates, depending on lipid solubility and the presence of specific carrier systems. The anatomical basis for this barrier appears to be the specialized junctions between adjacent pairs of Sertoli cells. The barrier develops only at puberty, as the first cells undergo meiosis, but the development may not be as sudden as previously believed. The barrier breaks down after efferent duct ligation when spermatogenesis is disrupted. Techniques for measuring the volume, the turnover rate, the composition and fate of the interstitial extracellular fluid are described, and the unsatisfactory features of the presently available techniques for collecting this fluid for analysis are emphasized. There is a relationship between the fluid in the testis and lymph from vessels in the spermatic cord and lymph may be important for the transport of hormones to the general circulation in some circumstances and to other organs close to the testis. The testicular blood vessels display certain unusual features, a very high susceptibility to the toxic effects of cadmium salts, a high level of alkaline phosphatase activity in all endothelial cells but only after puberty and a high level of gamma-glutamyl transpeptidase in the endothelial cells of the arterioles and the testicular artery. These same cells are the site for a specific transport system for leucine and phenylalanine, with kinetic characteristics similar to the system in brain. Flow of blood may limit hormone secretion by the aspermatogenic testis, but diffusion limitation may also be important under some circumstances. A fuller understanding of the ways in which substances move around in the testis, particularly how they cross the endothelial cell layer or penetrate into the tubules, will be important for a better appreciation of testicular function.

Animals↗
PubMed1986

Gamma glutamyl transpeptidase in the vasculature of the rat testis.

Activity of gamma glutamyl transpeptidase (GGT) in the testes of mature and prepuberal rats was investigated histochemically and biochemically. Histochemically, the enzyme activity was localized predominantly in the arterial and arteriolar endothelium and was absent from the capillaries and the seminiferous tubules. The activity in the arterial endothelium extended to the testicular artery on the surface of the testis and in the spermatic cord, but the veins in both the pampiniform plexus and on the testicular surface were negative. The endothelium of the testicular artery was already faintly positive at birth, and the activity increased during the second and third postnatal week during the branching and remodeling of the intratesticular arteries and arterioles. Activity of GGT was estimated quantitatively after dissection of the testis into tubular and interstitial tissue. The enzyme activity was very low in the tubules. It was fivefold stronger in the interstitium, and this activity was further enhanced by pretreatment of the dissected tissue with collagenase to remove the Leydig cells.

Animals↗
PubMed1986

Delayed puberty caused by hyperthyroidism in ram lambs is not a result of suppression in body growth.

Over a period of 8 weeks ram lambs (16 weeks old) were made hyperthyroidal (serum thyroxine approximately equal to 150 ng/ml, compared with control approximately equal to 48 ng/ml) by daily subcutaneous injections of thyroxine or maintained at a constant body weight by restriction of the feed intake. Hyperthyroidal and restricted-intake lambs remained at a constant body weight during the period of treatment whilst control rams gained body weight. Testicular growth was normal in restricted-intake lambs but was suppressed in hyperthyroidal animals. Hyperthyroidism, but not feed restriction, was also associated with decrease in LH pulse frequency (1.3 +/- 0.3/12 h compared with controls 4.8 +/- 0.9/12 h. Hyperthyroidal lambs showed normal LH responses to exogenous LHRH. After cessation of treatment testicular growth continued to be suppressed for up to 16 weeks in previously hyperthyroidic rams; thereafter testes began to increase in size but at 30 weeks after treatment were still smaller than those of control rams. It is concluded that elevated thyroxine concentrations directly influence sexual maturation in ram lambs through actions at hypothalamic and/or higher brain centres which control LH secretion. Transient hyperthyroidism during sexual maturation may cause permanent impairment of sexual development.

Animals↗
PubMed1986

Evidence of gonadal steroid-independent changes in activity of the central LH-releasing hormone pulse generator in developing bull calves.

To ascertain whether temporal changes in activity of the hypothalamo-pituitary axis in prepubertal bulls may occur independently of shifts in sensitivity to steroid feedback, the acute post-castration rise in serum gonadotrophins was monitored in bull calves castrated at monthly intervals from 4 to 9 months of age. Since a major feature of the gonadotrophin profiles of developing bulls is a change in LH pulse frequency early in life, pulsatile LH secretion after castration was used as an index of activity of the central LH-releasing hormone (LHRH) pulse generator. Relative to the day of castration (day 0) bull calves (n = 4) were bled at 20-min intervals for 8 h on day -3 and at 10-min intervals for 4 h on days 3, 5 and 7. During the first week after castration, 4-month-old bulls showed a higher (P less than 0.05) frequency of LH pulses compared with bulls at 8 and 9 months (1.13, 0.88 and 0.75 pulses/h respectively; pooled S.E.M. = 0.13). Mean LH levels before castration were higher (P less than 0.05) in 4-month-old bulls than in bulls at 7, 8 and 9 months (0.92, 0.37, 0.31, 0.38 micrograms/l respectively; pooled S.E.M. = 0.12). After castration mean LH levels did not differ with age. Mean FSH levels did not differ among age groups either before or after castration. Increased serum LH levels in 4-month-old bulls confirmed the transient rise in LH secretion that occurs at this time in developing bull calves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗