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Biomedical subjects

B P Setchell

Publications and source records attributed to B P Setchell.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1986

Reproductive hormone secretion and spermatogenic function in thyroidectomized rams receiving graded doses of exogenous thyroxine.

This study aimed to obtain a better understanding of the relationship between circulating thyroxine (T4) concentrations and reproductive endocrine function in the ram. Mature Merino rams were thyroidectomized and supplemented with 0, 30, 100 and 300% of normal T4 for 10 weeks. Thyroidectomy had no apparent effect on spermatogenic function but interfered with sperm maturation, the latter being returned to normal by 30% T4 replacement. Circulating testosterone levels were reduced by thyroidectomy and restored to control levels by 30% T4; when T4 levels were supranormal (300%), circulating testosterone levels were again reduced. The lowered circulating testosterone levels in thyroidectomized rams occurred as a result of suppressed testosterone secretion from the testis, observed under basal conditions and also following LH-releasing hormone (LHRH) and human chorionic gonadotrophin injection. In thyroidectomized rams, sex hormone binding globulin (SHBG) levels were depressed without changes in testosterone clearance rate (TCR), while in rams with supranormal T4 levels, TCR was increased without changes in SHBG levels. Subnormal levels of T4 also restored to normal the reduced LH pulse frequency in thyroidectomized rams. Reduced LH pulse frequency, together with diminished LH release following LHRH injection in thyroidectomized rams, suggested effects of T4 at the hypothalamo-pituitary axis. The present study demonstrates that complete lack of thyroid hormones suppresses normal reproductive endocrine function in the ram, but that this can be restored to normal by 30% T4 replacement. The results support the theory that T4 plays a permissive rather than a regulatory role in reproductive function in males.

Animals↗
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↗
PubMed1985

The importance of the Leydig cells in the vascular response to hCG in the rat testis.

The increase in permeability of the testicular blood vessels following an injection of hCG into rats is abolished completely if the animals are treated 3 days earlier with ethane dimethane sulphonate (EDS), a compound that effectively eliminates Leydig cells from the testes. As there is other evidence that androgens or prostaglandins are not involved in this vascular response, further studies will be necessary to determine whether these data mean that another vasoactive substance is secreted by the Leydig cells or whether the EDS also eliminates other cells besides the Leydig cells, for example the mast cells found in the vicinity of the testicular artery.

Animals↗
PubMed1985

Activity of the hypothalamo-pituitary axis and testicular development in prepubertal ram lambs with induced hypothyroidism or hyperthyroidism.

Prepubertal (16 weeks old) ram lambs were used to investigate the effects of hyperthyroidism and hypothyroidism on development of reproductive endocrine function. Over a period of 8 weeks, ram lambs were made hypothyroid (serum T4 less than or equal to 3 ng/ml compared with controls congruent to 30 ng/ml) by daily oral administration of methyl thiouracil or hyperthyroid (serum T4 congruent to 135 ng/ml) by daily sc injection of T4. Hyperthyroidism was associated with decreases in LH pulse frequency (2.25 +/- 0.75/12 h compared with controls 5.75 +/- 0.48/12 h), basal LH, and mean LH concentrations, together with arrested testicular growth and aspermatogenesis. Hypothyroid rams showed normal pubertal development. After iv injection of LHRH, hyperthyroid ram lambs showed similar LH responses to control and hypothyroid rams. Basal testosterone production (5.6 +/- 1.0 ng/min) and plasma testosterone concentrations after human CG (2.0 +/- 0.7 ng/ml) in hyperthyroid rams were significantly lower than in controls (67.5 +/- 24.0 ng/min and 5.2 +/- 1.0 ng/ml, respectively). It is concluded that retarded testicular development in hyperthyroid ram lambs results from changes in hypothalamo-pituitary activity manifested in a decreased LH pulse frequency.

Animals↗
PubMed1985

Motility of undiluted bull epididymal spermatozoa collected by micropuncture.

Motility of whole undiluted semen collected from different regions of the bull epididymis by micropuncture was determined by examining a droplet under paraffin oil. Bull caudal spermatozoa showed vigorous motility in undiluted semen. This motility was less in samples collected from nearer the testis: samples from the distal caput showed weak but detectable motility while those from the proximal and mid-caput were completely quiescent. Motility of spermatozoa from the distal caput and the proximal corpus was markedly increased after incubation at 34 or 37 degrees C for 1 h, but was depressed by incubation at 25 degrees C. Similar but smaller effects were observed with spermatozoa collected from the mid-corpus and the mid-cauda, except that motility of spermatozoa from the mid-corpus was reduced after incubation for 1 h at 37 degrees C. The inhibitory effect of low temperature was completely reversible. Incubation of caudal spermatozoa under anaerobic conditions produced partial and reversible inhibition of sperm motility. The results suggested that bull epididymal spermatozoa may not be completely quiescent in their native environment as previously assumed.

Anaerobiosis↗
PubMed1985

Differential effects of gonadectomy on sensitivity to testosterone of brain centres associated with gonadotrophin negative feedback and with mating behaviour in rams.

Castrated sheep were used to study the effects of gonadectomy on sensitivity to testosterone of brain centres associated with gonadotrophin negative feedback and with mating behaviour. In the first experiment serum LH and FSH concentrations were determined in intact rams, recently castrated (2 days and 3 weeks) and long-term castrated animals (greater than 2 years, wethers) during intravenous testosterone infusion at physiological and supraphysiological levels. In intact rams, testosterone infusions effectively suppressed serum LH whilst FSH levels were suppressed only after prolonged infusion at the supraphysiological dose. Recently castrated sheep, which had higher gonadotrophin levels than intact rams, were less sensitive to testosterone feedback. Neither rate of testosterone infusion had any effect on the raised gonadotrophin levels in wethers. In a second experiment gonadotrophin concentrations and mating behaviour were determined in wethers bearing subdermal polydimethylsiloxane implants of testosterone, dihydrotestosterone and oestradiol. Testosterone implants stimulated mating behaviour in all wethers but suppressed gonadotrophins in only a proportion (three out of seven) of the animals. Both oestradiol and dihydrotestosterone suppressed LH and FSH in all wethers, whilst oestradiol, but not dihydrotestosterone, also stimulated mating behaviour. The present findings indicate that testosterone imposes continuing negative feedback on gonadotrophin secretion and that changes in the gonadotrophin regulatory system, which lead eventually to a loss in sensitivity to testosterone feedback, develop soon after gonadectomy. The results also provide the first direct evidence that longterm gonadectomy in male sheep has differential effects on sensitivity to testosterone of brain centres associated with gonadotrophin negative feedback and with mating behaviour.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Spermatogenesis, seminal characteristics and reproductive hormone levels in mature rams with induced hypothyroidism and hyperthyroidism.

Mature Merino rams were made hypothyroid by daily oral drenching with methylthiouracil or hyperthyroid by daily subcutaneous injections of thyroxine for 8 weeks. Neither hypothyroidism nor hyperthyroidism had any apparent effect on either spermatogenesis or daily sperm production, but motility of ejaculated spermatozoa and circulating testosterone concentrations were reduced in both conditions. The ratio of testosterone concentrations in plasma from the internal spermatic vein to those in peripheral blood plasma was higher in hyperthyroid (21.2 +/- 3.5) than in control (11.1 +/- 4.4) and hypothyroid (7.6 +/- 1.4) rams. The basal secretion rate for testosterone was slightly lower in hypothyroid rams and testosterone responses to human chorionic gonadotrophin and after LH-releasing hormone (LHRH) were very much reduced. Basal serum LH levels were low in both hypothyroid and hyperthyroid rams compared with controls whereas there were no differences in FSH levels. The LH response to exogenous LHRH was reduced in hypothyroid rams but not in hyperthyroid rams. Serum prolactin levels on the other hand were higher than control in both hypothyroid and hyperthyroid rams. Reduced testosterone secretion in hypothyroid rams indicates that the normal function of Leydig cells depends on an adequate level of thyroid hormones. The decrease in circulating testosterone concentrations in hyperthyroid rams with normal secretion rates suggests an increased testosterone clearance rate in these animals. The decreased spermatozoal motility in hypo- and hyperthyroid rams suggests that the lowered testosterone level in these animals has altered the androgen-dependent maturation of spermatozoa in the epididymis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Pituitary and testicular responses in sexually mature bulls after intravenous injections of graded doses of LH-releasing hormone.

The capacity of the anterior pituitary gland and testes in mature bulls (705 +/- 9 (S.E.M.) kg body wt, n = 4) to respond to graded doses of LH-releasing hormone (LHRH) was assessed relative to endogenous profiles of LH and testosterone secretion. Endogenous hormone profiles were determined by bleeding bulls at 20-min intervals for 12 h. Responses to LHRH were assessed on successive days after single intravenous injections of 1, 5, 10, 50 or 100 ng LHRH/kg body wt. Blood samples were taken at -40, -20, 0, 10, 20, 30, 40, 60 and 120 min relative to LHRH injection. During a 12-h bleed bulls showed spontaneous pulses of LH and testosterone which had peak amplitudes of 2.6 +/- 0.5 micrograms/l and 44.5 +/- 7.1 nmol/l respectively. Respective peak LH (micrograms/l) and testosterone (nmol/l) responses to LHRH were as follows: 1 ng LHRH (3.0 +/- 0.7; 47.3 +/- 4.1); 5 ng LHRH (8.0 +/- 1.2; 52.8 +/- 6.2); 10 ng LHRH (11.1 +/- 2.3; 57.7 +/- 9.1); 50 ng LHRH (19.2 +/- 2.8; 47.9 +/- 8.6); 100 ng LHRH (19.1 +/- 4.7; 43.9 +/- 6.4). A dose of 1 ng LHRH/kg produced LH and testosterone responses which were comparable in amplitude to spontaneous peaks in the respective hormone. There was a linear (y = 0.28 X + 5.72; r = 0.81) increase in the LH response to doses of LHRH between 1 and 50 ng/kg; corresponding testosterone responses showed no relationship with the dose of LHRH. The capacity of the anterior pituitary gland to release amounts of LH eight to ten times in excess of those secreted during spontaneous peaks suggests that (1) there exists a large releasable store of LH in the anterior pituitary gland and (2) hypothalamic LHRH is a limiting factor in gonadotrophin secretion. In contrast to LH release, the androgenic response of the testes to acute gonadotrophic stimulation is determined largely by prevailing steroidogenic activity.

Animals↗
PubMed1983

Limitations imposed by testicular blood flow on the function of Leydig cells in rats in vivo.

Testis blood flow per testis closely follows testis weight in rats made aspermatogenic by a single exposure of the testis to 43 degrees C for 30 min or 500 rad (5 Gy) of irradiation from a caesium source, or following ligation of the efferent ducts. Aspermatogenesis following these treatments was associated with only minor changes in the concentrations of testosterone in peripheral blood before stimulation with human chorionic gonadotrophin (hCG), and a reduced responsiveness to hCG when testis weight had fallen after heating. The concentrations of testosterone in testicular venous blood was normal or above normal during aspermatogenesis resulting from heat or irradiation, and only slightly reduced following efferent duct ligation. Consequently testosterone production (defined as the product of plasma flow and the veno-arterial concentration difference for testosterone) was markedly reduced during aspermatogenesis, both before and after stimulation with hCG. It appears that the reduced blood flow limits the amount of testosterone leaving the testis, and while the Leydig cells are capable under some circumstances of compensating partially for this fall by increasing the concentration of testosterone in the testicular venous blood, this compensation is not complete when there are severe reductions in blood flow. Therefore one can conclude that the mass of the tubules is the main determinant of testis blood flow and the Leydig cells must manage with what the tubules require.

Animals↗
PubMed1983

The effects of acidic epididymal glycoprotein (AEG) and some other proteins on the motility of rat epididymal spermatozoa.

Acidic epididymal glycoprotein (AEG) had a slight stimulatory effect on the motility of spermatozoa showing low initial motility which had been removed by micropuncture from the caput and corpus epididymidis of rats. However, similar effects were seen when bovine serum albumin (BSA) or purified gammaglobulin against AEG was used instead of AEG. Furthermore, BSA, normal rabbit serum and serum from a rabbit immunized against AEG reduced the motility of spermatozoa which showed high initial motility after removal from the caput, while AEG had no effect. These studies emphasize the importance of the effects of proteins on the motility of spermatozoa but do not provide any clear evidence for a specific effect of AEG.

Animals↗
PubMed1983

Evidence for a defective seminiferous tubule barrier in testes of Tfm and Sxr mice.

The competence of the seminiferous tubule barrier was evaluated by determining the sucrose space in isolated testis preparations obtained from adult wild-type mice and from mutants having defects in spermatogenesis. The distribution of [3H]sucrose in testes from wild-type mice was in a space which constituted 18.5% of the [14C]urea space. The corresponding sucrose space in testes from Tfm/Y and Sxr/+ sterile mutants was elevated to 57.7% and 52.0%, respectively. Independent approaches to detect an impairment in the seminiferous tubule barrier of testes from Tfm/Y mice consisted of estimations of the osmotic barrier to hypertonic LiCl, using histological techniques, and determination of the testis sucrose space in vivo. With both approaches, results obtained supported the presence of an impaired barrier in testes of Tfm/Y mice. The sucrose space was within normal limits in testes of the other mutants examined, which were defective in spermatogenesis. The results do not provide any evidence for an impaired barrier in testes of mice having Movbr/Y and Gy/Y mutations, or the t6twl genotype.

Animals↗
PubMed1983

Transport of free and conjugated steroids from the boar testis in lymph, venous blood and rete testis fluid.

In 12 anaesthetized boars the concentrations of oestrone sulphate and dehydroepiandrosterone sulphate (DHAS) were 15- to 35-fold higher in lymph collected from a vessel in the spermatic cord than in testicular venous blood plasma from a vein in the spermatic cord. The concentrations of testosterone, total unconjugated oestrogens and dehydroepiandrosterone (DHA) were about twofold higher in lymph. The concentrations of all steroids studied were higher in testicular venous blood plasma than in arterial blood plasma (testosterone about sixfold; total unconjugated oestrogens about fourfold; oestrone sulphate about threefold; DHA and DHAS about twofold), but the concentrations of testosterone, total unconjugated oestrogens and oestrone sulphate in rete testis fluid were comparable to those in arterial blood plasma. Lymph flow from the pig testis was about 7% of plasma flow so that about 80% of the oestrone sulphate and DHAS produced by the testis leaves the organ in the lymph; the comparable values for testosterone, total unconjugated oestrogen and DHA were about 20%. In the 90-min period following an injection of human chorionic gonadotrophin there were substantial increases in the concentration of testosterone and smaller increases in the other steroids in arterial and spermatic venous blood plasma and in testicular lymph, but not in rete testis fluid; there were also small increases in lymph flow, but no change in blood flow.

Androgens↗
PubMed1983

Changes in testicular blood flow and testosterone production during aspermatogenesis after irradiation.

Exposure of the testes of anaesthetized adult rats to 527 rads of gamma-irradiation caused testis weight to fall slowly at first and then more rapidly from 21 days afterwards, reaching a minimum at 52 days, when spermatogenesis was severely disrupted. The weights of the accessory organs and the concentrations of testosterone in peripheral blood were slightly reduced; the concentrations in blood from the testicular veins were lower than control at shorter intervals after irradiation, but at later times tended to be similar or greater than control. Testicular blood flow per testis followed testis weight closely, and as a result the production of testosterone by the smaller testes (calculated as the product of plasma flow and the veno-arterial difference in testosterone concentration) was markedly reduced especially when the rats had been stimulated with human chorionic gonadotrophin (hCG). Serum FSH and LH rose appreciably as testis weight fell but there was a proportionately greater rise in FSH than LH, in comparison with surgically castrated animals. Increased amounts of extratubular, extracellular fluid were found in the aspermatogenic testes, but injection of hCG still caused increases in capillary permeability and the amount of fluid in the testis. These results indicate that during aspermatogenesis following irradiation (as with heat and efferent duct ligation) the capacity of the testes to secrete testosterone is severely limited by decreased testicular blood flow, not by the ability of the Leydig cells to release testosterone into their immediate environment.

Animals↗