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Biomedical subjects

H D Nicholson

Publications and source records attributed to H D Nicholson.

At least 19 recordsLinked to original sources
PubMed1998

Determination of a standard site for the measurement of bone mineral density of the human calcaneus.

Ultrasound of the calcaneus may be used as a cheap, ionising radiation-free and easy to use indicator of skeletal status, and hence of osteoporotic fracture risk. At present ultrasound is not widely used as it suffers from high precision errors. As ultrasound parameters are determined in part by bone mineral density (BMD), an increase in the accuracy and precision of BMD measurements should reduce the precision error associated with ultrasound measurements. The aim of this study was to define an anatomical site on the calcaneus at which accurate and precise measurements of BMD can be made. Ten dry calcanei and 10 cadaveric feet were scanned using a DXA scanner; 9 anatomically defined regions (1 cm2) were selected in the posterior part of the calcaneus for analysis. The centre of region 1 was positioned halfway along the line joining the anterior border of the calcaneal tubercle and the peak of the posterior superior tubercle, and the remaining 8 regions were placed around this central area. The BMD in these 9 regions was compared with the whole bone BMD and the variability of BMD within each of the 9 regions was measured. The reproducibility of the technique was assessed by taking 10 repeated measurements of 2 bone and 2 cadaveric specimens, each specimen being removed and repositioned between measurements. Region 1 was found to be the most representative of total BMD in cadaveric feet. This region also showed the least variability of BMD and consistently gave the lowest coefficients of variation in the reproducibility study both in the bone and the cadaveric specimens. This region is hence the most suitable site on the calcaneus for measuring absolute values of and changes in BMD. The surface position of region 1 was found to be consistently 5/9 along the line at 45 degrees to the vertical, from the lateral malleolus to the heel. The identification of the surface location of region 1 relative to anatomical landmarks of the foot has enabled the same anatomical site to be measured in all subjects. This allows meaningful intersubject comparisons to be made. Preliminary data suggest that precision errors using ultrasound are also reduced when measurements are taken at this region of the calcaneus. The reduction in the precision error of ultrasound assessment of skeletal status may provide a cheap and safe way to identify individuals at risk from osteoporotic fracture.

Aged↗
PubMed1998

Localization of oxytocin receptors in the human and macaque monkey male reproductive tracts: evidence for a physiological role of oxytocin in the male.

The peptide oxytocin is present in tissues of the male reproductive tract from a variety of mammalian species. In the human, specific mRNA for oxytocin and the peptide itself have been identified in the testis, epididymis and prostate. The peptide has been shown to modulate both steroidogenesis and contractility in the male reproductive tract and may be involved in the pathogenesis of benign prostatic hyperplasia. We have performed Western blots and immunohistochemistry using a specific antibody to the human oxytocin receptor (OTR) to investigate the distribution and localization of the receptor in the human and macaque monkey (Macaca fasicularis). An immunoreactive band of approximately 55 kDa was detected in human and monkey uterine, testicular and prostatic tissues and in preparations of monkey caput and cauda epididymis. A second, less intense, band of 60 kDa was also seen in testicular and uterine tissue samples. No specific bands were detected in monkey muscle or in any tissue following incubation with mouse immunoglobulin (Ig)M. In the human and monkey testis staining for the OTR was present in the interstitial tissue and in Sertoli cells. Localization of the OTRs varied throughout the epididymis being expressed by epithelial cells proximally but confined to cells at the base of the epididymal ducts and to the surrounding smooth muscle layers distally. In the prostate OTR were localized to the stromal tissue surrounding the ducts. These findings correlate with sites of local production of the peptide and the observed biological actions of oxytocin, and thus support the evidence that oxytocin may play a physiological role in the male reproductive tract.

Adult↗
PubMed1998

The extended lateral approach to the hindfoot. Anatomical basis and surgical implications.

We have recently described an extended lateral approach to the hindfoot for the operative treatment of displaced intra-articular fractures of the calcaneum. It has the advantage of avoiding damage to the sural nerve and preserving blood supply to allow prompt healing. We dissected 15 formalin-preserved cadavers, taking photographs to show the structures of the posterolateral aspect of the hindfoot and ankle. We describe a superficial and a deep triangle: the deep triangle contains a constant posterior peroneal artery which supplies the skin of the posterolateral heel. An approach designed to expose the sural nerve will divide this important artery and cause ischaemia of the posterior skin. The extended lateral approach elevates the sural nerve in a thick flap and preserves the blood supply of the skin. We have reviewed 150 consecutive patients after the use of this approach to study the indications for operation, the quality of wound healing, any damage to the sural nerve and other complications. We recommend the careful use of this approach. Our understanding of its anatomical basis has allowed us to widen the indications for its use.

Cadaver↗
PubMed1998

Characterisation of the biological effects of neurohypophysial peptides on seminiferous tubules.

Oxytocin (OT) is present in the mammalian testis and has been postulated to play a role in modulation of seminiferous tubule contractility. However, recent evidence suggests that the myoid cells responsible for such contractile activity do not express OT receptors. In this study computer-assisted analysis and time-lapse videomicrography were used to investigate the biological effects of neurohypophysial peptides and their analogues on seminiferous tubule contractility. Adult rat testes were placed in fresh oxygenated Dulbecco's modified Eagle's medium (DMEM) F12 medium, decapsulated and the tubules gently teased apart. A small section of tubule was placed in a microslide chamber and perifused with medium. Seminiferous tubules were treated with OT (2 nM), [Arg8]-vasopressin (AVP, 0.2 nM) or [Thr4,Gly7]-OT (TGOT, 2 nM, 8 nM and 0.2 microM). Specific antagonists were also given simultaneously with OT and AVP treatments. Data were analysed to give arbitrary units of contractility. Both OT and AVP increased tubule contractility, with AVP being at least 10 times more potent than OT. Treatment with the selective OT antagonist, desGly-NH2,d(CH2)5[d-Tyr2,Thr4]-ornithine vasotocin (OTA, 0.2 microM and 2 microM) significantly reduced OT-induced increases in seminiferous tubule contractility but had no effect on AVP-induced responses. In contrast, the AVP antagonist, Phaa-d-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-Tyr-NH2 (AVPA) was more potent at reducing AVP-induced increases than OT-induced responses. The selective non-peptide AVPA SR 49059 blocked the response to both peptides in a similar manner, whilst the non-peptide OTA L367,773 did not block OT-induced increases in seminiferous tubule contractility at doses that were slightly inhibitory to AVP-induced responses. The specific OT agonist TGOT did not induce a contractile response. The data in this study demonstrate that in the testis AVP acts via V1a receptors to stimulate contractile activity and suggest that OT may act via a receptor which differs from the classical V1a and uterine-type OT receptor. These findings support a role for OT in the regulation of seminiferous tubule contractility and raise the possibility that AVP may also be important in this process.

Analysis of Variance↗
PubMed1998

Stage-related differences in rat seminiferous tubule contractility in vitro and their response to oxytocin.

Oxytocin (OT) is present in the mammalian testis and has been shown to play a role in the modulation of seminiferous tubule contractility and steroidogenesis. However, stage-specific effects of the peptide have not been previously investigated. In this study, computer-assisted analysis and time-lapse videomicrography were used to investigate basal contractility and the response to OT of seminiferous tubules at specific stages of the spermatogenic cycle. Adult rat testes were placed in fresh oxygenated DMEM F12 medium, decapsulated, and the tubules gently teased apart. Stages were identified by transillumination and a 10 mm section of tubule at each of stages IV-V, VII-VIII and XIII-I was placed in a microslide chamber and perifused with medium. After a control period of 3 h, OT (2 nM) was given for 1 h, followed by another control period of 1 h. The experiment was repeated using tubules from different rats and data were analysed to give arbitrary units of tubule contractility. Contractility was observed in all the tubules studied and the contractile activity was shown to vary depending on the stage of the spermatogenic cycle. Mean basal contractility at stages VII-VIII, the time when sperm are shed from the epithelium, was significantly lower than that at stages IV-V and XIII-I. The response of the tubules to OT was also stage-dependent, with the peptide producing the largest increases in contractile activity at stages VII-VIII and having no effect at stages IV-V. We postulate that these stage-specific differences in basal and OT-stimulated contractility may be important in co-ordinating the movement of developing germ cells towards the lumen of the seminiferous epithelium and in the process of spermiation.

Animals↗
PubMed1996

Epididymal oxytocin in the rat: its origin and regulation.

Oxytocin is localized to the Leydig cells of the testis in the rat and several other species where it is postulated to play a role in steroidogenesis and seminiferous tubule contractility. Oxytocin has also been detected in the epididymis of the ram where active uptake of the peptide from luminal fluid has been demonstrated. This study was performed to investigate whether oxytocin is present in the rat epididymis, and the origin of the peptide. Immunoactive oxytocin was detected in the epididymis of all control animals examined (147.7 +/- 41.7 pg/g). Total epididymal oxytocin was reduced significantly following castration (p < 0.05). Testosterone treatment also reduced the epididymal concentration of the peptide in both intact and castrated rats. Efferent duct ligation (EDL) did not affect the presence of oxytocin in the epididymis. Immunoactive oxytocin was localized in discrete cells of the epithelium of the caput epididymis, with less staining apparent in the initial segment and cauda epididymis. Staining disappeared from the caput epididymis following castration, but reappeared following testosterone supplementation. No obvious alteration in staining was observed in the cauda epididymis after EDL. These data demonstrate for the first time the presence of oxytocin in the epididymis of the rat and that the peptide may be regulated by androgens. They further suggest an epididymal source of the peptide.

Animals↗
PubMed1996

Effects of oxytocin on sperm transport in the pubertal rat.

Oxytocin is present in the mammalian testis where it increases contractility of seminiferous tubules in vitro and has been implicated in sperm transport. The present study investigated whether oxytocin affects the transport of spermatozoa from the testis in vivo. In rats, mature spermatozoa are first seen in the testis 42 days postpartum and arrive in the epididymis at about day 45. Male Wistar rats were given daily subcutaneous injections of either oxytocin (0.5 micrograms), the oxytocin antagonist des Gly-NH2d(CH2)5-[D-Tyr2,Thr4]OVT (0.2 micrograms) or saline from day 40 postpartum. Groups of six animals were killed 2 h after their last injection on days 43, 44, 45 and 46 postpartum. Testes were removed and fixed in Bouin's fluid for histological examination and the number of spermatozoa in the epididymides was counted. Spermatozoa were seen in the epididymis earlier in the oxytocin-treated rats (day 43) than in the control animals (day 44), and treatment with the antagonist delayed the appearance of spermatozoa in the epididymis until day 45. When the testes were examined, residual bodies, which were used as an indicator of spermiation, were seen only in one control animal before day 44. Residual bodies were seen in the testes of all oxytocin-treated rats on day 43 but were not detected until day 45 in the oxytocin antagonist-treated rats. These data show that in rats oxytocin can affect the arrival of spermatozoa in the epididymis. Although this may be due in part to effects on tubal transport or the secretion of tubular fluid, these findings suggest that the peptide may affect spermiation.

Animals↗
PubMed1996

Oxytocin: a paracrine regulator of prostatic function.

It is now well established that the peptide oxytocin can act as a paracrine factor as well as a classic hormone. Oxytocin is produced locally in both the testis and ovary, where it may modulate both steroidogenesis and contractility of the male and female reproductive tracts. The peptide is also present in the prostate and seminal fluid and there is growing evidence that oxytocin may be produced in the prostate. Within the prostate, oxytocin has been shown to increase growth of the epithelial tissue and increase both muscular tone and contractile activity. Furthermore, prostatic concentrations of the peptide are regulated by androgens. It is hypothesized that oxytocin may act as a paracrine factor to regulate cell growth and that this may be secondary to its effects on the enzyme 5 alpha-reductase which converts testosterone to dihydrotestosterone. In addition, oxytocin may be involved in the pathophysiology of benign prostatic hyperplasia.

Humans↗
PubMed1995

Effect of oxytocin on testosterone production by isolated rat Leydig cells is mediated via a specific oxytocin receptor.

The effect of the neurohypophysial hormones oxytocin and arginine vasopressin (AVP) on testicular steroidogenesis was reevaluated by use of short-term (< 10 h) cultures of isolated adult rat Leydig cells. Oxytocin at 10(-9), 10(-7), and 10(-5) M concentrations significantly increased basal testosterone production in a dose-dependent manner but had no effect on LH-stimulated testosterone production. The specificity of the effect was determined by use of the specific oxytocin receptor antagonist (OTA). OTA from 10(-9) to 10(-5) M concentrations inhibited the oxytocin-stimulated increase in testosterone production. Furthermore, the oxytocin agonist Thr4 Gly7 oxytocin also induced a dose-dependent increase in basal testosterone production. In contrast, AVP from 10(-9) to 10(-5) M concentrations did not consistently affect basal testosterone production by isolated Leydig cells, but significantly decreased LH-stimulated testosterone production. Inclusion of 10(-7) and 10(-5) M OTA with 10(-7) M AVP did not alter the inhibitory effect of the AVP. These data show that oxytocin and AVP have different effects on testosterone production by Leydig cells in vitro and support the hypothesis that oxytocin acts in the testis through a specific oxytocin receptor.

Animals↗
PubMed1995

Oxytocin and prostatic function.

It is now well established that oxytocin is present in the mammalian testis and there is growing evidence that the peptide plays a role in the male reproductive tract by both assisting sperm transport and modulating steroidogenesis. In the testis, oxytocin has been shown not only to modulate testosterone production but also to increase the activity of the enzyme 5 alpha-reductase which converts testosterone to dihydrotestosterone (DHT). The prostate is an androgen-dependent organ with DHT being the active steroid. Oxytocin is present in the mammalian prostate. We have shown in the rat that levels of the peptide can be regulated by androgens, prostatic oxytocin concentrations being decreased by testosterone and increased following castration or treatment with an antiandrogen. Oxytocin treatment increases 5 alpha-reductase activity in the prostate of healthy young rats but, unlike the testis, this rise in enzyme activity is only transient. We thus propose that a local feedback mechanism may act to control prostatic levels of DHT and hence prostatic growth. Benign prostatic hyperplasia (BPH) is a common disease which affects both men and dogs. The aetiology of the disease is complex but both DHT and aging are important factors. Oxytocin levels are raised in prostatic tissue from dogs with BPH and the increase in peptide is accompanied by increased 5 alpha-reductase activity. Preliminary findings also suggest that prostatic oxytocin levels are raised in tissue from men with BPH. These data lead us to suggest that oxytocin may be involved in the pathophysiology of the prostate gland.

Aging↗
PubMed1994

Regulation of oxytocin production by purified adult rat Leydig cells in vitro: effects of LH, testosterone and lipoproteins.

The aim of the present study was to determine whether LH stimulates oxytocin production by adult rat Leydig cells directly or indirectly via testosterone. Purified adult rat Leydig cells were cultured in the presence or absence of 0.1 ng/ml LH or 1, 10 or 100 ng/ml testosterone for 22 h. Culture medium was collected at 2-hourly intervals and assayed for oxytocin and testosterone. In the presence of LH, Leydig cells produced significantly higher levels of both testosterone (basal production 1.4 +/- 0.13 ng, LH-stimulated 4.1 +/- 0.13 ng/10(6) cells per 2 h) and oxytocin (basal production 8.3 +/- 1.2 pg, LH-stimulated 20.2 +/- 1.3 pg/10(6) cells per 2 h). Testosterone also stimulated oxytocin secretion. However, the increase was smaller compared with that seen with LH and was not found to be dose-dependent. Furthermore, testosterone production was only significantly increased by LH during the first 10 h of the 22-h culture period whereas LH stimulated oxytocin production throughout the whole culture period. To further determine the effect of LH on oxytocin production, cultures were performed in the presence of LH and/or 400 microM aminoglutethimide. In the presence of aminoglutethimide both the basal and LH-stimulated production of testosterone was significantly reduced. However, in the same cultures aminoglutethimide did not alter either the basal or LH-stimulated production of oxytocin. These data show that LH does not act via testosterone to stimulate oxytocin production and therefore acts directly or by some alternative indirect mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglutethimide↗
PubMed1994

The effect of germ cell complement on the presence of oxytocin in the interstitial and seminiferous tubule fluid of the rat testis.

In the rat testis oxytocin has been localized to the Leydig cells, and these cells have been shown to produce oxytocin in vitro. The present study was performed to determine whether oxytocin is present in the interstitial fluid (IF) and seminiferous tubule fluid (TF) of the rat and whether concentrations of the peptide vary within the two compartments following germ cell destruction. In order to destroy germ cells adult male rats were anaesthetized and their scrotal regions placed in a water bath at 43 degrees C for 20 min. Control animals were subjected to anaesthesia alone. Groups of 6 animals were killed 3, 7 and 21 days after heat treatment and their testes removed for histological examination or fluid extraction. IF and TF were separated and the oxytocin content of the fluids measured by radioimmunoassay. Immunoreactive oxytocin was detected in both the IF (100 +/- 11 pg/ml) and TF (27 +/- 4 pg/ml) of control rats and this immunoreactivity co-eluted with the authentic peptide following HPLC. Three days after heat treatment IF levels of oxytocin were significantly reduced but TF levels of the peptide were significantly increased. These changes were associated with a lack of pachytene spermatocytes in the histological sections. Seven and 21 days after heat treatment the levels of oxytocin in the IF and TF were not significantly different from control levels. Similar changes in IF and TF oxytocin levels were seen in a second experiment when pachytene spermatocytes were removed using the testicular toxicant methoxyacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1993

Oxytocin, a male intragonadal hormone.

It is now well recognised that oxytocin is not confined to the hypothalamo-neurohypophysial system but present elsewhere in the body. However, the significance of the peptide in these peripheral sites is still unclear. This paper considers the evidence for oxytocin to be a male gonadal hormone and focusses on three of the criteria which need to be fulfilled for it to earn this title: oxytocin must be produced within the gonads; have a physiological action and be regulated by factors which alter gonadal function.

Animals↗
PubMed1992

A novel, [tyrosyl-3,5-3H]oxytocin binding, uterine cell population in the rat.

The cellular localization of uterine oxytocin binding sites in the rat was studied by means of in vitro receptor autoradiography. Using [tyrosyl-3,5-3H]oxytocin as ligand, binding sites were localized in tissue sections from uteri of estrous, mated, and artificially cervically stimulated rats (n = 4 per group), and specificity of binding was investigated by means of simultaneous incubations with oxytocin, [Gly4,Thr7]oxytocin and [Arg]vasopressin. A previously unidentified type of cell was densely labelled by tritiated oxytocin. The labelled cells were preferentially localized near the endomyometrial border and at the interface of the circular and longitudinal muscle layers. In addition, these cells were found in the muscle layers. The dense labelling of these cells, which did not constitute part of the endometrial epithelium or blood vessels, was abolished when oxytocin or [Arg]vasopressin, but not [Gly4,Thr7]oxytocin, was added to the incubation medium. Binding of the radioligand was also found on muscle cells of the circular and longitudinal layers of the myometrium and cells of the endometrial luminal and glandular epithelium. Whereas incubation with oxytocin and [Gly4,Thr7]oxytocin diminished the labelling in both myometrium and endometrium, incubation with [Arg]vasopressin reduced labelling only in the myometrium. Similar results were obtained in tissues from rats in different reproductive states. This study demonstrates the presence of oxytocin binding sites in three different types of cell in the uterus of the rat. While the sites in the myometrium may be associated with the contractile response of this type of tissue to oxytocin, the functional significance of oxytocin binding sites on the endometrial epithelium and in the densely labelled, scattered cells remains to be elucidated.

Animals↗
PubMed1992

Luteinizing hormone differentially regulates the secretion of testicular oxytocin and testosterone by purified adult rat Leydig cells in vitro.

The aims of the present study were to determine whether Leydig cells in vitro synthesize oxytocin, and whether LH modulates the secretion of oxytocin by Leydig cells. Highly purified adult Leydig cells were prepared from adult rats and cultured for 3 days in the presence or absence of 0.1 ng/ml ovine LH, and media were changed daily. The total amount of oxytocin present in the culture was estimated by RIA of cell extracts before culture (day 0) and at the end of day 3 of culture and in media on days 1-3. The content of immunoreactive oxytocin in cell extracts on day 0 (3.4 +/- 1.2 pg/10(6) cells) was significantly lower than the total amount that had been released into the medium and was present in the cell extracts at the end of day 3 (+LH, 27.8 +/- 3.3; -LH, 16.5 +/- 2.7 pg/10(6) cells), suggesting that Leydig cells are able to synthesize and secrete oxytocin. This hypothesis was supported by the observation that oxytocin release into the medium was significantly reduced during a 3-h treatment of Leydig cells with the protein synthesis inhibitor cycloheximide (5 micrograms/ml for 3 h). The role of LH in regulating testosterone production by Leydig cells is well defined, but whether LH also regulates oxytocin is unknown. Therefore, the effects of LH on oxytocin and testosterone production by Leydig cells were compared. The production of both hormones was stimulated by increasing doses of LH (0.001-100 ng/ml), but no further rise in oxytocin release could be elicited with amounts of LH greater than 0.1 ng/ml. Testosterone production, however, continued to increase with doses of LH up to 100 ng/ml. Furthermore, the two hormones differed in the rate of their responses to both 3- and 12-h exposures to LH; testosterone secretion increased more rapidly than that of oxytocin. These data provide direct evidence that adult Leydig cells produce immunoreactive oxytocin, and that their production of this peptide is regulated by LH.

Animals↗
PubMed1991

Testicular oxytocin: effects of intratesticular oxytocin in the rat.

The long-term effects of oxytocin administration on the testis were studied using intratesticular implants. Adult male rats had an Accurel device containing 20 micrograms oxytocin (releasing approximately 200 ng/day) implanted into the parenchyma of each testis; control animals received empty devices. The animals were killed at weekly intervals for 4 weeks. Some animals were perfused and the testes processed for light and electron microscopy. Blood was collected from the remaining animals for the measurement of testosterone, dihydrotestosterone, LH, FSH and oxytocin; epididymal sperm counts were measured and the testes were extracted and radioimmunoassayed for testosterone, dihydrotestosterone and oxytocin. Long-term administration of oxytocin resulted in a significant reduction in testicular and plasma testosterone levels throughout the 4-week period examined and, after 14 days of treatment, lipid droplets were seen in the Leydig cells of treated but not control animals. Concentrations of dihydrotestosterone in the plasma and testes of the oxytocin-treated animals, however, were significantly elevated after 7 and 14 days and at no time fell below control values. Plasma FSH levels were also lower in the oxytocin-treated animals. Intratesticular oxytocin treatment did not affect LH or oxytocin concentrations in the plasma, epididymal sperm counts or the number of Leydig cells in the testis. Empty Accurel devices had no effect on testicular morphology. This study provides the first evidence that oxytocin in vivo can modify steroidogenesis in the testis.

Animals↗