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Biomedical subjects

F C Wu

Publications and source records attributed to F C Wu.

At least 91 records · Page 5Linked to original sources
PubMed1989

Inflammatory bowel disease and male infertility: effects of sulfasalazine and 5-aminosalicylic acid on sperm-fertilizing capacity and reactive oxygen species generation.

To investigate the mechanism of the antifertility action of sulfasalazine, we prospectively measured sperm density, motility, hamster oocyte penetration capacity, and reactive oxygen species production in six men with inflammatory bowel disease being treated with sulfasalazine and 8 and 16 weeks after changing to 5-aminosalicylic acid (5-ASA). An improvement was observed after changing to 5-ASA in those with poor (n = 3), but not in those with normal (n = 3), sperm function on sulfasalazine. There was no correlation between reactive oxygen species production or acetylator phenotype with egg penetration capacity, sperm motility, or sperm density. We conclude that the mechanism of impairment and recovery of sperm function on and off sulfasalazine treatment is not related to an excess in reactive oxygen species.

Adult↗
PubMed1989

Suppression of sperm function by depot medroxyprogesterone acetate and testosterone enanthate in steroid male contraception.

Ten normal men were given three monthly intramuscular injections of 200 mg of depot medroxyprogesterone acetate (MPA) and 250 mg of testosterone (T) enanthate. Six men became azoospermic, while four remained oligozoospermic, with a mean sperm density of 1.5 +/- 0.3 standard error of the mean million/ml. Zona-free hamster oocyte penetration was abolished in all oligozoospermic samples at the end of treatment. Twenty of the 21 oligozoospermic samples yielding at least 0.6 to 5.0 million motile spermatozoa showed a complete absence of oocyte penetration. Semen parameters returned to normal, although some took up to 12 months. These findings demonstrated an antifertility action of MPA and T enanthate on the functional capacity of residual spermatozoa and support the view that extreme oligozoospermia may be a tenable target for reversible steroid male contraception.

Adult↗
PubMed1989

Gene VI of figwort mosaic virus (caulimovirus group) functions in posttranscriptional expression of genes on the full-length RNA transcript.

Experimental evidence for a molecular function for gene VI of the caulimoviruses is presented. Based on experiments with the figwort mosaic virus (FMV), it appears that gene VI has a role in the posttranscriptional expression of the closely packed genes (VII and I-V), which appear on the larger, full-length RNA transcript of this virus. Gene VI with its flanking 5'/3' expression signals included as a separate plasmid during electroporation of DNA into protoplasts of Nicotiana edwardsonii shows an unusual type of transactivation of a chloramphenicol acetyltransferase (CAT) gene fused at its 5' end to a small open reading frame (gene VII) of the long 5' leader of the full-length RNA transcript of the FMV genome. The level of activity of the CAT gene is increased up to 20-fold over the activity of control plasmids when gene VI is included in the electroporation mixture. Mutagenesis of the coding portions of gene VI of pGS1 RVI, a transactivating plasmid used in the electroporation experiments, demonstrated that it was probably the polypeptide product of gene VI that was responsible for the transactivating effect. Experiments with various portions of the 5' leader of the large, full-length RNA of FMV showed that the coding region of gene VII is necessary for the transactivation event. Clones of cauliflower mosaic virus (CaMV) or FMV with intact gene VI were found to reciprocally transactivate gene VII-CAT fusions (FMV) or gene I-CAT fusions (CaMV) located downstream of the 5' leader sequences of either viral genome.

Base Sequence↗
PubMed1989

LHRH pulse frequency in normal and infertile men.

The aim of this study was to examine the hypothesis that decreased LHRH pulse frequency may be responsible for the preferential rise in FSH in infertile men. The LH pulse pattern was determined as an index of hypothalamic LHRH secretion in 21 infertile patients with idiopathic azoospermia or oligoasthenozoospermia and 14 fertile age-matched controls by frequent blood sampling at 10-min intervals for 24 h. The infertile patients were further divided into three groups according to their relative concentrations of FSH and LH: (1) normal FSH and LH, (2) raised FSH but normal LH, and (3) raised FSH and LH. LH pulses were detected by a computerized algorithm (Munro) validated against a threshold method. Concentrations of FSH, testosterone, sex hormone-binding globulin and oestradiol were measured in pooled plasma. Luteinizing hormone pulse frequencies in normal men were not significantly different from the infertile group as a whole. Similarly, mean LH pulse frequencies in infertile subgroups 1, 2 and 3 were not significantly lower than normal. Pulse interval, however, was increased in subgroup 1 compared with normal. Mean 24 h LH in group 2 was significantly higher than normal, but still within the normal range. The total testosterone, but not the free testosterone index was significantly decreased in the infertile group compared with normal. There was no correlation between mean FSH and LH pulse frequency or interval. In conclusion, our results show that in patients with seminiferous tubular dysfunction, the typical pattern of raised plasma FSH, increased LH pulse amplitude, raised FSH: LH ratio and normal or marginally low testosterone was not associated with any significant deviations in LHRH pulse frequency from the range observed in normal fertile men. This is not compatible with the hypothesis that decreased LHRH pulse frequency is associated with or the cause of the preferential rise in FSH in men with idiopathic infertility. Thus unlike anovulatory infertility in females, functional defects of hypothalamic LHRH secretion remain an uncommon finding in male infertility. Attempts to treat idiopathic oligozoospermia by altering LHRH pulse frequency is therefore unlikely to yield any clinical benefit.

Adult↗
PubMed1989

Ontogeny of pulsatile gonadotrophin secretion and pituitary responsiveness in male puberty in man: a mixed longitudinal and cross-sectional study.

The onset of puberty is characterized by a sleep-associated increase in pulsatile LH secretion which is not observed in adults. The ontogeny of gonadotrophin secretion during pubertal maturation may reflect changes in endogenous LHRH secretion, pituitary sensitivity to LHRH and/or alterations in gonadal steroid feedback. To understand the interplay between these mechanisms, we have examined the pulsatile pattern of plasma LH, FSH, testosterone, oestradiol and prolactin between 20.00 and 09.00 h and the pituitary response to repeated exogenous LHRH stimulation in 16 boys with delayed puberty (age 16.3 +/- 2.7 (S.E.M.) years) on one to four occasions in a mixed longitudinal/cross-sectional analysis. Physical maturity was determined by Tanner G staging (1-5) and clinical progress followed for a mean duration of 22.4 +/- 8.5 months during which 33 hormone profiles were obtained. Nocturnal (23.00-09.00 h) LH pulse frequency increased to a peak of 0.54 +/- 0.03/h at stage 2 which was followed by a gradual decline to 0.42 +/- 0.04/h at stage 5. The appearance of LH pulses in the evening (20.00-23.00 h), probably representative of the rest of the day, was delayed until mid-puberty from which point frequency increased to a peak of 0.53 +/- 0.08/h at stage 5. LH pulse amplitude showed a linear increase from stages 1 to 5, with nocturnal pulse amplitudes being higher than evening pulses throughout. FSH did not show a clear pulsatile pattern. The LH:FSH ratio reversed from less than 1 to greater than 1 at stage 2. The LH response to exogenous LHRH increased in parallel with LH pulse amplitude. There was no difference in the pattern of LH response to repeated LHRH stimulation as puberty advanced; the first stimulus always elicited a greater response than subsequent doses. In contrast, the FSH response to LHRH was maximal at stage 1 and became attenuated thereafter. The estimated mean nocturnal LHRH concentration or amplitude did not show any increase during pubertal maturation from 20.42 +/- 11.57 at stage 1 to 35.96 +/- 20.83 ng/l at stage 5. In conclusion, the sequential changes in this study suggest that the sleep-entrained increase in LHRH pulse frequency plays a key role at the onset of puberty. By enhancing pituitary responsiveness and setting in motion a cascade of events, this peripubertal augmentation of LHRH pulse frequency can account for most of the subsequent changes in LH, FSH and testosterone secretion during pubertal development in the male without any apparent alteration in LHRH pulse amplitude.

Adolescent↗
PubMed1987

Relative ability of modified versions of the hamster oocyte penetration test, incorporating hyperosmotic medium or the ionophore A23187, to predict IVF outcome.

This study was designed to assess the relationship between IVF outcome and the results obtained with two modified versions of the zona-free hamster oocyte penetration test in which the spermatozoa were pre-incubated with either hyperosmotic medium or the divalent cation ionophore A23187. When the former system was used, a poor correlation with IVF outcome was observed. Samples screened prior to IVF exhibited a 60% false negative rate (failed penetration test, successful IVF), while for those assessed concurrently with IVF, the equivalent figure was 85.7%. Addition of A23187 optimized the penetration system giving higher levels of sperm--oocyte fusion and a more accurate prediction of the capacity of the spermatozoa to fertilize human ova in vitro. With this system the false negative rate was 4.3% for screened samples and 0% for those assessed simultaneously with IVF. These results suggest that the A23187-enhanced system may be of value as a screening criterion for IVF.

Animals↗
PubMed1987

Effects of gonadotropin-releasing hormone pulse-frequency modulation on luteinizing hormone, follicle-stimulating hormone and testosterone secretion in hypothalamo/pituitary-disconnected rams.

The effects of changes in pulse frequency of exogenously infused gonadotropin-releasing hormone (GnRH) were investigated in 6 adult surgically hypothalamo/pituitary-disconnected (HPD) gonadal-intact rams. Ten-minute sampling in 16 normal animals prior to HPD showed endogenous luteinizing hormone (LH) pulses occurring every 2.3 h with a mean pulse amplitude of 1.11 +/- 0.06 (SEM) ng/ml. Mean testosterone and follicle-stimulating hormone (FSH) concentrations were 3.0 +/- 0.14 ng/ml and 0.85 +/- 0.10 ng/ml, respectively. Before HPD, increasing single doses of GnRH (50-500 ng) elicited a dose-dependent rise of LH, 50 ng producing a response of similar amplitude to those of spontaneous LH pulses. The effects of varying the pulse frequency of a 100-ng GnRH dose weekly was investigated in 6 HPD animals; the pulse intervals explored were those at 1, 2, and 4 h. The pulsatile GnRH treatment was commenced 2-6 days after HPD when plasma testosterone concentrations were in the castrate range (less than 0.5 ng/ml) in all animals. Pulsatile LH and testosterone secretion was reestablished in all animals in the first 7 days by 2-h GnRH pulses, but the maximal pulse amplitudes of both hormones were only 50 and 62%, respectively, of endogenous pulses in the pre-HPD state. The plasma FSH pattern was nonpulsatile and FSH concentrations gradually increased in the first 7 days, although not to the pre-HPD range. Increasing GnRH pulse frequency from 2- to 1-hour immediately increased the LH baseline and pulse amplitude. As testosterone concentrations increased, the LH responses declined in a reciprocal fashion between Days 2 and 7. FSH concentration decreased gradually over the 7 days at the 1-h pulse frequency. Slowing the GnRH pulse to a 4-h frequency produced a progressive fall in testosterone concentrations, even though LH baselines were unchanged and LH pulse amplitudes increased transiently. FSH concentrations were unaltered during the 4-h regime. These results show that 1) the pulsatile pattern of LH and testosterone secretion in HPD rams can be reestablished by exogenous GnRH, 2) the magnitude of LH, FSH, and testosterone secretion were not fully restored to pre-HPD levels by the GnRH dose of 100 ng per pulse, and 3) changes in GnRH pulse frequency alone can influence both gonadotropin and testosterone secretion in the HPD model.

Animals↗
PubMed1987

Enhancement of Leydig cell testosterone secretion by isolated seminiferous tubules during co-perifusion in vitro: comparison with static co-culture systems.

The aim of this study was to identify an in-vitro test system for the reproducible demonstration of a modulatory effect of isolated seminiferous tubules (s-tubules) on testosterone production by purified rat Leydig cells. Co-incubation of s-tubules with various numbers of Leydig cells had no significant effect on basal and hCG-stimulated testosterone production over 4-24 h incubation. In contrast, addition of s-tubule conditioned medium (STCM) to Leydig cells enhanced both basal and hCG-stimulated testosterone production over 5 h, but this effect was variable in magnitude and was not completely reproducible. Co-perifusion of isolated s-tubules with Percoll-purified Leydig cells for 6 h produced significant and consistent increases in Leydig cell testosterone secretion compared with Leydig cells perifused on their own. In six experiments, s-tubules enhanced Leydig cell testosterone secretion by 26 +/- 5% (P less than 0.001) in the absence of LH stimulation and by 48 +/- 11% following pulsatile stimulation with 1 ng/ml ovine LH (oLH). The presence of s-tubules enhanced (P less than 0.01-0.001) testosterone secretion by Leydig cells in response to pulses of oLH at doses ranging from 0.1 to 10 ng/ml, but the magnitude of enhancement was greatest with 0.1 and 1 ng/ml doses. These stimulatory effects were not explained by Leydig cell contamination or by testosterone leakage from the isolated s-tubules. Co-perifusion of Leydig cells with isolated epididymal tubules as a control tissue had no significant effect on LH-stimulated Leydig cell testosterone production. Stimulatory effects of s-tubules on Leydig cell testosterone secretion were observed at a 'physiological' ratio of s-tubules to Leydig cells (200 cm tubules/3 million cells) and was mediated by a humoural agent(s), since perifusion of s-tubules and Leydig cells in series gave similar results to co-perifusion of these tissues. This system proved to be robust and, in contrast to static culture systems, gave highly reproducible results, which should allow detailed investigation of the dynamic interactions between s-tubules and Leydig cells and the hormonal control of these events.

Animals↗
PubMed1987

Isolation of human Leydig cells which are highly responsive to human chorionic gonadotropin.

Leydig cells were purified on discontinuous Percoll gradients after collagenase digestion of human or rat testes. Leydig cells from both species were found in three bands. As determined by positive staining for 3 beta-hydroxysteroid dehydrogenase, band 1 (lowest density cells) from both species contained only 12-28% Leydig cells. However, while band 3 was the most Leydig cell-enriched fraction in rat cell preparations (70-90% Leydig cells), human band 2 (48-70% Leydig cells) was consistently more Leydig cell enriched than was band 3 (30-56% Leydig cells). Despite their slightly different fractionation pattern, Leydig cells prepared from five men with prostatic carcinoma were similar to those from the rat, both in terms of the amount of testosterone produced basally per 10(6) Leydig cells (80-234 ng/20 h) and in terms of the magnitude of their response to hCG (764-1342 ng/10(6) Leydig cells X 20 h; 5- to 17-fold stimulation above basal). Cells prepared from five other men with prostatic carcinoma produced much lower amounts of testosterone, but still had up to a 6-fold response to hCG. Plasma LH, FSH, and testosterone concentrations in the latter group could not be distinguished from those in the group whose Leydig cells produced large amounts of testosterone in vitro. Morphologically, the testes from the latter group appeared to contain more darkly staining than lightly staining Leydig cells than did the former group. Rat Leydig cells responded in a dose-dependent fashion to hCG over the range 0.03-0.5 mU/mL, whereas human Leydig cells were 10- to 100-fold less sensitive, responding to hCG in the range 0.4-100 mU/mL. The number and affinity of Leydig cell LH (hCG) receptors were assessed from Scatchard analysis of [125I]hCG binding. Compared with rat cells, human Leydig cells contained approximately 20% of the number of LH receptors, while the affinity of the receptors (Kd, approximately 10(-10) M) was similar to that in rats. In conclusion, a method for the isolation of highly responsive human Leydig cells has been developed. The results so far suggest that the function of human Leydig cells may be more similar to that of the rat than thought previously.

Aged↗
PubMed1987

Inhibin bioactivity in human testicular extracts.

Inhibin bioactivity was measured in human testicular extracts by a sensitive sheep pituitary cell bioassay. The relationship between testicular inhibin bioactivity, daily sperm production (DSP) and plasma concentrations of FSH, LH, testosterone and oestradiol were examined. The mean level of testicular inhibin bioactivity was 4.4 +/- 1.3 U/g (mean +/- SD) with a significantly lower value in those who received radiotherapy (3.2 +/- 1.4 U/g) than in the untreated group (4.8 +/- 1.1 U/g). In contrast to the rat, human testicular inhibin bioactivity was not significantly correlated to FSH or DSP. These findings suggest that inhibin may have a complex role in normal and/or pathological testicular function.

Aged↗
PubMed1985

Erectile impotence.

Explore the source record for details and available documents.

Erectile Dysfunction↗
PubMed1985

The adrenal secretion of progesterone stimulates testicular steroidogenesis in the rat in vitro.

We have used a multicolumn isolated cell superfusion system to investigate the interaction between isolated rat adrenal and testicular cells in the secretion of sex steroids. The steroid responses of a mixed population of adrenal and testicular cells to the administration of ACTH 100 pg/ml was compared with the responses of the separate cell types. Steroid responses from 5 separate experiments were analysed. We have demonstrated increased secretion of 17 alpha-hydroxyprogesterone (P less than 0.0005), androstenedione (P less than 0.05) and testosterone (P less than 0.0005) by a mixture of cells when compared with the responses of either cell type alone. In contrast, the secretion of progesterone (P less than 0.0005) and corticosterone (P less than 0.005) was reduced in the mixed cell population, suggesting that progesterone is preferentially converted by testicular cells to 17 alpha-hydroxyprogesterone, androstenedione and testosterone. This is confirmed by increased secretion of 17 alpha-hydroxyprogesterone, androstenedione and testosterone but not corticosterone by a mixed population following the administration of progesterone 10 ng/ml. These results suggest that the adrenal secretion of progesterone can stimulate testicular steroidogenesis in the male rat in vitro.

Adrenal Glands↗
PubMed1985

Functional characterization of luteinizing hormone responsiveness and desensitization in perifused interstitial cells.

The characteristics of the steroidogenic response of isolated rat testis interstitial cells to repeated 10 min pulses of ovine LH at 2 h intervals were examined in a Bio-gel perifusion system. Maximal responsiveness of the perifused interstitial cells could be maintained for 6-8 h. Thereafter, both basal and LH-stimulated testosterone production declined gradually despite supplementation of the perifusion medium with 1% and 5% foetal calf serum or 0.5 microgram/ml insulin. In contrast to the time-related steroidogenic decline, a dose-dependent refractoriness of the interstitial cells could be induced by repeated exposure to LH pulses from 0.01 to 10 ng/ml during the first 6 h of perifusion. The higher the stimulating dose of LH, the greater was the rate and magnitude of the resultant desensitization. With lower doses (0.01 and 0.1 ng/ml) of LH, an initial sensitization or priming effect was also observed. These changes in steroidogenic response occurred in the absence of any significant alterations in LH/hCG receptor binding of the perifused interstitial cells, nor could the refractory state be overcome by stimulation with analogues of cAMP. The perifused interstitial cells, when desensitized with low doses of LH (0.1 ng/ml), were capable of increasing or maintaining testosterone production in response to further stimulation with higher doses of LH (1 and 10 ng/ml). The mechanism(s) underlying the in vitro desensitization of perifused interstitial cells by LH may best be explained on the basis of the interaction between the negative effects of substrate depletion and the positive influence of mobilization of substrate(s) into the metabolically active pool for cholesterol side-chain cleavage. It was concluded that the dose of LH used in the pulsatile stimulation of perifused interstitial cells is critically important not only in determining the total amount of testosterone produced, but also in the pattern of response in terms of the degree of sensitization and desensitization induced.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Male hypogonadism--current concepts and trends.

Important advances have been made recently in our knowledge of hypothalamic-pituitary-testicular functions. Current understanding of the hypothalamic control of pituitary gonadotrophin secretion and the mechanisms of testicular feedback is beginning to yield benefits in the clinical management of certain reproductive disorders. But much remains to be learned about the neuroendocrine control of hypothalamic GnRH secretion--an area which encompasses the mechanisms regulating the onset of puberty. Spermatogenesis is a highly complex process involving subtle interactions between endocrine, paracrine and autocrine regulators acting on different cell populations within and without the testis. Until basic research can advance the very limited knowledge in this area, we cannot expect to improve the currently unsatisfactory management of infertile men. It is not surprising that only limited information can accrue from conventional semen analysis and measurement of systemic hormones. Nor is it unexpected that empirical or seemingly rational treatments for male infertility are of dubious benefit. In future, assessment of the infertile man should be improved by studying sperm functional capacities and testicular synthesis and metabolism of gonadal steroids and by the definition of representative markers of Sertoli cell and epididymal functions. Reversible male contraception is another objective that remains beyond our reach at present. Hormonal disruption of spermatogenesis is often incomplete and invariably suppresses Leydig cell function, so that androgen replacement for sustaining sexual function is mandatory. Alternative approaches to male contraception aimed at the epididymis and sperm-egg interaction seem more promising avenues for future exploration.

Aging↗
PubMed1983

Changes in erectile responsiveness during androgen replacement therapy.

Erections in response to erotic films and fantasies were measured in eight hypogonadal men, with and without androgen replacement, and eight age-matched controls. Erections to films in the hypogonadal men did not differ from those of the controls and were not affected by androgen replacement. Erections to fantasy were significantly smaller and slower to develop in the hypogonadal men and did show significant improvement during androgen replacement. These preliminary results suggest that erections to certain types of stimuli are relatively independent of androgens, whereas the response to fantasy may be androgen dependent. The implications of these findings are discussed.

Adult↗
PubMed1982

The effects of diabetes on male sexual function.

Diabetic men are prone to a variety of sexual problems. It is probable that most of these sexual difficulties are the result of a progressive physical disorder upon which a psychological reaction is superimposed. Assessment needs to take account of both the physical and psychological components of the problem. The aim of management is to help the patient and his partner enjoy sexual function to the full within whatever limits are set by irreversible factors. Management therefore involves correcting potentially reversible physical and psychological factors, and helping the patient and his partner adapt to the remaining irreversible changes in sexual function. Using this approach it may be possible to improve the prognosis of what in the past has been dismissed as an intractable clinical problem.

Adolescent↗