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Biomedical subjects

W J Bremner

Publications and source records attributed to W J Bremner.

At least 127 records · Page 7Linked to original sources
PubMed1984

Abnormal patterns of pulsatile luteinizing hormone in women with luteal phase deficiency.

Luteal phase deficiency is usually a problem of inadequate progesterone production associated with inadequate ovarian follicular development. The hypothesis that luteal phase deficiency results from an abnormal secretion pattern of luteinizing hormone (LH) was tested in these women. To this end, the early follicular LH secretion pattern in four women with luteal phase deficiency was characterized and compared with patterns in normal women. Blood samples were obtained through indwelling catheters every ten minutes for eight hours (10 AM to 6 PM), and plasma levels of LH and FSH were measured. Luteinizing hormone and FSH secretion profiles were analyzed for pulse frequency, amplitude, and mean plasma level. A significantly greater LH pulse frequency in women with luteal phase deficiency was observed when compared with the frequency in normal controls (luteal phase deficiency, 10.5 pulses/eight hours; normal, 5.2 pulses/eight hours; P less than or equal to .05). The mean FSH concentration was less in the women with luteal phase deficiency, but the level was not significant. These data suggest that the abnormal LH secretion pattern observed in women with luteal phase deficiency is responsible for their inadequate luteal phase progesterone secretion and their infertility.

Adult↗
PubMed1983

Control of FSH and LH secretion.

The control of FSH and LH secretion by the pituitary gland is clearly multifactorial. The evidence that LHRH influences the release and stores of both FSH and LH is considerable, and equally well documented is the fact that testosterone and oestradiol will suppress the secretion not only of LH but also of FSH. Recently evidence points to the existence of inhibin which will suppress FSH secretion but which in higher doses will also decrease LH levels. It is therefore likely that the ratio of FSH to LH secreted by the gonadotrope is determined by the summation of the action of these factors on cellular mechanisms that remain to be determined.

Animals↗
PubMed1983

Elevated serum follicle-stimulating hormone levels in men with normal seminal fluid analyses.

Three men who volunteered as normal subjects were found to have abnormally high levels of serum follicle-stimulating hormone (FSH) despite having normal seminal fluid analyses and fertility. Two of the men had a history of previous orchitis, and one had an atrophic testis. Serum luteinizing hormone and testosterone levels were normal. These cases appear to represent compensated primary testicular disease, with normal sperm counts and fertility maintained at the expense of chronically elevated FSH levels. These results imply that in certain situations, the measurement of serum FSH levels may be a more sensitive index of testicular disease than the performance of seminal fluid analyses.

Adult↗
PubMed1983

Reinitiation of sperm production in gonadotropin-suppressed normal men by administration of follicle-stimulating hormone.

The specific roles of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in controlling human spermatogenesis are poorly understood. We studied the effect of an experimentally induced, selective LH deficiency on sperm production in normal men. After a 3-mo control period, five men received 200 mg testosterone enanthate (T) i.m./wk to suppress LH, FSH, and sperm counts. Then, while continuing T at the same dosage, human FSH (hFSH) was administered simultaneously to replace FSH activity, leaving LH activity suppressed. Four men received 100 IU hFSH s.c. daily plus T (high dosage hFSH) for 13-14 wk, while one man received 50 IU hFSH s.c. daily plus T (low dosage hFSH) for 5 mo. The effect on sperm production of the selective LH deficiency produced by hFSH plus T administration was assessed. In the four men who received the high dosage hFSH regimen, sperm counts were markedly suppressed during T administration alone (0.3+/-0.2 million/cm(3), mean+/-SE, compared with 94+/-12 million/cm(3) during the control period). Serum LH bioactivity (determined by in vitro mouse Leydig cell assay) was suppressd (140+/-7 ng/ml compared with 375+/-65 ng/ml during control period) and FSH levels (by radioimmunoassay) were reduced to undetectable levels (<25 ng/ml, compared with 98+/-21 ng/ml during control period) during T alone. With the addition of 100 IU hFSH s.c. daily to T, sperm counts increased significantly in all subjects (33+/-7 million/cm(3), P < 0.02 compared with T alone). However, no subject consistently achieved sperm counts within his control range. Sperm morphology and motility were normal in all four men and in vitro sperm penetration of hamster ova was normal in the two men tested during the hFSH-plus-T period. During high-dosage hFSH administration, serum FSH levels increased to 273+/-44 ng/ml (just above the normal range for FSH, 30-230 ng/ml). Serum LH bioactivity was not significantly changed compared with the T-alone period (147+/-9 ng/ml). After the hFSH-plus-T period, all four men continued to receive T alone after hFSH was stopped. Sperm counts were again severely suppressed (0.2+/-0.1 million/cm(3)), demonstrating the dependence of sperm production on hFSH administration. Serum T and estradiol (E(2)) levels increased two- to threefold during T administration alone compared with the control period. Both T and E(2) levels remained unchanged with the addition of hFSH to T, confirming the lack of significant LH activity in the hFSH preparation. In the one man who received low dosage hFSH treatment, sperm counts were reduced to severely oligospermic levels, serum FSH was suppressed to undetectable levels, and serum LH bioactivity was markedly lowered during the T-alone period. With the addition of 50 IU hFSH s.c. daily to T, sperm counts increased, to a mean of 11+/-3 million/cm(3). During this period, serum FSH levels increased to a mean of 105+/-11 ng/ml (slightly above this man's control range and within the normal adult range), while LH bioactivity remain suppressed. After hFSH was stopped and T alone was continued, sperm counts were again severely reduced to azoospermic levels. We conclude that FSH alone is sufficient to reinitiate sperm production in man during gonadotropin suppression induced by exogenous T administration. FSH may stimulate sperm production in this setting by increasing intratesticular T through androgenbinding protein production or by increasing the sensitivity of the spermatogenic response to the intratesticular T present during exogenous T administration.

Adult↗
PubMed1983

Diminished luteinizing hormone pulse frequency and amplitude with aging in the male rat.

Aging in the male rat is associated with a reduction in circulating testosterone levels. One possible cause of this decline is an age-related alteration of central nervous system-mediated LH secretion. To examine the effects of age on the hypothalamo-hypophyseal system, in the absence of gonadal steroid feedback, we studied the pattern of pulsatile LH secretion in castrate male Sprague-Dawley rats, aged 3 months (young), 8 months (middle-aged), and 26 months (old). All animals were castrated, and after 3 weeks, they were implanted with indwelling atrial catheters. One day later, duplicate 25 microliters blood samples were obtained at 4-min intervals for 4 h, while the animals were awake and unrestrained. Serum levels of LH, FSH, and testosterone were measured in animals before castration, and blood LH levels were measured in the postcastration, repeated sampling studies. After castration, middle-aged and old animals exhibited significantly lower mean serum LH levels, associated with a diminished amplitude of LH secretory episodes compared to young rats. In the oldest group, LH pulse frequency was significantly lower compared to middle-aged and young animals. Since the control of LH secretory episodes resides in the central nervous system, we propose that alterations in frequency of LH pulses observed in the aged, castrate male rat are the result of a diminished functional capacity of LHRH-containing neurons or of neurotransmitters that modulate their activity in the aging brain.

Aging↗
PubMed1983

Loss of circadian rhythmicity in blood testosterone levels with aging in normal men.

Previous studies concerning the relationship of serum testosterone levels to aging in normal men have yielded apparently inconsistent results. Studies performing blood sampling in the morning have often shown an age-related decrease in testosterone levels, while those using afternoon samples have failed to show such a decrease. These results suggested to us the possibility that the circadian rhythm in serum testosterone levels might be altered with normal aging in men. Hourly blood samples were obtained for 24 h from 17 young (mean age, 25.2 yr) and 12 old (mean age, 71 yr) healthy men. Total testosterone levels were measured by RIA. The circadian rhythm in serum testosterone levels found in normal young men was markedly attenuated or absent in healthy elderly men; the early morning rise in testosterone levels characteristic of young men was not present in old age. Mean testosterone levels for the entire 24-h day were lower in healthy old men than in young men. These results demonstrate a clear decrease in serum testosterone levels in healthy old men compared to those in young men and provide an explanation for the inability to demonstrate an age-related decline in testosterone levels in earlier studies using serum samples obtained in the afternoon.

Adult↗
PubMed1982

Regulation of luteinizing hormone pulse frequency and amplitude by testosterone in the adult male rat.

Our objective was to gain a better understanding of the role of testosterone (T) in regulating the minute to minute dynamics of LH secretion in the adult male rat. To this end, we examined the patterns of blood LH levels in intact animals and evaluated the effect of small physiological doses of T on mean blood LH and FSH levels and on LH pulse frequency and amplitude in the castrate animal. The intact rat exhibited low frequency (period, approximately 145 min) and low amplitude (approximately 16 ng/ml) LH pulses. After castration, LH pulse frequency (period, approximately 20 min) and amplitude (approximately 118 ng/ml) increased dramatically over that of intact animals. T, administered to castrate rats through Silastic implants, caused a dose-dependent and parallel reduction in mean blood LH and FSH levels. The lowest T dose, which increased mean plasma T levels to 0.5 ng/ml above those of the sham-treated castrates, produced a significant reduction in LH pulse frequency, with a significant increase in pulse amplitude. The next highest T dose caused a reduction in pulse amplitude to a value significantly lower than that in the sham-treated castrates. The highest T dose, which produced steady state mean plasma T levels (approximately 1.6 ng/ml) less than the mean level of the intact group (approximately 2.2 ng/ml), caused a profound reduction in pulse frequency to lower than that of the intact group. These observations demonstrate that T can exert a complex, dose-dependent effect on LH secretory dynamics and imply that one important site of T-mediated negative feedback is the brain's LHRH pulse generator.

Animals↗
PubMed1982

An automated technique for the radiographic determination of bone age.

We have developed an automated procedure for determining bone-age in the monkey, Macaca fascicularis. The status of epiphysial junctions and sesamoids were determined from radiographs. Epiphyses were scored as either open or closed, and sesamoids were scored as either present or absent. Bone-age was calculated by a computer program that stored and used a data base of probabilities for epiphysial closure and sesamoid appearance. The simplicity of scoring, combined with the speed and accuracy of the calculations, make this technique potentially adaptable for use in a variety of primate species.

Age Determination by Skeleton↗
PubMed1981

Follicle-stimulating hormone and human spermatogenesis.

The role of follicle-stimulating hormone (FSH) in the control of spermatogenesis is not well established in any species, including man. We studied the effect of an experimentally-induced, selective FSH deficiency on sperm production in normal men. After a 3-mo control period, five normal men received testosterone enanthate (T) 200 mg i. m. weekly to suppress luteinizing hormone (LH) and FSH, until three successive sperm counts revealed azoospermia or severe oligospermia (sperm counts <3 million/ml). Then, while continuing T, human chorionic gonadotropin (hCG) 5,000 IU i. m. three times weekly was administered simultaneously to replace LH activity, leaving FSH activity suppressed. The effect of the selective FSH deficiency produced by hCG plus T administration on sperm production was determined. Sperm counts (performed twice monthly throughout the study) were markedly suppressed during T administration alone (1.0+/-1.0 million/ml mean+/-SE, compared with 106+/-28 million/ml during the control period, P < 0.001). With the addition of hCG to T, sperm counts returned toward normal (46+/-16 million/ml, P < 0.001 compared with T alone). In two subjects, sperm counts during hCG plus T returned into the individual's control range. Sperm motility and morphology were consistently normal in all men during hCG plus T. Serum FSH levels by RIA were normal (110+/-10 ng/ml) in the control period and were suppressed to undetectable levels (<25 ng/ml) in the T alone and hCG plus T periods. Urinary FSH excretion was markedly suppressed in the T alone (60+/-15 mIU/h-2nd IRP, P < 0.01) and hCG plus T (37+/-9 mIU/h, P < 0.01) periods compared with the control period (334+/-78 mIU/h). We conclude that spermatogenesis as assessed by sperm counts, motilities, and morphologies may be reinitiated and maintained at normal levels in men with undetectable blood FSH levels and urinary excretion of FSH less than that of prepubertal children. This conclusion implies that, although FSH may exert effects on human testicular function, maintenance of normal spermatogenesis and reinitiation of sperm production after short-term suppression by exogenous steroids can occur in spite of nearly absent FSH stimulation.

Adult↗
PubMed1981

Effects of LH-RH infusion, castration and cryptorchidism on gonadotrophin and testosterone secretion in developing rams.

The relationship between the pituitary gland and testis in rams was studied from birth to sexual maturity. The concentrations of LH, FSH and testosterone increased between 5 and 7 weeks of age; the rise was not correlated with any specific cytological change in the testis. An augmented pituitary response to LH-RH was demonstrated as levels of gonadotrophin increased. It is unclear whether this change in sensitivity plays a role in initiation of the pubertal process because Sertoli cell maturation, the earliest detectable change in the seminiferous epithelium, occurs between 17 and 21 weeks of age. Spermatocytes were first seen in biopsies taken at 31-36 weeks and spermatogenesis was established fully by 45 weeks. This second phase of testicular development was characterized by increases in prolactin, testosterone and LH. Leydig cells previously difficult to identify became recognizable at the time of sexual maturation. In newborn rams, castration produced significant increases in LH and FSH levels within 2-3 weeks, but higher basal FSH levels (2- to 3-fold) were observed at 5 than at 3 weeks of age. Cryptorchidism did not elevate LH or FSH significantly during the first year of life. FSH rose after this period to levels 2- to 3-fold higher than in normal rams, while LH and testosterone values remained in the normal range in spite of diminished spermatogenic activity; spermatids were absent and testis size was approximately 60% of that recorded in a normal ram. These studies demonstrate a rise in gonadotrophin and testosterone secretion in rams during the first 5-7 weeks of life, followed by a quiescent period of 8-9 months before a secondary increase occurs coincident with the establishment of sexual maturity.

Aging↗
PubMed1981

The effect of intrauterine gonadectomy on fetal and neonatal gonadotrophin secretion in the lamb.

In Exp. 1, sheep fetuses (2 male and 3 female) were gonadectomized between Days 70 and 120 of gestation and their blood LH and FSH levels were compared to those of control animals (4 male, 6 female) at regular times during the first year after birth. In Exp. 2, fetuses (3 male and 5 female) were gonadectomized between Days 50 and 60 of gestation and gonadotrophin levels at Day 90 of gestation were compared to those of control fetuses of the same age. In neither study did the blood LH and FSH levels differ significantly between gonadectomized and intact lambs of either sex in utero or in the first week of life. However, by 2 weeks of age in the males and by 5 weeks of age in the females, gonadotrophin levels were higher in the gonadectomized than in the intact animals and this difference persisted throughout the first year of life. These results imply that fetal and neonatal gonadotrophin levels are suppressed by maternal and placental steroids in the sheep, and not by fetal gonadal hormones.

Aging↗
PubMed1978

Inhibition of fetal growth and survival by testosterone administration to pregnant sheep.

Testosterone (as testosterone enanthate, 250 mg i.m. every 2 wk) was administered to pregnant ewes (n = 16), and injections of vehicle were used in 10 control pregnant ewes between days 75 of gestation and term (day 147). Fetal survival (7 of 16 in the treated group versus 10 of 10 in the controls) and growth (birth weights 4.00 +- 0.51 kg in the treated group versus 5.79 +- 0.93, mean +- SD, in the controls) were markedly impaired by testosterone administration. The mechanism of the testosterone effect is unknown, but could be through metabolism to estrogens by the feto-placental unit. These results imply that alterations in the production or metabolism of androgens by the mother or the feto-placement unit may exert important effects on fetal growth and survival.

Animals↗