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Biomedical subjects

W J Bremner

Publications and source records attributed to W J Bremner.

At least 109 records · Page 6Linked to original sources
PubMed1987

The effects of inducing a follicular phase gonadotropin secretory pattern in normal women during the luteal phase.

It has been hypothesized that the slowing of the luteinizing hormone (LH) pulse frequency in the luteal phase may be necessary for the demise of the corpus luteum, the intercycle rise in baseline follicle-stimulating hormone (FSH), or ovarian follicular development in the subsequent cycle. For assessment of the physiologic role of the luteal phase LH pulse pattern, this pattern was converted to a follicular pattern in six normal women who used exogenous gonadotropin-releasing hormone administered with a portable pump (dose 50 to 100 ng/kg subcutaneously every 90 minutes beginning in the early luteal [n = 3] and midluteal [n = 3] cycle phases). There was no significant difference between the treated and the subsequent cycle for luteal progesterone production [186.3 versus 159.0 (ng/ml) day], preovulatory follicular size (23.1 versus 22.5 mm), estradiol levels, luteal phase length (15.6 versus 14.3 days), and daily gonadotropin concentrations including the intercycle FSH rise (160.5 versus 139.1 ng/ml). A follicular phase gonadotropin pulse pattern (increased frequency, decreased amplitude) in the luteal phase had no discernible effects on the corpus luteum or on follicular development in the subsequent cycle.

Adult↗
PubMed1987

Gonadotropin-releasing hormone-induced changes in testosterone secretion in normal women.

This study investigated the pattern of testosterone (T) secretion in spontaneous (n = 14) and gonadotropin-releasing hormone (GnRH)-treated (n = 6) menstrual cycles in normal women. In spontaneous cycles, T was found to increase progressively over the follicular phase (P less than or equal to 0.001), with the peak T value occurring on cycle day 0 (luteinizing hormone [LH] surge). The mean (+/- standard error of the mean [SEM]) T values on cycle day -14 and cycle day 0 were 35 +/- 4 and 51 +/- 4 ng/dl, respectively. GnRH was administered intravenously to six women at 1.3 to 1.7 micrograms per dose every 30 minutes in a study that assessed the ovarian effects of a rapid gonadotropin pulse frequency. In three of the women, the T levels followed a normal follicular phase pattern, whereas in the remaining three GnRH-treated women, there were marked increases in T with peak levels of 97, 123, and 81 ng/dl on day 0. The GnRH-treated subgroup with increased T levels had significantly increased follicular levels of LH, follicle-stimulating hormone (FSH), LH-bio and number of preovulatory ovarian follicles. This study demonstrated that increased levels of LH, FSH, and LH/FSH are capable of acutely increasing the secretion of ovarian androgens.

Adult↗
PubMed1986

Opioid regulation of luteinizing hormone secretion in the male rat.

Current evidence suggests that endogenous opioid peptides (EOPs) tonically inhibit secretion of luteinizing hormone (LH) by modulating the release of gonadotropin-releasing hormone (GnRH). Because of their apparent inhibitory actions, EOPs have been assumed to alter both pulse frequency and amplitude of LH in the rat; and it has been hypothesized that EOP pathways mediate the negative feedback actions of steroids on secretion of GnRH. In order to better delineate the role of EOPs in regulating secretion of LH in the male rat, we assessed the effects of a sustained blockade of opiate receptors by naloxone on pulsatile LH release in four groups: intact male rats, acutely castrated male rats implanted for 20 h with a 30-mm capsule made from Silastic and filled with testosterone, acutely castrated male rats implanted for 20 h with an osmotic minipump dispensing 10 mg morphine/24 h, and male rats castrated approximately 20 h before treatment with naloxone. We hypothesized that if EOPs tonically inhibited pulsatile LH secretion, a sustained blockade of opiate receptors should result in a sustained increase in LH release. We found that treatment with naloxone resulted in an immediate but transient increase in LH levels in intact males compared to controls treated with saline. Even though mean levels of LH increased from 0.15 +/- 0.04 to a high of 0.57 +/- 0.14 ng/ml, no significant difference was observed between the groups in either frequency or amplitude of LH pulses across the 4-h treatment period. The transient increase in LH did result in a 3- to 4-fold elevation in levels of plasma testosterone over baseline. This increase in testosterone appeared to correspond with the waning of the LH response to naloxone. The LH response to naloxone was eliminated in acutely castrated rats implanted with testosterone. Likewise, acutely castrated rats treated with morphine also failed to respond to naloxone with an increase in LH. These observations suggest that chronic morphine and chronic testosterone may act through the same mechanism to modulate secretion of LH, or once shut down, the GnRH pulse-generating system becomes refractory to stimulation by naloxone. In acutely castrated male rats, levels of LH were significantly increased above baseline throughout the period of naloxone treatment; this finding supports the hypothesis that the acute elevation in testosterone acting through mechanism independent of opioid is responsible for the transient response of LH to naloxone in the intact rat.

Animals↗
PubMed1986

Evidence for activation of the central nervous system-pituitary mechanism for gonadotropin secretion at the time of puberty in the male rat.

During sexual development in the male rat, serum testosterone (T) levels increase markedly at 45-60 days of age. At the time of the pubertal rise in T levels, activation of the hypothalamic-pituitary axis is difficult to demonstrate, since there is little change in serum LH levels and a decrease in serum FSH levels. We determined whether experimental maintenance of stable pubertal T levels in these animals as they passed through the normal age of puberty would allow demonstration of a major increase in serum gonadotropin levels. At 14-15 days of age, male rats were castrated and outfitted with either T-containing or empty Silastic capsules. Another group of rats was left intact and outfitted with empty capsules. At various times between 29 and 58 days of age, blood was drawn for measurement of serum LH, FSH, and T levels. In the T-implanted castrated rats, serum T levels were comparable to those in midpubertal intact rats, without significant differences among age groups. In this setting of stable T levels, serum LH and FSH were suppressed to levels at or below those in pubertal intact rats until 51 days of age, when they increased significantly into the untreated castrate range. In contrast, untreated castrate animals demonstrated markedly reduced serum T and elevated LH and FSH levels that did not change significantly throughout the entire study. In intact rats, serum T levels were stable until 58 days of age, when they increased over 2-fold; serum LH levels did not change significantly with age, and serum FSH levels decreased significantly by 54 days of age. A separate group of rats was castrated and outfitted with T-containing Silastic capsules at 21 days of age. In these animals, there were significant increases in hypothalamic LHRH, norepinephrine (NE), and dopamine levels and NE turnover rate at 56 compared to 36 days of age. We conclude that stable pubertal levels of T are able to suppress gonadotropin levels in castrated rats until the normal age of puberty, at which time LH and FSH levels increase markedly. This decrease in sensitivity of the hypothalamic-pituitary axis to T negative feedback at puberty is accompanied by increases in hypothalamic LHRH, NE, and dopamine levels and NE turnover rate. These results provide direct evidence for activation of the central nervous system-pituitary mechanism regulating gonadotropin secretion at puberty in the male rat.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Suppression of plasma gonadotropins and testosterone in adult male monkeys (Macaca fascicularis) by a potent inhibitory analog of gonadotropin-releasing hormone.

The reduction of circulating levels of gonadotropins and testosterone is of value for the treatment of steroid-dependent neoplasms and the control of fertility. We tested the ability of single and multiple doses of the GnRH antagonist [N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Ala10]GnRH (GnRH-Ant) to suppress levels of these hormones in intact and castrate adult male cynomolgus monkeys. In Exp I, single injections of the antagonist at doses of 0 (vehicle), 5, 50, 250, and 500 micrograms/kg BW were given to castrate and intact animals. In Exp II, daily injections of antagonist at doses of 0, 50, 100, or 250 micrograms/kg BW were given to intact animals for 21 days. Plasma levels of testosterone, FSH, and LH were determined by RIA, and in intact animals, LH levels were measured by bioassay. In Exp 1, a single injection of 5 micrograms/kg BW or more of GnRH-Ant to castrate animals significantly reduced plasma LH and FSH by 4 h after injection (P less than or equal to 0.01). Nadir levels (40% of preinjection control values) of LH and FSH were reached 8 and 24 h, respectively, after administration of 250 or 500 micrograms/kg BW, and these hormones remained significantly lower than preinjection values over at least 48 h (P less than or equal to 0.05). A single injection of 50 micrograms/kg BW or more of antagonist to intact animals markedly reduced plasma LH and testosterone by 6 h after administration (P less than or equal to 0.05), while 250 or 500 micrograms/kg BW antagonist maintained LH and testosterone levels below 30% (P less than or equal to 0.05) of preinjection values for 24 h. In Exp II, daily injections of 250 micrograms/kg BW antagonist to intact animals resulted in near-castrate levels of plasma testosterone which were achieved by 24 h after the first injection of antagonist and persisted for the ensuing 20 days. Daily injections of 100 micrograms/kg BW or less of antagonist were ineffective in suppressing testosterone. Thus, this potent GnRH antagonist acutely and chronically lowers gonadotropin and testosterone levels in adult male cynomolgus monkeys. By virtue of its inhibitory effect, this antagonist is potentially useful as a therapeutic agent in clinical situations requiring long term suppression of testicular function, such as fertility control, the treatment of steroid-dependent neoplasms, and precocious puberty.

Animals↗
PubMed1986

Chronic human chorionic gonadotropin administration in normal men: evidence that follicle-stimulating hormone is necessary for the maintenance of quantitatively normal spermatogenesis in man.

The role of FSH in the maintenance of spermatogenesis in man is poorly understood. To determine whether normal serum levels of FSH are necessary for the maintenance of quantitatively normal spermatogenesis, we first studied the effect on sperm production of selective FSH deficiency induced by chronic administration of hCG in normal men. Then, we determined the effect of FSH replacement in some of these men. After a 3-month control period, eight normal men (aged 30-39 yr) received 5000 IU hCG, im, twice weekly for 7 months. Then while continuing the same dosage of hCG, subjects simultaneously received 200 mg testosterone enanthate (T), im, weekly for an additional 6 months. hCG administration alone resulted in partial suppression of the mean sperm concentration from 88 +/- 24 (+/-SEM) million/ml during the control period to 22 +/- 7 million/ml during the last 4 months of hCG treatment (P less than 0.001 compared to control values). With the addition of T to hCG, sperm counts remained suppressed to the same degree. Except for one man who became azoospermic while receiving hCG plus T, sperm motilities and morphologies remained normal in all subjects throughout the entire study. During both the hCG alone and hCG plus T periods, serum FSH levels were undetectable (less than 25 ng/ml), and urinary FSH levels were comparable to those in prepubertal children and hypogonadotropic hypogonadal adults. We replaced FSH activity in four of the eight men in whom prolonged selective FSH deficiency and partial suppression of sperm production were induced by hCG administration. Immediately after the period of hCG plus T administration, T was stopped in four men who continued to receive hCG alone (5000 IU, im, twice weekly) for 3 months. Then, while continuing the same dosage of hCG, these men received 100 IU human FSH, sc, daily (n = 2) or 75 IU human menopausal gonadotropin, sc, daily (n = 2) for 5-8 months. During the second period of hCG administration alone, serum FSH levels were undetectable (less than 25 ng/ml), and sperm concentrations were suppressed (34 +/- 13 million/ml) compared to the control values for these four men (125 +/- 39 million/ml; P less than 0.001). With the addition of FSH to hCG, FSH levels increased (213 +/- 72 ng/ml) and sperm concentrations rose significantly, reaching a mean of 103 +/- 30 million/ml (P less than 0.03 compared to hCG alone).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Increased frequency of pulsatile luteinizing hormone-releasing hormone administration selectively decreases follicle-stimulating hormone levels in men with idiopathic azoospermia.

Men with idiopathic azoo-oligospermia and selective elevations of follicle-stimulating hormone (FSH) levels have evidence for decreased luteinizing hormone-releasing hormone (LH-RH) pulse frequency. We assessed whether increasing the frequency of pulsatile LH-RH stimulation can lower FSH levels in such men. We administered 5.0 microgram of pulsatile LH-RH subcutaneously at intervals of 30, 60, and 120 minutes for 1 week to four men who had azoospermia, elevated FSH levels, and normal LH and testosterone (T) levels. The order of administration was varied among subjects. Frequent blood samples were obtained for 6 hours before LH-RH treatment and during the last 6 hours of each regimen. Before LH-RH treatment, the FSH levels (mean +/- standard error of the mean) were 359 +/- 18 ng/ml (normal range, 30 to 230 ng/ml). During LH-RH treatment, FSH levels progressively declined from 397 +/- 68 ng/ml to 237 +/- 70 ng/ml to 175 +/- 43 ng/ml as the frequency of administration increased from every 120 to 60 to 30 minutes, respectively (P less than 0.05). Unlike the FSH levels, which showed a progressive decline, LH, T, and estradiol levels showed no consistent relationship to LH-RH pulse frequency. We conclude that (1) in men with idiopathic azoospermia and elevated FSH levels, it is possible to decrease FSH levels by increasing the frequency of pulsatile LH-RH stimulation; (2) this decline does not appear to be a result of changes in steroid feedback or pituitary down-regulation; and (3) the frequency of pulsatile LH-RH stimulation can differentially modulate LH and FSH secretion by the pituitary gland.

Adult↗
PubMed1986

Ovulation induction with pulsatile gonadotropin-releasing hormone: a study of the subcutaneous route of administration.

The efficacy of ovulation induction with the use of intermittent gonadotropin-releasing hormone (GnRH) therapy was examined in seven infertile women with hypothalamic amenorrhea. GnRH was administered every 90 minutes via the subcutaneous route in doses ranging from 50 to 300 ng/kg. Analysis of the induced gonadotropin pulse pattern revealed normal to modestly increased luteinizing hormone secretory parameters (e.g., pulse amplitude) in six of the seven patients. Six of seven women and 15 of 16 treatment cycles (94%) were ovulatory. The conception rate was 43% per woman and 19% per cycle. However, detailed hormonal analysis of 13 treatment cycles revealed that only 1 cycle was entirely normal in terms of duration and/or steroid secretion.

Adult↗
PubMed1985

The role of endogenous gonadotropin-releasing hormone in the control of luteinizing hormone and testosterone secretion in the juvenile male monkey, Macaca fascicularis.

To determine what changes occur in the activity of gonadotropin-releasing hormone (GnRH) neurons during pubertal development in primate species we tested the hypotheses that there are morphologic differences between GnRH-containing neurons in juvenile versus adult monkeys, and the low activity of the reproductive axis is governed by hypothalamic GnRH release in monkeys prior to puberty. We removed the brains from 5 juvenile and 5 adult male monkeys (Macaca fascicularis) and blocked, sectioned, and prepared each hypothalamus for light microscopic immunocytochemistry for GnRH-containing cells. The distribution and number of GnRH-containing neurons were similar in adult and juvenile brains; however, GnRH-containing perikarya in adult brains were significantly larger in total cross-sectional area (200 +/- 12 vs. 169 +/- 8 micron 2, P less than 0.05) and in cross-sectional area of the cytoplasm (139 +/- 2 vs. 88 +/- 6 micron 2, P less than 0.05) than in juvenile brains. In another group of 10 juvenile male macaques, we administered an antiserum to GnRH (Fraser #94; 2 ml/kg, i.v.) and monitored the effects on plasma luteinizing hormone (LH) and testosterone concentrations. The percentage of plasma samples with detectable LH levels decreased significantly (from 26.67 +/- 8.3% to 5.3 +/- 3.4%, P less than 0.05) after GnRH antiserum administration; however, plasma testosterone concentrations (0.08 +/- 0.02 ng/ml) remained unchanged. We conclude that during pubertal maturation in primate species there is increased synthesis and release of GnRH from a population of GnRH neurons that are active prior to puberty.

Animals↗
PubMed1985

Testosterone replacement in hypogonadal men: effects on obstructive sleep apnoea, respiratory drives, and sleep.

The obstructive sleep apnoea syndrome occurs predominantly in men. To determine the effect of testosterone on ventilatory function and whether testosterone may play a role in the development of obstructive apnoea, we performed waking ventilatory drive studies and sleep studies in five hypogonadal men. These androgen-deficient subjects were studied both while receiving no treatment and after six weeks of testosterone replacement therapy (testosterone oenanthate 200 mg i.m. every 2 weeks). Hypoxic ventilatory drive decreased significantly, from 158 +/- 39 (mean +/- SEM) off testosterone to 88 +/- 19 on testosterone therapy (P less than 0.05). Hypercapnoeic ventilatory drive did not change significantly on testosterone. Obstructive sleep apnoea developed in one man and markedly worsened in another man in association with testosterone administration. Both of these subjects also exhibited marked decreases in oxygen saturation with the development of cardiac dysrhythmias during sleep and large increases in haematocrit. The remaining three hypogonadal men did not demonstrate significant sleep apnoea either on or off testosterone. The percentage of sleep time spent in REM sleep increased from 14 +/- 3% to 22 +/- 2% when the men were receiving testosterone (P less than 0.01), but the episodes of sleep apnoea tended to occur during non-REM sleep. We conclude that in some hypogonadal men, replacement dosages of testosterone may affect ventilatory drives and induce or worsen obstructive sleep apnoea. The obstructive sleep apnoea syndrome is a potential complication of testosterone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Evidence for decreased luteinizing hormone-releasing hormone pulse frequency in men with selective elevations of follicle-stimulating hormone.

To examine the hypothesis that the frequency of endogenous pulsatile LHRH stimulation controls the relative secretion of FSH and LH from the pituitary, we studied men with elevated FSH levels and normal LH levels to determine whether they have an altered frequency of pulsatile LHRH secretion compared to normal men. Because peripheral blood measurements of LHRH do not reflect the pulsatile characteristics of hypothalamic LHRH secretion, and it is generally accepted that the pulse frequency of LH secretion is an index of the frequency of endogenous LHRH pulsation, we used LH pulse frequency as the indicator of LHRH pulse frequency. Frequent blood sampling was performed to characterize LH pulse patterns in five men with selective elevations of FSH and seven age-matched normal men. Beginning at 0800-0930 h, blood samples were obtained every 10 min for 24 h through an indwelling iv catheter. Serum LH and FSH levels were measured by RIA in each sample, and the pattern of LH secretion was determined. Testosterone (T), estradiol, sex hormone-binding globulin, and free T were measured in a pooled serum sample from each man. Men with selective elevations of FSH had fewer LH pulses per 24 h (mean +/- SEM, 10.6 +/- 0.5) than the control group (12.9 +/- 0.6; P less than 0.01). There was no statistically significant difference in LH pulse amplitude (23 +/- 4 vs. 17 +/- 3 ng/ml). There were no statistically significant differences in T (4.9 +/- 0.5 vs. 6.1 +/- 0.5 ng/ml), estradiol (23 +/- 7 vs. 31 +/- 5 pg/ml), sex hormone-binding globulin (7.7 +/- 1.4 vs. 7.7 +/- 1.2 ng bound dihydrotestosterone/ml), or free T (0.16 +/- 0.02 vs. 0.23 +/- 0.04 ng/ml) in these men vs. normal subjects. We conclude that 1) compared to normal men, men with selectively elevated FSH levels have decreased LH pulse frequency, which suggests decreased LHRH pulse frequency; and 2) the relative secretion rates of LH and FSH by the pituitary may be regulated by the frequency of pulsatile LHRH secretion from the hypothalamus.

Adult↗
PubMed1985

Nocturnal slowing of pulsatile luteinizing hormone secretion in women during the follicular phase of the menstrual cycle.

The gonadotropin secretion pattern in normal reproductive age women (n = 5) was evaluated for the presence of a circadian rhythm. The women volunteered for a series of 24-h admissions in different phases of their menstrual cycles (early follicular, late follicular, and midluteal). Plasma LH and FSH levels were determined by RIA in blood samples drawn through indwelling venous catheters at 20-min intervals throughout a normal 24-h sleep-wake cycle. The gonadotropin secretory pattern was subjected to cosine analysis for identifying rhythmicity. The LH interpulse interval fluctuated with a significant 24-h rhythm during the early follicular phase in four of the five women. The maximum interpulse intervals occurred during the early morning between 0100 and 0500 h (mean, 0250 h), with a corresponding increase in LH pulse amplitude occurring within the same time interval (mean, 0320 h). We found no consistent 24-h rhythms in overall mean plasma LH levels during any phase of the menstrual cycle, nor did we find a significant rhythmicity in either LH interpulse interval or LH pulse amplitude during the late follicular or luteal phase. These results demonstrate that the LH pulse-generating system is frequency modulated on a circadian basis during the early follicular phase of the human menstrual cycle.

Adult↗
PubMed1984

Bone mineral content of amenorrheic and eumenorrheic athletes.

This study was designed to determine whether the hypoestrogenic status of 14 amenorrheic athletes was associated with a decrease in regional bone mass relative to that of 14 of their eumenorrheic peers. The two groups of athletes were matched for age, height, weight, sport, and training regimens. Bone mass was measured by dual-photon and single-photon absorptiometry at the lumbar vertebrae (L1 to L4) and at two sites on the radius. Vertebral mineral density was significantly lower in the amenorrheic group (mean, 1.12 g per square centimeter) than in the eumenorrheic group (mean, 1.30 g per square centimeter). There was no significant difference at either radial site. Radioimmunoassay confirmed a lower mean estradiol concentration (amenorrheic group, 38.58 pg per milliliter; eumenorrheic group, 106.99 pg per milliliter) and progesterone peak (amenorrheic group, 1.25 ng per milliliter; eumenorrheic group, 12.75 ng per milliliter) in the amenorrheic women, in four venous samples drawn at seven-day intervals. A three-day dietary history showed no significant differences in nutritional intake, including calcium with and without supplements. The two groups were similar in percentage of body fat, age at menarche, years of athletic participation, and frequency and duration of training but differed in number of miles run per week (amenorrheic group, 41.8 miles [67.3 km]; eumenorrheic group, 24.9 miles [40.1 km]). We conclude that the amenorrhea that is observed in female athletes may be accompanied by a decrease in mineral density of the lumbar vertebrae.

Adult↗
PubMed1984

Reduced pulsatile luteinizing hormone and testosterone secretion with aging in the male rat.

To identify possible age-dependent changes in the feedback relationship between the brain-pituitary and testes, we examined the minute-to-minute patterns of plasma luteinizing hormone (LH) and testosterone (T) in intact, young male rats and compared these profiles to those of old animals. Young (3 mo; n = 11) and old (22 mo; n = 12) Sprague-Dawley rats were fitted with indwelling venous catheters and between 24 and 48 h later, were bled without anesthesia, by remote sampling, at 10-min intervals for 8 h. Blood samples of 400 microliter were withdrawn, and an equivalent volume of a blood replacement mixture was infused after each sample. Plasma LH and T levels in each sample were measured by radioimmunoassay (RIA). Plasma T levels in old animals failed to show the transient oscillations observed in young animals. Mean plasma T levels were 50% lower in old compared to young animals (P less than 0.001). Plasma patterns of LH in old animals, like their younger counterparts, showed statistically significant episodic increases, whose apparent pulse frequency was inappropriately low for their circulating T level (although not statistically different from the young group). Pulse amplitude in the old animals was 66% lower in the old compared to the young group (P less than 0.015). We conclude that age-associated alterations in brain mechanisms governing LH secretion underline these endocrine changes.

Aging↗
PubMed1984

Progesterone modulation of pulsatile luteinizing hormone secretion in normal women.

Recent studies show that the frequency and amplitude of pulsatile LH secretion change during the normal human menstrual cycle; however, the neuroendocrine mechanisms underlying these changes are poorly understood. To assess the role of progesterone (P) in regulating LH secretion patterns, we treated normal women (n = 5) with im P in oil during the follicular phase of their cycle and compared LH pulse frequency, amplitude, and mean plasma level during treatment to those in normal cycling women. Normal women were studied five times in five menstrual cycles. Each study lasted 24 h, with a sampling interval of 20 min. The cycle phases studied were early follicular (twice), late follicular (LF), midluteal, and LF with P therapy to simulate luteal phase plasma P levels. LH pulse frequency was slower (P less than or equal to 0.001) in the midluteal phase than in either the early follicular phase or LF, and furthermore, P, administered in the normal follicular phase, slowed LH pulse frequency, augmented pulse amplitude, and reduced mean plasma LH levels compared to those in untreated women studied at the same cycle phase (P less than or equal to 0.02). We infer that P secretion by the ovary mediates the change in the LH secretory pattern during the luteal phase of the normal menstrual cycle, and that at least part of this effect is mediated by the central nervous system.

Adult↗
PubMed1984

Modulation of pulsatile gonadotropin secretion by testosterone in man.

In experimental animals, primary testicular deficiency leads to increased LH pulse frequency. Pulsatile FSH secretion has not been well characterized in any species. To determine the effect of testosterone (T) on the pattern of pulsatile gonadotropin secretion in man, we performed frequent blood-sampling studies in six normal men and six men with primary hypogonadism. All primary hypogonadal men were studied 6-8 weeks after stopping T replacement therapy. Five of the six hypogonadal men were restudied 6-8 weeks after treatment with T enanthate (200 mg, im, every 2 weeks; sampling in this group was 2 weeks after their last T injection). Blood sampling was done at 10-min intervals for 12 h in all subjects, and the pattern of episodic LH and FSH secretion was determined. Normal men had a serum T level of 6.3 +/- 0.3 ng/ml (mean +/- SEM), a LH level of 34 +/- 3 ng/ml, and a LH pulse pattern characterized by low frequency (7.6 +/- 0.7 pulses/12 h) and low amplitude (16 +/- 1 ng/ml). Compared to normal men, primary hypogonadal men had a significantly lower T level (2.9 +/- 0.4 ng/ml) and significantly higher LH pulse frequency (13.0 +/- 1.3 pulses/12 h), amplitude (51 +/- 7 ng/ml), and mean level (222 +/- 26 ng/ml). Reinstitution of T replacement therapy in hypogonadal men resulted in a significant increase in the T level (4.7 +/- 0.5 ng/ml) and significant decreases in LH pulse frequency (7.2 +/- 1.6 pulses/12 h) and amplitude (41 +/- 5 ng/ml) as well as mean LH level (75 +/- 15 ng/ml). FSH levels fluctuated in a distinctly pulsatile pattern in all three groups. Differences in pulsatile FSH secretion between primary hypogonadal men before and during T therapy and normal men paralleled those in pulsatile LH secretion in both frequency and amplitude. These results demonstrate that in man 1) diminished T negative feedback results in high frequency (circhoral), high amplitude LH and FSH pulses; 2) T replacement decreased LH and FSH pulse frequency and amplitude as well as mean levels; and 3) the decreased LH and FSH pulse frequency with T treatment implies that T or a metabolite of T acts on the central nervous system to slow the hypothalamic LHRH pulse generator.

Adult↗
PubMed1984

Stimulation of sperm production by human luteinizing hormone in gonadotropin-suppressed normal men.

The relative roles of FSH and LH in the control of human spermatogenesis are not well established. We previously reported that supraphysiological doses of hCG can stimulate sperm production in gonadotropin-suppressed normal men despite prepubertal FSH levels. To determine whether more nearly physiological levels of human LH (hLH) also can stimulate spermatogenesis when FSH levels are suppressed, we administered hLH to normal men whose endogenous gonadotropin levels and sperm production were suppressed by exogenous testosterone enanthate (T). After a 3-month control period, 11 normal men received 200 mg T, im, weekly to suppress LH and FSH. T administration alone was continued for 3-4 months until 3 successive sperm concentrations (performed twice monthly) revealed azoospermia or severe oligospermia (sperm concentrations, less than 4 million/ml). Then, while continuing T, 4 of the 11 men (experimental subjects) simultaneously received 1100 IU hLH, sc, daily for 4-6 months to replace LH activity, leaving FSH activity suppressed. The effect on sperm production of the selective FSH deficiency produced by hLH plus T administration was determined. The remaining 7 men (control subjects) continued to receive T alone at the same dosage, without gonadotropin replacement, for an additional 6 months. In the four experimental subjects, sperm concentrations increased significantly from 0.7 +/- 0.7 million/ml (mean +/- SEM) during T treatment alone to 19 +/- 4 million/ml during hLH plus T administration (P less than 0.001). However, none of the men achieved sperm concentrations consistently in their own pretreatment range. Sperm motilities and morphologies were normal in all four subjects by the end of hLH plus T administration. In contrast, sperm concentrations in the seven control subjects remained suppressed (less than 3 million/ml) throughout the entire period of prolonged T administration alone. Serum LH bioactivity, determined monthly by in vitro mouse Leydig cell bioassay in all four experimental subjects, was markedly suppressed during T administration alone (120 +/- 10 ng/ml) compared to that during the control period (390 +/- 20 ng/ml; P less than 0.001). With the addition of hLH to T, LH bioactivity returned to control levels (400 +/- 40 ng/ml; P = NS compared to control value). Serum FSH levels determined monthly by RIA were reduced from 98 +/- 12 ng/ml during the control period to undetectable levels (less than 25 ng/ml) during the T alone and the hLH plus T periods (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗