Spectrum of the pulsatile characteristics of LH release in normal men

To assess the spectrum of LH pulse characteristics in normal men, blood samples from 36 individuals were drawn at 20-minute intervals for 8 hours. The subsequent immunoactive LH concentrations were analyzed by computer algorithms to delineate the frequency and amplitude characteristics of pulsatile LH secretion. The absolute range for LH pulse frequency estimated by a modified threshold method was 1-6 pulses/8 hr, with a mean (+/- SEM) of 3.36 +/- 0.17 (median -3)pulses/8 hr. The distribution differed significantly from a Gaussian pattern. The mean LH pulse amplitude expressed as a percent increase above nadir was 92.1 +/- 6.1 (median-91.5%). When LH pulse amplitude was defined as an increment (mIU/ml) above nadir, the mean value was 5.13 +/- 0.4 (median -4.8) mIU/ml. These two expressions of amplitude were positively correlated (P less than 0.01), while the incremental (mIU/ml) pulse amplitude correlated inversely with pulse frequency (P less than 0.01). To examine the influence of more intensified rates of venous sampling on the spectrum of LH pulse properties, blood was sampled at 4-minute intervals for 8 hours in a subgroup of 13 men. Under these conditions, estimated LH pulse frequency was significantly higher, with a mean of 10.31 +/- 1.87 (median -9) pulses/8 hr compared with 20-minute sampling in the same individuals (P less than 0.001). Although the estimates of LH pulse frequency at 4-minute and 20-minute sampling intervals were significantly correlated (P less than 0.01), the dispersion of the LH pulse frequency estimates was considerably larger at more rapid rates of sampling. There was an absolute range of 2-20 pulses/8 hr for the 4-minute sampling, and 1-6 pulses/8 hr for the 20-minute sampling in the same individuals. This increase in LH pulse frequency and the broader dispersion of the range of frequencies estimated at 4-minute compared with 20-minute sampling intervals were confirmed using either another pulse detection algorithm, or separate criteria designed to adjust false-positive error rates in relation to sampling intensity. It was concluded that eugonadal men exhibit a broad spectrum of pulsatile LH characteristics, and the range of LH pulse attributes is even greater at more intensive rates of venous sampling. The results of this study in normal men demonstrate that a wider dispersion of physiologic LH pulse characteristics must be recognized in man.(ABSTRACT TRUNCATED AT 400 WORDS)     

Appraising the instantaneous secretory rates of luteinizing hormone and testosterone in response to selective mu opiate receptor blockade in late pubertal boys

The pulsatile properties of gonadotropin and testosterone release were examined before and after chronic mu opiate receptor blockade with naltrexone, 50 mg every other day, in four normal boys in late puberty (ages 14 8/12 to 15 1/12 years). The nature of spontaneous secretory events was appraised for immunoactive LH and testosterone in blood withdrawn every 20 minutes for 24 hours, using a novel, discrete deconvolution algorithm to estimate apparent instantaneous secretory rates. The application of this methodology revealed that the frequency of discrete LH instantaneous secretory rates increased after mu opiate receptor blockade (P = 0.011). More strikingly, all parameters of testosterone secretory events responded significantly to mu opiate receptor blockade, including increases in mean estimated secretory rate (+47%, P = 0.02), testosterone pulse frequency (+ 64%, P less than 0.001) and amplitude (+ 20%, P = 0.027). Correspondingly, decreases in testosterone interpulse secretory intervals (-35%, P = 0.001), secretory pulse duration (-19%, P = 0.042) and interpulse valley duration (-35%, P = 0.006) also were noted. There was a prominent diurnal rhythm in testosterone secretion with maximal values in the morning and late evening, and marked reductions in the afternoon, sometimes to prepubertal levels. This variation in the testosterone secretory profile paralleled that of LH. In response to naltrexone, the FSH concentration series showed a significant increase in the mean FSH concentration (+ 18%) P = 0.003) and mean peak amplitude (+ 15%, P = 0.002). These data provide indirect evidence of functional coupling of the opiate system with the hypothalamic GnRH pulse generator.(ABSTRACT TRUNCATED AT 250 WORDS)     

The physiological significance of pulsatile LHRH secretion in man: gonadotrophin responses to physiological doses of pulsatile versus continuous LHRH administration

This study tested whether pulsatile LHRH stimulation of the pituitary is required for normal gonadotrophin secretion in man. Four men with idiopathic hypogonadotrophic hypogonadism (IHH) and presumed endogenous LHRH deficiency were taken off all hormonal replacement for 5-6 weeks, then 5 micrograms LHRH was administered every 2 h for 1 week in order to prime pituitary gonadotrophin responsiveness. A physiological dose of LHRH (10 micrograms every 2 h) was then administered in both pulsatile and continuous regimens, in varying order, to each man. Pulsatile LHRH was capable of stimulating LH (as measured by bioassay) and FSH secretion, while continuous administration of LHRH was not. Serum LH, measured by RIA and bioassay, and FSH and free alpha-subunit levels, measured by RIA, increased significantly (P less than 0.05) over pretreatment levels during pulsatile LHRH administration. In contrast, bioactive LH and immunoactive FSH did not change significantly compared to pretreatment values during continuous infusion of the same total LHRH dose, although immunoactive LH and free alpha-subunit levels did increase significantly (P less than 0.05). The ratio of LH bioactivity to immunoactivity was significantly lower during the continuous compared to pulsatile LHRH regimen (P less than 0.001). Similar serum LHRH levels were achieved during pulsatile and continuous infusions. Serum testosterone and oestradiol levels did not increase significantly from pretreatment levels during either regimen of LHRH administration. It is concluded that a pulsatile LHRH signal pattern is essential for normal pituitary gonadotrophin secretion in men with IHH. Continuous infusion of a physiological dose of LHRH, which produced serum LHRH levels which were indistinguishable from those found during pulsatile administration, failed to stimulate FSH or bioactive LH secretion.     

Hypogonadism of male prolactinomas: Relation to pulsatile secretion of LH: Hypogonadisms des Mannes mit Prolaktinomen: Beziehungen zur pulsatilen LH-Sekretion

In order to investigate whether a hypothalamic disorder cause hypogonadism in male prolactinomas, LH pulsatile secretion was studied in 13 male patients. Serum PRL levels ranged from 186 to 45,000 ng ml-1 before treatment, and all the tumors were macroadenomas. Reduced LH secretion was revealed in 5 of 13 patients, and FSH was reduced in 1 of 13. Serum testosterone (T) levels were lower than the normal limit in all the patients. HCG tests in 3 patients showed good responses, but the peak values of T were lower than those of normal men. LH pulsatilities were examined in 5 hyperprolactinemic patients before treatment, in 4 hyperprolactinemic patients after operation, and in 8 normoprolactinemic patients after operation and/or bromocriptine treatment. There was no significant difference of the mean LH values, the frequencies of LH pulses, and amplitudes among the hyperprolactinemic patients before operation (n = 5), the normoprolactinemic patients after operation (n = 8), and normal men (n = 7). From these results, it was evident that the hypothalamus and pituitary function of male prolactinomas were well preserved, in spite of higher serum PRL levels and larger tumor size than those reported in females. It is suggested that the main cause of hypogonadism in these patients is due to testicular dysfunction resulting from excessive serum PRL.     

Clomiphene citrate administration to normogonadotropic subfertile men: blood hormone changes and activation of acid phosphatase in seminal fluid

Clomiphene citrate was administered as a 50 mg oral daily dose to 44 normogonadotrophic (serum FSH 2-10 mIU/ml) subfertile men for 3 months. The treatment resulted in significant increases in FSH and LH concentrations, whereas prolactin remained unchanged. Serum testosterone and oestradiol both increased highly significantly. The increased testosterone levels suggest that the elevated LH levels had not led to "down regulation" of Leydig cell LH/hCG receptors, neither had the greatly increased estradiol led to depletion of these receptors. This is suggested to be a result of the blocking of testicular oestradiol receptors by the estrogen antagonist, clomiphene. Sperm count increased highly unchanged. The spermatic fluid concentrations of zinc and magnesium ions were also increased, whereas fructose remained unchanged. The katalytic activity of acid phosphatase in spermatic fluid increased highly significantly, whereas the concentration of the main prostate-specific acid phosphatase, as measured by a specific radioimmunological method, remained unchanged. Therefore, the increased Zn and Mg ion concentrations may be responsible for activation of acid phosphatase (s) in semen, or the treatment led to increased secretion of other prostatic acid phosphatase(s) than the main enzyme. However, it is clear that the secretion of the main prostatic acid phosphatase into semen is under different control than that of Zn++ and Mg++.     

Effects of short-term stimulation of serotoninergic pathways on the pulsatile secretion of luteinizing hormone in the absence and presence of acute opiate-receptor blockage

To investigate the role of the serotoninergic system in regulating pulsatile gonadotropin secretion in man, we tested the influences of a novel selective serotonin re-uptake inhibitor (fluoxetine HCl) on episodic LH release in men. Spontaneous LH pulsatility was assessed by computerized analysis of serial LH concentrations measured in blood samples withdrawn at 10 min intervals for 24 h. Possible alterations in pituitary responsiveness were tested by administering three consecutive two-hourly intravenous pulses of GnRH (10 micrograms, 10 micrograms, and 100 micrograms). The effects of fluoxetine (20 mg orally three times daily for one wk) were assessed in a double-blind, placebo-controlled design. Compared with the placebo, fluoxetine elicited no changes in 24 h mean serum LH concentrations, LH pulse characteristics (Cluster analysis), or LH secretion and clearance parameters assessed in response to exogenous GnRH administration (deconvolution analysis) in the presence of normal opiatergic tone (nine healthy young men), and during acute blockade of the opiatergic system (seven young men treated with the mu-opiate receptor antagonist, naltrexone). In summary, a selective enhancer of serotoninergic activity (fluoxetine HCl) does not affect pulsatile LH release basally or in the presence of acute inhibitory opiatergic tone. Since this probe does modify prolactin secretion in man, we conclude that stimulation of the serotoninergic system by this selective neuroendocrine probe shows no demonstrable coupling between the serotoninergic and the opiatergic pathways that modulate pulsatile LH release in man.     

The pattern of LH release in the adult ram influences the testicular steroidogenic response to individual LH pulses and is regulated by testosterone negative feedback

Two experiments were conducted with adult intact rams (approximately 58 kg in body weight) in the nonbreeding season to investigate interrelationships between LH and testosterone secretion. In Experiment 1, LH pulse frequency was increased from approximately two to six peaks per 8 hours (for 56 hours) by injecting (iv) 10 micrograms NIH-LH-S18 every 80 minutes. Induction of a breeding season peak frequency produced a progressive 3-fold increase (P less than 0.01) in mean serum testosterone levels to values during the last 8 hours of treatment (12.6 +/- 1.2 ng/ml) that were 50% of those in the fall. In response to LH pulsing, testosterone peak amplitude increased (P less than 0.05) from 3.5 +/- 0.8 ng/ml to 6.7 +/- 0.7 ng/ml. In Experiment 2, the mean testosterone level was increased to breeding season values (for 96 hours) by injecting (im) 5 mg testosterone every 4 hours. Mean LH levels and LH peak frequency were decreased (approximately 70%, P less than 0.01) following 36 hours of treatment, and the LH response to exogenous GnRH was decreased (approximately 45%, P less than 0.01) by the final 4 hours Results indicate that for rams in the nonbreeding season, the testicular steroidogenic response to individual LH pulses is enhanced when pulse frequency is increased. When blood testosterone is elevated to breeding season levels, LH pulse frequency is severely impaired, while pituitary responsiveness to GnRH is diminished, as in the fall.     

Clomiphene citrate administration to normogonadotropic subfertile men: Blood hormone changes and activation of acid phosphatase in seminal fluid

Clomiphene citrate was administered as a 50 mg oral daily dose to 44 normogonadotrophic (serum FSH 2–10 mIU/ml) subfertile men for 3 months. The treatment resulted in significant increases in FSH and LH concentrations, whereas prolactin remained unchanged. Serum testosterone and oestradiol both increased highly significantly. The increased testosterone levels suggest that the elevated LH levels had not led to "down regulation" of Leydig cell LH/hCG receptors, neither had the greatly increased estradiol led to depletion of these receptors. This is suggested to be a result of the blocking of testicular oestradiol receptors by the estrogen antagonist, clomiphene. Sperm count increased highly significantly during the treatment. The spermatic fluid concentrations of zinc and magnesium ions were also increased, whereas fructose remained unchanged. The katalytic activity of acid phosphatase in spermatic fluid increased highly significantly, whereas the concentration of the main prostate-specific acid phosphatase, as measured by a specific radioimmunological method, remained unchanged. Therefore, the increased Zn and Mg ion concentrations may be responsible for activation of acid phosphatase (s) in semen, or the treatment led to increased secretion of other prostatic acid phosphatase(s) than the main enzyme. However, it is clear that the secretion of the main prostatic acid phosphatase into semen is under different control than that of Zn⁺⁺ and Mg⁺⁺.     

Alterations in the pulsatile properties of gonadotropin secretion in alcoholic men

The functional characteristics of the hypothalamic-pituitary-testicular axis were examined quantitatively in 10 chronic alcoholic men without hepatic dysfunction or clinical nutritional deficiencies. Spontaneous gonadotropin pulsatility was analyzed in blood sampled every 20 minutes over a 24-hour period 3 to 16 days after abstinence from alcohol and again 29 to 39 days later. The numbers of LH and FSH pulses per 24 hours were normal in these alcoholic men compared with controls. However, we found increased mean 24-hour concentrations of immunoactive LH (P = 0.012) and FSH (P = 0.018), increased peak heights for LH (P = 0.035) and FSH (P = 0.004), decreased fractional LH (P = 0.002) and FSH (P = 0.044) pulse amplitudes and increased interpulse valley mean LH (P = 0.010) and FSH (P = 0.018) concentrations. Serum levels of total testosterone, total estradiol and estrone were normal, whereas concentrations of free testosterone and free estradiol were increased. Pituitary release of LH and FSH was normal in response to low (5-micrograms) and high (95-micrograms) doses of GnRH given intravenously. The present observations indicate that in chronically alcoholic men, acute abstinence from ethanol is associated with elevated circulating concentrations of immunoactive gonadotropins in the presence of intact spontaneous gonadotropin pulsatility, preserved pituitary responsiveness to exogenous GnRH, and increased concentrations of free testosterone and free estradiol. Such findings are consistent with alterations in the endogenous feedback actions of sex steroid hormones in this setting.     

Individual differences in LH and FSH responses to orchidectomy and testosterone replacement therapy in rams

Profiles of LH and FSH levels and pituitary LH responses to exogenous luteinizing hormone releasing hormone (LHRH) have been characterized in rams, castrated rams (wethers), and wethers implanted with testosterone. Rams were castrated when adult, and, at the time of castration, two groups of wethers were implanted with either four or eight testosterone capsules. Rams showed random pulses of LH and testosterone which were temporally related. The number of LH and testosterone pulses per 24 hours differed among rams, giving rise to large differences in the mean levels of these hormones. Mean FSH levels and pituitary LH responses to LHRH also differed among rams and were positively correlated to differences in LH levels. All three nonimplanted wethers showed a rhythmic pulsatile pattern of LH secretion and had elevated mean LH and FSH levels. There were, however, appreciable differences between wethers with regard to mean LH and FSH levels and pituitary LH responses to LHRH. Both four and eight testosterone capsules were effective in suppressing pulsatile LH secretion and mean LH and FSH levels in two out of three wethers. In a third animal within each of these groups, however, LH and FSH profiles and LH responses to LHRH were characteristic of nonimplanted wethers. These data suggest that individual rams have different inherent capacities to secrete gonadotropins which influence LH and FSH responses to castration and testosterone replacement therapy.     

Specific regulatory actions of dihydrotestosterone and estradiol on the dynamics of FSH secretion and clearance in humans

The authors investigated immunoactive and bioactive follicle-stimulating hormone (FSH) secretion and clearance in six healthy young men during steady-state infusions of vehicle (basal, B, 28 hours), dihydrotestosterone (DHT, 4.5 days), or estradiol (4.5 days) accompanied by blood sampling at 10-minute intervals for 28 hours. Serum FSH concentrations were assayed by a two-site immunoradiometric assay (IRMA) and two separate in vitro bioassays (rat granulosa and Sertoli cell systems). FSH measurements included: 24-hour mean serum concentrations (IRMA and bioassay), multiple-parameter deconvolution of 24-hour pulsatile FSH time series and FSH release in response to exogenous gonadotropin-releasing hormone (GnRH) boluses (IRMA) to assess secretion and clearance, and circadian serum FSH concentration rhythms by cosinor analysis (IRMA). We found: 1) a significant decrease in 24-hour mean IRMA FSH concentrations during DHT infusion while both in vitro estimates of FSH bioactivity were unchanged; 2) significant decreases in the mass of IRMA FSH secreted per 24 hours during DHT infusion; 3) significant decreases in the IRMA FSH half-life during estradiol infusion without any change in FSH interpulse interval; 4) no steroidal effects on FSH secretory responses to exogenous GnRH; and 5) abolition of basal circadian FSH rhythms during sex-steroid infusions. Based on these findings, we conclude that steady-state sex-steroid hormone infusions selectively alter IRMA FSH secretion and clearance without affecting IRMA FSH pulse frequency or mean concentrations of bioactive FSH.     

健康成年男子黄体生成素脉冲释放分析

对７名健康男子每１０分钟采血一次，历时２４小时，测定血清ＬＨ浓度并进行脉冲分析。结果平均ＬＨ脉冲频率为１６．９±２．１次／２４ｈ，周期为８７±ｌ０ｍｉｎ／次，脉冲间期为３０～３００分钟不等，幅度为１．０±０．６ＩＵ／Ｌ。采血间期为５分钟的另外３名健康男子１２小时ＬＨ脉冲频率为１０．３±０．９次，周期为６９±８分钟，间期为６２±３７分钟，幅度为１３±０．４ＩＵ／Ｌ。采血间期和设定的脉冲阈值不同对ＬＨ脉冲频率和脉冲周期均有影响，但对平均浓度和脉冲幅度的影响不明显     

Neuroendocrine mechanisms mediating awakening of the human gonadotropic axis in puberty

The hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator presides over the pulsatile and feedback-regulated activities of the pituitary-gonadal axis. Awakening of synchronous activity of the GnRH neuronal ensemble in the earliest stages of puberty heralds the onset of full activation of the reproductive axis in girls and boys. Progression from prepuberty to adulthood in boys is directed by marked (30-fold) amplitude enhancement of pulsatile luteinizing hormone (LH) secretion, as assessed by an ultrasensitive immunofluorometric assay and deconvolution analysis. There is a much less apparent rise in LH secretory burst frequency (approximately 1.3-fold increase). Consequently, human puberty is an amplitudedriven neuroendocrine maturational process. However, less is known about pulsatile follicle-stimulating hormone (FSH) release in puberty. Multiple pathophysiologies that result in hypogonadotropic hypogonadism can converge on a final common mechanism of attenuated hypothalamic GnRH pulse generator output and hence reduced LH (and FSH) secretion. Disturbances may take the form of reduced GnRH pulse frequency and/or attenuated GnRH secretory burst mass. When the pathophysiology of hypogonadism originates exclusively in a failed GnRH pulse generator, then either treatment of the primary disease process where possible (e.g., by refeeding in starvation, improved metabolic control in diabetes mellitus, dopamine agonist treatment in hyperprolactinemia, etc.) and/or treatment with pulsatile GnRH (e.g., in Kallmann's syndrome, isolated hypothalamic lesions, etc.) can provide relevant therapeutic options in children and adults.     

Hormone profile in hyperprolactinemic infertile men

Serum levels of FSH, LH, prolactin, testosterone, and estradiol in 46 infertile men with hyperprolactinemia were compared with the same in 50 infertile and 30 fertile men with normal serum prolactin levels. Serum FSH levels in hyperprolactinemic men were significantly higher than in the other groups, indicating disturbance of spermatogenic process among those men. Significantly raised serum LH levels were in infertile men with serum prolactin over 1000 U/liter. All men with hyperprolactinemia had significantly lower serum testosterone levels than other infertile and fertile men. Although serum testosterone was not under the lower limit of normal range and high LH levels demonstrated disturbance of Leydig cell function in hyperprolactinemic infertile men, serum estradiol levels were not different among investigated groups. Azoospermic men with raised serum prolactin had higher serum FSH and LH levels than oligospermic men with hyperprolactinemia. These data demonstrated disturbance in hypothalamopituitary-testicular axis in infertile men with hyperprolactinemia. Further studies of prolactin in males with reproductive failure could probably clear this problem.     

The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastasis

OBJECTIVE: To evaluate whether pretreatment serum hormone levels are a prognostic factor for prostatic cancer with bony metastasis under hormonal treatment. PATIENTS AND METHODS: Between 1980 and 1994, 96 patients with prostate cancer and bony metastasis were included for an evaluation by a retrospective review of their charts. All 96 had received hormonal treatment after a diagnosis of metastatic prostatic carcinoma. Serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were assessed before treatment. The patients were divided into two groups according to their response during the follow-up. Group 1 (good response) had no change or resolution of metastatic lesion(s) on the bone scan and a declining prostate-specific antigen (PSA) level. Group 2 had increased PSA or progression of metastatic lesion(s) on the bone scan. Tumours were graded as low (2-4), intermediate (5-7) and high (8-10) using the Gleason score. RESULTS: There were 43 patients in group 1 and 53 in group 2; the overall mean (sd) age was 72.5 (6.8) years and the follow-up 29.5 (0.5) months. The respective mean (sd) levels of testosterone, LH, FSH and prolactin before treatment were 4.6 (1.6) ng/mL, 20.2 (13.3) mIU/mL, 19.6 (18.6) mIU/mL and 20.7 (12.1) ng/mL in group 1, and 2.6 (1.0) ng/mL, 27.3 (11.0) mIU/mL, 27.1 (9.8) mIU/mL and 41.3 (28.4) ng/mL in group 2. The level of testosterone was significantly higher in group 1 than in group 2, while LH, FSH and prolactin were significantly lower in group 1 than in group 2. When stratified by tumour grade, patients in group 1 still had significantly higher pretreatment testosterone and lower LH, FSH and prolactin than those in group 2. CONCLUSION: Higher testosterone and lower LH, FSH and prolactin levels were good prognostic factors for patients with metastatic prostatic cancer under hormonal treatment, irrespective of tumour grading.     

Pulsatile LHRH therapy in patients with oligozoospermia and disturbed LH pulsatility

Pulsatile administration of LHRH can drive the pituitary to secrete LH and FSH in a pattern that closely mimics the physiological pattern of the hypothalamic-pituitary-gonadal axis. As there is evidence that infertility in some men is due to dysfunction of this axis, 14 men with reported infertility of more than 2 years duration were treated by long-term pulsatile LHRH therapy. They were 24-42 years of age, with variable degrees of oligozoospermia, elevated FSH levels but normal LH and testosterone levels. The number of endogenous LH pulses/24 h was less than eight in all 14 subjects. The degree of testicular damage was assessed semi-thin sections prepared from biopsies of both testes. Scores for spermatogonia per seminiferous tubule (SPT) were calculated from the actual number of Ad-spermatogonia/tubule. Patients were grouped according to sperm density and SPT score (groups I-III). Pulsatile LHRH therapy was administered by means of a portable infusion pump; 4 micrograms LHRH were administered subcutaneously every 120 min for a period of 6 months. This treatment restored the normal pattern of LH secretion to 12 LH pulses/24 h in all patients. A statistically significant decrease of mean FSH levels to normal, and an increase of mean LH levels was observed in most of the 14 patients. Testosterone values did not change in any group. Marked improvement of the sperm count was observed in eight out of 14 patients (groups I and II) and three pregnancies were reported during the treatment periods. These results suggest that some states of male infertility are due to hormonal dysregulation and that these patients may benefit from pulsatile LHRH therapy.     

Modulation of immunoradiometric and bioactive follicle stimulating hormone secretion and clearance in young and elderly men during treatment with tamoxifen or flutamide.

The secretion and clearance of immunoactive and bioactive follicle-stimulating hormone (FSH) in healthy young men (N = 10) and elderly men (N = 7) during blockade of endogenous sex steroid hormones with tamoxifen, an antiestrogen, and flutamide, an antiandrogen, was investigated. To this end, subjects underwent blood sampling basally every 10 minutes for 24 hours, and then received 2 consecutive intravenous pulses of synthetic gonadotropin releasing hormone (GnRH; 10 micrograms and 100 micrograms) every 2 hours. This paradigm was repeated on two subsequent visits, in which subjects received either flutamide HCl, a specific nonsteroidal competitive antagonist of the androgen receptor (750 mg daily for 3 days), or tamoxifen, a selective antagonist of the estrogen receptor (20 mg daily for 9 days). Serum immunoactive FSH concentrations were measured in each sample by immunoradiometric assay (IRMA). Serum bioactive FSH concentrations were determined by an in vitro bioassay (rat granulosa cell aromatase system) on 24-hour serum pools. Deconvolution analysis was used to analyze both the FSH IRMA 24-hour time series and FSH release after GnRH. Comparisons between young and elderly men of the basal state showed significantly increased 24-hour mean serum immunoactive and bioactive FSH concentrations and significantly decreased free testosterone concentrations in elderly men. By deconvolution analysis, elderly men had a significant decrease in FSH secretory burst duration, and an increase in FSH half-life and FSH secretory burst amplitude compared with younger men. In response to sex steroid receptor blockade in young men, there was a significant increase in mean serum bioactive FSH concentrations during antiandrogen treatment, but not during antiestrogen treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Experimental Hyperprolactinemia and Clomiphene on Pituitary Responsiveness to LHRH and TRH in Men

The effect of clomiphene citrate during sulpiride-induced hyperprolactinemia on pituitary function was tested in 8 healthy men, who ingested 100 mg of clomiphene, 150 mg of sulpiride or 100 mg of clomiphene + 150 mg of sulpiride daily for 7 days. Clomiphene treatment increased FSH and LH plasma concentrations and this increase was unaffected by sulpiride-induced hyperprolactinemia. Sulpiride intake alone did not alter serum gonadotropin concentrations. A reduced LH response to LHRH during sulpiride intake was seen, whereas the FSH response was unchanged. The prolactin response to TRH was unaffected during the combined sulpiride + clomiphene ingestion. Sulpiride treatment did not change the basal and/or clomiphene-stimulated gonadotropin secretion in healthy men. Thus, oligozoospermic men using psychotropic drugs and/or with hyperprolactinemia may be suitable candidates for clomiphene treatment.     

Negative feedback regulation of pulsatile LH secretion during treatment with an LHRH antagonist in rams

Suppression of LH and testosterone secretion in sexually active rams by the short-term administration of an LHRH antagonist results in a compensatory increase in the release of LHRH from the hypothalamus. This is inferred from the observed increase in the frequency of LH pulses in peripheral blood during the period of recovery when the pituitary regains its responsiveness to LHRH. To investigate the nature of the inhibitory feedback signal which triggers this compensatory response, a single intravenous injection of 1 mg of an LHRH antagonist (28 micrograms/kg; N-Ac-D-pCl-Phe 1, D-pCl-Phe 2, D-Trp 3, D-hArg (Et 2) 6, D-Ala 10, LHRH) was given to groups of intact, testosterone-implanted castrated and castrated rams housed under stimulatory short days. Pulsatile LH secretion was monitored in blood samples collected every 10 min for 34 h. The treatment caused an immediate blockade of LH pulses in all three groups of rams followed by a progressive recovery of LH secretion from 12-30 h. Compared to the pretreatment period, intact rams showed a significant increase in frequency of LH pulses during the recovery period. Castrated rams did not show this increase, with or without supplementary testosterone. Since the circulating testosterone concentration decreased after the blockage of LH secretion in the intact rams, but not in the castrated or testosterone-implanted castrated rams, we conclude that it is the reduction in the steroid negative feedback signal which leads to a compensatory increase in the activity of the LH pulse generator.     

Pulse pattern of luteinizing hormone (LH) in patients with varicocele: a preliminary report

Serum concentrations of LH were measured every 20 minutes for 6 hours in 4 varicocele patients and 4 control subjects. In both groups, a pulsatile pattern of LH secretion was observed. Also in the two groups, LH pulse rate (2-5/6 hour) and amplitude (23.5-61%) were identical. These findings suggest that Gonadotrophin releasing hormone (Gn RH) and LH secretions have no role in the deranged sperm parameters often found in infertile men with varicocele.