Pulsatile bioactive luteinizing hormone secretion in men with chronic renal failure and following renal transplantation

We have measured plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (To) by radioimmunoassay (RIA) and bioactive LH (B-LH) by in vitro bioassay at 10-min intervals over 6 h in men treated by haemodialysis for renal failure and in men after renal transplantation. Eleven normal male volunteers acted as controls. Immunoreactive LH (I-LH) and FSH levels were elevated (p less than 0.03) in uraemia (mean +/- SE; 10.0 +/- 1.0 and 4.6 +/- 0.7 IU/l for LH and FSH, respectively) and following renal transplantation (8.1 +/- 1.2 and 5.3 +/- 0.5 IU/l) compared to controls (C) 4.9 +/- 0.5 and 2.7 +/- 0.4 IU/l) whereas B-LH [17.3 +/- 2.5, 14.8 +/- 1.8 and 12.9 +/- 1.3 IU/l in dialysis (D), transplant (T) and C groups, respectively] levels were normal. Prolactin levels were elevated (p less than 0.03) in the D group (median 348, range 162-1,780 mU/l) compared to the T group (161, 91-206 mU/l) and controls (163, 124-312 mU/l) whereas total To levels (mean +/- SE; 17.3 +/- 4.8, 15.5 +/- 1.3 and 19.6 +/- 2.1 nmol/l in the D, T and C groups, respectively) were similar as was the free To index. B-LH (median frequency, 2 and range 1-3 pulses/6 h) and I-LH (median frequency, 2 and range 1-2 pulses/6 h) was pulsatile in all the C group but B- and I-LH pulses were absent in 2 of the 5 subjects treated by dialysis. Following renal transplantation B-LH pulses were detected in all subjects, whilst I-LH pulses were absent in 1 subject.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination of a GnRH agonist with an antiandrogen or bromocriptine in the treatment of prostatic cancer; slight potentiation of antigonadal effects

The effect of combined treatment with a GnRH agonist (buserelin depot, BUS, 6.6 mg every 2 months) with an antiandrogen (cyproterone acetate, CPA, 300 mg day-1) or a prolactin-suppressing agent (bromocriptine, BR, 20 mg day-1) on pituitary-testicular function were studied in patients with advanced prostatic carcinoma. The patients (n = 5-6 per group) were treated in this fashion for 6 months and thereafter orchidectomized. Serum testosterone and gonadotrophin responses were followed during treatment, and histology and certain endocrine parameters were studied using testicular tissue obtained at orchidectomy. Serum LH was suppressed in all treatment groups from mean levels of 4-6 IU l-1 to less than 0.1 IU l-1, whilst serum FSH levels decreased in all groups during the first month of therapy from 4.5-7 to 1-2 IU l-1, but recovered thereafter. Only minor increases in serum gonadotrophin levels were evident 3 months after castration. No differences in gonadotrophin responses were seen between the different treatment groups. Serum levels of testosterone were suppressed from 15-20 nmol l-1 to the castrate range (approximately 1 nmol l-1), in each of the treatment groups. Testicular weight decreased significantly more (P less than 0.05) in the BUS + CPA group, compared to the other treatments. No differences were found in the testicular concentration of testosterone, or LH and FSH receptors between the three treatment groups. On histological examination, spermatogenesis was found to be impaired severely in all groups, with the lowest Johnsen score in the BUS + BR group (2.16 +/- 0.13, vs. 2.73 +/- 0.25 with BUS alone, P less than 0.05). Seminiferous tubular diameters were reduced similarly in all treatment groups. In conclusion, the combination of CPA or BR with BUS in the treatment of prostatic carcinoma does not potentiate the suppression of gonadotrophin or testosterone secretion, evidently because the GnRH agonist exerts a maximal suppressing effect. However, other antigonadal effects were enhanced slightly, including suppressed testicular weights by CPA and further suppression of spermatogenesis by BR.     

Sexual inactivity results in reversible reduction of LH bioavailability

We have recently documented significantly reduced serum testosterone (T) levels in patients with erectile dysfunction (ED). To understand the mechanism of this hypotestosteronemia, which was independent of the etiology of ED, and its reversibility only in patients in whom a variety of nonhormonal therapies restored sexual activity, we measured serum luteinizing hormone (LH) in the same cohort of ED patients (n=83; 70% organic, 30% nonorganic). Both immunoreactive LH (I-LH) and bioactive LH (B-LH) were measured at entry and 3 months after therapy. Based on outcome (ie number of successful attempts of intercourse per month), patients were categorized as full responders (namely, at least eight attempts; n=51), partial responders (at least one attempt; n=20) and non-responders (n=16). Compared to 30 healthy men with no ED, baseline B-LH (mean+/-s.d.) in the 83 patients was decreased (13.6+/-5.5 vs 31.7+/-6.9 IU/L, P<0.001), in the face of a slightly increased, but in the normal range, I-LH (5.3+/-1.8 vs 3.4+/-0.9 IU/L, P<0.001); consequently, the B/I LH ratio was decreased (3.6+/-3.9 vs 9.7+/-3.3, P<0.001). Similar to our previous observation for serum T, the three outcome groups did not differ significantly for any of these three parameters at baseline. However, outcome groups differed after therapy. Bioactivity of LH increased markedly in full responders (pre-therapy=13.7+/-5.3, post-therapy=22.6+/-5.4, P<0.001), modestly in partial responders (14.8+/-6.9 vs 17.2+/-7.0, P<0.05) but remained unchanged in non-responders (11.2+/-2.2 vs 12.2+/-5.1). The corresponding changes went in the opposite direction for I-LH (5.2+/-1.7 vs 2.6+/-5.4, P<0.001; 5.4+/-2.2 vs 4.0+/-1.7, P<0.05; 5.6+/-1.2 vs 5.0+/-1.2, respectively), and in the same direction as B-LH for the B/I ratio (3.7+/-4.1 vs 11.8+/-7.8, P<0.001; 4.2+/-4.3 vs 5.8+/-4.2, P<0.05; 2.1+/-0.7 vs 2.6+/-1.3, respectively). We hypothesize that the hypotestosteronemia of ED patients is due to impaired bioactivity of LH. This reduced bioactivity is reversible, provided that resumption of sexual activity is achieved regardless of the therapeutic modality. Because biopotency of pituitary hormones is controlled by the hypothalamus, LH hypoactivity should be due to the hypothalamic functional damage associated to the psychological disturbances which unavoidably follow sexual inactivity.     

Primary gonadal failure in men selectively amplifies the mass of follicle stimulating hormone (FSH) secreted per burst and increases the disorderliness of FSH release patterns: reversibility with testosterone replacement

The neuroendocrine mechanisms by which primary gonadal failure in men increases mean serum FSH concentrations (castration-like response) are not known. To investigate the testosterone-dependent mechanisms of the FSH castration response: (i) blood was sampled at 10-min intervals for 24 h for later FSH assay in seven normal middle-aged men and in six patients with primary testicular failure, during testosterone withdrawal and after 6 weeks of parenteral testosterone replacement; (ii) using a specific two-site IRMA, serum FSH concentrations were measured, since this assay correlates well with an in-vitro Sertoli cell bioassay; (iii) multiparameter deconvolution analysis was then applied to estimate the frequency, amplitude, duration, and mass of underlying FSH secretory bursts, and the half-life of endogenous FSH, and (iv) approximate entropy was calculated to quantify the relative orderliness of FSH release over 24 h. Mean (+/- SEM) 24-h serum FSH concentrations were 3.9 +/- 0.8 IU/L in control subjects and 39 +/- 10 IU/L in unreplaced hypogonadal patients (p = 0.034). Deconvolution analysis revealed similar estimated mean FSH half-lives of 346 +/- 40 min (control) and 321 +/- 47 min (untreated patients), and indistinguishable FSH secretory burst frequencies, namely, 20 +/- 0.95 (normal) and 21 +/- 1.3 (patients) pulses per 24 h. In contrast, the daily production rate of FSH was markedly increased in testosterone-withdrawn hypogonadal men at 117 +/- 25 vs. 9.3 +/- 1.8 IU/L/day (control) (p < 0.01). This was due to a 10-fold higher calculated maximal rate (amplitude) of FSH secretion achieved within each FSH release episode (normal 0.078 +/- 0.02 vs. gonadal failure 0.74 +/- 0.087 IU/L/min, p < 0.01), yielding a 10-fold increase in the mass of FSH secreted per burst (control 0.53 +/- 0.06 vs. patients 5.3 +/- 0.81 IU/L, p < 0.01). In contrast, the mean half-duration of FSH secretory bursts was unaltered in unreplaced hypogonadal men at 8.2 +/- 2.2 min (control) vs. 7.0 +/- 1.0 min (patients). Approximate entropy (ApEn), a scale- and model-independent statistic designed to quantify the orderliness or regularity of hormone release, revealed greater irregularity of serum FSH concentrations in the hypoandrogenic state: ApEn = 1.8 +/- 0.025 (testosterone-withdrawn) vs. 1.6 +/- 0.037 (control) (p < 0.05). Parenteral testosterone replacement for 6 weeks significantly decreased mean serum FSH concentrations by reducing the daily FSH secretion rate and FSH secretory burst amplitude and mass, and concomitantly restored the orderliness of FSH release patterns. Testosterone treatment did not change FSH secretory burst half-duration, number, interburst interval, or half-life. It is concluded that primary gonadal failure in men evokes FSH hypersecretion which is marked by more disorderly FSH release patterns and a selectively amplified mass of FSH secreted per burst. These hypergonadotrophic mechanisms are, to a significant extent, testosterone-suppressible.     

Post-transplant erythrocytosis: role of erythropoietin and male sex hormones.

Seventeen patients with post-renal transplant erythrocytosis and 17 non-erythrocytotic controls, matched in age, sex, serum creatinine and source of donor kidney, were studied to determine the role of erythropoietin, male sex hormones (testosterone, FSH, LH), and various patient risk factors in post-transplant erythrocytosis. Serum erythropoietin was significantly greater in erythrocytotic patients (35.6 +/- 5.7 mU/ml) than non-erythrocytotic patients (18.8 +/- 2.6 mU/ml) (P less than 0.05) and normal subjects (22.5 +/- 0.95 mU/ml) P less than 0.05). Serum testosterone was similar between the male study (13.2 +/- 6.2 nmol/l) and control (13.1 +/- 6.0 nmol/l) patients. This might be due to the greater basal LH in the male control subjects (13.9 +/- 11.7 IU/l versus 8.0 +/- 3.3 IU/l in erythrocytotic males, P = 0.084). Basal FSH in the male controls was greater than that in the study group (13.7 +/- 14 IU/l versus 6.8 +/- 2.9 IU/l, P = 0.067). Among the demographic risk factors, only the smoking history was important. There were more smokers among the erythrocytotic patients than controls (P = 0.051).     

Effect of sho-saiko-to (xiao-chai-hu-tang) on hepatic injury induced by halothane in rats]

The etiology of halothane induced hepatitis is unknown. This study investigated effect of oral administration of Sho-saiko-to on hepatic injury induced by exposure to 1.1% halothane under hypoxic condition (FIO2 = 0.12) for 2 hr in rats. Serum transaminase, histological score and area of necrosis were examined in rats treated with Sho-saiko-to (900 mg.kg-1) before and after halothane exposure. Twenty-four hours following halothane exposure, serum transaminase levels were significantly depressed; the level of sGOT was significantly lower in rats with treatment of Sho-saiko-to (211 +/- 34 IU.l-1) than in rats without treatment (264 +/- 42 IU.l-1) (P less than 0.05), and the level of sGPT was significantly lower in rats with treatment of Sho-saiko-to (144 +/- 20 IU.l-1) than in rats without treatment (215 +/- 46 IU.l-1) (P less than 0.01). Histological score in rats treated with Sho-saiko-to was significantly lower (3.8 +/- 0.6) than in rats without treatment (4.5 +/- 0.7) (P less than 0.05). The area of centrilobular necrosis was significantly lower in rats with treatment of Sho-saiko-to (21.2 +/- 8.7%) than in rats without treatment (34.5 +/- 12.7%) (P less than 0.05), too. These results indicate that Sho-saiko-to inhibits the hepatic necrosis and functional disorder following exposure to halothane.     

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.     

Seminal lead and copper in fertile and infertile men: Blei und Kupfer im Spermaplasma bei fertilen und infertilen Männern

Lead and copper concentrations were determined by atomic absorption spectroscopy in semen from 18 fertile and 172 infertile men. Significant correlations between copper concentrations in semen and sperm concentration (r = 0.32, P less than 0.001), percentage progressive motility (r = 0.23, P less than 0.005) and normal morphology (r = 0.22, P less than 0.005) were observed, while no such correlation existed for lead. However, semen copper concentrations of infertile men (194.99 +/- 5.70 micrograms l-1) and fertile men (183.39 +/- 14.37 micrograms l-1) did not differ significantly. Mean lead concentration in semen of fertile men was 11.18 +/- 0.62 micrograms l-1 and significantly higher than lead concentration in semen of fertile men (5.61 +/- 0.53 micrograms l-1, P less than 0.006). Reinvestigation of 18 infertile men after 2 years showed a significant drop of lead concentrations in semen from 17.31 +/- 1.41 to 6.94 +/- 1.32 micrograms l-1 (P less than 0.0002), which might be related to the decreasing use of leaded petrol in the Federal Republic of Germany.     

Spermatic and peripheral oestradiol levels in patients affected by azoospermia due to seminiferous tubular damage

Plasma levels of testosterone, androstenedione and oestradiol were determined in the spermatic venous blood of both testes of 17 patient affected by azoospermia due to tubular damage (Group I). The results were compared with those found in 5 patients affected by azoospermia of obstructive origin and 5 patients with an inguinal hernia (Group II). Mean spermatic levels of testosterone and androstenedione were not significantly different in the two groups, while the mean (+/- SE) oestradiol spermatic level was significantly higher in patients of Group I (5.02 +/- 0.75 nM/l vs. 2.20 +/- 0.365 nM/l; P less than 0.05). Moreover, while the testosterone/androstenedione and the androstenedione/oestradiol ratios were not significantly different in the two groups, the mean (+/- SE) testosterone/oestradiol ratio was significantly lower in patients of Group I (552.71 +/- 80.94 vs. 939.86 +/- 129.45; P less than 0.025). Peripheral testosterone and androstenedione mean levels were not significantly different between the two groups while the mean peripheral oestradiol level (+/- SE) was significantly higher in Group I (0.107 +/- 0.021 nM/l vs. 0.038 +/- 0.05 nM/l; P less than 0.025). Peripheral oestradiol was not significantly related to peripheral FSH, nor to spermatic oestradiol in both groups. These results suggest the possibility that oestradiol may be involved in the pathogenesis of some cases of male infertility.     

Testicular pathology in 46,XY dysgenetic male pseudohermaphroditism: an approach to pathogenesis of testis cancer.

Eleven children with dysgenic male pseudohermaphroditism (DMP) and 18 boys with isolated penile hypospadias, all with 46,XY karyotype, were studied. Testicular dysgenesis was associated with significantly lower testosterone response to human chorionic gonadotropin (0.9 +/- 0.2 ng/mL) than it was in hypospadias (3.3 +/- 0.1 ng/mL), and with significantly higher mean serum follicle-stimulating hormone (FSH) levels (8.4 +/- 2.3 IU/L vs 1.5 +/- 0.3 IU/L). Gonadoblastoma, a tumor that arises from the sex cords, was found in more than 1/4 of patients with DMP, whereas testicular carcinoma in situ (CIS) cells were present in all of these patients. Forty-two percent to 98% of CIS cells revealed an aneuploid pattern of nuclear DNA, indicating that most of them are neoplastic cells. In patients with hypospadias, CIS was not seen, and no other abnormalities were detected. In children with DMP, the percentage of tubules populated with germ cells was significantly lower than it was in those with hypospadias (48.3% +/- 10.6% vs 92.4% +/- 4.0%). The total number of germ cells (CIS cells + spermatogonia) did not differ significantly between the 2 groups, but the number of spermatogonia was significantly reduced in children with DMP (0.08 +/- 0.05 vs 3.65 +/- 0.2), suggesting impaired differentiation of gonocytes to spermatogonia. The following significant correlations were present with DMP: 1) the higher the seminiferous tubule cross-section area, the higher the number of CIS cells (r = 0.78); and 2) the higher the serum gonadotropin levels, the higher were tubular diameter (r = 0.93 for FSH and r = 0.75 for luteinizing hormone [LH]), area (r = 0.79 for FSH and r = 0.82 for LH), percentage of tubules populated with germ cells (r = 0.86 for FSH and r = 0.81 for LH), and number of CIS cells (r = 0.87 for FSH and r = 0.79 for LH). The results indicate that in intersex children with 46,XY karyotype, CIS occurs in dysgenetic testes in all cases and is frequently associated with gonadoblastoma. Impaired organogenesis of sex cords, relative inhibition of testosterone secretion, and the associated increased secretion of gonadotropins may create a milieu that induces or is favorable for the formation or maintenance of neoplastic lesions in dysgenetic testes early in childhood.     

Differential patterns of inhibin secretion in response to gonadotrophin stimulation in normal men

Inhibin B is produced by the testis, and its constituent alpha and beta B subunits have been localized immunohistochemically to Leydig as well as Sertoli cells in both rodent and human testes. Whether Leydig cells contribute to circulating inhibin B concentrations, however, is uncertain. We have investigated this by selectively stimulating Leydig and Sertoli cells with hCG and FSH, respectively. The study was a randomized crossover trial, investigating responses to 225 IU recombinant FSH or 3000 IU hCG administered s/c 4-6 weeks apart. Ten normal men were recruited to participate. Blood was taken twice before treatment and after 8, 24, 48, 72 and 96 h. Serum was assayed for FSH, LH and testosterone by radioimmunoassay (RIA); inhibin B and pro-alpha C inhibin forms by ELISA. Administration of hCG, but not FSH, caused a rapid increase in blood testosterone levels, which reached a maximum after 72 h (22.2 +/- 2.7-50.1 +/- 4.5 nmol/L, p < 0.001). Inhibin B concentrations in blood were unchanged following either treatment. Conversely, pro-alpha C concentrations increased following both treatments. FSH administration resulted in a gradual increase in pro-alpha C concentrations (369 +/- 18 pg/mL pre-treatment to 453 +/- 33 pg/mL after 96 h, p=0.013). Administration of hCG resulted in a more rapid response, with pro-alpha C concentrations rising from 384 +/- 23 pg/mL pre-treatment to a peak at 48 h of 535 +/- 45 pg/mL (p=0.007). This response was more rapid than that of testosterone. These results demonstrate that adult human Leydig, as well as Sertoli, cells secrete inhibin alpha subunit in response to gonadotrophin stimulation but provide no evidence for the secretion of inhibin B from Leydig cells. The lack of change in inhibin B secretion in response to FSH suggests that more prolonged or intense stimulation of Sertoli cells may be required for secretion of the dimeric form.     

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)     

血清抑制素B对非阻塞性无精子症睾丸精子存在的预测价值

目的:探讨血清抑制素B(INHB)对非阻塞性无精子症(NOA)患者睾丸精子存在与否的预测价值。方法:分别对40例NOA、20例阻塞性无精子症(OA)及10例正常生育男性以双抗体夹心ELISA法测定其血清INHB水平。并用化学发光法检测了上述研究对象的卵泡刺激素(FSH)水平。结果:NOA患者的血清FSH[(21.34±12.15)IU/L]明显高于OA组和正常生育男性组[(3.94±1.52)IU/L和(4.27±2.84 IU/L],而血清INHB水平[(53.15±58.74)ng/L]明显低于后两者[(162.49±78.38)ng/L和(228.49±110.68)ng/L]。正常生育男性与OA组患者的血清INHB水平差异无显著性(P>0.05)。NOA患者血清INHB水平与其睾丸精子抽吸(TESE)的结果有相关性(r=0.528,P<0.01)。TESE获得精子者血清INHB水平[(90.31±72.18)ng/L]显著高于TESE无精子者[(19.54±20.38)ng/L,P<0.01];而两者的血清FSH差异无显著性(P>0.05)。结论:血清INHB可作为预测TESE的参考指标。血清INHB的测定有望替代睾丸活检确定睾丸精子的存在与否。     

Intratesticular testosterone concentrations comparable with serum levels are not sufficient to maintain normal sperm production in men receiving a hormonal contraceptive regimen

Intratesticular testosterone (ITT) is thought to play a key role in the control of spermatogenesis in man but is rarely measured. The purposes of this study were 1) to examine the relationship between intratesticular fluid and serum testosterone (T) at baseline and during treatment with a contraceptive regimen known to suppress spermatogenesis and 2) to measure intratesticular fluid androgenic bioactivity. Seven men received 6 months of T enanthate (TE) 100 mg weekly intramuscularly plus levonorgestrel (LNG) 62.5 or 31.25 microg orally daily. Testicular fluid was obtained by percutaneous aspiration at baseline and during month 6. Mean luteinizing hormone (LH) was suppressed 98% from 3.79 +/- 0.80 IU/L at baseline to 0.08 +/- 0.03 IU/L. Mean follicle stimulating hormone (FSH) was suppressed 97%, from 3.29 +/- 0.67 IU/L to 0.10 +/- 0.03 IU/L. Mean serum T levels were similar before (22.8 +/- 1.9 nmol/L) and during treatment (28.7 +/- 2.0 nmol/L) (P = .12). ITT (822 +/- 136 nmol/L) was approximately 40x higher than serum T (P < .001) at baseline. ITT was suppressed 98% during treatment to 13.1 +/- 4.5 nmol/L, a level similar to baseline serum T (P = .08) but significantly lower than on-treatment serum T (P = .01). At baseline, intratesticular fluid androgenic bioactivity (583 +/- 145 nmol/L) was 70% of the ITT concentration measured by radioimmunoassay. Intratesticular androgenic bioactivity was suppressed 93% to 40 +/- 22 nmol/L (P < .01) during treatment, but was 3x higher than ITT (13.1 +/- 4.5 nmol/L). Sperm counts declined from 65 +/- 15 million/mL to 1.3 +/- 1.3 million/mL. In summary, TE plus LNG dramatically suppressed ITT (98%) and intratesticular androgenic bioactivity (93%) to levels approximating those in serum. ITT levels comparable with serum T were insufficient to support normal spermatogenesis. Intratesticular androgenic bioactivity was higher than ITT during treatment, suggesting that other androgens may be prevalent in the low-ITT environment.     

Quantitative changes of cerebral neocortical structure in insulin-treated long-term streptozocin-induced diabetes in rats

The brains of rats with streptozocin-induced diabetes treated with a low-dose insulin regimen (1 IU/day) were studied with morphometric techniques. After 1 yr of diabetes, brain weight decreased slightly (1350 +/- 71 vs. 1521 +/- 55 mg, 2P less than .01) as did the volume of the neocortex (498 +/- 36 vs. 567 +/- 40 mm3, 2P less than .05). A significant loss of neocortical neurons occurred (38 +/- 2 X 10(6) vs. 46 +/- 3 X 10(6), 2P less than .01), and the length of the capillary network in the neocortical tissue shortened disproportionately (405 +/- 102 vs. 631 +/- 47 m, 2P less than .01), leading to increased diffusion distance. The mechanisms underlying cerebral loss in this model are unknown, but abnormalities of the vascular supply with prolongation of the route of diffusion might play a role.     

Effects of hCG stimulation after withdrawal of long-term oestrogen treatment in patients with prostate carcinoma

Testosterone depletion is the keystone for therapy of patients metastic prostatic carcinoma. Our objective was to investigate Leydig cell function and testosterone levels after withdrawal of long-term endocrine treatment in patients with prostatic carcinoma. Thirteen patients with prostatic carcinoma, previously treated with oestrogens for at least 4 y, were stimulated with 5000 IU human chorionic gonadotrophin (hCG). The stimulation was performed 3-6 y after cessation of the oestrogen therapy. Serum concentrations of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured before and 24 and 48 h after hCG stimulation. Before hCG stimulation all patients had low serum testosterone concentrations (mean 2.0+/-0.2 nmol/l) and 24 and 48 h after hCG stimulation the values had not significantly increased (mean 2.4+/-0.2 and 2.5+/-1.1 nmol/l, respectively). LH and FSH were within or above the normal range before but after hCG stimulation the values significantly increased. In conclusion, the study shows that the Leydig cells were unable to respond to hCG stimulation more than 3 y after cessation of oestrogen therapy. The Leydig cell function seems to be irreversibly impaired by long-term oestrogen treatment.     

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)     

The effect of chronic mechanical circulatory support on neuroendocrine activation in patients with end-stage heart failure.

OBJECTIVE: To evaluate if the improvement of patients supported with a Novacor was associated with a normalization in neuroendocrine activity. METHODS: Six patients had a Novacor implanted for end-stage heart failure. Four patients were transplanted after a mean of 4.5 months (range 3-6). One patient was weaned after 5 months and one died of a cerebral haemorrhage 5 weeks after implantation. Analysis of neuroendocrine activity was made prior to implantation and after 14, 30, 60 and 90 days. Levels of aldosterone, renin, cortisol, testosterone and T3 were measured using radio-immunoassays. Twenty-four hour urinary collections were made for assessment of adrenaline and noradrenaline excretion. RESULTS: Renin activity fell to normal after 14 days (16 +/- 3.0 ng/ml per h to 4.28 +/- 2.1 ng/ml per h, P < 0.05) and was maintained at 90 days. A similar picture was seen with aldosterone (1.5 +/- 0.4 nM to 0.12 +/- 0.07 nM, P < 0.05). Norepinephrine (67.46 +/- 14.1 microg/24 h) and epinephrine 12.9 +/- 2.5 microg/24 h) fell to normal physiological levels during the same time period. Cortisol levels were above normal pre-implantation but fell by day 30 (665.25 +/- 80.0 nM to 461.8 +/- 43.0 nM, P < 0.01). T3 and testosterone were lower than normal pre-implantation (T3 50 +/- 9.5 ng/dl vs. 90-200 ng/dl, testosterone 6.83 +/- 1.7 nM vs. 13-35 nM). T3 normalized after 90 days (81 +/- 11.7 ng/dl) and testosterone after 60 days (16.3 +/- 1.7 nM). CONCLUSION: Neuroendocrine function is abnormal in patients with cardiac failure who require circulatory support. The Novacor improved this, but metabolic recovery was delayed. The positive effect on the neuroendocrine axis, in the absence of activation of other endocrine systems, suggests that prolonged support may be well tolerated.     

Pulsatile secretion of gonadotropins and prolactin in male marathon runners. Relation to the endogenous opiate system

We tested the hypothesis that sustained, strenuous physical training alters the neuroendocrine regulation of pulsatile gonadotropin and/or prolactin secretion in men. Blood was sampled at 20-minute intervals over 8 hours in five endurance-trained men after a 10-15 mile run in the middle of the active training season, and in 11 nonendurance trained normal controls. In these two groups, basal patterns of physiologically pulsatile secretion of LH, FSH, and prolactin (PRL) were not significantly different in relation to the following parameters: mean serum concentration of each of the three hormones (N = 25 samples); areas under the hormone concentration vs. time curves; fractional, incremental, and absolute pulse amplitudes; and pulse frequency, or periodicity. To test for enhanced suppressive effects of endogenous opiates in trained male marathon runners, subjects were administered the potent opiate-receptor antagonist, naltrexone (1 mg/kg). This antagonist significantly stimulated pulsatile LH secretion by increasing mean serum LH values from 10.94 to 13.58 mIU/ml (P = 0.007); area under the LH concentration vs. time curve increased from 5370 to 6510 mIU/ml X 8 hours (P = 0.05) and, pulse frequency rose from 2.8 to 4.9 pulses/8 hours (P = 0.006). Naltrexone also enhanced pulse frequency of FSH secretion from 3.4 to 5.4 pulses/8 hours (P = 0.009), but did not alter serum prolactin concentrations. None of these responses differed significantly from those in normal sedentary controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperglycemia in global cerebral ischemia and reperfusion: a 31-phosphorous NMR spectroscopy study in rats

31-phosphorous magnetic resonance spectroscopy was used in a rat model of 10 min severe incomplete forebrain ischemia (two-vessel occlusion with hypotension) to assess the effect of hyperglycemia on intracellular pH and high energy phosphates during ischemia and early reperfusion. One group (n = 8) with preischemic hyperglycemia (serum glucose 20 mmol.l-1) showed an increased intracellular acidosis (pH 6.35) during ischemia compared to 6.55 in the normoglycemic control group (n = 7, P less than 0.001), but the recovery of phosphocreatine and ATP in early reperfusion was the same in the two groups. Another group (n = 7) was normoglycemic during ischemia, but received an i.v. bolus of glucose during the first minute of reperfusion. In this group the recovery of intracellular pH in early reperfusion was slower than in the control group (0.034 +/- 0.006 pH units per minute compared to 0.052 +/- 0.11 in the controls, +/- s.d. and P less than 0.01).