Gonadal dysfunction after testicular torsion: luteinizing hormone and follicle-stimulating hormone response to gonadotropin releasing hormone

We studied 14 postpubertal patients at an average of 33 months after treatment for testicular torsion. Of these patients 11 had been treated by detorsion and 3 by orchiectomy. Five normal male volunteers of the approximate age of the study group served as controls. The patients treated by detorsion were subdivided into 3 groups based on the degree of atrophy of the detorsed testicle: group 1--no testicular atrophy (5), group 2--25 per cent testicular atrophy (2) and group 3--greater than 90 per cent testicular atrophy (4). Mean duration of torsion was greatest in the orchiectomy group (161 hours) compared to 6, 16 and 29 hours for groups 1, 2 and 3, respectively. The serum luteinizing hormone and follicle-stimulating hormone response to an intravenous bolus of 100 mcg. synthetic gonadotropin releasing hormone was measured in all patients. All groups had a greater mean follicle-stimulating hormone response to gonadotropin releasing hormone stimulation than controls (p less than 0.05). Patients who underwent orchiectomy had the greatest follicle-stimulating hormone response to gonadotropin releasing hormone stimulation. Mean luteinizing hormone response to gonadotropin releasing hormone stimulation was normal in patients without atrophy (group 1) but it was greater than controls in patients who had atrophy (groups 2 and 3) or who underwent orchiectomy (p less than 0.05). Several conclusions could be made from our study. All patient groups treated for torsion had evidence of testicular dysfunction. Patients who underwent orchiectomy displayed more testicular dysfunction than patients who had atrophy after detorsion. Testicular dysfunction after torsion is more likely to involve spermatogenic before Leydig cell function.     

Cervical sympathectomy affects gonadotropin-releasing hormone,luteinizing hormone and testosterone in male rats

To examine the effects of bilateral cervical sympathectomy on the secretion of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and testosterone (TS), 24 male rats were divided into four groups: control (C), light (L), sympathectomy (S), and light-sympathectomy (LS) groups. The C and S groups were kept under a 12-h light-dark cycle and the L and LS groups were kept under continuous light for 2 weeks. After 2 weeks, blood was collected and the rats were perfused with a fixative. GnRH neurons in the hypothalamus were stained immunohistochemically, and serum LH and TS levels were measured by radioimmunoassay. Although the difference in the number of GnRH neurons between the C and S groups was not significant, the L group was significantly lower than the C or LS groups. The serum LH and TS levels in the L group were higher than in the other groups. The present results suggest that continuous light increases GnRH secretion in the hypothalamus, followed by increased secretions of LH in the pituitary and TS in the testes, and bilateral cervical sympathectomy under continuous light inhibits these hormonal changes. However, a normal circadian rhythm does not affect gonadotropin secretion. Therefore, long-term and repeated stellate ganglion block may inhibit the increases of GnRH, LH, and TS secretions induced by continuous light.     

Orchiectomy in young rats results in differential regulation of follicle-stimulating hormone and luteinizing hormone content

While it is generally accepted that GnRH stimulates release of pituitary gonadotropins, it is not clear what regulates synthesis. The orchiectomized immature rat, with sustained high plasma levels of LH and FSH, provides an opportunity to study how gonadotropin biosynthesis responds to loss of the gonad. We have measured plasma and pituitary LH and FSH in castrate and sham operated rats after orchiectomy at 15, 30, 45, and 60 days of age. Plasma FSH and LH concentrations by RIA were markedly elevated in castrates within one to three days after castration, and they remained elevated in all groups. By contrast, pituitary content measurements revealed differences between the two gonadotropins: while LH content in castrates consistently exceeded that in controls, FSH content in castrates was lower. Pituitary LH excess was evident by seven to ten days after castration. The pituitary FSH deficit in younger animals was similarly apparent by seven to ten days. In the older groups, however, FSH content decreased as early as three days, but returned toward normal by 21 days. In orchiectomized young rats, pituitary LH is elevated, but FSH content is depressed. This discrepancy is delayed, but more marked, in younger rats. In view of sustained high plasma levels after castration, our findings imply differential regulation of synthesis, processing, or storage of the two gonadotropins.     

Testosterone dose-dependency of sexual and nonsexual behaviors in the gonadotropin-releasing hormone antagonist-treated male rat

The testosterone dose-dependency of several mating and nonmating behaviors was examined in the male rat, chemically castrated with a GnRH antagonist analog. Graded doses of testosterone enanthate (TE) were given to male rats to reinstate behaviors abolished by GnRH antagonist treatment. GnRH antagonist treatment alone markedly lowered serum LH, FSH and T concentrations and ventral prostate and testis weights. Open field behaviors were not significantly affected by GnRH antagonist treatment or castration. Scent-marking behavior was markedly suppressed by both castration and GnRH antagonist and restored by the lowest dose of TE (0.05 mg). All measures of male sexual behavior were impaired by GnRH antagonist treatment and castration and restored by the lowest dose of TE (0.05 mg). The doses of TE required to restore normal ventral prostate weights and testis weights were higher than those required to maintain scent marking and mating behaviors. No direct behavioral effects of the GnRH antagonist, other than those that can be explained by GnRH antagonist-induced suppression of testosterone were observed. The finding that sexual and nonsexual behaviors in the male rat have different testosterone requirements from those maintaining spermatogenesis and fertility may have significant implications for contraception.     

Long-term suppression of luteinizing hormone, follicle-stimulating hormone and testosterone by daily administration of leuprolide

The chronic effect of long-term injections of leuprolide on the hypothalamic, pituitary and gonadal axes have been studied in men with advanced prostatic cancer. The possibility of transient acute changes in luteinizing hormone, follicle-stimulating hormone and testosterone after each daily injection was studied in 31 patients treated for more than 1 year. No evidence of escape from daily 1.0 mg. doses was noted. No pituitary responsiveness was observed at any time point examined. Thus, daily administration of 1.0 mg. leuprolide acetate subcutaneously produces durable, complete suppression of gonadotropins and testosterone for prolonged periods.     

Extracellular calcium and luteinizing hormone effects on 22-hydroxycholesterol used for testosterone production in mouse Leydig cells

The effect of extracellular calcium on testosterone synthesis in response to luteinizing hormone (LH) or 22-hydroxycholesterol (22-OH-C) by isolated adult mouse Leydig cells was studied. Leydig cells were isolated by linear density gradient centrifugation. The cells were incubated in minimum essential medium with or without calcium (1.36 mmol/L) in an atmosphere of 95% air and 5% carbon dioxide at 37 degrees C for 3 hours with or without LH (10 ng/sample), or with or without 22-OH-C (10 mumol/L). Testosterone production in response to LH was significantly lower (P less than 0.02) in the absence of extracellular calcium and in the presence of verapamil (10 mumol/L), a calcium channel blocking agent. Extracellular calcium did not significantly (P greater than 0.05) affect testosterone production in cells incubated with 22-OH-C in either the presence or absence of LH. The results suggest that steps in steroidogenesis from 22-OH-C to testosterone are unaffected by extracellular calcium content and that extracellular calcium affects the use of intracellular cholesterol by the cholesterol side-chain cleavage enzyme.     

Regulation of testicular ornithine decarboxylase in vitro. Effect of age, follicle-stimulating hormone, and luteinizing hormone

We have examined hormonal regulation of ornithine decarboxylase (ODC) activity in decapsulated rat testis, isolated testicular interstitial cells, and purified Leydig cells under defined conditions in vitro. Both immature (15 to 26 days old) and adult (60 to 90 days old) rat testes were employed. Basal (fresh tissue) ODC activity varied widely among rats of the same age but was similar (less than 5% difference) in pairs of testes from the same animal. For this reason, pairs of testes were compared in subsequent in vitro studies. ODC activity of decapsulated testes of adult rats declined (to 25 to 30% of basal) during 4 hours of incubation in Medium 199 + 0.1% bovine serum albumin + 0.1 mM 3-isobutyl-1-methylxanthine at 34 C. The addition of FSH, LH, prolactin, prostaglandin E2, epidermal growth factor, insulin, or 10% fetal calf serum singly or in combination failed to prevent this decline in ODC activity. In contrast, ODC activity of decapsulated testes of immature rats remained stable (versus fresh tissue) during 4 hours of incubation. The addition of FSH (100 ng/ml) caused a small but statistically significant (P less than 0.005) stimulation of the enzyme activity, and 8-bromo cyclic AMP (0.5 mM) mimicked the effect of FSH. In isolated interstitial cells from adult rats, LH stimulated ODC activity in a dose- (10 pg-200 ng/ml) and time-dependent fashion. 8-Bromo cyclic AMP mimicked the effect of LH. Prolactin, FSH, estradiol, insulin, prostaglandin E2, and epidermal growth factor did not alter the enzyme activity. LH also stimulated ODC activity of purified Leydig cells. This study demonstrates for the first time direct in vitro stimulation of rodent testicular ODC activity by gonadotropins and reveals marked age-dependent differences in regulation of this enzyme in vitro.     

Follicle stimulating hormone, luteinizing hormone and testicular Leydig cell responses to estradiol immunization in Ile-de-France rams

Active immunization of Ile-de-France rams against estradiol (E2) resulted in the production of E2-neutralizing antibodies and an elevation in the plasma concentrations of FSH, LH, and testosterone. The presence of E2 antibodies did not affect the testosterone metabolic clearance rate, indicating that the immunization-mediated 10-fold increase in plasma testosterone was the result of a 10-fold increase in testicular testosterone production. Testis weights, as well as nuclear and cytoplasmic volumes of individual peritubular and perivascular Leydig cells, were greater in E2-immunized rams than in albumin-immunized controls. Leydig cell numbers were not affected by treatment. The E2 antibodies were capable not only of neutralizing the inhibitory effects of endogenous E2 on gonadotropin levels in intact rams, but were able to block the effects of exogenously administered E2 on their FSH and LH secretory response to castration. It is concluded that circulating E2 in the ram is involved in pituitary-testicular endocrine homeostasis and that E2 immunoneutralization can be employed to enhance testosterone secretion in this species.     

卵泡刺激素受体研究进展

卵泡刺激素 (FSH)是哺乳动物重要的生殖激素 ,其生理作用是通过其受体 (FSHR)介导的。FSHR属于G蛋白偶联受体超家族中的糖蛋白亚家族成员 ,它的细胞外域具有FSH特异性结合位点 ,细胞外域有 3或 4个潜在的糖基化位点 ,这些糖基对受体的折叠及转运激素至膜表面是必须的 ;其跨膜域参与蛋白激酶A(PKA)介导的信号转导 ,启动受体活化后的胞内事件 ;受体的脱敏可导致受体解偶联和受体数量下调。大多数哺乳动物FSHRcDNA开放阅读框由 2 0 85个核苷酸构成 ,人和大鼠FSHR基因为单拷贝基因 ,它包含 1 0个外显子和 9个内含子 ,其 5’侧翼区缺乏规则的TAT或CCAAT启动子元件 ,在 3’末端非翻译区含有 2个推断的多聚腺苷酸信号。FSHR存在活性突变和非活性突变 ,FSHR不足可导致原发性不育     

Diethylstilbestrol in treatment of postorchiectomy vasomotor symptoms and its relationship with serum follicle-stimulating hormone, luteinizing hormone, and testosterone.

Vasomotor symptoms such as hot flushes and profuse sweating have been described after bilateral orchiectomy. We evaluated 26 patients who had undergone bilateral orchiectomy for prostatic carcinoma to determine the incidence of vasomotor symptoms and the efficacy of low-dose diethylstilbestrol (DES) in the treatment of those symptoms. Measurements of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were performed to look for endocrine patterns which may be related to the presence of vasomotor symptoms. Fourteen patients (54%) reported the presence of vasomotor symptoms beginning one to four weeks after surgery. These patients were treated with DES or placebo in a double-blind crossover trial. The frequency and severity of hot flushes were significantly reduced during the time DES was given. This was accomplished with a low dose of 1 mg daily of DES which avoids the cardiovascular complications of higher doses. We found no correlation between the presence, severity, or frequency of hot flushes and serum gonadotropin or testosterone concentrations.     

Altered responses of prolactin, luteinizing hormone and follicle stimulating hormone secretion to thyrotrophin releasing hormone/gonadotrophin releasing hormone stimulation in cyclical mastalgia

A generalized abnormality of hypothalamopituitary function was found in 17 patients with cyclical pronounced mastalgia compared with 11 controls by using a combined thyrotrophin releasing hormone and gonadotrophin releasing hormone test. The release of prolactin, luteinizing hormone and follicle stimulating hormone was significantly greater in cyclical mastalgia patients than in controls. Basal thyrotrophin, T3 and T4 levels were within the normal range in both groups indicating normal thyroid status in benign breast disease. The single measurement of oestrogen and progesterone in the luteal phase was not abnormal. These data demonstrate an alteration in lactotroph and gonadotroph function in patients with cyclical mastalgia. It is unknown at present whether this represents an appropriate cellular response to altered central or peripheral signals. There is no evidence to suggest, however, that the anterior pituitary cell types are abnormal per se.     

Reverse hemolytic plaque assay study of luteinizing and follicle-stimulating hormone and thyrotropin secretion in diabetic rat pituitary glands

Numerous studies indicate that an impaired hypothalamopituitary axis plays an important role in reproductive and thyroid disorders in diabetic humans and animal models. Yet, several questions about the pathogenesis of these diabetic complications have not been answered. To evaluate the basal secretion of single gonadotrophs and thyrotrophs in vitro, uncultured pituitary cells from control rats and 1-mo streptozocin-induced diabetic (STZ-D) rats were studied with a reverse hemolytic plaque assay and morphometry. After light-microscopy immunocytochemistry for gonadotropin and thyrotropin (TSH), we recorded the ratio of plaque-forming to non-plaque-forming cells. The area of plaques produced by luteinizing hormone (LH), follicle-stimulating hormone (FSH), and TSH cells and the area of plaque-forming and non-plaque-forming cells were clearly smaller in diabetic than control rats. The plaque area, however, was more severely reduced than the cell area. The percentage of LH-, FSH-, and TSH-immunoreactive plaque-forming cells was greatly decreased in diabetic compared with control animals. In conclusion, our findings demonstrate that the LH-, FSH-, and TSH-secreting cells of diabetic rats released less hormone and were less numerous than the corresponding cells of control rats. Thus, several pathogenetic mechanisms might be involved in reduced gonadotropin and TSH release at the cellular level: 1) anatomical lesions of organelles involved in glycoprotein hormone synthesis and secretion, possibly due to insulin deficiency; 2) decreased gonadotropin-releasing hormone (GnRH) and thyrotropin-releasing hormone (TRH) receptors on pituitary cells; 3) inadequate GnRH and TRH stimulation; 4) high plasma corticosterone levels; or 5) a combination of points 1-4.     

Testosterone and erectile function recovery after radiotherapy and long-term androgen deprivation with luteinizing hormone-releasing hormone agonists

OBJECTIVE: To study the recovery of testosterone levels and erectile function in men who received radiotherapy plus long-term adjuvant androgen deprivation (LTAD) with luteinizing hormone-releasing hormone (LHRH) agonists. PATIENTS AND METHODS: From April 2000 to July 2001, men who had completed prostate radiotherapy with > or = 2 years of LTAD, and had their last LHRH agonist injection at least 6 months before, were invited to participate. At study entry, the men completed the International Index of Erectile Function (IIEF), and their serum total testosterone (TT), prostate-specific antigen, LH, follicle-stimulating hormone, haemoglobin, and body mass were measured. This assessment was repeated at 1 year. RESULTS: In all, 20 men were recruited, with a mean (range) age of 70 (55-81) years. Defining a normal TT level as > or = 8.0 nmol/L, the median time to a normal level was 2.3 years (95% confidence interval (CI), 1.9-4.2). The median duration of castrate TT levels was 8 months (95% CI, 6.2-14.9). LH recovered before TT, suggesting that the rate-limiting step in the recovery of TT may be at the testicular level. The median time to recovery of normal LH levels was 3.8 months, compared to 8.0 months to reach supracastrate TT levels, and 2.3 years to reach normal TT levels. Age and the LH/TT ratio were associated with the time to recovery of both supracastrate and normal levels of TT. The IIEF was completed by 17 men; there were no significant changes in the scores in any domain of the IIEF during the study. CONCLUSIONS: Most men recover supracastrate testosterone levels after LTAD and external beam radiotherapy, but recovery of 'normal' testosterone levels is slow. Few men recover potency and sexual desire. The patients age and LH/TT ratio may be predictive of the time to recovery of both supracastrate and normal testosterone levels.     

Plasma cortisol,luteinizing hormone (LH), and prolactin secretory responses to cardiopulmonary bypass

We measured the plasma levels of cortisol, luteinizing hormone (LH), and prolactin before, during, and after open heart surgery using cardiopulmonary bypass in seven male patients.The levels of cortisol and prolactin were high immediately before the beginning of perfusion. During and after perfusion, increased secretion of cortisol and prolactin was observed.The secretion of LH increased 30 min after the skin incision, but it decreased to the control levels immediately before perfusion. These levels did not change during and after perfusion. The secretory responses of these hormones during perfusion were almost identical to those in the state of physiological circulation.     

控制性超排卵中黄体生成素的过度抑制和黄体生成素预处理

体外受精-胚胎移植(IVF-ET)降调方案中,使用促性腺激素释放激素激动剂(GnRH-a)降调后,部分患者可能出现卵巢过度抑制,对卵泡刺激素(FSH)的反应延迟.而GnRH-a主要抑制黄体生成素(LH),因此可能存在LH不足,对IVF中出现卵巢过度抑制的患者可考虑LH预治疗.     

Clinical effects of gonadotropin-releasing hormone analogue in metastatic carcinoma of prostate

Leuprolide is a new, potent analogue of gonadotropin-releasing hormone which, after an initial transient stimulation, causes a profound suppression of serum gonadotropins and testosterone. One hundred eighteen patients with advanced carcinoma of the prostate have undergone treatment with leuprolide in a multi-institutional trial. Minimal evidence of objective response was seen in patients who had failed prior endocrine therapy with orchiectomy or estrogens. In patients without previous hormonal treatment, leuprolide induced an objective disease response (72%) comparable to alternative primary endocrine therapy. Considering the lack of significant side effects seen with long-term GnRH agonists, compounds such as leuprolide may prove to be the preferred initial endocrine therapy for selected patients with metastatic carcinoma of the prostate.     

高黄体生成素水平与早发黄体生成素峰的概念

<正> 黄体生成素(luteinizing hormone,LH)是由垂体前叶促性腺激素(gonadotropin,Gn)细胞合成分泌的糖蛋白激素。LH的分泌呈脉冲式,受下丘脑促性腺激素释放激素(gonadotropin releasing hormone,GnRH)、卵巢雌激素、孕激素和抑制素的综