Changes in plasma inhibin levels following pulsatile gonadotrophin-releasing hormone therapy in a man with idiopathic hypogonadotrophic hypogonadism

Changes in circulating inhibin levels were related to changes in testosterone (T) and the gonadotrophins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in a hypogonadotrophic hypogonadal man before and during pulsatile gonadotrophin-releasing hormone therapy which resulted in normal spermatogenesis. Before treatment, the plasma inhibin levels in the patient (210 +/- 50 U/l; mean +/- SD of four samples) were lower than in normal controls (552 +/- 150 U/l; p less than 0.01), as were T (1.1 nmol/l) and gonadotrophin (less than 1.0 IU/l) levels. Within 1 week of gonadotrophin-releasing hormone treatment, plasma LH (14.1 +/- 0.7 IU/l) and FSH (14.4 +/- 0.6 IU/l) reached supraphysiological levels. In response, T and inhibin concentrations increased progressively to reach high normal levels (27.7 +/- 1.6 nmol/l and 609 +/- 140 U/l) at 4 weeks, by which time the gonadotrophin levels stared to decline and gradually returned to the normal range between 12 and 24 weeks of treatment. There was a concomitant decrease in T and inhibin levels which remained within the normal range. The decline in the FSH level following the rise in testicular hormones was earlier and steeper than that of LH (37.5% decrease at 4 weeks vs. 30.4% at 12 weeks), suggesting that T and inhibin may act together to inhibit pituitary FSH secretion as opposed to LH secretion which is primarily controlled by T. It is concluded that, in man, during maturation of the pituitary-testicular axis, changes in circulating inhibin parallel those of T, and quantitatively normal inhibin secretion is dependent on gonadotrophin stimulation. FSH secretion may be regulated through negative feedback control, by both T and inhibin.     

Chronic treatment of male tammar wallabies with deslorelin implants during pouch life: effects on development, puberty, and reproduction in adulthood

The present study evaluated the effects of chronic GnRH agonist (deslorelin) treatment on sexual maturation in the male tammar wallaby. Slow-release deslorelin or placebo implants were administered to male pouch young (n = 10/group) when they were between 180 and 200 days old, to determine if disruption of the pituitary-testicular axis during development altered the timing of sexual maturation or had long-term effects on adult reproductive function. Deslorelin treatment caused retardation of testicular growth and reduced the serum FSH and testosterone concentrations between 12 and 24 mo of age. Maturation of the hypothalamic-pituitary-testicular axis was also delayed in treated animals at 13 and 19 mo of age. Despite these alterations in the pattern and timing of neuroendocrine development, sexual maturation was not permanently blocked in these animals and deslorelin-treated animals reached sexual maturity at the same age as treated animals, as evidenced by a fully functional pituitary-testicular axis and proven fertility at 25 mo of age. The ability of the treated animals to reach puberty at the same time as control animals, despite delayed maturation of the hypothalamic-pituitary-testicular axis, suggests that puberty in the male tammar wallaby is additionally regulated by other, gonadotropin-independent factors.     

Neonatal treatment of male rats with a gonadotropin-releasing hormone antagonist results in altered function of the pituitary-testicular axis in adult age

In most mammals, pituitary-testicular hormone secretion is very active during the perinatal period, but the physiological significance of this function for later pituitary-gonadal interactions and sexual maturation is largely unknown. Short-term neonatal treatment with gonadotropin-releasing hormone (GnRH) antagonist results in delayed sexual maturation and infertility in male rats. We have now extended our earlier findings and studied in more detail the pituitary-gonadal function in adult rats after such neonatal treatment. In this study, the pituitary-testicular activity of newborn male rats was temporarily blocked by treatment with a GnRH antagonist analogue (N-Ac-4-Cl-D-Phe1, 4-Cl-D-Phe2, D-Trp3, D-Phe6, des-Gly10-GnRH-D-alanylamide; Organon 30039; 2 mg/kg s.c. twice daily) on Days 1-5 of life. Timing of puberty was slightly delayed in the treated rats (average: 2 days, p less than 0.05), as determined by the age of the balano-preputial separation. In adult rats (90-110 days), only 3 of the 17 rats treated neonatally with GnRH antagonist were fertile (14 of 17 controls, p less than 0.01), despite normal circulating androgen levels. Pituitary and serum follicle-stimulating hormone (FSH) levels were slightly but consistently elevated (20-30%; p less than 0.05) in antagonist-treated animals, whereas luteinizing hormone (LH) levels (both immunoreactive and bioactive) were unaffected. The pituitary contents of GnRH receptors were increased in antagonist-treated animals 85 +/- 6.6 (mean +/- SEM, n = 19) vs. 58 +/- 4.1 fmol/gland in controls (n = 20; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a major androgen-dependent urinary protein, alpha 2u-globulin on the pituitary-gonadal axis and hypothalamic monoamines in adult male mice.

The purpose of the present study was to evaluate the effects of alpha-2u-globulin, a sex-dependent male rat urinary protein on pituitary-gonadal functions and hypothalamic monoamine contents in male mice. Adult male mice, maintained under standardized laboratory conditions (L:D, 14:10) were injected subcutaneously with alpha-2u-globulin at a dose of 1 mg/animal/day or with vehicle daily for 14 days and killed 16 h after the last injection. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and testicular levels of T were measured by radioimmunoassays. The concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in medial basal hypothalamus (MBH) and anterior hypothalamus (AH) were measured by high performance liquid chromatography. Administration of alpha-2u-globulin led to a significant increase in plasma FSH and LH levels (P less than 0.05) as well as in plasma and testicular T levels (P less than 0.025). In the MBH of alpha-2u-globulin treated mice, there were significant elevations of NE (P less than 0.025), DA (P less than 0.01) and 5-HT (P less than 0.025) contents. In the AH, both DA (P less than 0.025) and 5-HT (P less than 0.01) contents were decreased while NE content remained unaltered. These results indicate that administration of alpha-2u-globulin can lead to a significant stimulation of pituitary-testicular axis and that this effect may be mediated through alteration of hypothalamic monoamines.     

Maturation of the pituitary-thyroid axis during the perinatal period.

To clarify the maturation process of the pituitary-thyroid axis during the perinatal period, thyrotropin (TSH) response to thyrotropin releasing hormone (TRH) and serum thyroid hormone levels were examined in 26 healthy infants of 30 to 40 weeks gestation. A TRH stimulation test was performed on 10 to 20 postnatal days. Basal concentrations of serum thyroxine (T4), free thyroxine (free T4) and triiodothyronine (T3) were positively correlated to gestational age and birth weight (p less than 0.001-0.01). Seven infants of 30 to 35 gestational weeks demonstrated an exaggerated TSH response to TRH (49.7 +/- 6.7 microU/ml versus 22.1 +/- 4.8 microU/ml, p less than 0.001), which was gradually reduced with gestational age and normalized after 37 weeks gestation. A similar decrease in TSH responsiveness to TRH was also observed longitudinally in all of 5 high responders repeatedly examined. There was a negative correlation between basal or peak TSH concentrations and postconceptional age in high responders (r = -0.59 p less than 0.05, r = -0.66 p less than 0.01), whereas in the normal responders TSH response, remained at a constant level during 31 to 43 postconceptional weeks. On the other hand, there was no correlation between basal or peak TSH levels and serum thyroid hormones. These results indicate that (1) maturation of the pituitary-thyroid axis is intrinsically controlled by gestational age rather than by serum thyroid hormone levels, (2) hypersecretion of TSH in preterm infants induces a progressive increase in serum thyroid hormones, and (3) although there is individual variation in the maturation process, the feedback regulation of the pituitary-thyroid axis matures by approximately the 37th gestational week.     

Identifying the Functional Flexion-extension Axis of the Knee: An In-Vivo Kinematics Study

Purpose

This study aimed to calculate the flexion-extension axis (FEA) of the knee through in-vivo knee kinematics data, and then compare it with two major anatomical axes of the femoral condyles: the transepicondylar axis (TEA) defined by connecting the medial sulcus and lateral prominence, and the cylinder axis (CA) defined by connecting the centers of posterior condyles.

Methods

The knee kinematics data of 20 healthy subjects were acquired under weight-bearing condition using bi-planar x-ray imaging and 3D-2D registration techniques. By tracking the vertical coordinate change of all points on the surface of femur during knee flexion, the FEA was determined as the line connecting the points with the least vertical shift in the medial and lateral condyles respectively. Angular deviation and distance among the TEA, CA and FEA were measured.

Results

The TEA-FEA angular deviation was significantly larger than that of the CA-FEA in 3D and transverse plane (3.45° vs. 1.98°, p < 0.001; 2.72° vs. 1.19°, p = 0.002), but not in the coronal plane (1.61° vs. 0.83°, p = 0.076). The TEA-FEA distance was significantly greater than that of the CA-FEA in the medial side (6.7 mm vs. 1.9 mm, p < 0.001), but not in the lateral side (3.2 mm vs. 2.0 mm, p = 0.16).

Conclusion

The CA is closer to the FEA compared with the TEA; it can better serve as an anatomical surrogate for the functional knee axis.     

Effect of streptozotocin diabetes on the pituitary-testicular axis in the rat

The pituitary-testicular axis was investigated in the streptozotocin diabetic male rat to determine the relationship between hormonal alterations and steroidogenic activity. Male Sprague-Dawley rats weighing 250-300 g were used in all experiments. Diabetes was induced by intraperitoneal injection (40 mg/kg body wt.) of streptozotocin and they were studied with non-diabetic controls. The observations on these animals were compared to those from diabetic rats treated with 1-5 IU protamine zinc insulin. Steroidogenic activity was determined by measuring the per cent of [4-14C]-cholesterol converted to [4-14C]-pregnenolone and [4-14C]-progesterone. Plasma concentrations of LH, FSH and prolactin were measured by RIA. Streptozotocin induced diabetes resulted in significantly reduced plasma LH (34%, p less than 0.20) and prolactin (53%, p less than 0.001) but did not modify FSH concentrations. Insulin treatment completely and partially restored abnormal LH and prolactin release. The activity of the enzyme cleaving the side-chain of cholesterol (rate limiting step in steroidogenesis) was considerably reduced in the diabetic state (59%, p less than 0.002) and insulin treatment restored it to even supranormal levels (not significant). Our findings suggest that insulin may play a physiological and differential role in regulating the secretory activity of the anterior pituitary. The insulin is needed for normal LH and prolactin release and Leydig cells function but its role in FSH release and Sertoli cells function is not clear.     

Preoperative carbohydrate antigen 195 (CA195) and CEA serum levels as prognostic factors in patients with colorectal cancer

We evaluated in 214 patients with primary colorectal cancer the prognostic value of the preoperative serum levels of CEA and CA195. For CEA these levels were above the cutoff of 6 ng/ml in 31.3% of patients, whereas for CA195 they were higher than 12 U/ml in 35.9% of patients. The simultaneous use of both antigens increased the sensitivity to 49%, which was significantly higher than that of CEA (p < 0.001) and CA195 (p < 0.01) taken singly. The mean preoperative CEA levels were significantly (p < 0.001) correlated with Dukes' stage only, while there was a significant correlation between preoperative serum levels of CA195 and Dukes' stage (p < 0.001), grade of differentiation (p < 0.01) and tumor location (p < 0.05). The results indicated that high preoperative serum levels of CEA and CA195 were associated with a shorter overall survival (p < 0.0001). In addition, separate Cox multivariate analysis showed that preoperative CA195 was, after Dukes' stage, the strongest factor to predict overall survival (p < 0.0001).     

Diagnostic value of CA 15-3 antibody in detecting metastatic adenocarcinoma

OBJECTIVE: To determine the diagnostic value of CA 15-3 in detecting metastatic adenocarcinoma in body fluids using PreservCyt solution (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) as collection fluid. STUDY DESIGN: Cytospin slides prepared from 72 cases with unequivocally benign or malignant diagnosis were studied. Of the cases studied, 34 were breast carcinomas, and 17 were benign pleural effusions. Slides were stained for CA 15-3 by using the avidin-biotin complex method. Cases were evaluated for the presence of membranous or cytoplasmic staining. The percentage of cells exhibiting strong staining was estimated for both breast carcinoma and all adenocarcinomas as a group. These results were compared with CA 15-3 staining exhibited by benign mesothelium. RESULTS: Ninety-one percent of the breast cancer cases studied showed a positive reaction with CA 15-3, while 6% of the benign mesothelium cases were positive (p < 0.01). The sensitivity of CA 15-3 was 91 % for breast carcinoma and 80% for all adenocarcinomas. Specificity was 94% for breast carcinoma and for all adenocarcinoma. CONCLUSION: CA 15-3 is a sensitive and specific marker for diagnosing adenocarcinoma in cytologic specimens using PreservCyt solution as collection fluid.     

人类免疫缺陷病毒Ⅰ型核心蛋白(p24)在大肠杆菌中的表达、纯化及鉴定

在大肠杆菌中,利用新构建的含T7g-10L RBS以及λ-PR启动子的新型原核表达载体,通过表达gag-pol基因片段,获得了具有天然序列的人类免疫缺陷病毒1型(HIV-1)核心蛋白p24的高效表达。克隆的gag-pol基因片段在其阅读框架移位区域插入了4bp碱基,其表达的病毒蛋白酶在阅读框架上与gag一致,从而实现了对gag-pol融合蛋白的有效加工,产生成熟的核心蛋白p24及其它产物。重组p24以可溶形式存在,可以被抗p24的单克隆抗体特异识别。测定的N端8个氨基酸序列与从病毒纯化的p24完全一致。在使用硫酸铵沉淀后,采用两步离子柱层析,可将重组蛋白纯化到95％以上的纯度。结果表明,纯化的p24可以作为特异性很强的试剂而用于HIV感染的诊断及病情的预后,并可用于p24的生化及结构分析。     

Effects of drugs on brain neurotransmitter and pituitary-testicular function in male rats.

The effects of different drugs influencing brain neurotransmitter contents have been tested on the pituitary-testicular function in male rats. L-dopa (200 mg/kg body weight, i.p.) increased the dopamine and noradrenaline contents of the hypothalamus, amygdala, striatum and mesencephalon, but it was ineffective as regards the 5-hydroxytryptamine contents of the same brain areas, and increased the plasma testosterone level. alpha-Methyl-p-tyrosine (250 mg/kg b.w., i.p.) decreased the dopamine and noradrenaline contents of these brain areas, but it was ineffective to 5-hydroxytryptamine, and decreased the plasma testosterone level. Diethyldithiocarbamate (400 mg/kg b.w., i.p. twice a day) increased the dopamine levels in the hypothalamus, amygdala, striatum and mesencephalon, decreased the noradrenaline contents in the same brain regions but had no effect on the 5-hydroxytryptamine contents of these brain areas or on the testosterone level in the peripheral blood. p-Chlorophenylalanine (300 mg/kg b.w., i.p.) decreased the 5-hydroxytryptamine contents of the different brain areas, while it had no effect on the dopamine and noradrenaline levels or on the plasma testosterone level. 5-Hydroxytryptophan (200 mg/kg b.w., i.p.) increased the 5-hydroxytryptamine contents of all brain areas studied, but was without effect on the dopamine and noradrenaline contents or the plasma testosterone level. The data suggest that both dopamine and noradrenaline may be involved in the regulation of the pituitary-testicular function, and the ratio of the two transmitters might be more important that their actual levels in definite brain areas.     

冷刺激诱导的弱精子症大鼠模型肾上腺轴与甲状腺轴功能改变的研究

目的:研究冷刺激诱导建立的弱精子症模型大鼠HPA轴与HPT轴功能改变,探讨其生殖生物学意义。方法:取28只SPF级性成熟雄性SD大鼠随机分为正常对照组(N组,12只)与冷刺激组(C组,16只)。造模结束前对大鼠一般情况包括精神状态、体重、核心体温、尿量等进行检测。23周后通过精子功能的评定筛选弱精子症大鼠并建立弱精子症组(CA组),同时取外周血清、HPA轴、HPT轴相关组织;ELISA法和放射免疫法测定各组大鼠外周血清HPA、HPT轴相关激素水平,并在光镜下观察HPA轴和HPT轴相关组织形态学改变。结果:与N组相比,CA组大鼠反应迟钝,活动能力降低,夹尾试验评分显著降低,核心体温及尿量升高,差异显著(P0.05)。血清激素结果表现为CA组EPI显著升高,T3/T4比值亦显著升高,差异均具有统计学意义(P0.05)。光镜下可见N组各组织形态正常,与N组相比,CA组下丘脑室旁核神经细胞增生,排列紊乱;垂体细胞水肿,血窦不明显,嗜酸性细胞增多;肾上腺以皮、髓质水肿改变为主;甲状腺滤泡萎缩,上皮细胞增生。结论:冷刺激诱导建立的弱精子症大鼠模型可发生HPA轴功能改变,呈现慢性应激反应现象,提示,HPA轴功能改变参与该模型弱精子症的的发生发展过程。     

Prognostic value of CA125 kinetics and half-life in advanced ovarian cancer

This retrospective study was undertaken in order to assess the prognostic value of prechemotherapy serum CA125 level, CA125 kinetics, and CA125 half-life compared to the ten common clinicopathological variables in patients with advanced ovarian cancer (AOC). CA125 serum levels were determined before and during induction cisplatin polychemotherapy in 222 patients. A prechemotherapy CA125 level higher than 35 U/mL was found in 134 patients. Blood samples were further obtained before each course of chemotherapy (CT). CA125 half-life values were calculated in 112 patients with CA125 levels above 60 U/mL using van der Burg's exponential regression model. The prechemotherapy CA125 level had no prognostic value for survival. However, the median survival time of patients with CA125 levels below the upper normal limit of normality after two courses of CT was 101 months compared to a median survival of 21 months in patients without CA125 normalization (p=0.0000). Half-life calculation showed a significant correlation with survival. The median survival times of patients with T1/2 <20 days and T1/2 >20 days were 101+ and 18 months, respectively (p=0.0003). In a survival analysis using the Cox proportional hazard model, independent prognostic variables for survival included therapeutic response (p<0.0001), Karnofsky index (p<0.0001), residual disease (p<0.0001), tumor grade (p=0.0002), CA125 half-life (p=0.007), and CA125 kinetics (p=0.04). As a consequence, the possibility to predict treatment response by the CA125 half-life during chemotherapy and the time needed for normalization of CA125 levels can divide patients into good and poor prognostic groups early during chemotherapy.     

Interrelationship between oxidative stress,DNA damage and cancer risk in diabetes (Type 2) in Riyadh,KSA

Type 2 Diabetes Mellitus (T2DM) is the most widely known type of disorder of the endocrine system marked by hyperglycemia resulting either due to deficiency of insulin and or resistance. Persistent hyperglycemia induces oxidative stress and is suggested to play a prominent role in the pathophysiology underlying T2DM. Besides, oxidative stress can result in DNA damage leading to high cancer risk. Current study aimed to evaluate status of oxidative damage, damage to DNA and cancer biomarkers in regard to increased glucose in T2DM patients and to correlate the glycemic state with cancer. A total of 150 subjects consisting of control (50) and T2DM patients (1 0 0) were enrolled. Additionally, three tertiles were created among the two groups based on levels of HbA1c (Tertile I = 5.37 ± 0.34, n = 50; Tertile II = 6.74 ± 0.20, n = 50; Tertile III = 9.21 ± 1.47, n = 50). Oxidative stress parameters including malondialedehyde (MDA) and antioxidant enzymes were measured. Damage to DNA was analyzed by measuring the levels of DNA damage adduct-8 hydroxy deoxy Guanosine (8-OHdG). To detect cancer resulting from oxidative stress, cancer biomarkers CEA, AFP, CA125, CA-15, CA19-9, prolactin were measured in these subjects. All measurements were analysed by SPSS software. Levels of MDA and antioxidant enzymes altered significantly in T2DM group at p < 0.001 and p < 0.05 level of significance. Significant DNA damage accompanied with elevated levels of CEA, CA19-9 and decreased CA125, AFP and prolactin were noted in T2DM group. CA 19-9 and CEA levels increased at p < 0.05, whereas levels of prolactin decreased significantly (p < 0.001) in T2DM group compared to control. Additionally the mean values of DNA damage adduct 8-OHdG differ significantly at P < 0.01 between the two groups. However, no significant correlation in oxidative stress parameter, antioxidant enzymes, DNA damage and neither with the highest tertile of HbA1c (>7.5%) was noted. Based on the results obtained in the present study, we conclude that there is considerable change in oxidative stress and DNA damage in T2DM patients. Hence, assumption that the oxidative stress could cause cancer in T2DM as a result of hyperglycemic state was not speculated in this study.     

Serum tumor markers may precede instrumental response to chemotherapy in patients with metastatic cancer

PURPOSE: Although serum tumor markers (STMs) are widely used in clinical practice, their predictive role for the response to anticancer treatment is still controversial. The correlation of CEA, CA 15.3, CA 19.9, CA 125 (only with peritoneal involvement) and NSE levels with imaging response and clinical benefit was investigated in 60 non-selected patients with metastatic epithelial cancers treated by single-agent docetaxel chemotherapy. METHODS: STM measurement was performed at baseline and subsequently every three to four weeks. We applied the WHO criteria to evaluate both STM and instrumental responses. Concordance analysis was performed by the Cohen Kw index, and the significance of the results was established using the Fleiss, Cohen & Everitt test. Qualitative interpretation of data was obtained with the Landis & Koch scale. Correlations of STM response with clinical benefit (PS or pain improvement) were evaluated by the chi-square test. RESULTS: The primary tumors included breast cancers (38 patients), gastrointestinal non-colorectal cancers (12 patients), and lung cancers (10 patients). An overall significant good degree of agreement was observed between STM and instrumental response (p < 0.0005). The degree of agreement for each marker was as follows: excellent for CEA (p < 0.0005) and CA 125 (p = 0.006), good for CA 15.3 (p < 0.0005) and CA 19.9 (p = 0.011). Restricted analysis for the correlation of each marker with primary tumor origin showed good prediction of radiological response for CA 15.3 and CEA in breast cancer patients (p<0.0005 for both), for CEA and CA 19.9 in gastrointestinal cancer patients (p = 0.01 and 0.04, respectively), and for CEA+NSE in lung cancer patients (p = 0.01). Conversely, STM response did not correlate significantly with the clinical benefit for the patients, both in terms of PS and pain improvement (p = 0.24 and p=0.42, respectively). CONCLUSION: This study showed STMs to be good predictors of tumor response. Although STMs cannot replace diagnostic imaging, in metastatic cancer they might be useful to optimize the timing of radiological re-evaluation in the palliative setting.     

Total cardiopulmonary bypass in rabbits. Techniques and the effect of pulsatile perfusion pressure on hemodynamic parameters]

Fifty-two total cardiopulmonary bypasses (CA) have been performed in rabbits in order to obtain a stable preparation. The present paper deals with techniques and haemodynamic results. 1. Two kinds of priming solution have been used. Best results were obtained by using Ringer-lactate-gelatin (65 ml) and T.H.A.M. (5 ml). 2. Pulsatile arterial perfusion was performed either at uniform frequency (series A:10 experiments) or in accordance with the arterial mechanical resonance frequency of each animal (series B: experiments). The later setting resulted in better levels of maximal arterial pressure throughout the experiments (p less than 0,001). 3. The perfusion pressure flows (integrated at minute intervals), and total peripheral resistances, were studied on two groups of 4 animals each, A' and B' forming a part of A and B respectively. The flows were higher in B' after 5 min of CA (p less than 0,001), and after 40 min of CA (p less than 0,025); the flow increased during the experiment in group A' but remained in a steady state in group B'. The differences in total peripheral resistances were not statistically significant after 5 min of CA, but were smaller in A' after 40 min of CA (p less than or equal to 0,025); the difference in the variation of total peripheral resistances was statistically significant (p less than 0,025).     

Short-term fasting attenuates the response of the HPG axis to kisspeptin challenge in the adult male rhesus monkey (Macaca mulatta)

AIMS: In primates, changes in nutritional status affect the hypothalamic-pituitary-gonadal (HPG) axis by still poorly understood mechanisms. Recently, hypothalamic kisspeptin-GPR54 signaling has emerged as a significant regulator of this neuroendocrine axis. The present study was designed to examine whether suppression of the reproductive function by acute food-restriction in a non-human primate is mediated by decreased responsiveness of the HPG axis to endogenous kisspeptin drive. MAIN METHODS: Five intact adult male rhesus monkeys habituated to chair-restraint, received intravenous boli of human kisspeptin-10 (KP10, 50 microg), hCG (50 IU), and vehicle (1 ml) in both fed and 48-h fasting conditions. Plasma concentrations of glucose, cortisol and testosterone (T) were measured by using enzymatic and specific RIAs, respectively. KEY FINDINGS: The acute 48-h fasting decreased plasma glucose (P<0.01) and T (P<0.005) levels, and increased cortisol levels (P<0.05). KP10 administration caused a robust stimulation of T secretion in both fed and fasted monkeys. However, mean T concentration and T AUC after KP10 administration were significantly (P<0.01-0.005) reduced in fasted monkeys. Likewise, the time of the first significant increase in post-KP10 T levels was also significantly (P<0.01) delayed. T response to hCG stimulation was similar in fed and fasted monkeys. SIGNIFICANCE: The present results indicate that under fasting conditions the KP10 induced T response is delayed and suppressed. These data support the notion that fasting-induced suppression of the HPG axis in the adult male rhesus monkey may involve, at least in part, a reduction in the sensitivity of the GnRH neuronal network to endogenous kisspeptin stimulation.     

Evaluation of the pituitary-testicular function during experimental nephrosis

To investigate the pituitary-testicular function in nephrotic rats, a sequence of experiments was undertaken in adult male rats after a single dose of puromycin aminonucleoside (PAN). Endocrine modifications were evaluated chronologically throughout the experimental disease in order to determine the appearance of hormone alterations which lead to the axis dysfunction. Serum concentration of LH, FSH, androstenedione, total and free testosterone, estradiol as well as urine testosterone were measured by specific RIAs on days 3, 7 and 10 after treatment on nephrotic and control groups. Prolactin was also evaluated on day 10. Likewise, total weight of various androgen responsive tissues from both groups was recorded, and the number of androgen receptor (AR) binding sites were determined. To know the functional status of the hipophyseal-testicular unit, groups of nephrotic and control rats were stimulated with LHRH (300 ng/100 g b.w.) or with one or four doses of hCG (8 UI), respectively. Additionally, the relative in vitro biological activity of FSH from nephrotic and control rats before and after LHRH stimulus was determined. The results from the hormonal profile revealed clear endocrine disorders characterized by a progressive diminution of all serum hormones except prolactin and urine testosterone, which remained unmodified. The weight of the main androgen responsive tissues, the ventral prostate and the seminal vesicle, decreased parallelly to androgen diminution. The binding analysis of AR shows a significant elevation of the available androgen sites in all analyzed tissues except kidney and hypothalamus. The secretion of LH and FSH from nephrotic animals after LHRH administration was lower than that from intact animals at the registered times. Interestingly, the biological activity of FSH from nephrotic rats was not detectable at both, before and after LHRH administration. Testicular response to hCG stimuli, in terms of testosterone synthesis was not significantly different in the two groups analyzed with respect to the intact animals. By contrast, no response was observed in terms of estradiol production at either one or four doses of hCG. On the whole, the results presented herein allow us to conclude that experimental nephrosis has a harmful effect on the pituitary-testicular axis, and strongly suggests that the endocrine dysfunction is initiated at the hypophyseal level; even though a specific testicular damage is also present.     

Insulin-like growth factor I (Igf-1) gene polymorphism in patients with non-metastatic breast cancer

We aimed to assess the association between IGF-I gene (CA repeats) polymorphism in breast cancer patients and their clinicopathological features, as well as disease recurrence and survival. Seventy-six non-metastatic breast cancer patients were enrolled in the present study. The IGF-I (CA) repeats were studied with polymerase chain reaction by using proper primers belonging to these gene areas from DNA samples. Results show that the non 19- non 19 homozygote were more common in patients without lymph node involvement (p=0.04), with low histological grade (p=0.04), with positive hormone receptor status (p=0.01), and in patients without recurrence (p=0.06). These results suggest that the non 19-non 19 carriers have some favorable prognostic factors, and IGF-I gene polymorphism (CA repeats) may affect disease recurrence and overall survival.     

Effect of implanting bull calves with testosterone propionate, dihydrotestosterone propionate or oestradiol-17 beta prepubertally on the pituitary-testicular axis and on postpubertal social and sexual behaviour.

Twelve non-implanted crossbred bull calves served as controls and 30 crossbred bull calves (10/treatment) were implanted for 82 days, beginning at 34 days of age, to determine the influence of testosterone propionate (TP), dihydrotestosterone propionate (DHTP) and oestradiol-17 beta (E2) on prepubertal and pubertal pituitary-testicular function and on postpubertal social and sexual behaviour. Compared with control bulls, concentrations of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and inhibin concentrations were suppressed (P less than 0.01) in all implanted bulls. Testosterone (T) concentration increased (P less than 0.001) in TP-implanted, but decreased (P less than 0.01) in DHTP and E2 bulls during the implant period. LH response to gonadotrophin-releasing hormone (GnRH) challenge during the implant period (2.5 months of age) was less (P less than 0.01) in TP, E2 and DHTP bulls than in controls. A small but significant T response to GnRH occurred in control bulls at 2.5 months of age. LH and T responses to GnRH challenge at 7 months of age (100 days after implant removal) was similar (P greater than 0.20) in control and implanted bulls. Steroid implants administered prepubertally had no effect (P greater than 0.10) on postpubertal social and sexual behaviours, including number of flehmen responses, abortive mounts, services and competitive order score. Body weight did not differ (P greater than 0.10) between treatment groups, but testis size was reduced (P less than 0.01) during the implant period and up to 10 months of age in treated bulls compared with controls. Testes remained smaller in E2-treated bulls up to the end of the study (23 months of age), but daily sperm production and epididymal weight did not differ (P greater than 0.10) between treatment groups at slaughter. Control bulls reached puberty earlier (P less than 0.01; 270 +/- 11 days of age) than did TP (302 +/- 11 days), DHTP (309 +/- 11 days) or E2 (327 +/- 11 days) bulls. Although puberty was delayed in all implant groups, there was no difference in scrotal circumference at puberty (average 28.4 +/- 0.4 cm) between treatment groups. Our findings indicate that TP, DHTP and E2 implants administered prepubertally result in acute suppression of serum LH, FSH and inhibin during the implant period and in post-implant suppression of testis size and delayed puberty in bulls. The lack of treatment effect on behaviour suggests that steroidal programming of sexual behaviour occurs before 1 month of age in bulls.