Prevalence of endocrine dysfunction in HIV-infected men

OBJECTIVE: Endocrine dysfunction is a common problem in patients with human immunodeficiency virus infection (HIV). We therefore evaluated the endocrine function in 31 male homosexual HIV-1-infected men: mean age 37 +/- 7.2 years (range 24-52). METHODS AND MATERIALS: Blood was obtained for baseline T3, T4, TSH, LH, FSH, prolactin, testosterone, ACTH and cortisol values. Endocrine function tests were performed as TRH, CRH, ACTH, LH-RH and HCG tests. RESULTS: Thyroid function: There was a temporarily increased TSH in 3 of 17 patients but normal levels for T3, T4 and fT4 (without thyroid antibodies). One patient showed signs of latent hyperthyroidism (no response in TRH test). Adrenocortical function: Two patients had adrenal insufficiency. They showed a normal baseline cortisol level, an elevated ACTH level and no increase in cortisol levels after stimulation with CRH. All other patients revealed normal responses on the CRH/ACTH tests. Gonadal function: 9 patients had elevated FSH levels (tubular insufficiency), 4 patients additionally had increased LH levels (hypergonadotropic hypogonadism). 5 patients showed signs of tertiary hypogonadism (low LH and testosterone, increase of LH after stimulation with LH-RH). CONCLUSION: In disorders of thyroid and adrenocortical function of primary or tertiary origin, a substitution of hormones should be taken into consideration.     

Plasma ghrelin levels in patients with end-stage renal disease

Ghrelin is an acylated peptide stimulating secretion of the growth hormone (GH). It was originally isolated from the rat stomach as an endogenous ligand for the growth hormone secretagogue receptor. Although being predominantly produced by endocrine cells of the gastric fundus, its secretion has been found in various tissues including the kidney. To study the influence of renal failure on plasma ghrelin levels we examined 16 patients with end-stage renal disease (ESRD) receiving hemodialysis (8 men and 8 women) and 19 controls (10 men and 9 women). Both groups were comparable in age and BMI. In all subjects we assessed plasma levels of ghrelin, leptin, soluble leptin receptor, insulin, IGF-I, IGFBP-1, IGFBP-3 and IGFBP-6. Ghrelin levels were significantly higher in the group of dialyzed patients (4.49+/-0.74 vs. 1.79+/-0.15 ng/ml; p<0.001). These patients had significantly higher levels of GH, IGFBP-1, IGFBP-6, leptin and percentage of body fat (p<0.05). In the group of patients with ESRD plasma ghrelin levels positively correlated with IGFBP-1 (p<0.01). In the control group, ghrelin positively correlated with GH concentrations (p<0.01) and negatively correlated with the levels of insulin and creatinine (p<0.05). In conclusion, patients with ESRD have higher ghrelin concentrations, which might be caused by a decreased excretion/metabolism of ghrelin in the kidney during renal failure.     

Hypothalamic site of progesterone action on gonadotropin release

Tonic gonadotropin secretion was monitored at 20 min intervals for a total of 9 hours in 3 female volunteers during the mid-luteal phase of an ovulatory cycle. This control period was followed by repeated LH-RH stimulation (12 micrograms LH-RH as i.v. bolus once every hour for another 5 hours). During the control period spontaneous albeit low-frequent pulsatile secretion was observed for LH (a pulse occurring once every 3-8 hours) but not for FSH. While intermittent exogenous LH-RH stimulation was being performed at circhoral LH-RH pulse frequency pulsatile gonadotropin release was established at synchronous episodicity and systemic gonadotropin levels consecutively increased. These data provide indirect evidence that the pituitary gland is not rendered refractory to LH-RH by luteal progesterone secretion but readily responds to LH-RH stimuli even when these simulate a follicular phase LH-RH pulse frequency. Thus, it is concluded that spontaneous pulsatile LH release at low frequency during the luteal phase of the cycle reflects low frequent LH-RH discharges from the hypothalamus. Underlying mechanisms are discussed.     

Accuracy of serum luteinizing hormone and serum testosterone measurements to assess the efficacy of medical castration in prostate cancer patients

Background

Luteinizing hormone-releasing hormone (LH-RH) agonists are the standard for androgen deprivation therapy (ADT) in prostate cancer (PCa) patients. Current guidelines recommend serum testosterone measurement to assess the efficacy of ADT and to define castration resistance. However, serum testosterone does not reflect the exclusive effect of castration due to its extratesticular production. The aim of this study is to analyze if serum LH reflects better than serum testosterone the activity of LH-RH agonists.

Methods

Serum LH and serum testosterone were measured with chemiluminescent immunoassay (CLIA) in a cohort study of 1091 participants: 488 PCa patients “on LH-RH agonists”, 303 “off LH-RH agonist” in whom LH-RH agonists were withdrawn, and 350 men with PCa suspicion “no LH-RH agonist” who never received LH-RH agonists. In a validation cohort of 147 PCa patients, 124 on “LH-RH agonists” and 19 “off LH-RH agonists”, serum testosterone was also measured with liquid chromatography and tandem mass spectrometry (LC MSMS).

Results

The area under the curve (AUC) to distinguish patients “on versus off LH-RH agonists” was 0.997 for serum LH and 0.740 for serum testosterone, P < 0.001. The 97.5 percentile of serum LH in patients “on LH-RH agonists” was 0.97 U/L, been the most efficient threshold 1.1 U/L. The AUCs for serum LH, testosterone measured with CLIA and with LC MSMS, in the validation cohort, were respectively 1.000, 0.646 and 0.814, P < 0.001. The efficacy to distinguish patients “on versus off LH-RH agonists” was 98.6%, 78.3%, and 89.5% respectively, using 1.1 U/L as threshold for serum LH and 50 ng/dL for serum testosterone regardless the method.

Conclusions

Serum LH is more accurate than serum testosterone regardless the method, to distinguish patients “on versus off LH-RH agonists”. The castrate level of serum LH is 1.1 U/l. These findings suggest that assessment of LH-RH agonist efficacy and castration resistance definition should be reviewed.

     

Cyclosporine A inhibits the secretion of certain anterior pituitary hormones in patients with nephrotic syndrome.

To clarify the effects of cyclosporine A (CsA) on the secretion of serum thyrotropin (TSH), prolactin (PRL), luteinizing hormone (LH) and follicular stimulating hormone (FSH), we performed TRH and LH-RH testing in 4 patients with the nephrotic syndrome before and after the administration of CsA, 6 mg/kg/day for 4 to 12 weeks. Prior to CsA all patients responded normally to TRH with respect to TSH and PRL secretion. Two patients showed normal response of LH and FSH to LH-RH stimulation while the response in 2 other patients, who were both menopausal, was exaggerated. By the third or fourth week of CsA administration the basal and peak TSH and PRL values declined significantly in all patients in response to TRH stimulation while those of LH and FSH showed only a modest decrease in response to LH-RH stimulation. Two to 4 weeks after the cessation of CsA the response of TSH, PRL and FSH returned to the pretreatment level. These observations suggest that: 1) CsA exerts an inhibitory effect on the secretion of at least TSH and PRL in humans, and 2) the effect of CsA on the pituitary may be partially reversible after the cessation of the therapy.     

三维斑点追踪技术对慢性肾功能不全患者左心室收缩功能和右心室功能的评估价值研究

摘要 目的：探讨慢性肾功能不全患者应用三维斑点追踪技术对其左心室收缩功能和右心室功能的评估价值。方法：选择我院收治的慢性肾功能不全患者82例,根据患者肾功能将其分为轻度慢性肾功能不全组[慢性肾脏病（CKD） 2期,47例],中-重度慢性肾功能不全组（CKD 3~5期,35例）,另选取同期医院体检的健康志愿者30例作为对照组,应用二维超声及三维斑点追踪技术检测各组心脏指标,比较三组二维超声指标、三维斑点追踪技术指标,应用受试者工作特征（ROC）曲线分析三维斑点追踪技术对患者左心室收缩功能和右心室功能的评估价值。结果：中-重度慢性肾功能不全组室间隔舒张末期厚度（IVSTd）、肺动脉收缩压（PASP）显著高于轻度慢性肾功能不全组、对照组,右心室面积变化分数（RVFAC）、组织运动三尖瓣环位移（TAPSE）、左心室射血分数（LVEF）显著低于轻度慢性肾功能不全组、对照组（P<0.05）。中-重度慢性肾功能不全组左室整体圆周收缩期峰值应变（LGCS）、左室整体纵向收缩期峰值应变（LGLS）、右室整体圆周收缩期峰值应变（RGCS）右室整体纵向收缩期峰值应变（RGLS）、显著高于轻度慢性肾功能不全组、对照组,左室整体径向收缩期峰值应变（LGRS）、三维左室射血分数（3D-LVEF）、右室整体径向收缩期峰值应变（RGRS）、三维右室射血分数（3D-RVEF）显著低于轻度慢性肾功能不全组、对照组（P<0.05）。ROC曲线分析显示,三维斑点追踪技术对慢性肾功能不全患者左心室收缩功能和右心室功能的评估价值较高。结论：三维斑点追踪技术可以准确检测心脏的纵向运动、圆周运动、径向运动,为临床早期发现慢性肾功能不全患者的心脏功能异常提供依据。     

Effect of neonatal testosterone and oestradiol treatment on the development of the hypothalamo-hypophysial axis in the female rat.

The hypothalamic LH-RH content and the concentrations of pituitary and plasma LH were measured at various ages in female rats treated daily with 10 micrograms testosterone propionate or 10 micrograms oestradiol-17beta from birth to Day 15. Persistent vaginal oestrus was induced in all the treated rats. Both hormones significantly reduced the hypothalamic LH-RH content and pituitary and plasma LH concentrations. Hypothalamic LH-RH increased after cessation of treatment but pituitary LH did not return to normal levels. Plasma LH levels were significantly lower than those in control rats. It is concluded that testosterone propionate and oestradiol-17beta (1) have a direct negative feed-back influence on the hypothalamus in the neonatal female rat; (2) alter the normal pattern of plasma and pituitary LH in developing female rats; (3) prevent the cyclic secretion of plasma LH after maturity; and (4) probably cause a chronic impairment in the release of LH-RH.     

Effect of insulin administration on water drinking in children

The effect of insulin administration on water intake, was studied in children submitted to standard protocols for stimulation of secretion of hypophyseal hormones by i.v. treatment with several different drugs: insulin, insulin plus TRH and LH-RH; and propranolol, clonidine or LH-RH. Drinking was measured from 0 to 90 min after drug administration; from blood samples taken at 60 min for hypophyseal hormones analysis, microhaematocrit values were measured, as well as plasma renin activity (PRA) and glycaemia. Water intake was significantly higher in both groups of patients receiving insulin than in the control group (no insulin). Haematocrit values did not change after 60 min. There was a significant correlation of glycaemia of individuals from all three groups and water intake at 60 min. PRA was significantly higher in insulin treated individuals.     

The feedback effects of sex steroid hormones on pituitary gonadotropin release in Turner's syndrome and Klinefelter's syndrome.

The present study was designed to elucidate the feedback relationship between the release of pituitary gonadotropins and sex steroid hormones in Turner's syndrome and Klinefelter's syndrome. LH-RH stimulation test was employed to evaluate the effects of sex steroids on the release of gonadotropins. The release of gonadotropins in response to LH-RH as well as in baseline level was suppressed after the treatment with estrogen (mestranol 0.08 mg/day) for 10 days, followed by the treatment of the same period with estrogen (mestranol 0.08 mg/day) and progesterone (chlormadinone acetate 2.0 mg/day) in combination in both syndromes. The inhibitory effect of the combined treatment was greater than that of the treatment with estrogen alone. Administration of testosterone propionate (25 mg/day) for 3 days resulted in suppression of the release of both gonadotropins in baseline level and in response to LH-RH in both syndromes, but the suppressive effect appeared to be less complete as compared with that of estrogen or estrogen-progesterone. It was thus verified that the feedback interaction between the pituitary gonadotropin release and sex steroids such as estrogen, estrogen-progesterone or testosterone was operative in the same fashion in the patients with Turner's syndrome and Klinefelter's syndrome.     

高通量血液透析对慢性肾衰竭尿毒症患者TLC 及免疫球蛋白水平的影响

目的:探究高通量血液透析对慢性肾衰竭尿毒症患者TLC及免疫球蛋白水平的影响。方法:选取我院收治的慢性肾衰竭尿毒症患者100例,随机分为实验组和对照组。对照组采用常规血液透析治疗,实验组采用高通量血液透析治疗。观察并比较两组患者治疗前后TLC及免疫球蛋白水平的变化情况以及临床疗效。结果:实验组治疗有效率(96.0%)高于对照组(86.0%),差异有统计学意义(P0.05);与治疗前相比,两组患者治疗后血肌酐水平下降,IgA,IgM及IgG水平升高,肺功能TLC水平升高,差异具有统计学意义(P0.05);与对照组相比,实验组患者治疗后血肌酐水平较低,IgA,IgM及IgG水平较高,肺功能TLC水平较高,差异具有统计学意义(P0.05)。结论:高通量血液透析治疗能够改善慢性肾衰竭尿毒症患者的肺功能,增强免疫功能。     

Evaluation of oxidative stress biomarkers in patients with chronic renal failure: a case control study

Background

Oxidative stress is related to several diseases, including chronic renal insufficiency. The disequilibrium in the oxidant-antioxidant balance is the result of several metabolic changes. The majority of studies to-date have evaluated the grade of oxidative stress with a single biomarker, or a very limited number of them.

Findings

The present study used several important biomarkers to establish a score relating to oxidative stress status (glutathione S-transferase, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced and oxidized glutathione, thiobarbituric acid reactive substances and hemolysis test). The score of oxidative stress (SOS) was then applied to a group of patients with renal insufficiency not on hemodialysis, and compared to healthy control individuals.The score for patients with chronic renal insufficiency was significantly different from that of the healthy control group (0.62 ± 1.41 vs. -0.05 ± 0.94; p < 0.001). The comparison between patients with chronic renal insufficiency and control individuals showed significant differences with respect to changes in the enzymatic antioxidant systems (glutathione S-transferase, glutathione reductase), non-enzymatic antioxidant system (oxidized glutathione) and oxidizability (hemolysis test) indicating significant oxidative stress associated with chronic renal insufficiency.

Conclusions

Patients with chronic renal insufficiency not on hemodialysis are susceptible to oxidative stress. The mechanisms that underlie this status are the consequence of changes in glutathione and related enzymes. The SOS scoring system is a useful biochemical parameter to evaluate the influence of oxidative stress on the clinical status of these patients.

     

慢性肾功能不全对中老年非瓣膜性房颤患者全因死亡、心脑血管疾病死亡及血栓终点事件的影响

目的：探讨中老年非瓣膜性房颤患者全因死亡、心脑血管疾病死亡及血栓终点事件的危险因素及慢性肾功能不全是否为其独立危险因素。方法：纳入未应用抗凝药物的中老年非瓣膜性房颤患者825例,平均年龄为76.52±11.80岁,其中女性占18.91%,75岁以上患者占64.73%,记录基线特征及各终点事件发生情况。通过Cox生存分析,探讨肾功能不全对各终点事件的影响。结果：入选患者中位数随访时间为33.5个月,随访期间发生全因死亡209例、心脑血管疾病死亡61例及血栓终点事件139例。合并慢性肾功能不全的房颤患者各终点事件发生率均显著高于对照组,在校正CHA₂DS₂-VASc评分危险因素及其他传统危险因素后,慢性肾功能不全仍是全因死亡、心脑血管疾病死亡及血栓终点事件的独立危险因素。结论：慢性肾功能不全是未服用抗凝药物的中老年非瓣膜性房颤患者全因死亡、心脑血管疾病死亡及发生血栓事件的独立危险因素之一。     

Changes in serum levels of glycoprotein hormone alpha subunits in patients with alphoma-type pituitary tumors during LHRH and TRH stimulation tests

A group of 21 patients with the alphoma-type pituitary tumors was studied. In 9 cases the tumor was associated with acromegaly. Alpha subunit concentration was determined in all the patients and in control subjects in the course of dynamic tests consisting in simultaneous intravenous administration of 200 micrograms TRH and 100 micrograms LH-RH. In basal conditions the concentration of alpha subunit in patients with the alphoma-type tumors ranged between 2.1 and 30 micrograms/l (mean 7.5 +/- 6.6 micrograms/l), and in controls the respective values ranged between 0.2 and 1.6 micrograms/l (mean 0.78 +/- 0.36 micrograms/l). In the course of the LH-RH + TRH test there was an increase in the alpha subunit level both in the patients with alphoma associated with acromegaly and in the remaining cases of alphoma. Statistical analysis of the results obtained for the whole group of patients revealed a significant linear correlation between the alpha unit concentration 20, 30, 60 and 90 minutes following stimulation with the neurohormones and that before stimulation. For 9 patients with the acromegaly-associated tumors a statistically significant increase in the alpha subunit concentration was noted only at the 90-th minute of the stimulation test, while for the remaining 12 patients with alphoma an increase was statistically significant for the whole time of the duration of the test. In healthy subjects the concentration of alpha subunit never exceeded the limits of the normal values in the course of the LH-RH + TRH stimulation test.     

Negative feedback effects of chlormadinone acetate and ethynylestradiol on gonadotropin secretion in patients with prostatic cancer and male rats

Serum LH and FSH levels were determined before and after LH-RH injection (100 micrograms, i.m.) in patients with prostatic cancer who were chronically treated with either chlormadinone acetate (CMA, 100 mg/day) or ethynylestradiol (EE, 1 mg/day). In patients treated with EE, the levels of serum LH and FSH before and after injection of LH-RH were significantly lower than those in controls. On the other hand in patients treated with CMA, the basal levels of serum gonadotropins did not differ from those in controls, and the increase in gonadotropin after LH-RH injection was comparable to that in controls. To examine the effects of these steroids on the hypothalamo-hypophysial axis in the regulation of gonadotropin secretion, CMA or EE was implanted in castrated male rats. CMA, EE or cholesterol (control) was implanted in the hypothalamic median eminence-arcuate nucleus region through a stainless doublecannula. EE implantation resulted in a 75% decrease in serum LH (p < 0.001) and a 38% decrease in serum FSH (p < 0.05) from the control levels on day 5 of implantation. On the other hand, CMA implantation induced a 33% decrease in serum LH (p < 0.05) from the control level on day 3 of implantation, but no significant change in serum FSH levels. The injection of 2 micrograms/kg of LH-RH on day 7 of implantation induced significant lowering of LH and FSH levels. There was no significant difference between serum levels of the hormones 20 min after LH-RH injection for these two groups and those for the control group. These studies suggest that EE has a potent negative feedback effect on both LH and FSH secretion, and that CMA has a mild negative feedback effect on LH secretion.     

Menstrual disturbances in chronic renal failure.

Twelve female patients undergoing intermittent hemodialysis (HD) and 5 females posttransplantation (PT) were studied. All the HD patients had menstrual disturbances and 5 had galactorrhea. The mean basal LH level was significantly elevated (p less than .05) in patients on HD compared to normal controls, but the mean LH response to luteinizing hormone releasing hormone (LRH) was not significantly different from the control group. Mean basal FSH and the FSH response to LRH was normal. In the PT pateints the LH response to LRH was significantly greater at 120 min when compared to normal females. In the HD group the serum 17B estradiol, progesterone and testosterone levels were significantly lower than in the controls but in the PT group only testosterone levels were significantly lower. These results differ from those previously found in uremic males. Elevated prolactin levels were found in the patients on hemodialysis and correlated well with the presence of galactorrhea. These was no correlation between the elevated prolactin levels and amenorrhea in the patients on hemodialysis but one PT patient with amenorrhea had elevated prolactin levels.     

LH-RH antagonist inhibits gonadal steroid secretion in vitro

This investigation was aimed at studying the direct action of LH-RH derivatives on gonadal function. Modulation by LH-RH antagonist (Ac-[D-beta-Nal1, D-p-Cl-Phe2, D-Trp3, D-Arg6, D-Ala10]-LH-RH) and agonist of LH-RH (D-Ser(TBU)6, AzaGly10-LH-RH) and native LH-RH of HCG-stimulated steroidogenesis in testicular Leydig cells and luteal cells was studied in vitro. The LH-RH antagonist (3.2 X 10(-8) M) was found to change ED50 of HCG from 2 X 10(-11) M to 5.5 X 10(-11) M in the Leydig cell culture system. In addition, the antagonist was noted to override the stimulatory action of native LH-RH in Leydig cells. Furthermore, the agonist was found to augment HCG-provoked testosterone secretion. Similarly, the LH-RH antagonist at 10(-9) M blunted HCG-stimulated progesterone secretion in the luteal cell culture system and increased the ED50 of HCG from 8.7 X 10(-13) to 7.7 X 10(-12) M. In contrast to the Leydig cell culture system native LH-RH (10(-8) M) and the agonist (10(-8) M) increased the ED50 of HCG in luteal cells from 8.7 X 10(-13) M to 3 X 10(-12) M and 2.3 X 10(-12) M, respectively. Present data combine to suggest that LH-RH antagonists act at least partially at the gonadal level and may be clinically useful to inhibit Leydig cell and ovarian function.     

On the correlation between FSH, LH and prolactin serum levels.

In 188 males FSH, LH, and prolactin serum levels determined from a single blood sample were found to be closely correlated. No correlation appeared to testosterone levels. The same correlation is observed, if serum levels of FSH, LH, and prolactin are measured after stimulation with LH-RH and TRH. In order to explain the close correlation, in five young men hormone levels were measured at 2-min-intervals over a period of 2 hours. Peaks of prolactin often correspond to those of FSH and LH, and a statistical correlation was found in two cases between FSH and prolactin. Results suggest a common releasing mechanism, which is superposed to the main mediating mechanism.     

Acute and chronic influence of hemodialysis according to the membrane used on phagocytic function of neutrophils and monocytes and pro-inflammatory cytokines production in chronic renal failure patients

This work evaluated the phagocytic capacity of monocytes and neutrophils, and tumor necrosis factor-alpha, interleukin 6, 1 and 8 serum levels in chronic renal failure patients under peritoneal dialysis and hemodialysis treatment, compared with chronic renal failure patients without dialysis treatment and healthy individuals, in order to contribute to a better understanding of the action of these therapies on the evolution of chronic renal failure patients. All patients with chronic renal failure (under dialysis or not) showed decreased phagocytic capacity of neutrophils and monocytes. All those in hemodialysis (cellulose acetate or polysulfone membranes) showed a decreased phagocytic capacity. The phagocytic index for neutrophil was 13 times lower than that of the control group for both membranes, whereas for monocytes, only those using polysulfone membrane showed a significant decrease of 4.9 times in phagocytic capacity. There was an acute stimulation of the phagocytosis by neutrophils after a single session of dialysis with both types of membrane, while only cellulose acetate membrane decreased the phagocytic index of monocytes after the hemodialysis session. Patients using cellulose acetate showed a chronic increase in tumor necrosis factor-alpha serum levels, while those using polysulfone showed a chronic increase in interleukin 6. After a single hemodialysis procedure, no acute effect of the treatment on tumor necrosis factor-alpha and interleukin 6 levels was identified. The decreased phagocytic function of neutrophils and monocytes may account for the high levels of susceptibility of chronic renal failure patients to infections with pyogenic bacteria and tuberculosis. Furthermore, inflammatory activity may occur with both types of membrane studied, suggesting that it will be useful for these patients to evaluate some anti-inflammatory or anti-cytokine therapies against tumor necrosis factor-alpha and interleukin 6, in order to avoid cardiovascular complication.     

Restoration of normal gonadotropin responses to naloxone by chronic bromocriptine treatment in elderly men.

Naloxone is unable to stimulate FSH and LH secretion in elderly men, suggesting a reduced endogenous opioid control of gonadotropin secretion in senescence. In the present study, we examined whether in elderly men a chronic dopaminergic stimulation with bromocriptine (5 mg/day for 7 days) modifies the gonadotropin response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 h). Eleven younger men (group 1, 22-40 years old) participated as controls. Twenty-two elderly men were selected from a larger population and were divided into two groups: subjects with compensated gonadal failure (normal blood testosterone and elevated gonadotropin concentrations; group 2, n = 11; 62-80 years old) and men with normal gonadal function (normal blood testosterone and gonadotropin levels; group 3, n = 11; 61-82 years old). Naloxone induced a striking LH and a slight but significant FSH increase in group 1, but was unable to change serum gonadotropin concentrations in elderly subjects of both groups 2 and 3. When experiments were repeated after bromocriptine treatment, no significant differences in LH and FSH responses to naloxone were observed in the younger subjects. On the other hand, bromocriptine restored significant gonadotropin responses to naloxone in elderly men. In fact, after bromocriptine, naloxone-induced FSH and LH increments in groups 2 and 3 were indistinguishable from those observed in group 1. These data suggest that in men age-related dopaminergic alterations may underlie the defective endogenous opioid control of gonadotropin secretion.     

Does estradiol treatment normalize the hypothalamic-pituitary-adrenal axis in streptozotocin-induced ovariectomized diabetic female rats?

We recently found circulating corticosterone (CS) levels to be significantly lower in diabetic female rats as compared with proestrous control animals. This reduction in CS was correlated with the hypoestrogenic state of the diabetic female. It was the purpose of this study to evaluate basal and corticotropin releasing hormone (CRH)-stimulated CS secretion in ovariectomized (OVX) control (C) and streptozotocin-induced diabetic (D) rats given blank, 5 mcg and 20 mcg estradiol (E2) implants to determine if adrenal CS secretion in the diabetic is normalized by E2 treatment. After 3 weeks of diabetes, pituitary-adrenal function was assessed in rats from each group with a CRH stimulation test. The remaining rats were sacrificed for determination of CS, E2, testosterone and fructosamine in serum. Suppressed CS secretion in OVX female diabetic rats was partially restored with E2 therapy. Basal CS levels were significantly higher in 20 mcg E2 treated C and D rats compared with OVX rats. However, C rats had significantly higher basal CS compared with D rats in similarly E2 treated groups. The CS response to CRH stimulation was not different between OVX female diabetic and control rats. Estrogen enhanced the CS response to CRH stimulation in control animals but not in diabetic animals suggesting altered estrogen action at the pituitary level in diabetic animals.