生长激素释放激素在垂体生长激素瘤中的作用

目的探索Gsα和生长激素释放激素受体（GHRHR）基因突变和生长激素释放激素（GHRH）在生长激素瘤形成中的作用。方法对26例垂体生长激素瘤标本用ABC免疫组化法观察GHRH及其受体在垂体生长激素瘤细胞中的表达，提取组织DNA行PCR扩增并进行测序研究Gsα和GHRHR基因突变。结果免疫组化显示GHRH阳性率为15．4％，GHRHR阳性率为30．8％。2例Gsα突变在第201位，1例在第210位，总突变发生率为11．5％；2例GHRHR基因突变在第225位。结论Gsα突变是生长激素瘤发生的重要原因，GHRH在垂体瘤中阳性表达提示部分生长激素瘤可能分泌GHRH，并通过自分泌或旁分泌作用于瘤细胞，导致肿瘤的发生。     

Use of growth hormone in non-growth hormone deficient children

The easy availability of growth hormone (GH) in the Indian market has led to its increased use in the management of short stature. However, the therapy is expensive for most families. The possible benefits of such a therapy have to be carefully weighed against the cost and adverse effects. We discuss the drawbacks of relying on data based on predicted height to evaluate the benefits of GH therapy reported in the literature. It is the final adult height which is the true indicator of the efficacy of GH therapy. The only clear indications for GH therapy are short stature associated with GH deficiency and Turner syndrome. Classifying short stature may not be of much help in deciding the utility of GH therapy and the use of auxological criteria alone will increase the burden on society. At present, the use of GH in idiopathic short stature is not indicated in routine clinical practice.     

Intranasal treatment with luteinising hormone releasing hormone agonist in women with endometriosis

An agonist analogue of luteinising hormone releasing hormone (buserelin) was successfully used to treat women with endometriosis. A dose of 200 micrograms administered intranasally thrice daily was found to be effective in five patients, in whom the endometriotic lesions resolved after six months' treatment. Failure occurred in a sixth patient, who received only 400 micrograms once daily. Anovulation was induced in all subjects together with suppression of menstruation after the first month of treatment. Symptoms of abdominal pain, dysmenorrhoea, and dyspareunia were relieved during treatment, and one previously infertile patient conceived within two months of stopping treatment. No side effects were reported with this dosage, and the results suggest a new form of treatment for patients with endometriosis.     

Acromegaly secondary to growth hormone releasing hormone secretion

Background Acromegaly secondary to growth hormone releasing hormone (GHRH) secretion is exceptionally rare. Aim To report a case of acromegaly diagnosed in 1984 and assumed to be pituitary in origin. Sixteen years later, the cause was found to be a GHRH secreting neuroendocrine pancreatic tumour. Method A case report. Conclusion Although ectopic GHRH production is very rare, endocrinologists should be aware of this possibility in acromegaly patients if a pituitary tumour was not detected using pituitary imaging.     

GnRH拮抗剂在前列腺癌内分泌治疗中的临床应用和发展前景

晚期前列腺癌的一线治疗方案是内分泌治疗,即去除雄激素治疗.目前去除雄激素治疗最常用的药物是促性腺激素释放激素(GnRH)激动剂,但其初次使用时可能导致睾酮激增,维持用药时也存在睾酮波动的风险,需要联合应用抗雄激素药物来缓解病情的恶化.研究表明,GnRH拮抗剂也可应用于前列腺癌治疗,且其直接抑制受体活性,不存在诱发睾酮激增的风险.本文综述了GnRH激动剂和GnRH拮抗剂的作用机制、GnRH拮抗剂的发展历史及其在前列腺癌治疗中的临床应用,评价了GnRH拮抗剂的安全性和有效性,揭示了GnRH拮抗剂的临床价值和发展前景.     

保幼激素及其生理学作用的研究进展

保幼激素(JH)是在昆虫咽侧体内通过甲羟戊酸途径合成的一类倍半萜类化合物,分泌后进入血淋巴,调节昆虫的生长发育、变态及生殖等生理学功能。本文主要综述了近年来JH的生物合成与代谢以及对昆虫的生理效应,尤其是对卵黄发生的调节方面的研究,以期对保幼激素在昆虫卵黄发生调节过程中有更全面和深入的了解。     

Growth hormone deficiency in adults and clinical use of recombinant human growth hormone

OBJECTIVE: To review the modern recognition of growth hormone deficiency (GHD) in adults and the beneficial effects of growth hormone (GH) treatment in such cases. DATA SOURCES AND METHODS: Most published original articles about GH and GHD in recent domestic and world wide related literatures were available. STUDY SELECTION: More than 65 originally identified articles were reviewed and 29 were selected that especially addressed the stated purpose. RESULTS: Treatment of GHD in adult human beings became an option following the development of rhGH and the numerous reports on the effect of rhGH therapy in such patients. The syndrome of GH deficiency in adults principally comprises abnormalities in body composition, cardiovascular risk factor, and psychological well-being. In comparison with normal individuals, these patients have increased total-body fat mass (particularly visceral adiposity), reduced muscle mass, reduced muscle strength exercise performance, and reduced bone mass. The psychological dysfunction comprises self-reported reduction in energy, mood, and sleep, along with objective reductions in marital and socioeconomic performance. CONCLUSION: The evidence that rhGH administration may be beneficial for the prevention, as well as treatment, of various clinical situations.     

CRH刺激大鼠下丘脑脑片CRH及CRH1R的表达研究

目的　通过CRH刺激大鼠下丘脑脑片 ,探讨下丘脑CRH和CRH1R在下丘脑中的分布和表达规律。方法　采用大鼠下丘脑脑片实验模型 ,运用免疫组织化学技术 ,观察CRH刺激大鼠下丘脑脑片后CRH和CRH1R在下丘脑中的分布和表达规律。结果　CRH刺激下丘脑脑片后下丘脑CRH和CRHlR含量明显增多 ,而CP 15 45 2 6、H89可显著抑制CRH和CRHlR的增加。结论　CRH刺激下丘脑脑片后增多的CRH与CRHlR结合后进一步引起下丘脑神经元CRH和CRHlR表达增加。提示在严重创伤应激反应中 ,CRH通过PKA途径实现对下丘脑神经元CRH的表达的超短正反馈调节。     

体外颗粒细胞培养中抗苗勒管激素与卵泡刺激素受体mRNA表达的相关性

目的体外培养小鼠原代颗粒细胞培养液中,加入不同浓度的抗苗勒管激素(AMH),比较各组间小鼠颗粒细胞上卵泡刺激素受体(FSHR)mRNA的表达情况,探讨体外培养颗粒细胞中AMH与FSHR mRNA表达的关系。方法选取4～5周的昆明雌性小鼠,腹腔注射孕马血清促性腺激素,48～54 h后颈椎脱臼法处死小鼠,取双侧卵巢,采用机械分离法释放颗粒细胞,胰蛋白酶消化细胞,低速离心分离细胞,用含15%胎牛血清的DMEM/F12培养基置于37℃、5%CO2培养箱中培养。显微镜观察细胞形态,流式细胞术分离细胞,并用免疫荧光法对所培养的颗粒细胞进行鉴定。同时在体外培养的小鼠原代颗粒细胞培养液中加入不同浓度(5、10、20、30、40ng/mL)的AMH,测定每组培养基中AMH的终浓度,并用荧光定量PCR技术检测每组颗粒细胞中FSHR mRNA的表达。结果分离培养的颗粒细胞纯度大于80%;随AMH浓度加大,小鼠颗粒细胞中FSHR mRNA的表达逐渐降低,当AMH浓度为5和10 ng/mL时,与对照组比较差异有统计学意义(P<0.05),且5 ng/mL浓度组颗粒细胞上FSHR mRNA的表达量最高。结论用机械分离加胰酶消化加低速离心能得到纯度较高活性很好的颗粒细胞,用FSHR鉴定颗粒细胞是一种简便易行的方法,AMH浓度与颗粒细胞上FSHR mRNA表达呈一定负相关,表明AMH有可能通过抑制FSHR表达降低FSH敏感性,从而参与卵巢早衰的病理生理过程。     

Induction of ovulation with pulsatile luteinising hormone releasing hormone

Ovulation was successfully induced with luteinising hormone releasing hormone in 28 women with hypothalamic amenorrhoea who had failed to respond to treatment with clomiphene. Luteinising hormone releasing hormone was administered in a pulsatile manner with miniaturised automatic infusion systems. The rate of ovarian follicular maturation, as monitored by serial pelvic ultrasonography, was similar to that observed in spontaneous cycles. Endocrine assessment by serial measurement of gonadotrophin, oestradiol, and progesterone concentrations showed hormone concentrations to be within the normal range. Intravenous treatment was required in only two patients, the remainder responding satisfactorily to subcutaneous infusion. All patients conceived within six cycles of treatment, and only one multiple pregnancy occurred.     

超排卵时卵巢对促性腺激素的反应与颗粒细胞促卵泡激素受体的表达

目的 :探讨促排卵周期卵巢对促性腺激素反应性与颗粒细胞促卵泡激素受体 (FSHR)表达的关系。方法 :根据取卵时卵泡发育数不同 ,将卵巢对促排卵药物的反应分为低反应型 (卵泡数≤ 3个 )、中反应型 (卵泡数 4～13个 )和高反应型 (卵泡数≥ 14个 ) ,分别为 11例、15例和 13例。采用逆转录聚合酶链反应 (RT- PCR)测定 3种反应类型的卵泡颗粒细胞 FSHR m RNA的表达量。结果 :低反应型 FSHR m RNA表达量显著低于中、高反应型 (相对积分值分别为 0 .5 4± 0 .0 7、0 .90± 0 .17和 1.2 0± 0 .4 5 ,P<0 .0 5 )。结论 :卵巢对促性腺激素的反应与颗粒细胞FSHR m RNA的表达量高低有关。     

Growth hormone, prolactin and thyrotrophin responses to thyrotrophin-releasing hormone in diabetic patients.

Growth hormone (GH), prolactin (PRL) and thyrotrophin (TSH) responses to thyrotrophin-releasing hormone (TRH) were studied in 15 insulin-dependent diabetic patients. Basal plasma GH levels were raised above 5 mu./l in 6 patients and following the injection of TRH there was a significant rise in plasma GH levels in 9. The mean rise in plasma GH from basal to peak values was significant in the group as a whole (P < 0.01). Basal PRL and TSH levels were normal and rose normally in response to TRH. GH release may be qualitatively abnormal in some diabetics and any such loss of specificity of GH-releasing mechanisms would further contribute to the raised GH levels found in many diabetics which would be of importance if GH is a factor in the aetiology of diabetic microangiopathy.     

Ethical issues in growth hormone therapy

Pediatricians face clinical and ethical dilemmas about therapy to augment growth in short children who do not meet classic criteria for growth hormone (GH) deficiency. Biologic norms of health are unhelpful because of the uncertain relationship between stature, GH secretion, health, and disease. Instead, we suggest that GH therapy be evaluated from the perspective of cultural norms. We compare GH therapy for short normal children with currently accepted therapies for non--life-threatening pediatric conditions such as well-child care, cosmetic therapy, treatment of psychological problems, and invasive outpatient therapy for chronic conditions. Based on this analysis, we argue that the burdens of therapy, the uncertainty about long-term risks and benefits, the unclear therapeutic end point, and the implications for child health policy place routine GH therapy for children without documented deficiency of GH secretion outside current pediatric ethical norms. Such therapy is properly administered within a comprehensive clinical research protocol.     

Current trends in hormone replacement therapy

As life span increases, more and more women live longer after the menopause, and see its long-term consequences. The menopause and climacteric have major consequences for the well being of most women, resulting in a variety of symptoms including vasomotor, psychological, sexual symptoms and increased risk of osteoporosis and atherosclerosis. Prevention of osteoporosis and reduction in cardiovascular risks are the long-term goals of post-menopausal hormone replacement therapy. Post-menopausal women who receive hormone replacement therapy have approximately half of the rate of coronary artery disease compared to those who do not take it. Similarly, estrogen replacement alone for 5 years results in 50% reduction in the risk of overall fracture and is a major factor in the prevention and management of osteoporosis. A wide range of estrogen preparations is available for administration by various routes. The choice depends on indications, side effects and convenience. Oral estrogen is the most commonly used preparation followed by transdermal preparation. Controversy still exists over the efficacy and safety of hormone replacement therapy among both the medical and lay authorities. There is overwhelming evidence that hormone replacement therapy improves the quality of life and reduces the morbidity and mortality by reversing the metabolic and pathological changes induced by the menopause. The benefits of hormone replacement therapy out weigh any increased risk of venous thromboembolism or breast, ovarian and endometrial cancers.