Endocrine contribution to the sexual dysfunction in patients with advanced chronic kidney disease and the role of hyperprolactinemia

In this study, we investigated the prevalence of sexual dysfunction among males with advanced chronic kidney disease and the effect of treating hyperprolactinemia among these patients. In this prospective study, patients were assessed with history, physical examination, hormonal assessment, and two questionnaires, IIEF and AIPE. Patients with hyperprolactinemia received treatment with cabergoline 0.5 mg once per week for 6 months and were re-evaluated. A total of 102 patients were included in this study, 75 (73.53%) were on hemodialysis, 13 (12.75%) on peritoneal dialysis and 14 (13.73%) on medical treatment alone. Ninety (88.24%) patients had premature ejaculation, 85 (83.33%) had anything from mild-to-moderate-to-severe erectile dysfunction. The incidence of hypogonadism and hyperprolactinemia was 34.4%. Patients treated with cabergoline (n = 26) showed a significant increase in LH levels (p = .003) and a significant decrease in prolactin levels (p = .003). Testosterone levels and the incidence of erectile dysfunction or premature ejaculation did not improve significantly. There is a high incidence of sexual dysfunction among patients. Treatment of hyperprolactinemia is effective in correcting prolactin levels, but does not improve erectile dysfunction or premature ejaculation. Therefore, treating hyperprolactinemia is not an overall effective treatment for erectile dysfunction in these patients.     

清肝袋泡剂治疗高催乳素血症临床与实验研究

目的：进一步观察清肝袋泡剂对高催乳素血症（ＨＰＲＬ）患者的临床疗效,探讨其作用机制。方法：随机将患者分为治疗组１２０例（清肝袋泡剂）,对照组４０例（溴隐亭）。观察血中催乳素（ＰＲＬ）和相关激素水平及症状变化情况,进行疗效对比。同时通过动物实验对内分泌水平及卵巢、子宫、乳腺的组织形态变化进行同步观察。结果：清肝袋泡剂可显著降低患者血清ＰＲＬ水平,对相关激素有良性调节作用,临床疗效良好,与对照组比较无显著性差异（Ｐ＞０．０５）;动物实验证明能促进卵泡发育,使子宫内膜出现各动情周期的变化,抑制乳腺腺体增生。结论：清肝袋泡剂可有效治疗ＨＰＲＬ。     

高泌乳素患者不同时间段泌乳素水平研究

目的 探讨高泌乳素血症患者泌乳素水平在不同时间段的变化。方法 使用电化学发光法、罗氏E170全自动免疫分析仪测定124例高泌乳素(PRL>880 uIU/ml),女性患者在7:30AM,10:00AM及4:00PM不同时间段血浆泌乳素(PRL)水平,并根据经聚乙二醇(PEG)6000沉淀巨泌乳素后的PRL回收率分成巨泌乳素组(回收率≤40%)、单泌乳素组(回收率>60%)、可疑泌乳素组(40%<回收率≤60%),同时检测45例正常对照组的PRL水平。结果 高泌乳素组巨泌乳素阳性率(33.1%)与正常对照组中巨泌乳素阳性率(0.0%)比较,差异有统计学意义(χ2=17.886 7,P<0.05),巨泌乳素组及单体泌乳素组经PEG处理前在10:00AM时间段的泌乳素浓度(1160±714 uIU/ml,885±801 uIU/ml)与7:30AM时间段的泌乳素浓度(1 521±914 uIU/ml,1 497±845 uIU/ml)差异均有统计学意义(t=1.993,4.46,P<0.05),巨泌乳素组及单体泌乳素组经PEG处理后在10:00AM时间段的泌乳素浓度(316±231 uIU/ml,766±611 uIU/ml)与7:30AM时间段的泌乳素浓度(488±394 uIU/ml,1235±912 uIU/ml)差异均有统计学意义(t=2.411 4,3.625 2,P<0.05),单泌乳素组4:00PM时间段处理前的泌乳素浓度(1 033±911 uIU/ml)与7:30AM时间段处理前的泌乳素浓度(1 497±845 uIU/ml)差异也有统计学意义(t=3.168 6,P<0.05)。结论 不同时间段泌乳素水平有变化,确定正确的采血时间,有助于临床对高泌乳素血症的诊断。     

Progressive prostate hyperplasia in adult prolactin transgenic mice is not dependent on elevated serum androgen levels

BACKGROUND: Transgenic mice overexpressing the rat prolactin (PRL) gene under control of the metallothionein-1 promoter (Mt-1) develop a dramatic prostatic enlargement. These animals also display significantly elevated testosterone serum levels. In this study, we aim to clarify the role of circulating androgen levels in the promotion of abnormal prostate growth in the adult PRL transgenic mouse prostate. METHODS: Prostate morphology and androgen-receptor distribution patterns were analyzed in castrated and testosterone substituted adult PRL transgenic and in wild-type males. RESULTS: Progressive prostatic hyperplasia in adult PRL transgenic males was not affected by substitution to serum testosterone levels corresponding to wild-type. Furthermore, prolonged testosterone treatment in adult wild-type males did not produce any significant changes in prostate growth or morphology compared with wild-type controls. Immunohistochemical studies revealed a significantly increased proportion of androgen receptor positive epithelial cells in all lobes of the PRL transgenic prostate versus wild-type. CONCLUSION: The present study demonstrates that progressive prostate hyperplasia in adult PRL transgenic mice is not dependent on elevated serum androgen levels. Furthermore, prolonged androgen treatment in adult wild-type male mice appears to have no significant effect on prostate growth. In addition, our results suggest that prolonged hyperprolactinemia results in changes in prostate epithelial and stromal cell androgen receptor distribution.     

溴隐亭治疗垂体泌乳素瘤57例

作者分析了１９８７年至１９９４年经妇科内分泌门诊确诊为脑垂体泌乳素瘤５７例用溴隐亭治疗的情况。５７例中巨大腺瘤１１例，微腺瘤４６例。５７例均用溴隐亭治疗，其中９例手术，术后继续服用溴隐亭。结果血清泌乳素值迅速下降至正常范围者占８９．４７％，８５．９６％病例泌乳减少或停止，８７．７２％月经恢复，６３．４１％病例妊娠。所有足月产的２３例婴儿无一例畸形或先天性疾病。可见，溴隐亭治疗垂体泌乳素瘤的效果非常显著，而且副作用小，无致畸作用。     

Unmodified prolactin (PRL) promotes PRL secretion and acidophil hypertrophy and is associated with pituitary hyperplasia in female rats

In this study, we have tested the hypothesis that unmodified prolactin (U-PRL) and phosphorylated prolactin (P-PRL) have differential roles in the autoregulation of PRL secretion in vivo. Recombinant human U-PRL and a molecular mimic of P-PRL (S179D PRL) were administered to male rats and to female rats in different physiological states and the effect on rat PRL release was measured. Administration of U-PRL elevated rat PRL in all female animals, but was without effect in males. By contrast, S179D PRL was inactive in females, but inhibited PRL release in males. Morphometric and immunohistochemical analyses demonstrated acidophil hypertrophy and evidence of increased PRL secretion in the pituitaries of U-PRL-treated females. Analysis of the two forms of PRL during prolactinoma induction in two differentially susceptible strains of rats found a strong temporal correlation among increased ratios of U-PRL: P-PRL, increased circulating PRL, and increased cell proliferation. We conclude (1) that the autoregulatory mechanism(s) can distinguish between the two major forms of PRL and that higher proportions of U-PRL not only allow for higher circulating levels of PRL, but are also autostimulatory, (2) that the autoregulatory mechanism(s) are set differently in males and females such that females are more sensitive to autostimulation by U-PRL and less sensitive to inhibition by P-PRL, and (3) that U-PRL and P-PRL may also have differential roles in the regulation of pituitary cell proliferation.     

高泌乳血症的诊治分析

目的 探讨高泌乳血症的诊断和治疗。方法 观察分析本院62例高泌乳血症病例（功能性高泌乳血症40例，垂体微小腺瘤22例）。结果 功能性高泌乳血症药物（溴隐亭）治疗后80％患者泌乳停止，月经恢复，妊娠率达30％。垂体微小腺瘤（10mm左右），经蝶显微手术后全部恢复排卵性月经，PRL降至20ng／ml以内。结论 功能性高泌乳血症予药物治疗，而垂体微小腺瘤以手术为宜。     

Effects of Estrogen and Ectopic Pituitary Transplants on the Responsiveness of Pituitary Prolactin Release to Luteinizing Hormone-Releasing Hormone and Dopamine

The responsiveness of prolactin release to regulatory inputs depends on the functional state of the lactotrophs. In the present study, we have examined the effects of luteinizing hormone-releasing hormone (LHRH; 10^–7 or 10^–6 M) on the release of prolactin in vitro from hyperplastic pituitaries of estrogen-treated male Fischer rats, ectopic pituitary transplants and in situ pituitaries of grafted and control rats. The effects of dopamine (10^–8 or 10^–7 M) in this system were also examined. The extent of inhibition of prolactin release by dopamine was not related to the amounts of prolactin secreted under basal conditions or to plasma prolactin levels. LHRH significantly suppressed prolactin secretion in all groups but its effect was most pronounced in the ectopic pituitary transplants and in the hyperplastic pituitaries of animals after chronic exposure to estrogen followed by a period of recovery. Thus, the effects of LHRH on prolactin release appear to be related to the secretory activity and/or to the absolute or relative number of the lactotrophs.     

Preclinical risk assessment of drug-induced hypo- and hyperprolactinemia

Drug-induced changes in prolactin signaling may obscure interpretation of preclinical toxicological endpoints. However, with informed consideration, classic hallmarks of hypo-/hyperprolactinemia can be recognized in short- and long-term rodent bioassays. Findings can be supported and expanded with additional in vivo and in vitro datasets. When taken together with human epidemiological evidence pertaining to the consequences of drug-induced hypo-/hyperprolactinemia, such findings permit both an analysis of human relevance and an assessment of human risk.