Role of prolactin in modulating the effects of tamoxifen on growth of the Dunning R3327 rat prostate adenocarcinoma

Tamoxifen (TAM) has previously been shown to inhibit growth of the Dunning R3327 rat prostate adenocarcinoma and to elevate serum prolactin levels. The purpose of this study was to determine the role of prolactin in modulating the effects of tamoxifen on growth of the R3327 prostatic adenocarcinoma. Intact and castrated Copenhagen-Fischer male rats bearing the Dunning R3327 rat prostatic tumor were divided into groups and injected sc five times per week for 16 weeks as follows: vehicle; TAM (0.5 mg/kg); haloperidol (HALO; 0.5 mg/kg); bromocriptine (CB-154; 5 mg/kg); TAM plus HALO; or TAM plus CB-154. In both intact and castrated rats, agents that either raised (HALO) or lowered (CB-154) serum prolactin had little effect on prostatic tumor growth when administered singly. In intact rats, average tumor diameter in vehicle-treated controls increased 421% 16 weeks after the start of the experiment, and treatment with TAM or TAM plus HALO reduced this tumor growth by approximately one-half. Interestingly, CB-154 administered in combination with TAM completely blocked TAM inhibition of tumor growth in intact rats. In contrast to these results in intact rats, average tumor diameter increased 129% in TAM- and 118% in TAM plus HALO-treated castrated rats and was significantly greater than the characteristic retardation of tumor growth (49% increase) that occurred in the vehicle-treated castrate controls. In addition, combined treatment of TAM plus CB-154 in castrate rats resulted in an even greater increase (188%) in average tumor diameter. The inhibitory effect of TAM on R3327 prostatic tumor growth in intact rats appears to be an indirect effect resulting from its ability to reduce serum testosterone levels. In contrast, the stimulatory effect of TAM in castrate rats appears to result directly from an estrogen-like action, which can directly enhance prostatic tumor growth in the presence of low levels of circulating androgens; this stimulatory effect of TAM is more pronounced when prolactin levels are suppressed by CB-154. Clearly, castration alone is more effective than TAM therapy alone or in combination with castration in the retardation of the growth of the androgen-dependent R3327 prostatic tumor in rats.     

溴隐亭治疗垂体腺瘤23例临床观察

对ＣＴ或ＭＲＩ确诊的垂体腺瘤２３例分析表明，垂体微腺瘤和巨腺瘤血清泌乳素（也称催乳素）分别为１１７．７５±８６．５５和２６８．７３±１２５．５μｇ／Ｌ，两组差别有显著性意义（Ｐ＜００１）；经溴麦角隐亭（简称嗅隐亭）治疗后６０ｄ，两组泌乳素水平显著降低，分别为２３．６９±８．７４和８５．６２±２７．３５μｇ／Ｌ（Ｐ＜０．００１），而且巨腺瘤组血清睾酮也由３．４３±１．４９降至２．６９±１．２３ｎｍｏｌ／Ｌ（Ｐ＜００５），两组妊娠率无统计学差异。资料提示，血清泌乳素水平可用于垂体腺瘤的诊断及治疗效果评价，较大剂量的溴隐亭可降低血清睾酮。     

女性高催乳素血症48例临床分析

目的 探讨高催乳素血症患者的病因、临床特点、诊断方法及治疗.方法 回顾性分析近两年在西安交通大学医学院第一附属医院妇产科生殖内分泌门诊及研究室就诊的48例女性高催乳素血症患者的临床资料.结果 48例高催乳素血症患者中,垂体微腺瘤22例,巨腺瘤1例,空蝶鞍综合征2例,原发性甲状腺功能减低2例,多囊卵巢综合征5例,药物因素所致3例,特发性高催乳素血症13例;1例巨腺瘤应用伽玛刀后加溴隐亭治疗,2例原发性甲状腺功能减低补充甲状腺激素,5例多囊卵巢综合征患者用二甲双胍加安体舒通治疗,余40例均服用溴隐亭治疗;41例血清催乳素降至正常范围,14例溢乳明显减少,8例溢乳停止,21例月经恢复正常,16例B超监测有排卵并获妊娠,4例分娩正常婴儿.结论 高催乳素血症是育龄期妇女不孕症的主要原因之一,而垂体催乳素腺瘤是女性高催乳素血症的最常见原因,其治疗针对病因处理,除垂体大腺瘤神经压迫症状需手术治疗外,溴隐亭是治疗高催乳素血症首选的安全且有效的药物.     

高催乳素血症与不孕的探讨

作对４０例高催乳素血症患引起不孕的原因进行了探讨，发现高催乳素血症患基础体温、经前子宫内膜活检及黄体期孕酮测定均提示黄体功能不全，是导致高催乳素血症患不孕的主要原因，经溴隐亭后，催乳素下降，基础体温黄体期正常，黄体期孕酮水平明显提高，４０例中１８例受孕，作还对溴隐亭治疗后分娩的１５例小孩作了体格和染色体检查，未发现异常，似可说明溴隐亭治疗是安全的，它不仅可用于高催乳素血症患，也可用于治     

In Vitro Method of Studying the Site of Action of Bromocryptine on Hypothalamus-Pituitary-Testis Function in Rats

The effects of bromocryptine, a specific dopaminergic agonist, were studied in vitro on the system comprising the hypothalamic tissue, the collagenase-digested, isolated anterior pituitary cells, and the Leydig cells, by measuring the testosterone production of the Leydig cells.
The in vitro testosterone production and the HCG sensitivity of the isolated Leydig cells decreased in the presence of 10^-5 M bromocryptine, whereas 10^-8–10^-6 M concentrations were ineffective. However, bromocryptine in concentrations of 10^-7–10^-6 M inhibited the isolated adenohypophyseal cell-induced stimulation of the Leydig cells. The same inhibitory effect of bromocryptine was observed when the stimulation of the pituitary cell – Leydig cell system was induced by LHRH or hypothalamic tissue in vitro . Bromocryptine in a concentration of 10^-6 M did not alter the LHRH content and release of the hypothalamus measured by radioimmunoassay in the hypothalamic tissue and in the medium after an in vitro incubation.
The results suggest an inhibitory effect of bromocryptine on the pituitarytestis axis by acting on the pituitary and testis levels in the in vitro system studied.     

Norepinephrine content in the paraventicular nucleus of the hypothalamus as a function of photoperiod and dopaminergic tone

The decline in the release of various anterior pituitary hormones, particularly prolactin (PRL), as a result of exposure to inhibitory, short-day photoperiods in long-day breeders is a well-documented phenomenon. This alteration in the hypothalamic-hypophyseal-gonadal axis is largely controlled by changes in the duration of the nocturnal melatonin pulse secreted by the pineal gland. Increased duration of melatonin secretion serves to increase the inhibitory activity of the tuberoinfundibular dopaminergic (TIDA) neurons, which in turn suppress PRL release and synthesis. However, other hypothalamic factors also appear to stimulate anterior pituitary function, working in concert with changes in TIDA activity to modulate circulating PRL levels under different photoperiod conditions. Past work from this laboratory has suggested that neurochemical changes at the level of the hypothalamic paraventricular nuclei (PVN), particularly changes in norepinephrine (NE) activity, may represent one of these modulatory influences. The current study investigated potential alterations in NF, content within the PVN during the early stages of short-day exposure in Siberian hamsters. In addition, the interaction of NE content with the modulatory dopamine (DA) system was investigated via administration of a DA agonist (CB154) or antagonist (pimozide). Hamsters received CB 154 (500 μg), pimozide (45 μg), or control solution via the drinking water under either long days (16L:8D) or short days (10L:14D), and were sacrificed at 1, 3, or 5 wk of photoperiod and drug treatment. The brains were removed, and the PVN microdissected from the hypothalamus and analyzed for catecholamine content using high-pressure liquid chromatography with electrochemical detection (HPLC-EC). The results revealed the expected stimulation of circulating PRL under both photoperiods following pimozide administration, as well as the expected trend toward an accelerated suppression of PRL under short days induced by CB 154. For control animals, there were no changes in NE content, or the ratio of 3-methoxy-4-hydroxyphenyglycol (MHPG)/NE in long-day exposed animalx, but for short-day animals, both NE content and the ratio of MHPG/NE declined over time. Administration of CB 154 had only a marginal effect on NE content and the ratio of MHPG/NE, but pimozide administration resulted in a decline in NE content and an increase in the MHPG/NE ratio under short days, and an increase in NE content and the MHPG/NE ratio over time for long-day animals. These results suggest that both photoperiod and administration of a DA antagonist that increases circulating PRL levels induce alterations in NE terminal activity within the hypothalamic PVN.     

Diagnosis and management of prolactinomas

Prolactin secreting tumors account for ten to twenty percent of all intracranial lesions. The patients harboring these tumors present with amenorrhea, galactorrhea, other ovulatory disorders, infertility, delays in puberty and mixed polyendocrinopathy. These tumors are diagnosed by the measurement of serum prolactin levels, Goldmann-Bowl perimetry, and either computed axial tomography or magnetic resonance imaging. Protein secreting tumors are usually benign lesions and historically have been treated by partial or total hypophysectomy or radiation therapy. Surgical resection of the lesion often is followed by recurrence and administration of proton beam radiation therapy results in the development of a panhypopituitary state. Growth of pituitary tumors is controlled with the administration of dopamine agonists such as bromocriptine and prospective studies have suggested that these drugs are now the preferred method of treatment for primary lesions and recurrences.Department of Obstetrics and Gynecology University of Alabama at Birmingham     

Expression of prolactin receptors in rat reproductive tissues during periovulatory prolactin imbalance

Indirect immunoperoxidase technique in combination with cytophotometry showed that prolactin imbalance in the periovulatory period is characterized by considerable changes in the expression of prolactin receptors in uterine glands and endometrial stroma (but not in the myometrium) and in the pituitary gland and hypothalamus, while receptor compartmentalization pattern remaines unchanged. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 6, pp. 712–716, June, 2000