Combined effects of vasoactive intestinal peptide and dopamine on adenylate cyclase in prolactin-secreting cells

VIP stimulates adenylate cyclase activity of male and female rat anterior pituitaries and human prolactinomas, while dopamine inhibits the enzyme activity of female rat pituitaries and prolactinomas. A dopamine inhibited cyclase can be detected also in male rats provided the enzyme activity is increased by VIP. The analysis of the dose-response curves for one agent (VIP or dopamine) in the absence or in the presence of the other indicates that the two agents exhibit a different pattern of interaction in the different systems. In fact, in female rat pituitaries and in human prolactinomas, the curves for dopamine±VIP and for VIP±dopamine were parallel, indicating that the two agents exherted their effects independently from one another. On the contrary, in male rat pituitaries, the curves were definitively non parallel, that is, the inhibitory effect of dopamine was greatly amplified by VIP. In no case was the apparent affinity (EC₅₀) of one agent modified by the presence of the other. It is concluded that two different modes of interaction between stimulatory and inhibitory neurohormones might exist at the level of adenylate cyclase from anterior pituitary cells.     

Global analysis of gene expression in the estrogen induced pituitary tumor of the F344 rat

The F344 rat rapidly forms large prolactinomas in response to chronic estrogen treatment. To identify genes expressed in the course of this estrogen induced pituitary tumor growth, we performed microarray analysis on the F344 rat pituitary after chronic estrogen treatment and on untreated controls. At a significance level set to minimize type I error, some 72 genes were found to be differentially expressed between estrogen treated and untreated. Of those genes, 70 have not been reported previously as being affected by estrogen in the F344 rat pituitary. Since many other investigators have studied the effect of estrogen on specific gene expression in rat pituitary, we also examined the mRNA expression of the 36 genes that have been previously reported as having their expression affected by estrogen in the rat pituitary. Of these, 13 were found to have their expression affected by estrogen treatment in the same direction as had been reported by others.     

Evolución del microprolactinoma a largo plazo con tratamiento médico

IntroductionProlactinoma is the most frequent functioning pituitary adenoma. Most commonly occurs as microprolactinoma (less than 1 cm in size), which may be cured with medical therapy, but few long-term studies are available about optimal duration of treatment with dopamine agonists to ensure cure after drug discontinuation and its withdrawal without recurrence are do not report consistent results.ObjectiveTo establish criteria for cure of microprolactinoma with medical treatment and to analyze the potential predictors involved.PatientsA retrospective study was conducted on 47 adult women with microprolactinoma followed up between 1975 and 2010; none of them had undergone prior surgery or radiotherapy, and all of them received treatment with a dopamine agonist for at least 4 years. They were divided into two groups for analysis: cured patients with at least 4 years with normal prolactin levels after drug discontinuation, and not cured patients.ResultsCure was achieved in 57.4% of patients. Only age at diagnosis was a significant predictor: there were more young patients in the cured group and youngest patients needed less time to cure. Development of empty sella turcica or normal MRI were similar regarding time to cure.ConclusionsMicroprolactinoma may be cured with dopamine agonists, and life-long treatment is not required, although more than 10 years may be required to achieve cure, 11,6 ± 5,3 years in our experience.     

Role of vasoactive intestinal polypeptide (VIP) in regulating the pituitary function in man

Intramuscular injection of synthetic VIP (200 micrograms) resulted in a rapid increase in plasma prolactin (PRL) concentrations in normal women, which was accompanied by the 4- to 7-fold increase in plasma VIP levels. Mean (+/- SE) peak values of plasma PRL obtained 15 min after the injection of VIP were higher than those of saline control (28.1 +/- 6.7 ng/ml vs. 11.4 +/- 1.6 ng/ml, p less than 0.05). Plasma growth hormone (GH) and cortisol levels were not affected by VIP in normal subjects. VIP injection raised plasma PRL levels (greater than 120% of the basal value) in all of 5 patients with prolactinoma. In 3 of 8 acromegalic patients, plasma GH was increased (greater than 150% of the basal value) by VIP injection. In the in vitro experiments, VIP (10(-8), 10(-7) and 10(-6) M) stimulated PRL release in a dose-related manner from the superfused pituitary adenoma cells obtained from two patients with prolactinoma. VIP-induced GH release from the superfused pituitary adenoma cells was also shown in 5 out of 6 acromegalic patients. VIP concentrations in the CSF were increased in most patients with hyperprolactinemia and a few cases with acromegaly. These findings indicate that VIP may play a role in regulating PRL secretion in man and may affect GH secretion from pituitary adenoma in acromegaly.     

Genetically modified mouse models addressing gonadotropin function

The development of genetically modified animals has been useful to understand the mechanisms involved in the regulation of the gonadotropin function. It is well known that alterations in the secretion of a single hormone is capable of producing profound reproductive abnormalities. Human chorionic gonadotropin (hCG) is a glycoprotein hormone normally secreted by the human placenta, and structurally and functionally it is related to pituitary LH. LH and hCG bind to the same LH/hCG receptor, and hCG is often used as an analog of LH to boost gonadotropin action. There are many physiological and pathological conditions where LH/hCG levels and actions are elevated. In order to understand how elevated LH/hCG levels may impact on the hypothalamic–pituitary–gonadal axis we have developed a transgenic mouse model with chronic hCG hypersecretion. Female mice develop many gonadal and extragonadal phenotypes including obesity, infertility, hyperprolactinemia, and pituitary and mammary gland tumors. This article summarizes recent findings on the mechanisms involved in pituitary gland tumorigenesis and hyperprolactinemia in the female mice hypersecreting hCG, in particular the relationship of progesterone with the hyperprolactinemic condition of the model. In addition, we describe the role of hyperprolactinemia as the main cause of infertility and the phenotypic abnormalities in these mice, and the use of dopamine agonists bromocriptine and cabergoline to normalize these conditions.     

17－β－雌二醇诱发SD大鼠催乳素瘤形成过程中催乳素基因的表达

给ＳＤ大鼠皮下埋植内含１７－β－雌二醇硅橡胶管３０、６０、１２０天后，发现大鼠垂体重量随给药时间延长呈持续性增加；用放射免疫法测定血浆催乳素（ｐｒｏｌａｃｔｉｎ，ＰＲＬ）含量，亦明显依次升高；用Ｎｏｒｔｈｅｒｎ印迹杂交方法检测垂体细胞中ＰＲＬ基因，发现ＰＲＬｍＲＮＡ含量也依次有显著增加，但其增加却远低于血浆ＰＲＬ含量的增加，提示１７－β－雌二醇除了促进ＰＲＬ基因的转录外，还可能增加ＰＲＬｍＲＮＡ的翻译效率。     

血清泌乳素水平对泌乳素瘤患者的临床价值研究

目的:分析术前血清泌乳素水平对泌乳素瘤患者的临床价值。方法:选择2011年1月至2016年12月于青岛大学附属医院行垂体腺瘤切除术且术前测得泌乳素(prolactin,PRL)水平、术后行病理免疫组化染色的垂体腺瘤164例,通过Spearman相关分析PRL水平与肿瘤大小的相关性,通过Kappa值判断PRL水平与病理诊断的一致性。采用ROC曲线获得PRL水平最佳临床诊断临界值。结果:(1)164例垂体瘤患者中,病理诊断单激素PRL瘤25例,主要表现为男性性功能低下及头痛、头晕,女性月经紊乱、闭经、泌乳;(2)术前PRL水平与年龄、性别无显著相关性(P均0.05),与肿瘤大小呈中度正相关(r=0.530,P0.05);(3)以正常范围上限值(23.3 ng/m L)为基线,分别以PRL23.3 ng/mL(1倍)、46.6 ng/m L(2倍)、69.9 ng/ml(3倍)、100 ng/mL、150 ng/m L、200 ng/mL为诊断标准,与病理免疫组化的一致性分析显示PRL69.9ng/m L作为诊断标准时符合率和Kappa系数最高,分别为82.3%和0.533;(4)以病理免疫组化作为诊断金标准作泌乳素瘤ROC曲线,以血清PRL为69.785 ng/m L作为诊断标准时,曲线下面积最大,此时符合率和Kappa系数分别为82.3%和0.553,灵敏度49.1%,特异度98.3%。结论:泌乳素瘤血清学诊断与病理免疫组化诊断一致性较高,血清PRL水平69.9 ng/mL(3倍于正常上限值)是诊断泌乳素瘤的最佳参考值。