Probable Hypothalamic Disorder Requiring Corticoid Therapy in Patients with Pituitary Adenoma or Craniopharyngioma

From findings in six patients with pituitary adenoma or craniopharyngioma correlations were sought between (a) radiological and other evidence of anatomical suprasellar or intrasellar disturbance and (b) clinical and laboratory indicators of pituitary function. Two patients with grossly enlarged sellae (most of the contents of the pituitary fossa had been removed in one) had essentially normal hypophyseal function. Two others with no sellar enlargement had disabling hypopituitarism. The need for corticoid therapy was not associated with impairment of (1) urine 17-hydroxycorticoid (17-OH) response to intravenous ACTH in two patients, (2) RAI uptake in two and (3) PBI in three. There was no 17-OH response to oral methopyrapone (750 mg. every four hours for six doses) in all four cases requiring corticoids for hypopituitarism. Four control subjects showed 17-OH levels of 12 to 18 mg. per day (twofold to threefold rises above baseline) on the day after methopyrapone was given. In no instance was the urine concentrating ability impaired remarkably. The suprasellar effects of such tumours are more often responsible for anterior pituitary deficiency than is generally recognized. Methopyrapone offers desirable sensitivity and specificity in the testing of pituitary function.     

Incidence of Pituitary Apoplexy and Its Risk Factors in Chinese People: A Database Study of Patients with Pituitary Adenoma

Background

There are few studies of the incidence and clinical characteristics of pituitary apoplexy (PA) in pituitary adenoma patients, and the findings have been inconsistent.

Objective

The aim of the study was to retrospectively assess the incidence, clinical presentation, surgical management and postoperative complications of PA in pituitary adenoma patients.

Methods

A database was specifically designed to collect clinical, therapeutic, prognostic and histological information about pituitary adenoma patients. Using multivariate logistic regression, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify associated factors.

Results

A total of 2021 pituitary adenoma patients were recruited. 97 (4.8%) patients had PA. The incidence of PA was 10.11% in patients with pituitary macroadenoma, and 0.36% in patients with microadenoma. Variables for the logistic regression model independently associated with PA were sex (male vs. female, OR = 2.54, 95% CI: 1.59~4.07), tumor type (negative staining vs. positive staining, OR = 2.04, 95% CI: 1.29~3.23), and tumor size (macroadenoma vs. microadenoma, OR = 26.46, 95% CI = 9.66~72.46). Headache, visual deterioration, and vomiting were the most common symptoms in patients with pituitary adenoma. Patients with and without PA had similar frequency of visual deterioration, head trauma, acromegalic appearance, galactorrhoea, cold intolerance and Cushingoid appearance, but headache, vomiting, ptosis, diplopia, fever and blindness were significantly more common in patients with PA. Pearson Chi-Square tests revealed a significant difference in surgical approach between patients with and without PA (95.88% vs. 85.57%, P = 0.01).

Conclusion

Our findings suggest that PA is not a rare event. Male sex, non-functioning tumor, and macroadenoma are associated with an increased risk of PA. Compared with pituitary adenoma patients without PA, patients with PA have more severe symptoms.     

Hyperprolactinemia in monkeys: Induction by an estrogen-progesterone synergy

To evaluate the synergistic effect of estrogens and progesterone on prolactin secretion, rhesus and cynomolgus monkeys in the early follicular phase received estradiol benzoate (100 μg/kg/day, sc) alone for 14 days, then in combination with progesterone (subcutaneous silastic capsule) for an additional 14 days. Blood was drawn daily by femoral venipuncture under ketamine hydrochloride anesthesia (15mg/kg). Similarly, this protocol for exogenous steroid treatment was employed in a monkey having a chronically indwelling (femoral insertion into the vena cava) cannula maintained by a vest and mobile tether apparatus; however, no anesthesia was used to obtain serum specimens. In addition, this assembly was applied to six monkeys to determine the acute effects of ketamine hydrochloride on prolactin secretion. Concentrations of prolactin, estradiol-17β, and progesterone in serum were determined by conventional radioimmunoassays. Under estrogen therapy alone, mean circulating prolactin levels declined from ~15 to < 5 ng/ml; in contrast, the addition of progesterone caused an abrupt serum prolactin elevation, ~8–12 fold. This estradiol-progesterone course led to sustained hyperprolactinemia in the chronically catheterized Monkey, whereas ketamine administration raised serum prolactin only briefly, the elevation lasting less than three hours after injection. These findings establish that an estrogen-progesterone synergy, separate from the transient effects of ketamine, Induced hyperprolactinemia in cycling monkeys having prevailing levels of estrogen and progesterone near those characteristic of late gestation, when sustained prolactin elevations are observed normally.     

MiR-26a在人垂体腺瘤组织及血清中表达的研究

目的：miRNA遍及生命体的发生、发育、分化和死亡的过程。它在肿瘤、心血管、糖尿病等多种疾病的各个阶段中起到调控癌基因作用。miRNA在垂体腺瘤中异常表达,且影响垂体腺瘤的增殖、侵袭及凋亡情况。本研究通过探讨miRNA家族中的miR-26a在垂体腺瘤组织及血清中的表达变化情况,为垂体瘤的早期诊断及疗效监测提供依据,以便更好的指导临床诊断及治疗工作。方法：收集哈尔滨医科大学附属第四医院微创神经外科手术切除并经病理证实的垂体腺瘤20例,取其组织及采集血清标本：年龄在20-74岁（平均50岁）,术前均未进行任何治疗。既往无内分泌疾病的正常死亡人的垂体组织及其血清标本20例作为对照组。采用实时定量聚合酶链式反应（Real-timePCR）方法分别检测垂体腺瘤病人和正常人组织及血清中的miRNA-26a的表达情况。用SPSSl3．0统计分析软件运用Mann—WhitneyU检验方法对数据进行统计学分析。结果：miRNA-26a在垂体腺瘤组织中的表达量为22．30,正常垂体组织中的表达量为23．38,垂体腺瘤患者血清中miRNA-26a的表达表达量为25．04,正常对照组血清中的表达量为24．95,垂体腺瘤组织中的表达较正常垂体组织中的表达明显升高（P〈0．05）,垂体腺瘤患者血清与正常人血清中miRNA-26a的表达无明显差异（P〉0．05）。结论：垂体腺瘤组织中miRNA-26a的高表达与血清学检测miRNA-26a的正常表达,为预防脑垂体腺瘤的发生和发展提供了重要的临床诊断依据。     

Hyperprolactinemia in chronic renal insufficiency: an interesting model of hypothalamo-hypophyseal dysfunction

It is note that hyperprolactinemia is frequently associated to chronic renal failure (CRF). The etiopathogenesis of this endocrine disorder is not clearly understood, trying to evaluate the possible hypothalamic-pituitary cause we have evaluated the Prl levels under some pharmacological tests: TRH (200 mcg i.v.),Domperidone (DOM)(10 mg i.v.),Nomifensine (NOM)(200 mg p.o.)and Bromocriptine (BRC)(2.5 mg p.o.) in 3 groups of patients: CRF(8 cases), dysfunctional (8 cases) and tumoral (9 cases) hyperPrl. Prl plasma levels have been evaluated by RIA (kits,Biodata,Roma). In patients affected by CRF either direct (BRC) than indirect (NOM) agonist acting dopaminergic drugs failed to induce a reduction in Prl plasma levels, like to tumoral patients for NOM, and in contrast to the significant decrease after BRC (-70%) in tumoral and (-74%) in dysfunctional and NOM (-50%) observed in dysfunctional patients. CRF and dysfunctional patients showed significant response to TRH and DOM, being prolactinoma bearing patients unresponsive to these tests. These results show an hyporesponsivity of pituitary Prl secreting cells to dopaminergic control suggesting the existence of central etiopathological factor in inducing hyperprolactinemia in CRF patients.     

Structural Differences Between Dopamine D2 Receptors Present in a Rat Pituitary Adenoma and in Transplantable Rat Pituitary Tumors 7315a and MtTW15

We have investigated the structure of dopamine (DA) D2 receptors present in an estrone-induced, prolactin (PRL)-secreting, DA-sensitive adenoma and in two PRL-secreting and DA-insensitive transplantable tumors 7315a and MtTW15, in order to identify better the anomalies present in DA-resistant lactotrophs. D2 receptors were found in both a high- and a low-affinity state in adenomatous lactotrophs as shown by displacement studies with the agonist N-propylnorapomorphine (NPA), but only in the low-affinity state in the two DA-resistant tumors. Treatment with the alkylating agent N-ethylmaleimide induced a disappearance of the high-affinity state of the D2 receptor in the adenoma and a reduction in receptor concentration, but did not have any effect on the affinity of receptors present in DA-resistant tumors. Moreover, target size analysis and radiation inactivation studies of D2 receptors, using membranes preincubated with NPA and [3H]spiperone as ligand or using [3H]NPA as ligand on membranes preparations, have shown the presence of distinct structural differences between adenomatous and tumoral D2 receptors and between the two tumoral receptors themselves; these results suggest that the normal functional unit of the D2 receptor is a dimer associated with a guanine nucleotide-binding protein (G protein) subunit and that tumoral D2 receptors may exist in various polymeric forms unassociated with G proteins. The anomalies found to be present in tumoral D2 receptor complexes may be responsible for the insensitivity of these tumors to dopaminergic agonists' inhibitory activity on PRL release and tumor growth.     

Seasonally Dependent Effect of Ectopic Pituitary Grafts on 24-Hour Rhythms in Serum Prolactin and Gonadotropins in Rats

To assess to what extent the presence of an ectopic pituitary differentially affected circulating prolactin (PRL) and gonadotropin levels at different times of the year, rats kept under 12h light, 12h dark (12:12 LD) photoperi-ods and receiving a pituitary graft or a sham operation in summer or winter were examined 3 months later. In both male and female sham-operated rats, a circadian variation in serum PRL levels was found, with an acrophase varying from 21:53h to 00:54h and the mesor and amplitude higher in spring than autumn in males and higher in autumn than in spring in females. After grafting a pituitary, changes in serum PRL related to time of day were no longer observed. In pituitary-grafted male rats killed during spring, serum PRL levels were higher than controls at only a few time points throughout the 24h cycle, whereas in rats killed during autumn, there were no significant differences in PRL levels between grafted and control rats. Pituitary-grafted female rats killed during spring showed serum PRL levels significantly higher than those of sham-operated rats, while in female rats killed in autumn, PRL levels of pituitary-grafted and sham-operated rats did not differ. Significant variations of luteinizing hormone (LH) related to time of day were found in sham-operated male rats only, with acrophases at 23:52h and 00:24h for spring and autumn, respectively, and the mesor and amplitude of the rhythm significantly higher in autumn. Pituitary transplants suppressed 24h variations in circulating LH and depressed its levels during the two seasons examined. As far as follicle-stimulating hormone (FSH), pituitary grafts decreased circulating levels, with the extent of decrease higher during autumn than in spring. The results indicate that some endocrine consequences of the grafting of an ectopic pituitary are dependent on time of year.     

Seasonally Dependent Effect of Ectopic Pituitary Grafts on 24-Hour Rhythms in Serum Prolactin and Gonadotropins in Rats

To assess to what extent the presence of an ectopic pituitary differentially affected circulating prolactin (PRL) and gonadotropin levels at different times of the year, rats kept under 12h light, 12h dark (12:12 LD) photoperi-ods and receiving a pituitary graft or a sham operation in summer or winter were examined 3 months later. In both male and female sham-operated rats, a circadian variation in serum PRL levels was found, with an acrophase varying from 21:53h to 00:54h and the mesor and amplitude higher in spring than autumn in males and higher in autumn than in spring in females. After grafting a pituitary, changes in serum PRL related to time of day were no longer observed. In pituitary-grafted male rats killed during spring, serum PRL levels were higher than controls at only a few time points throughout the 24h cycle, whereas in rats killed during autumn, there were no significant differences in PRL levels between grafted and control rats. Pituitary-grafted female rats killed during spring showed serum PRL levels significantly higher than those of sham-operated rats, while in female rats killed in autumn, PRL levels of pituitary-grafted and sham-operated rats did not differ. Significant variations of luteinizing hormone (LH) related to time of day were found in sham-operated male rats only, with acrophases at 23:52h and 00:24h for spring and autumn, respectively, and the mesor and amplitude of the rhythm significantly higher in autumn. Pituitary transplants suppressed 24h variations in circulating LH and depressed its levels during the two seasons examined. As far as follicle-stimulating hormone (FSH), pituitary grafts decreased circulating levels, with the extent of decrease higher during autumn than in spring. The results indicate that some endocrine consequences of the grafting of an ectopic pituitary are dependent on time of year.     

Hyperprolactinemia associated with chronic renal failure in the rat

Patients with CRF exhibit hyperprolactinemia and resistance to the prolactin-suppressive effects of dopamine. In order to explore the pathogenetic mechanisms involved, an animal model of CRF was developed in the adult male rat bearing an indwelling right atrial catheter by performing a two stage 5/6 nephrectomy (NX). Following NX, serum creatinine levels rose to a value of 1.36 +/- 0.2 mg/dl at 8 weeks as compared to sham-operated controls (0.31 +/- 0.1, P less than 0.01). There was a parallel increase in plasma prolactin levels in NX animals with values significantly greater than in controls by 8 weeks (49 +/- 11 vs 17 +/- 2 ng/ml, P less than 0.02). At 8 weeks, the plasma prolactin responses to metoclopramide (500 micrograms/kg, iv) were similar in unanesthetized NX and sham-operated control animals. The prolactin-suppressive effects of an iv dopamine infusion (6 micrograms/kg/min X 30 min) was also similar in the two groups (46 +/- 8% vs 40 +/- 10% suppression). The responses of lactotrophs in vitro were compared in NX and control animals at 8 weeks. Basal prolactin release during 4 h was similar in the two groups as were the suppressive responses to dopamine and bromocriptine. The results indicate that the rat with CRF, like human develops hyperprolactinemia. In contrast to the human, however, responses to dopaminergic agonists and antagonists in vivo and in vitro are unimpaired, indicating that hyperprolactinemia in rats with CRF occurs on a non-dopaminergic basis.     

Activity of the c-myc Replicator at an Ectopic Chromosomal Location

DNA replication starts at multiple discrete sites across the human chromosomal c-myc region, including two or more sites within 2.4 kb upstream of the c-myc gene. The corresponding 2.4-kb c-myc origin fragment confers autonomously replicating sequence (ARS) activity on plasmids, which specifically initiate replication in the origin fragment in vitro and in vivo. To test whether the region that displays plasmid replicator activity also acts as a chromosomal replicator, HeLa cell sublines that each contain a single copy of the Saccharomyces cerevisiae FLP recombinase target (FRT) sequence flanked by selectable markers were constructed. A clonal line containing a single unrearranged copy of the transduced c-myc origin was produced by cotransfecting a donor plasmid containing the 2.4-kb c-myc origin fragment and FRT, along with a plasmid expressing the yeast FLP recombinase, into cells containing a chromosomal FRT acceptor site. The amount of short nascent DNA strands at the chromosomal acceptor site was quantitated before and after targeted integration of the origin fragment. Competitive PCR quantitation showed that the c-myc origin construct substantially increased the amount of nascent DNA relative to that at the unoccupied acceptor site and to that after the insertion of non-myc DNA. The abundance of nascent strands was greatest close to the c-myc insert of the integrated donor plasmid, and significant increases in nascent strand abundance were observed at sites flanking the insertion. These results provide biochemical and genetic evidence for the existence of chromosomal replicators in metazoan cells and are consistent with the presence of chromosomal replicator activity in the 2.4-kb region of c-myc origin DNA.     

替莫唑胺在侵袭性垂体瘤及垂体腺癌中的治疗进展

替莫唑胺(TMZ)是一种口服二代咪唑并四嗪类具有抗肿瘤活性的烷化剂,通过对DNA鸟嘌呤的甲基化来干扰基因转录而诱导DNA损伤,目前是治疗恶性胶质瘤的一线化疗药物.最近有关于TMZ治疗侵袭性垂体腺瘤及垂体癌的报道,有效率分别为60％和69％,且未发生明显并发症.O6-甲基鸟嘌呤-DNA转移酶(MGMT)的表达水平与其疗效呈负相关,从而可能干扰其疗效,由于目前缺乏对垂体癌及侵袭性垂体瘤的有效治疗手段,所以不应否认TMZ对此类患者的治疗有效性.TMZ对侵袭性垂体瘤及垂体癌的治疗机制及有效性仍需进一步探索.     

Ectopic Darier's Disease of the Cervix: an Extraordinary Cause of an Abnormal Smear

A small number of skin diseases may involve either extremity of the alimentary tract or the vulva. Fortunately for patients and cytoscreeners, they rarely involve the cervix or vagina. When they do, difficulty in diagnosis may arise if a full history is not provided. A case is described of cervicovaginal Darier's disease, which presented with an abnormal cervical smear and led to a dermatological referral.
Un petit nombre de pathologies cutanées peuvent concerner une extrémité du tractus digestif ou la vulve. Heureusement pour les maladies et pour les cytotechniciens, ces affections touchent rarement le col ou le vagin. Lorsqu'elles le font, des difficultés diagnostiques peuvent exister si l'histoire clinique compléte n'est pas transmise. Ce travail décruit un cas de localisation cervico-vaginale de maladie de Darier, qui s'est présenté avec un frottis cervical anormal et qui à conduit a une consultation dermatologique.
Eine kleine Zahl von Hauterkrankungen befällt gelegentlich auch die Analregion und die Vulva. 1st dies der Fall kann bei Fehlen der Anamnese eine zytologische Beurteilung schwierig sein. Ein derartiger Fall, der ein dermatologisches Konzil crforderlich machte, wird vorgestellt.     

The TGL2 Gene of Saccharomyces cerevisiae Encodes an Active Acylglycerol Lipase Located in the Mitochondria

The Saccharomyces cerevisiae Tgl2 protein shows sequence homology to Pseudomonas triacylglycerol (TAG) lipases, but its role in the yeast lipid metabolism is not known. Using hemagglutinin-tagged Tgl2p purified from yeast, we report that this protein carries a significant lipolytic activity toward long-chain TAG. Importantly, mutant hemagglutinin-Tgl2p^S144A, which contains alanine 144 in place of serine 144 in the lipase consensus sequence (G/A)XSXG exhibits no such activity. Although cellular TAG hydrolysis is reduced in the tgl2 deletion mutant, overproduction of Tgl2p in this mutant leads to an increase in TAG degradation in the presence of fatty acid synthesis inhibitor cerulenin, but that of Tgl2p^S144A does not. This result demonstrates the lipolytic function of Tgl2p in yeast. Although other yeast TAG lipases are localized to lipid particles, Tgl2p is enriched in the mitochondria. The mitochondrial fraction purified from the TGL2-overexpressing yeast shows a strong lipolytic activity, which was absent in the tgl2 deletion mutant. Therefore, we conclude that Tgl2p is a functional lipase of the yeast mitochondria. By analyzing phenotypic effects of TGL2-deficient yeast, we also find that lipolysis-competent Tgl2p is required for the viability of cells treated with antimitotic drug. The addition of oleic acid, the product of Tgl2p-catalyzed lipolysis, fully complements the antimitotic drug sensitivity of the tgl2 null mutation. Thus, we propose that the mitochondrial Tgl2p-dependent lipolysis is crucial for the survival of cells under antimitotic drug treatment.     

Ectopic expression of an activated RAC in Arabidopsis disrupts membrane cycling

Rho GTPases regulate the actin cytoskeleton, exocytosis, endocytosis, and other signaling cascades. Rhos are subdivided into four subfamilies designated Rho, Racs, Cdc42, and a plant-specific group designated RACs/Rops. This research demonstrates that ectopic expression of a constitutive active Arabidopsis RAC, AtRAC10, disrupts actin cytoskeleton organization and membrane cycling. We created transgenic plants expressing either wild-type or constitutive active AtRAC10 fused to the green fluorescent protein. The activated AtRAC10 induced deformation of root hairs and leaf epidermal cells and was primarily localized in Triton X-100-insoluble fractions of the plasma membrane. Actin cytoskeleton reorganization was revealed by creating double transgenic plants expressing activated AtRAC10 and the actin marker YFP-Talin. Plants were further analyzed by membrane staining with N-[3-triethylammoniumpropyl]-4-[p-diethylaminophenylhexatrienyl] pyridinium dibromide (FM4-64) under different treatments, including the protein trafficking inhibitor brefeldin A or the actin-depolymeryzing agents latrunculin-B (Lat-B) and cytochalasin-D (CD). After drug treatments, activated AtRAC10 did not accumulate in brefeldin A compartments, but rather reduced their number and colocalized with FM4-64-labeled membranes in large intracellular vesicles. Furthermore, endocytosis was compromised in root hairs of activated AtRAC10 transgenic plants. FM4-64 was endocytosed in nontransgenic root hairs treated with the actin-stabilizing drug jasplakinolide. These findings suggest complex regulation of membrane cycling by plant RACs.     

Ectopic testes in the Norway rat

Animals with ectopic testes, some unilateral (on either the right or left side) and some bilateral, have appeared in a colony of King-Holtzman rats. This heritable defect has been given the genetic symbol "ect." Females carrying the gene are unaffected by it. When such females are bred to apparently normal males, they produce no ect offspring. Since 25% of their F2 generation carry the gene, it is assumed it is autosomal recessive. Studies involving selective breeding for males with ectopic testes indicate that some males have genomes resistant to the expression of the ect gene and that the apparent thresholds essential to left side, right side, and bilateral expression appear to be a secondary control of the multifactorial type.