Pituitary transcription factor Prop-1 stimulates porcine pituitary glycoprotein hormone alpha subunit gene expression.

PubMed

Sato, Takanobu; Kitahara, Kousuke; Susa, Takao; Kato, Takako; Kato, Yukio

2006-10-01

Recently, we have reported that a Prophet of Pit-1 homeodomain factor, Prop-1, is a novel transcription factor for the porcine follicle-stimulating hormone beta subunit (FSHbeta) gene. This study subsequently aimed to examine the role of Prop-1 in the gene expression of two other porcine gonadotropin subunits, pituitary glycoprotein hormone alpha subunit (alphaGSU), and luteinizing hormone beta subunit (LHbeta). A series of deletion mutants of the porcine alphaGSU (up to -1059 bp) and LHbeta (up to -1277 bp) promoters were constructed in the reporter vector, fused with the secreted alkaline phosphatase gene (pSEAP2-Basic). Transient transfection studies using GH3 cells were carried out to estimate the activation of the porcine alphaGSU and LHbeta promoters by Prop-1, which was found to activate the alphaGSU promoter of -1059/+12 bp up to 11.7-fold but not the LHbeta promoter. Electrophoretic mobility shift assay and DNase I footprinting analysis revealed that Prop-1 binds to six positions, -1038/-1026, -942/-928, -495/-479, -338/-326, -153/-146, and -131/-124 bp, that comprise the A/T cluster. Oligonucleotides of six Prop-1 binding sites were directly connected to the minimum promoter of alphaGSU, fused in the pSEAP2-Basic vector, followed by transfecting GH3 cells to determine the cis-acting activity. Finally, we concluded that at least five Prop-1 binding sites are the cis-acting elements for alphaGSU gene expression. The present results revealed a notable feature of the proximal region, where three Prop-1-binding sites are close to and/or overlap the pituitary glycoprotein hormone basal element, GATA-binding element, and junctional regulatory element. To our knowledge, this is the first demonstration of the role of Prop-1 in the regulation of alphaGSU gene expression. These results, taken together with our previous finding that Prop-1 is a transcription factor for FSHbeta gene, confirm that Prop-1 modulates the synthesis of FSH at the transcriptional level. On

Pituitary Microsomal Autoantibodies in Patients with Childhood-Onset Combined Pituitary Hormone Deficiency: an Antigen Identification Attempt.

PubMed

Ziemnicka, Katarzyna; Gut, Paweł; Gołąb, Monika; Dworacki, Grzegorz; Wrotkowska, Elżbieta; Stajgis, Marek; Katulska, Katarzyna; Rabska-Pietrzak, Barbara; Obara-Moszyńska, Monika; Niedziela, Marek; Budny, Bartłomiej; Kałużna, Małgorzata; Waśko, Ryszard; Ruchała, Marek

2016-12-01

The role of autoimmunization in the pathogenesis of pituitary disorders is poorly understood. The presence of pituitary autoantibodies (APA) has been detected in various pituitary disorders. Their role, however, remains elusive. Childhood-onset combined pituitary hormone deficiency (CPHD) may be caused by environmental or genetic factors. In some of patients, causes of the disease remain unclear and contributions of autoimmune processes have been postulated. The aim of this study was to identify the microsomes-derived pituitary antigens (MPA) as potential immunogenic autoantigens in patients with hypopituitarism, therefore 62 CPHD patients, 100 healthy controls and five autoimmune polyglandular syndrome type II (APS II) patients were included in the study. The clinical evaluation included hormonal tests and magnetic resonance imaging of the pituitary. The sources of MPA were pituitary glands taken from autopsies. Isolated MPA were then separated on SDS-PAGE gel and incubated with sera obtained from patients and controls. Microsomal APA were detected using Western blot and radioimmunological method. In all CPHD and APS II patients and in 9 % individuals from control group marked immunoreactivity was detected against MPA. Antibodies showed high affinity to 67, 60, 50 and 36 kDa MPAs. Since the identified autoantigens were of unknown nature, an in silico exploration of UniProt database was applied and indicated their possible relationship with chaperones, golgins and already known autoantigens like GAD67. Reactivity against MPA indicates that these proteins certainly play a role in the processes undergoing within pituitary of CPHD patients. The identification and further detailed studies on their role in the pathogenesis of CPHD should be continued.

Successful Pregnancies After Adequate Hormonal Replacement in Patients With Combined Pituitary Hormone Deficiencies

PubMed Central

Bianchi, Paulo H. M.; Franca, Marcela M.; Otto, Aline P.; Rodrigues, Rodrigo J. M.; Ejzenberg, Dani; Serafini, Paulo C.; Baracat, Edmundo Chada; Francisco, Rossana P. V.; Brito, Vinicius N.; Arnhold, Ivo J. P.; Mendonca, Berenice B.

2017-01-01

Context: Women with hypopituitarism have lower pregnancy rates after ovulation induction. Associated pituitary hormone deficiencies might play a role in this poorer outcome. Objective: We evaluated fertility treatment and pregnancy outcomes in five women with childhood-onset combined pituitary hormone deficiencies (CPHD). Patients and Methods: Five women with CPHD were referred for fertility treatment after adequacy of hormone replacement was determined. Patients were subjected to controlled ovarian stimulation (COS) for timed intercourse, intrauterine insemination, or in vitro fertilization, according to the presence or absence of other infertility factors (male or tubal). Results: All women became pregnant. The number of COS attempts until pregnancy was achieved varied between 1 and 5. The duration of COS resulting in at least one dominant follicle varied between 9 and 28 days, and total gonadotropin consumed varied between 1200 and 3450 IU. Two patients with severely suppressed basal gonadotropin levels since an early age had a cancelled COS cycle. All pregnancies were singleton except one (monochorionic twin gestation). The gestational ages at birth ranged from 35 weeks to 39 weeks and 4 days; three patients underwent cesarean section, and two had vaginal deliveries. Only one newborn was small for gestational age (delivered at 35 weeks). Conclusion: Adequate hormonal replacement prior to ovarian stimulation resulted in successful pregnancies in patients with childhood-onset CPHD, indicating that hormone replacement, including growth hormone, is an important step prior to fertility treatments in these patients. PMID:29264457

Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone.

PubMed

Sen, Orhan; Ertorer, M Eda; Aydin, M Volkan; Erdogan, Bulent; Altinors, Nur; Zorludemir, Suzan; Guvener, Nilgun

2005-04-01

Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

In vivo correlation between c-Fos expression and corticotroph stimulation by adrenocorticotrophic hormone secretagogues in rat anterior pituitary gland.

PubMed

Takigami, Shu; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

2008-03-01

In the anterior pituitary gland, c-Fos expression is evoked by various stimuli. However, whether c-Fos expression is directly related to the stimulation of anterior pituitary cells by hypothalamic secretagogues is unclear. To confirm whether the reception of hormone-releasing stimuli evokes c-Fos expression in anterior pituitary cells, we have examined c-Fos expression of anterior pituitary glands in rats administered with synthetic corticotrophin-releasing hormone (CRH) intravenously or subjected to restraint stress. Single intravenous administration of CRH increases the number of c-Fos-expressing cells, and this number does not change even if the dose is increased. Double-immunostaining has revealed that most of the c-Fos-expressing cells contain adrenocorticotrophic hormone (ACTH); corticotrophs that do not express c-Fos in response to CRH have also been found. However, restraint stress evokes c-Fos expression in most of the corticotrophs and in a partial population of lactotrophs. These results suggest that c-Fos expression increases in corticotrophs stimulated by ACTH secretagogues, including CRH. Furthermore, we have found restricted numbers of corticotrophs expressing c-Fos in response to CRH. Although the mechanism underlying the different responses to CRH is not apparent, c-Fos is probably a useful immunohistochemical marker for corticotrophs stimulated by ACTH secretagogues.

Ghrelin-stimulation test in the diagnosis of canine pituitary dwarfism.

PubMed

Bhatti, S F M; De Vliegher, S P; Mol, J A; Van Ham, L M L; Kooistra, H S

2006-08-01

This study investigated whether ghrelin, a potent releaser of growth hormone (GH) secretion, is a valuable tool in the diagnosis of canine pituitary dwarfism. The effect of intravenous administration of ghrelin on the release of GH and other adenohypophyseal hormones was investigated in German shepherd dogs with congenital combined pituitary hormone deficiency and in healthy Beagles. Analysis of the maximal increment (i.e. difference between pre- and maximal post-ghrelin plasma hormone concentration) indicated that the GH response was significantly lower in the dwarf dogs compared with the healthy dogs. In none of the pituitary dwarfs, the ghrelin-induced plasma GH concentration exceeded 5 microg/l at any time. However, this was also true for 3 healthy dogs. In all dogs, ghrelin administration did not affect the plasma concentrations of ACTH, cortisol, TSH, LH and PRL . Thus, while a ghrelin-induced plasma GH concentration above 5 microg/l excludes GH deficiency, false-negative results may occur.

Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Xenopus Metamorphosis

EPA Science Inventory

Serum thyroid hormone (TH) concentrations in anuran larvae rise rapidly during metamorphosis. Such a rise in an adult anuran would inevitably trigger a negative feedback response resulting in decreased synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary....

Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency.

PubMed

Fofanova, O V; Takamura, N; Kinoshita, E; Yoshimoto, M; Tsuji, Y; Peterkova, V A; Evgrafov, O V; Dedov, I I; Goncharov, N P; Yamashita, S

1998-06-05

To ascertain the molecular background of combined pituitary hormone deficiency, screening for mutations in the pituitary-specific transcription factor (Pit-1/GHF-1) gene (PIT1) was performed on a cohort of 15 children from Russia with combined growth hormone (GH)/prolactin (Prl)/thyroid-stimulating hormone (TSH) deficiency. The group of patients, suspected of PIT1 mutations, consisted of four familial cases (seven patients) and eight sporadic cases. All had complete GH deficiency and complete or partial Prl and TSH deficiency. Direct sequencing of all six exons of PIT1 and its promoter region showed a C to T transition mutation at codon 14 of exon 1 in a 3 8/12-year-old girl. This novel PIT1 mutation results in a proline to leucine substitution (P14L). The patient was heterozygous for mutant and normal alleles. The heterozygous P14L mutation was also present in her mother as well as in her maternal aunt and grandmother, all of whom were phenotypically normal. There was no mutation in the father's DNA, suggesting the need for reevaluation of genomic imprinting. In other children of our series, no mutation in PIT1 or in its promotor region was identified. This is the first report on the analysis of PIT1 and its promoter region in Russian children with GH/Prl/TSH deficiency. However, as the involvement of PIT1 mutation is rare in Russia, the other negative cases need to be analyzed for another candidate gene responsible for combined GH/Pr/TSH deficiency.

Infrasellar pituitary gangliocytoma causing Cushing's syndrome.

PubMed

Domingue, Marie-Eve; Marbaix, Etienne; Do Rego, Jean-Luc; Col, Vincent; Raftopoulos, Christian; Duprez, Thierry; Vaudry, Hubert; Maiter, Dominique

2015-10-01

Pituitary gangliocytomas are uncommon neuronal tumours that may present with endocrine disorders, the most frequent being acromegaly caused by growth hormone hypersecretion. Cushing's syndrome is very rarely seen with gangliocytomas. We report the unique case of a 62 year-old woman whose clinical picture and endocrine testing clearly demonstrated adrenocorticotropin (ACTH)-dependent Cushing's syndrome. Pituitary magnetic resonance imaging showed a 12-mm homogeneous, infra- and retrosellar mass first diagnosed as pituitary macroadenoma. Transsphenoidal surgery was performed and allowed complete resection of the tumour with sparing of normal anterior pituitary. Very low postoperative serum cortisol and ACTH levels were observed in the early postoperative period and the patient is still in remission 18 months after surgery, thus demonstrating that the resected lesion was entirely responsible for the clinical picture. Histological and immunocytochemical analyses demonstrated a benign tumour composed of mature neuronal cells suggestive of a gangliocytoma, expressing both ACTH and corticotropin-releasing hormone (CRH). The tumour was surrounded by a rim of pituitary tissue containing ACTH-producing endocrine cells. Careful analysis of the resected lesion did not reveal any pituitary microadenoma. We search literature for similar cases and retraced only nine cases of gangliocytomas associated with Cushing's syndrome. In most of them, the tumour was combined with either pituitary corticotroph adenoma or hyperplasia. Our case represents a unique case of an infrasellar pituitary gangliocytoma which was able to cause Cushing's syndrome by both direct ACTH production and CRH-induced stimulation of neighbour normal corticotroph cells.

Long-term follow-up of combined pituitary hormone deficiency in two siblings with a Prophet of Pit-1 gene mutation.

PubMed

Georgopoulos, Neoklis A; Katsikis, Ilias; Giamalis, Petros; Koika, Vasiliki; Adonakis, George; Kourtis, Anargyros; Kourounis, George; Panidis, Dimitrios

2006-12-01

Combined pituitary hormone deficiency (CPHD) is a rare disorder resulting from an impaired pituitary function due to different causes, characterized by impaired secretion of growth hormone (GH) and one or more of the other anterior pituitary hormones. To date, 16 distinct human Prophet of Pit-1 (Prop1) gene mutations have been identified in patients with CPHD, inducing a phenotype involving GH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and thyroid-stimulating hormone (TSH), and rarely adrenocorticotropic hormone, deficiency. Herein we present two siblings of different sexes from a family with parental consanguinity presenting the 301-302delAG mutation in the Prop1 gene. The female presented failure of growth from the age of 6 years and was treated for 10 years with GH, ending in a final height (standard deviation score) of -0.28. TSH deficiency was manifested after the initiation of GH and was treated with thyroxine while puberty was initiated with conjugated estrogens. The male presented TSH deficiency since childhood, treated with thyroxine, and growth failure at the age of 14 years, treated for a period of 2 years with GH. Puberty was initiated with increasing doses of testosterone, while human chorionic gonadotropin was added in order to achieve increased testicular volume. In conclusion, these two siblings of different sexes with CPHD carrying the 301-302delAG mutation in the Prop1 gene presented a variable phenotype characterized by GH, TSH, LH and FSH deficiency.

Leptin Stimulates Prolactin mRNA Expression in the Goldfish Pituitary through a Combination of the PI3K/Akt/mTOR, MKK3/6/p38MAPK and MEK1/2/ERK1/2 Signalling Pathways.

PubMed

Yan, Aifen; Chen, Yanfeng; Chen, Shuang; Li, Shuisheng; Zhang, Yong; Jia, Jirong; Yu, Hui; Liu, Lian; Liu, Fang; Hu, Chaoqun; Tang, Dongsheng; Chen, Ting

2017-12-20

Leptin actions at the pituitary level have been extensively investigated in mammalian species, but remain insufficiently characterized in lower vertebrates, especially in teleost fish. Prolactin (PRL) is a pituitary hormone of central importance to osmoregulation in fish. Using goldfish as a model, we examined the global and brain-pituitary distribution of a leptin receptor (lepR) and examined the relationship between expression of lepR and major pituitary hormones in different pituitary regions. The effects of recombinant goldfish leptin-AI and leptin-AII on PRL mRNA expression in the pituitary were further analysed, and the mechanisms underlying signal transduction for leptin-induced PRL expression were determined by pharmacological approaches. Our results showed that goldfish lepR is abundantly expressed in the brain-pituitary regions, with highly overlapping PRL transcripts within the pituitary. Recombinant goldfish leptin-AI and leptin-AII proteins could stimulate PRL mRNA expression in dose- and time-dependent manners in the goldfish pituitary, by both intraperitoneal injection and primary cell incubation approaches. Moreover, the PI3K/Akt/mTOR, MKK 3/6 /p 38 MAPK, and MEK 1/2 /ERK 1/2 -but not JAK2/STAT 1, 3 and 5 cascades-were involved in leptin-induced PRL mRNA expression in the goldfish pituitary.

Combined effects of androgen anabolic steroids and physical activity on the hypothalamic-pituitary-gonadal axis.

PubMed

Hengevoss, Jonas; Piechotta, Marion; Müller, Dennis; Hanft, Fabian; Parr, Maria Kristina; Schänzer, Wilhelm; Diel, Patrick

2015-06-01

Analysing effects of pharmaceutical substances and training on feedback mechanisms of the hypothalamic-pituitary-gonadal axis may be helpful to quantify the benefit of strategies preventing loss of muscle mass, and in the fight against doping. In this study we analysed combined effects of anabolic steroids and training on the hypothalamic-pituitary-gonadal axis. Therefore intact male Wistar rats were dose-dependently treated with metandienone, estradienedione and the selective androgen receptor modulator (SARM) S-1. In serum cortisol, testosterone, 17β-estradiol (E2), prolactin, inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Insulin-like growth factor 1 (IGF-1), and thyroxine (T4) concentrations were determined. Six human volunteers were single treated with 1-androstenedione. In addition abusing and clean body builders were analysed. Serum concentrations of inhibin B, IGF-1, cortisol, prolactin, T4, thyroid-stimulating hormone (TSH), testosterone and LH were determined. In rats, administration of metandienone, estradienedione and S-1 resulted in an increase of muscle fiber diameter. Metandienone and estradienedione but not S-1 administration significantly decreases LH and inhibin B serum concentration. Administration of estradienedione resulted in an increase of E2 and S-1 in an increase of cortisol. Single administration of 1-androstenedione in humans decreased cortisol and inhibin B serum concentrations. LH was not affected. In abusing body builders a significantly decrease of LH, TSH and inhibin B and an increase of prolactin, IGF-1 and T4 was detected. In clean body builders only T4 and TSH were affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Progression from isolated growth hormone deficiency to combined pituitary hormone deficiency.

PubMed

Cerbone, Manuela; Dattani, Mehul T

2017-12-01

Growth hormone deficiency (GHD) can present at any time of life from the neonatal period to adulthood, as a result of congenital or acquired insults. It can present as an isolated problem (IGHD) or in combination with other pituitary hormone deficiencies (CPHD). Pituitary deficits can evolve at any time from GHD diagnosis. The number, severity and timing of occurrence of additional endocrinopathies are highly variable. The risk of progression from IGHD to CPHD in children varies depending on the etiology (idiopathic vs organic). The highest risk is displayed by children with abnormalities in the Hypothalamo-Pituitary (H-P) region. Heterogeneous data have been reported on the type and timing of onset of additional pituitary hormone deficits, with TSH deficiency being most frequent and Diabetes Insipidus the least frequent additional deficit in the majority, but not all, of the studies. ACTH deficiency may gradually evolve at any time during follow-up in children or adults with childhood onset IGHD, particularly (but not only) in presence of H-P abnormalities and/or TSH deficiency. Hence there is a need in these patients for lifelong monitoring for ACTH deficiency. GH treatment unmasks central hypothyroidism mainly in patients with organic GHD, but all patients starting GH should have their thyroid function monitored closely. Main risk factors for development of CPHD include organic etiology, H-P abnormalities (in particular pituitary stalk abnormalities, empty sella and ectopic posterior pituitary), midline brain (corpus callosum) and optic nerves abnormalities, genetic defects and longer duration of follow-up. The current available evidence supports longstanding recommendations for the need, in all patients diagnosed with IGHD, of a careful and indefinite follow-up for additional pituitary hormone deficiencies. Copyright © 2017 Elsevier Ltd. All rights reserved.

A primer on pituitary injury for the obstetrician gynecologist: Simmond's disease, Sheehan's Syndrome, traumatic injury, Dahan's Syndrome, pituitary apoplexy and lymphocytic hypophysitis.

PubMed

Dahan, Michael H; Tan, Seang L

2017-04-01

The pituitary gland plays a critical role in reproduction. In response to the hypothalamus the anterior pituitary secretes prolactin, thyroid-stimulating hormone, adreno-corticotropic hormone, follicle-stimulating hormone, luteinizing hormone and growth hormone. Dysregulation in these hormones often lead to reproductive failure. Multiple mechanisms of pituitary injury exist. Simmond's disease is atrophy or destruction of the anterior lobe of the pituitary gland resulting in hypopituitarism. Sheehan's syndrome is post-partum pituitary injury due to massive hemorrhage. Traumatic injury resulting in hemorrhage in a non-pregnancy state can also cause partial or complete pituitary failure. Dahan's syndrome is pituitary injury due to severe vasospasm, without significant hemorrhage. Pituitary apoplexy is infarction of a pituitary adenoma and intra-mass hemorrhage with result injury to hormone production by the gland. Lymphocytic infiltration is the most common cause of hypophysitis and the mechanism is often unknown, although it may be autoimmune-related. The mechanism and treatments of each of these pathologies will be discussed in a context of reproduction.

Combined pituitary hormone deficiency (CPHD) due to a complete PROP1 deletion.

PubMed

Abrão, M G; Leite, M V; Carvalho, L R; Billerbeck, A E C; Nishi, M Y; Barbosa, A S; Martin, R M; Arnhold, I J P; Mendonca, B B

2006-09-01

PROP1 mutations are the most common cause of genetic combined pituitary hormone deficiency (CPHD). The aim of this study was to investigate the PROP1 gene in two siblings with CPHD. Pituitary function and imaging assessment and molecular analysis of PROP1. Two siblings, born to consanguineous parents, presented with GH deficiency associated with other pituitary hormone deficiencies (TSH, PRL and gonadotrophins). The male sibling also had an evolving cortisol deficiency. Pituitary size was evaluated by magnetic resonance imaging (MRI). PROP1 gene analysis was performed by polymerase chain reaction (PCR), automatic sequencing and Southern blotting. Amplification of sequence tag sites (STS) and the Q8N6H0 gene flanking PROP1 were performed to define the extension of PROP1 deletion. MRI revealed a hypoplastic anterior pituitary in the girl at 14 years and pituitary enlargement in the boy at 18 years. The PROP1 gene failed to amplify in both siblings, whereas other genes were amplified. Southern blotting analysis revealed the PROP1 band in the controls and confirmed complete PROP1 deletion in both siblings. The extension of the deletion was 18.4 kb. The region flanking PROP1 contains several Alu core sequences that might have facilitated stem-loop-mediated excision of PROP1. We report here a complete deletion of PROP1 in two siblings with CPHD phenotype.

[Effects of electroacupuncture with branch-foundation acupoint combination on the pituitary-target gland axis in aging rats with yang deficiency].

PubMed

Hao, Qing; Wu, Song; Liu, Jian-min; Wang, Hua

2014-10-01

To observe the effects of electroacupuncture (EA) with branch-foundation acupoint combination on the indices regarding pituitary-target gland axis in aging rats with yang deficiency, so as to explore its regulating mechanism on aging rats with yang deficiency. Forty healthy Sprague-Dawley female rats were randomly divided into a normal control group, a model group, an EA group and an EA control group, 10 rats in each group. Except the normal control group, the rats in the rest 3 groups were all treated with subcutaneous injection of D-galactose for 40 d, followed by intramuscular injection of hydrocortisone for 7 d to establish aging model with yang deficiency. After the successful establishment of model, the EA group was treated with EA at "Guanyuan" (CV 4), "Housanli" (ST 36) and "Baihui "(GV 20) while the EA control group was treated with EA at "Zhongji" (CV 3) "Yinlingquan" (SP 9) and "Yintang" (GV 29); the rats in the normal control group and model group were immobilized and fixed during the same time period. The treatments were given 6 times per week totally for 4 weeks. With radiation immunity analysis method, the 8 biological indices of pituitary-target gland axis, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), tetraiodothyronine-4 (T4), adrenocorticotropic hormone (ACTH), corticosterone (CORT), estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were detected to observe the changes of their content. Compared with the normal control group, the serum level of TSH, T3, T4 and E2 were reduced in the model group (P<0.05, P< 0.01) while those of ACTH, CORT, FSH and LH were increased (P<0.05, P<0.01). Compared with the model group, the serum level of TSH, T3, T4 and E2 were increased in the EA group (P<0.05, P<0.01) while those of ACTH, CORT, FSH and LH were significantly reduced (P<0.05, P<0.01). Compared with the EA control group, the content of TSH was increased in the EA group without statistical significance

Plurihormonal cells of normal anterior pituitary: Facts and conclusions

PubMed Central

Mitrofanova, Lubov B.; Konovalov, Petr V.; Krylova, Julia S.; Polyakova, Victoria O.; Kvetnoy, Igor M.

2017-01-01

Introduction plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. Objective To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. Materials and methods We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. Results We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Conclusion Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment. PMID:28418929

Prolactin gene expression in the pituitary of rats subjected to vaginocervical stimulation requires Erk-1/2 signaling.

PubMed

Reuquen, Patricia; Guajardo-Correa, Emanuel; Oróstica, María L; Curotto, Constanza; Parada-Bustamante, Alexis; Cardenas, Hugo; Orihuela, Pedro A

2017-12-01

Vaginocervical stimulation (VCS) induces twice-daily prolactin (PRL) surges resulting in pseudopregnancy in the rat. Furthermore, activation of the extracellular signal-regulated kinase-1/2 (Erk-1/2) is involved in the effect of estradiol (E 2 ) on the Prl gene expression in pituitary cells. Herein, we investigated whether Erk-1/2 signaling is involved in the control of Prl expression in the pituitary of VCS rats and whether VCS regulates the effect of E 2 on Erk-1/2 and Prl in the pituitary. Estrous rats were assigned as control or VCS groups and 0, 6, 12 or 24h later the levels and localization of phosphorylated Erk-1/2 (p-Erk-1/2) were analyzed in the pituitary. The effect of an Erk-1/2 inhibitor PD98059 on the Prl level in the pituitary of control or VCS rats was also analyzed. Other control or VCS rats were treated with E 2 and the level of p-Erk-1/2 and Prl were measured in the pituitary. In control rats, p-Erk-1/2 decreased at 6 and 12h and increased at 24h while Erk-1/2 was phosphorylated at all time points in VCS rats. p-Erk-1/2 was localized only in the anterior pituitary. PD98059 decreased Prl level in VCS, but not in control rats. Estradiol decreased Erk-1/2 phosphorylation although did not change Prl level in the pituitary of control or VCS rats. These findings show that prolonged activation of Erk-1/2 is necessary to induce Prl expression in the pituitary of VCS rats; however, VCS does not influence the role of E 2 on the activation of Erk-1/2 and Prl expression the pituitary. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Genetic causes of isolated and combined pituitary hormone deficiency.

PubMed

Giordano, Mara

2016-12-01

Research over the last 20 years has led to the elucidation of the genetic aetiologies of Isolated Growth Hormone Deficiency (IGHD) and Combined Pituitary Hormone Deficiency (CPHD). The pituitary plays a central role in growth regulation, coordinating the multitude of central and peripheral signals to maintain the body's internal balance. Naturally occurring mutation in humans and in mice have demonstrated a role for several factors in the aetiology of IGHD/CPHD. Mutations in the GH1 and GHRHR genes shed light on the phenotype and pathogenesis of IGHD whereas mutations in transcription factors such as HESX1, PROP1, POU1F1, LHX3, LHX4, GLI2 and SOX3 contributed to the understanding of CPHD. Depending upon the expression patterns of these molecules, the phenotype may consist of isolated hypopituitarism, or more complex disorders such as septo-optic dysplasia (SOD) and holoprosencephaly. Although numerous monogenic causes of growth disorders have been identified, most of the patients with IGHD/CPHD remain with an explained aetiology as shown by the relatively low mutation detection rate. The introduction of novel diagnostic approaches is now leading to the disclosure of novel genetic causes in disorders characterized by pituitary hormone defects. Copyright © 2016. Published by Elsevier Ltd.

[Clinical values of triptorelin stimulating test in assessing hypothalamus-pituitary-gonad axis function in male patients with hypothalamus-pituitary-gonad axis disorders].

PubMed

Wu, Xue-yan; Nie, Min; Lu, Shuang-yu; Mao, Jiang-feng

2011-03-15

To investigate the clinical values of luteinizing hormone-releasing hormone (LHRH) α (triptorelin) stimulating test in the differential diagnoses of hypothalamus-pituitary-gonad axis (HPGA) disorders. A total of 229 male patients with various HPGA disorders were recruited for triptorelin stimulating test. And all patients were followed up for 12 - 48 months until a definite diagnosis was made. The values of triptorelin stimulating test in the differential diagnoses of HPGA disorders were assessed by examining the close relationship between LHmax and the final clinical diagnosis. (1) LH levels rose steady after an intramuscular injection of triptorelin 100 µg and the time of LHmax appeared at 45 - 60 min. (2) LHmax < 4 U/L indicated the function of HPGA was not activated. LHmax in the range of 4 - 12 U/L indicated the patients might have constitutional delayed puberty development. LHmax > 12 U/L indicated the fulfilled puberty development. Triptorelin stimulating test can precisely evaluate the functions of HPGA in various HPGA disorders and provide valuable information for the differential diagnoses in constitutional delayed puberty development, hypogonadotropic hypogonadism, central and peripheral precocious puberty disorders.

Purinergic receptor ligands stimulate pro-opiomelanocortin gene expression in AtT-20 pituitary corticotroph cells.

PubMed

Zhao, L-F; Iwasaki, Y; Oki, Y; Tsugita, M; Taguchi, T; Nishiyama, M; Takao, T; Kambayashi, M; Hashimoto, K

2006-04-01

Although recent studies have suggested that purinergic receptors are expressed in the anterior pituitary gland, their involvement in the regulation of pituitary hormone gene expression is not completely understood. In the present study, we examined the expression of purinergic receptors and the effects of purinergic receptor ligands on pro-opiomelanocortin (POMC) gene expression, in AtT20 mouse corticotroph cells. We identified the expression of most of the purinergic receptor subtypes (A1, A2, P2X1, 3-7, P2Y1, 2, 4) mRNAs, analysed by the reverse transcriptase-polymerase chain reaction. We also found that adenosine and ATP, two representative and endogenous agonists of A1-3 and P2X/P2Y receptors, respectively, stimulated the 5'-promoter activity of the POMC gene in a dose- and time-related manner. When these ligands were simultaneously used with corticotrophin-releasing hormone (CRH), effects that were more than additive were observed, suggesting an enhancing role of these compounds in CRH-mediated adrenocorticotrophic hormone (ACTH) synthesis. These ligands also stimulated the expression of transcription factors involved in the regulation of the POMC gene, but did not enhance ACTH secretion. Finally, the positive effect of adenosine as well as CRH was completely inhibited by the protein kinase A inhibitor H89, whereas that of ATP was not influenced, indicating that different intracellular signalling pathways mediate these effects. Altogether, our results suggest a stimulatory role for these purinergic receptor ligands in the regulation of POMC gene expression in corticotroph cells. Because adenosine and ATP are known to be produced within the pituitary gland, it is possible they may be acting in an autocrine/paracrine fashion.

Gene analysis of PROP1 in dwarfism with combined pituitary hormone deficiency.

PubMed

Takamura, N; Fofanova, O V; Kinoshita, E; Yamashita, S

1999-06-01

The prophet of Pit-1 gene (PROP1), a novel pituitary-specific homeodomain factor, has been proved to be one of the causative genes for combined pituitary hormone deficiency (CPHD). Recently, PROP1 mutations have been identified in CPHD families, including our Russian cohort. The 2-bp deletion, 296delGA (A301G302del), is the most common mutational hot spot. Furthermore, in our cohort, PROP1 mutations are more common in comparison with human POU1F1 gene mutations. Here we review the gene analysis of PROP1 in patients with CPHD.

Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation

PubMed Central

Asakura, Yumi; Muroya, Koji; Hanakawa, Junko; Sato, Takeshi; Aida, Noriko; Narumi, Satoshi; Hasegawa, Tomonobu; Adachi, Masanori

2015-01-01

Abstract Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic nerve malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient’s mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD. PMID:25678757

Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation.

PubMed

Asakura, Yumi; Muroya, Koji; Hanakawa, Junko; Sato, Takeshi; Aida, Noriko; Narumi, Satoshi; Hasegawa, Tomonobu; Adachi, Masanori

2015-01-01

Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic nerve malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient's mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD.

Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

PubMed

Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

2010-06-01

To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Stimulation of growth hormone secretion from seabream pituitary cells in primary culture by growth hormone secretagogues is independent of growth hormone transcription.

PubMed

Chan, C B; Fung, C K; Fung, Wendy; Tse, Margaret C L; Cheng, Christopher H K

2004-10-01

The action of a number of growth hormone secretagogues (GHS) on growth hormone (GH) secretion and gene expression was studied in a primary culture of pituitary cells isolated from the black seabream Acanthopagrus schlegeli. The peptide GHS employed included growth hormone-releasing peptide (GHRP)-2, ipamorelin, and human ghrelin. The nonpeptide GHS employed included the benzolactam GHS L692,585 and the spiropiperidine GHS L163,540. Secreted GH was measured in the culture medium by an enzyme-linked immunosorbent assay (ELISA) method using a specific antibody against seabream GH. The GH mRNA content in the incubated cells was assessed by reverse transcription polymerase chain reaction (RT-PCR) using a pair of gene-specific primers designed from the cloned black seabream GH cDNA sequence. A dose-dependent stimulation of GH release was demonstrated by all the GHS tested, except human ghrelin, with EC(50) values in the nanomolar range. Simultaneous measurement of GH mRNA levels in the incubated seabream pituitary cells indicated that the GHS-stimulated increase in GH secretion was not paralleled by corresponding changes in GH gene expression. In contrast to the situation previously reported in the rat, no change in GH gene expression was noticed in the seabream pituitary cells even though the time of stimulation by GHS was increased up to 48 h, confirming that the GHS-stimulated GH secretion in seabream is independent of GH gene transcription.

Pituitary and ovarian hormone activity during the 7-day hormone-free interval of various combined oral contraceptive regimens.

PubMed

Cho, Michael; Atrio, Jessica; Lim, Aaron H; Azen, Colleen; Stanczyk, Frank Z

2014-07-01

The objective was to investigate changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) during the hormone-free interval (HFI) of 6 combined oral contraceptives (COCs). Blood samples were obtained from 62 women. When COCs were grouped by ethinyl estradiol (EE) dose, there was a significant positive mean slope for LH and FSH during the HFI for the 30- and 35 mcg-EE doses, whereas 20 showed a gradual nonsignificant slope. All E2 slopes were significant. P remained suppressed with all doses. A more rapid rebound of gonadotropin levels is found with higher doses of EE during the HFI. This study showed a more rapid rebound of pituitary hormone levels among women using higher-EE-dosage formulations, which was demonstrated by the statistically significant slope for mean LH and FSH from day 1 to day 7 of the HFI. The degree of suppression did not vary across progestin generations. It remains to be established whether women who experience side effects during their HFI may benefit from using a COC with a lower EE dose to minimize changes in endogenous pituitary hormone levels. Copyright © 2014 Elsevier Inc. All rights reserved.

Thyrotropin-producing pituitary adenoma simultaneously existing with Graves' disease: a case report.

PubMed

Arai, Nobuhiko; Inaba, Makoto; Ichijyo, Takamasa; Kagami, Hiroshi; Mine, Yutaka

2017-01-06

Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody. Her levels of serum thyroid-stimulating hormone, which ranged from low to normal in the presence of high levels of serum free thyroid hormones, were considered to be close to a state of syndrome of inappropriate secretion of thyroid-stimulating hormone. Magnetic resonance imaging showed a macropituitary tumor. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease was suspected. Initial therapy included anti-thyroid medication, which was immediately discontinued due to worsening symptoms. Subsequently, surgical therapy for the pituitary tumor was conducted, and her levels of free thyroid hormones, including the thyroid-stimulating hormone, became normal. On postoperative examination, her anti-thyroid-stimulating hormone receptor antibody levels decreased, and the anti-thyroglobulin antibody became negative. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease is rarely reported. The diagnosis of this condition is complicated, and the appropriate treatment strategy has not been clearly established. This case suggests that physicians should consider the coexistence of thyrotropin-producing pituitary adenoma with Graves' disease in cases in which thyroid-stimulating hormone values range from low to normal in the presence of thyrotoxicosis, and the surgical treatment of thyrotropin-producing pituitary adenoma could be the first-line therapy in patients with both thyrotropin-producing pituitary adenoma

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome.

PubMed

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Won Kyoung; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-03-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

Central hypogonadism due to a giant, "silent" FSH-secreting, atypical pituitary adenoma: effects of adenoma dissection and short-term Leydig cell stimulation by luteinizing hormone (LH) and human chorionic gonadotropin (hCG).

PubMed

Santi, Daniele; Spaggiari, Giorgia; Casarini, Livio; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Granata, Antonio R M; Carani, Cesare; Simoni, Manuela

2017-06-01

We present a case report of an atypical giant pituitary adenoma secreting follicle-stimulating hormone (FSH). A 55-year-old patient presented for erectile dysfunction, loss of libido and fatigue. The biochemical evaluation showed very high FSH serum levels in the presence of central hypogonadism. Neither testicular enlargement nor increased sperm count was observed, thus a secretion of FSH with reduced biological activity was supposed. The histological examination after neuro-surgery showed an atypical pituitary adenoma with FSH-positive cells. Hypogonadism persisted and semen analyses impaired until azoospermia in conjunction with the reduction in FSH levels suggesting that, at least in part, this gonadotropin should be biologically active. Thus, we hypothesized a concomitant primary testicular insufficiency. The patient underwent short-term treatment trials with low doses of either recombinant luteinizing hormone (LH) or human chorionic gonadotropin (hCG) in three consecutive treatment schemes, showing an equal efficacy in stimulating testosterone (T) increase. This is the first case of atypical, giant FSH-secreting pituitary adenoma with high FSH serum levels without signs of testicular hyperstimulation, in presence of hypogonadism with plausible combined primary and secondary etiology. Hypophysectomized patients may represent a good model to assess both pharmacodynamics and effective dose of LH and hCG in the male.

A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty

PubMed Central

Arroyo, Armando; Pernasetti, Flavia; Vasilyev, Vyacheslav V.; Amato, Paula; Yen, Samuel S. C.; Mellon, Pamela L.

2010-01-01

Summary We report a 28-year-old-female who presented with primary amenorrhoea, absence of puberty, obesity and normal stature. The subject was clearly short as a child, with a height more than 2 SD below normal until the age of 15 years. The pubertal growth spurt failed to develop. She continued growing at a prepubertal rate until growth ceased at the age of 20 years, reaching her final adult height of 157 cm (SDS −0.86) without hormonal treatment. A combined pituitary hormone stimulation test of anterior pituitary function showed deficiencies of GH, LH and FSH, and low normal serum levels of TSH and PRL. Magnetic resonance imaging revealed a hypoplastic pituitary with markedly reduced pituitary height. In addition, a whole body dual energy X-ray absorptiometry scan showed high levels of body fat (54%). Combined pituitary hormone deficiencies with a hypoplastic pituitary suggested the diagnosis of a Prophet of Pit-1 (PROP1) gene mutation. Normal stature in this case, however, confounded this diagnosis. Sequencing of PROP1 revealed homozygosity for a single base-pair substitution (C to T), resulting in the replacement of an Arg by a Cys at codon 120 (R120C) in the third helix of the homeodomain of the Prop-1 protein. To our knowledge, this is the first report of a patient with a mutation in the PROP1 gene that attained normal height without hormonal treatment, indicating a new variability in the PROP1 phenotype, with important implications for the diagnosis of these patients. We suggest that this can be explained by (i) the presence of low levels of GH in the circulation during childhood and adolescence; (ii) the lack of circulating oestrogen delaying epiphyseal fusion, resulting in growth beyond the period of normal growth; and (iii) fusion of the epiphyseal plates, possibly as a result of circulating oestrogens originating from peripheral conversion of androgens by adipose tissue. PMID:12153609

Antibodies to pituitary surface antigens during various pituitary disease states.

PubMed

Keda, Y M; Krjukova, I V; Ilovaiskaia, I A; Morozova, M S; Fofanova, O V; Babarina, M B; Marova, E I; Pankov, Y A; Kandror, V I

2002-11-01

Autoantibodies to cell surface antigens of human somatotropinoma (ASAS), human prolactinoma (ASAP) and rat adenohypophysis (ASARA) were assayed in the serum of patients with pituitary diseases associated with GH deficiency (GHD), such as pituitary dwarfism and primary empty sella syndrome (ESS), and in the serum of patients with hyperprolactinaemia of different etiologies: idiopathic hyperprolactinaemia, prolactinoma and ESS. The investigation was carried out with a cellular variant of an ELISA. Among children with GHD, the highest percentage of antibody-positive patients was found in the group with idiopathic isolated GHD (89% of ASAS(+) patients and 30% of ASARA(+) patients vs 33.3% and 0% respectively in the group with idiopathic combined pituitary hormone deficiency, and 33.3% and 9% in patients with pituitary hypoplasia associated with isolated GHD or combined pituitary hormone deficiency). Among hyperprolactinaemic patients, the highest ASAP and ASARA frequency was observed in patients with idiopathic hyperprolactinaemia (67.7% and 41.9% respectively) where it was twice as high as in the group of patients with prolactinoma. The proportion of ASAS(+) and ASARA(+) did not differ significantly between the groups of patients with ess with or without GHD. Similarly, there was no significant difference between the number of ESS ASAP(+) and ASARA(+) patients with or without hyperprolactinaemia. The data obtained suggested that autoimmune disorders may be primary, and responsible, at least in part, for pituitary dysfunction in the cases of idiopathic isolated GHD and idiopathic hyperprolactinaemia. At the same time, the autoimmune disorders in the patients with prolactinoma or ESS are probably secondary to the organic pituitary lesion and their significance in the development of the pituitary dysfunction is obscure.

Stages of Pituitary Tumors

MedlinePlus

... ACTH . A clinical trial of stereotactic radiation surgery . Growth Hormone–Producing Pituitary Tumors Treatment may include the ... Drug therapy to stop the tumor from making growth hormone . Thyroid-Stimulating Hormone–Producing Tumors Treatment may ...

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

PubMed Central

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-01-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD. PMID:28443260

A newborn with combined pituitary hormone deficiency developing shock and sludge.

PubMed

Ueda, Yasuhiro; Aoyagi, Hayato; Tajima, Toshihiro

2017-11-27

A male neonate was born at 41 weeks of gestation with a birth weight of 3320 g. Artificial respiratory management was required due to respiratory disturbance 1 h after birth, and subsequently catecholamine-refractory low cardiac output-induced shock occurred. Severe combined pituitary hormone deficiency (CPHD) was considered based on the presence of his respiratory disturbance, hypoglycemia and micropenis. After hydrocortisone (HDC) administration, circulatory dynamics rapidly improved. Brain magnetic resonance imaging (MRI) showed aplasia of the anterior pituitary gland and ectopic posterior gland. γ-Glutamyltranspeptidase (γ-GTP) increased from day 10 after birth and direct bilirubin increased from day 18. On ultrasonography, sludge filling the common bile duct and gall bladder was observed. After initiating treatment with both ursodeoxycholic acid and recombinant human growth hormone (rhGH), cholestasis improved and the sludge disappeared at 3 months after birth. In newborns with CPHD, severe central adrenal insufficiency might induce cardiogenic shock after birth. Early diagnosis and intervention are necessary.

Treatment Options for Pituitary Tumors

MedlinePlus

... ACTH . A clinical trial of stereotactic radiation surgery . Growth Hormone–Producing Pituitary Tumors Treatment may include the ... Drug therapy to stop the tumor from making growth hormone . Thyroid-Stimulating Hormone–Producing Tumors Treatment may ...

Treatment Option Overview (Pituitary Tumors)

MedlinePlus

... ACTH . A clinical trial of stereotactic radiation surgery . Growth Hormone–Producing Pituitary Tumors Treatment may include the ... Drug therapy to stop the tumor from making growth hormone . Thyroid-Stimulating Hormone–Producing Tumors Treatment may ...

T cell lymphoblastic lymphoma/leukemia within an adrenocorticotropic hormone and thyroid stimulating hormone positive pituitary adenoma: A cytohistological correlation emphasizing importance of intra-operative squash smear.

PubMed

Gupta, Rakesh K; Saran, Ravindra K; Srivastava, Arvind K; Jagetia, Anita; Garg, Lalit; Sharma, Mehar C

2017-08-01

We present a rare case of primary pituitary T cell lymphoma/leukemia (T-LBL) in association with adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) expressing pituitary adenoma in a 55-year-old woman highlighting the importance of intra-operative squash smears examination. The patient presented with complaints of headache, diminution of vision and recent onset altered sensorium. MRI revealed a mass lesion in the sellar-suprasellar region with non-visualization of pituitary gland separately, extending to involve adjacent structures diagnosed as invasive pituitary macroadenoma. Intra-operative tissue was sent for squash smear examination. The cytology showed a tumor comprising of sheets of immature lymphoid cells intermixed with clusters of pituitary acinar cells with many mitoses and tingible body macrophages. A diagnosis of presence of immature lymphoid cells within the pituitary was offered and differentials of infiltration by lymphoma cells from systemic disease versus primary central nervous lymphoma-like lymphoma arising in the pituitary adenoma were considered. Later paraffin section examination and immunohistochemistry corroborated with the squash findings and a final diagnosis of primary pituitary T cell lymphoma/leukemia in association with ACTH and TSH expressing pituitary adenoma was made. To date, only six cases of primary pituitary T cell lymphomas, including three T-LBL cases, have been reported. This is the seventh case and first one additionally describing cytohistological correlation and importance of intra-operative cytology. © 2017 Japanese Society of Neuropathology.

Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

PubMed

Mangupli, Ruth; Rostomyan, Liliya; Castermans, Emilie; Caberg, Jean-Hubert; Camperos, Paul; Krivoy, Jaime; Cuauro, Elvia; Bours, Vincent; Daly, Adrian F; Beckers, Albert

2016-10-01

Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.

Modification of hormonal secretion in clinically silent pituitary adenomas.

PubMed

Daems, Tania; Verhelst, Johan; Michotte, Alex; Abrams, Pascale; De Ridder, Dirk; Abs, Roger

2009-01-01

Silent pituitary adenomas are a subtype of adenomas characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression, although in some occasions enhanced or changed secretory activity can develop over time. Silent corticotroph adenomas are the classical example of this phenomenon. A series of about 500 pituitary adenomas seen over a period of 20 years were screened for modification in hormonal secretion. Biochemical and immunohistochemical data were reviewed. Two cases were retrieved, one silent somatotroph adenoma and one thyrotroph adenoma, both without specific clinical features or biochemical abnormalities, which presented 20 years after initial surgery with evidence of acromegaly and hyperthyroidism, respectively. While the acromegaly was controlled by a combination of somatostatin analogs and growth hormone (GH) receptor antagonist therapy, neurosurgery was necessary to manage the thyrotroph adenoma. Immunohistochemical examination demonstrated an increase in the number of thyroid stimulating hormone (TSH)-immunoreactive cells compared to the first tissue. Apparently, the mechanisms responsible for the secretory modifications are different, being a change in secretory capacity in the silent somatotroph adenoma and a quantitative change in the silent thyrotroph adenoma. These two cases, one somatotroph and one thyrotroph adenoma, are an illustration that clinically silent pituitary adenomas may in rare circumstances evolve over time and become active, as previously demonstrated in silent corticotroph adenomas.

Unilateral agenesis of internal carotid artery associated with congenital combined pituitary hormone deficiency and pituitary stalk interruption without HESX1, LHX4 or OTX2 mutation: a case report.

PubMed

Lamine, Faïza; Kanoun, Faouzi; Chihaoui, Melika; Saveanu, Alexandru; Menif, Emna; Barlier, Anne; Enjalbert, Alain; Brue, Thierry; Slimane, Hédia

2012-12-01

Agenesis of internal carotid artery (ICA) is an unusual finding in subjects with congenital Combined Pituitary hormone deficiency (CPHD) with only nine cases being reported to date but to our best knowledge none of them was genetically investigated. A 10-years old girl presented with severe growth failure (height 103 cm) with substantial bone age delay (3 years). She had no history of perinatal insults or familial CPHD. There was no evidence of mental retardation or craniofacial dysmorphism or ophtalmological abnormalities. She was first diagnosed with GH and TSH deficiency. Cerebral magnetic resonance imaging (MRI) showed hypoplastic anterior pituitary, flat sella turcica, absent pituitary stalk with ectopic posterior pituitary as well as agenesis of the left ICA and the left carotid canal. Genomic analysis of pituitary transcription factor HESX1, LHX4 and OTX2 showed no mutations. Treatment with GH and thyroxine was started. The patient remained free of neurovascular symptoms for 5 years but she presented at the age of 15 years with delayed puberty related to an evolving gonadotropin deficiency. ICA agenesis associated with CPHD is unusual and is often asymptomatic in children. Since the CPHD with pituitary stalk interruption cannot be due to HESX1, LHX4 or OTX2 mutation in our case, other pathogenetic mechanisms may be responsible for CPHD associated with unilateral ICA agenesis.

Luteinizing hormone-stimulated pituitary adenylate cyclase-activating polypeptide system and its role in progesterone production in human luteinized granulosa cells.

PubMed

Park, Hyun-Jeong; Choi, Bum-Chae; Song, Sang-Jin; Lee, Dong-Sik; Roh, Jaesook; Chun, Sang-Young

2010-01-01

The present study examined the gonadotropin regulation of pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP type I receptor (PAC(1)-R) expression, and its role in progesterone production in the human luteinized granulosa cells. The stimulation of both PACAP and PAC(1)-R mRNA levels by LH was detected using a competitive reverse transcription-polymerase chain reaction (RT-PCR). PACAP transcript was stimulated by LH reaching maximum levels at 12 hours in a dose dependent manner. LH treatment also stimulated PAC(1)-R mRNA levels within 24 hours. Addition of PACAP-38 (10(-7) M) as well as LH significantly stimulated progesterone production during 48 hours culture. Furthermore, co-treatment with PACAP antagonist partially inhibited LH-stimulated progesterone production. Treatment with vasoactive intestinal peptide, however, did not affect progesterone production. Taken together, the present study demonstrates that LH causes a transient stimulation of PACAP and PAC(1)-R expression and that PACAP stimulates progesterone production in the human luteinized granulosa cells, suggesting a possible role of PACAP as a local ovarian regulator in luteinization.

Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma.

PubMed

Berker, Dilek; Isik, Serhat; Aydin, Yusuf; Tutuncu, Yasemin; Akdemir, Gokhan; Ozcan, Hatice Nursun; Guler, Serdar

2011-01-01

Thyroid stimulating hormone (TSH) secreting pituitary adenomas are rare tumors manifested as hyperthyroidism with goiter in the presence of elevated TSH. We present a case with pituitary adenoma secreting both TSH and growth hormone (GH) with the prominent clinical findings of hyperthyroidism but without clinical findings of acromegaly. Pituitary magnetic resonance imaging revealed a macroadenoma. Transsphenoidal surgery was performed twice. The immunohistochemical staining showed that tumor cells were strongly reactive to GH and relatively mildly reactive to TSH. Control pituitary imaging revealed a residual macroadenoma, and long acting octreotide treatment was administered. After two years of the treatment, tumor size remained the same while thyroid function tests and insulin-like growth factor 1 (IGF-I) values returned to normal ranges. In conclusion, we always recommend hormonal examinations for all patients who have pituitary adenoma without signs and symptoms of acromegaly.

Hypopituitarism after stereotactic radiosurgery for pituitary adenomas.

PubMed

Xu, Zhiyuan; Lee Vance, Mary; Schlesinger, David; Sheehan, Jason P

2013-04-01

Studies of new-onset Gamma Knife stereotactic radiosurgery (SRS)-induced hypopituitarism in large cohort of pituitary adenoma patients with long-term follow-up are lacking. We investigated the outcomes of SRS for pituitary adenoma patients with regard to newly developed hypopituitarism. This was a retrospective review of patients treated with SRS at the University of Virginia between 1994 and 2006. A total of 262 patients with a pituitary adenoma treated with SRS were reviewed. Thorough endocrine assessment was performed immediately before SRS and in regular follow-ups. Assessment consisted of 24-hour urine free cortisol (patients with Cushing disease), serum adrenocorticotropic hormone, cortisol, follicle-stimulating hormone, luteinizing hormone, insulin-like growth factor-1, growth hormone, testosterone (men), prolactin, thyroid-stimulating hormone, and free T(4). Endocrine remission occurred in 144 of 199 patients with a functioning adenoma. Tumor control rate was 89%. Eighty patients experienced at least 1 axis of new-onset SRS-induced hypopituitarism. The new hypopituitarism rate was 30% based on endocrine follow-up ranging from 6 to 150 months; the actuarial rate of new pituitary hormone deficiency was 31.5% at 5 years after SRS. On univariate and multivariate analyses, variables regarding the increased risk of hypopituitarism included suprasellar extension and higher radiation dose to the tumor margin; there were no correlations among tumor volume, prior transsphenoidal adenomectomy, prior radiation therapy, and age at SRS. SRS provides an effective and safe treatment option for patients with a pituitary adenoma. Higher margin radiation dose to the adenoma and suprasellar extension were 2 independent predictors of SRS-induced hypopituitarism.

Relationship between pituitary stalk (PS) visibility and the severity of hormone deficiencies: PS interruption syndrome revisited.

PubMed

Wang, Weiqing; Wang, Shuwei; Jiang, Yiran; Yan, Fuhua; Su, Tingwei; Zhou, Weiwei; Jiang, Lei; Zhang, Yifei; Ning, Guang

2015-09-01

Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined pituitary hormone deficiency characterized by a triad shown in pituitary imaging, yet it has never been evaluated due to the visibility of pituitary stalk (PS) in imaging findings. The major objective of the study was to systematically describe the disease including clinical presentations, imaging findings and to estimate the severity of anterior pituitary hormone deficiency based on the visibility of the PS. This was a retrospective study including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS according to the findings on MRI, while the rest had a thin or intersected PS. Basic characteristics and hormonal status were compared. Of the 74 patients with PSIS, age at diagnosis was 25 (22-28) years. Absent pubertal development (97·3%) was the most common presenting symptom, followed by short stature. Insulin tolerance test (ITT) and gonadotrophin-releasing hormone (GnRH) stimulation test were used to evaluate the function of anterior pituitary. The prevalence of isolated deficiency in growth hormone (GH), gonadotrophins, corticotrophin and thyrotrophin were 100%, 97·2%, 88·2% and 70·3%, respectively. Although the ratio of each deficiency did not vary between patients with invisible PS and with visible PS, panhypopituitarism occurred significantly more frequent in patients with invisible PS. Patients with invisible PS had significantly lower levels of luteinizing hormone (LH), follicle stimulation hormone (FSH) and hormones from targeted glands including morning cortisol, 24-h urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and testosterone (T) in male than patients with visible PS. Moreover, patients with invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak cortisol in ITT while peak GH remained unchanged between two groups. The prevalence

Paraventricular Stimulation with Glutamate Elicits Bradycardia and Pituitary Responses

NASA Technical Reports Server (NTRS)

Darlington, Daniel N.; Miyamoto, Michael; Keil, Lanny C.; Dallman, Mary F.

1989-01-01

The excitatory neurotransmitter, L-glutamate (0.5 M, pH 7.4), or the organic acid, acetate (0.5 M, pH 7.4), was microinjected (50 nl over 2 min) directly into the paraventricular nuclei (PVN) of pentobarbital sodium-anesthetized rats while arterial blood pressure and heart rate and plasma adrenocorticotropic hormone (ACTH), vasopressin, and oxytocin were measured. Activation of PVN neurons with L-glutamate led to increases in plasma ACTH, vasopressin, and oxytocin and a profound bradycardia (-80 beats/min) with little change in arterial blood pressure. Microinjection of acetate had no effect on the above variables. The decrease in heart rate was shown to be dependent on the concentration of glutamate injected and the volume of injectate. The bradycardia was mediated through the autonomic nervous system because ganglionic blockade (pentolinium tartrate) eliminated the response; atropine and propranolol severely attenuated the bradycardia. The bradycardia was greatest when L-glutamate was microinjected into the caudal PVN. Injections into the rostral PVN or into nuclei surrounding the PVN led to small or nonsignificant decreases in heart rate. Focal electric stimulation (2-50 pA) of the PVN also led to decreases in heart rate and arterial blood pressure. These data suggest that activation of PVN neurons leads to the release of ACTH, vasopressin, and oxytocin from the pituitary and a bradycardia that is mediated by the autonomic nervous system.

Adrenocorticotropin-producing pituitary carcinoma with liver metastasis.

PubMed

Lormeau, B; Miossec, P; Sibony, M; Valensi, P; Attali, J R

1997-04-01

We report here the extremely rare case of a twenty-eight year-old woman with a metastatic ACTH-secreting pituitary carcinoma. This is the thirteenth case to be described in the literature. Ten years ago Cushing's disease was diagnosed. After pituitary surgery, then bilateral adrenalectomy, a Nelson's syndrome appeared. The particularly extensive pituitary secondary development led to several pituitary surgical procedures, radiotherapy, and octreotide treatment. Eight years after Cushing's disease was diagnosed, liver tumors were discovered. Pathological examination and ACTH immunostaining demonstrated the secretory nature of these metastases. The lack of ectopic tumor, the LPH/ACTH equimolar ratio and a study of the plasma proopiomelanocortin derivatives by HPLC showed that the ACTH secretion originated in pituitary tissues (in situ and liver metastases). The processing of POMC seems thus to be normal in this kind of tumor and metastases. Intact POMC levels were very high, indicating an aggressive tumor, and ACTH/LPH production was paradoxically stimulated by octreotide. This case is also exceptional because of the slow development of the disease, which may be due to the complementary hepatic chemoembolization treatment.

Identification of SLC20A1 and SLC15A4 among other genes as potential risk factors for combined pituitary hormone deficiency.

PubMed

Simm, Franziska; Griesbeck, Anne; Choukair, Daniela; Weiß, Birgit; Paramasivam, Nagarajan; Klammt, Jürgen; Schlesner, Matthias; Wiemann, Stefan; Martinez, Cristina; Hoffmann, Georg F; Pfäffle, Roland W; Bettendorf, Markus; Rappold, Gudrun A

2017-10-26

PurposeCombined pituitary hormone deficiency (CPHD) is characterized by a malformed or underdeveloped pituitary gland resulting in an impaired pituitary hormone secretion. Several transcription factors have been described in its etiology, but defects in known genes account for only a small proportion of cases.MethodsTo identify novel genetic causes for congenital hypopituitarism, we performed exome-sequencing studies on 10 patients with CPHD and their unaffected parents. Two candidate genes were sequenced in further 200 patients. Genotype data of known hypopituitary genes are reviewed.ResultsWe discovered 51 likely damaging variants in 38 genes; 12 of the 51 variants represent de novo events (24%); 11 of the 38 genes (29%) were present in the E12.5/E14.5 pituitary transcriptome. Targeted sequencing of two candidate genes, SLC20A1 and SLC15A4, of the solute carrier membrane transport protein family in 200 additional patients demonstrated two further variants predicted as damaging. We also found combinations of de novo (SLC20A1/SLC15A4) and transmitted variants (GLI2/LHX3) in the same individuals, leading to the full-blown CPHD phenotype.ConclusionThese data expand the pituitary target genes repertoire for diagnostics and further functional studies. Exome sequencing has identified a combination of rare variants in different genes that might explain incomplete penetrance in CPHD.Genetics in Medicine advance online publication, 26 October 2017; doi:10.1038/gim.2017.165.

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

PubMed

Sliutz, G; Speiser, P; Schultz, A M; Spona, J; Zeillinger, R

1993-05-01

In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

NASA Technical Reports Server (NTRS)

Gosselink, K. L.; Grindeland, R. E.; Roy, R. R.; Zhong, H.; Bigbee, A. J.; Grossman, E. J.; Edgerton, V. R.

1998-01-01

There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

Pituitary tumors. Current concepts in diagnosis and management.

PubMed Central

Aron, D C; Tyrrell, J B; Wilson, C B

1995-01-01

Diagnostic advances have resulted in earlier and more frequent recognition of pituitary tumors. Pituitary tumors cause problems owing to the hormones they secrete or the effects of an expanding sellar mass--hypopituitarism, visual field abnormalities, and neurologic deficits. Prolactin-secreting tumors (prolactinomas), which cause amenorrhea, galactorrhea, and hypogonadism, constitute the most common type of primary pituitary tumors, followed by growth hormone-secreting tumors, which cause acromegaly, and corticotropin-secreting tumors, which cause Cushing's syndrome. Hypersecretion of thyroid-stimulating hormone, the gonadotrophins, or alpha-subunits is unusual. Nonfunctional tumors currently represent only 10% of all clinically diagnosed pituitary adenomas, and some of these are alpha-subunit-secreting adenomas. Insights into the pathogenesis and biologic behavior of these usually benign tumors have been gained from genetic studies. We review some of the recent advances and salient features of the diagnosis and management of pituitary tumors, including biochemical and radiologic diagnosis, transsphenoidal surgery, radiation therapy, and medical therapy. Each type of lesion requires a comprehensive but individualized treatment approach, and regardless of the mode of therapy, careful follow-up is essential. Images PMID:7747500

A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve.

PubMed

Gorbenko Del Blanco, Darya; Romero, Christopher J; Diaczok, Daniel; de Graaff, Laura C G; Radovick, Sally; Hokken-Koelega, Anita C S

2012-09-01

Orthodenticle homolog 2 (OTX2) is a homeobox family transcription factor required for brain and eye formation. Various genetic alterations in OTX2 have been described, mostly in patients with severe ocular malformations. In order to expand the knowledge of the spectrum of OTX2 mutation, we performed OTX2 mutation screening in 92 patients with combined pituitary hormone deficiency (CPHD). We directly sequenced the coding regions and exon-intron boundaries of OTX2 in 92 CPHD patients from the Dutch HYPOPIT study in whom mutations in the classical CPHD genes PROP1, POU1F1, HESX1, LHX3, and LHX4 had been ruled out. Among 92 CPHD patients, we identified a novel heterozygous missense mutation c.401C>G (p.Pro134Arg) in a patient with CPHD, pituitary malformation, and an underdeveloped left optic nerve. Binding of both the wild-type and mutant OTX2 proteins to bicoid binding sites was equivalent; however, the mutant OTX2 exhibited decreased transactivation. We describe a novel missense heterozygous OTX2 mutation that acts as a dominant negative inhibitor of target gene expression in a patient with CPHD, pituitary malformation, and optic nerve hypoplasia. We provide an overview of all OTX2 mutations described till date, which show that OTX2 is a promising candidate gene for genetic screening of patients with CPHD or isolated GH deficiency (IGHD). As the majority of the OTX2 mutations found in patients with CPHD, IGHD, or short stature have been found in exon 5, we recommend starting mutational screening in those patients in exon 5 of the gene.

Frequency of mutations in PROP-1 gene in Turkish children with combined pituitary hormone deficiency.

PubMed

Kandemir, Nurgün; Vurallı, Doğuş; Taşkıran, Ekim; Gönç, Nazlı; Özön, Alev; Alikaşifoğlu, Ayfer; Yılmaz, Engin

2012-01-01

Mutations in the prophet of Pit-1 (PROP-1) gene are responsible for most of the cases of combined pituitary hormone deficiencies (CPHD). We performed this study to determine the prevalence of PROP-1 mutations in a group of Turkish children with CPHD. Fifty-three children with the diagnosis of CPHD were included in this study. Clinical data were obtained from medical files, and hormonal evaluation and genetic screening for PROP-1 mutations were performed. A homozygous S109X mutation was found in the second exon in two brothers, and they had growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies and normal prolactin levels. In the third exon of the PROP-1 gene, a heterozygous A142T polymorphism was found in 14 patients and a homozygous A142T polymorphism was found in 3 patients. In the first exon, a homozygous A9A polymorphism was found in 7 patients and a heterozygous A9A polymorphism was found in 31 patients. We assumed that mutations in the PROP-1 gene in cases with CPHD were expected to be more prevalent in our population due to consanguinity, but it was found that these mutations were far less than expected and that it was rare in non-familial cases.

Carbenoxolone Disodium Treatment for Canine Pituitary-Dependent Hyperadrenocorticism.

PubMed

Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Uchiyama, Rion; Koyama, Hidekazu

2016-01-01

Pituitary-dependent hyperadrenocorticism (PDH) is mainly caused by pituitary corticotroph tumors in dogs. A characteristic feature of corticotroph tumors is their resistance to negative feedback by glucocorticoids. In some animal species, including dogs, the aberrant expression of 11β-hydroxysteroid dehydrogenase (11HSD), a cortisol metabolic enzyme, is observed in corticotroph tumors. We previously reported that carbenoxolone (CBX), an inhibitor of 11HSD, suppressed ACTH secretion from the pituitary gland, and decreased cortisol concentrations in healthy dogs. Therefore, the aim of this study was to investigate the therapeutic effects of CBX on dogs with PDH. Six dogs with PDH were treated with 60 to 80 mg/kg/day of CBX for 6 weeks, followed by trilostane, which is a commonly used agent for canine PDH. CBX treatment led to a gradual decrease in both basal and in corticotropic releasing hormone (CRH)-stimulated plasma ACTH concentrations and CRH-stimulated serum cortisol concentrations, without side effects. However, basal and stimulated ACTH and cortisol concentrations remained higher than those of healthy dogs, and clinical symptoms such as polydipsia and polyuria were not ameliorated. After a 2-week wash-out interval, trilostane was administered for 2 weeks. Although basal plasma ACTH concentrations were higher after trilostane treatment than CBX treatment, polydipsia and polyuria resolved in all six dogs. The reason for the lack of improvement in polydipsia and polyuria with CBX treatment is unclear. Other mechanisms, in addition to a partial decrease in ACTH secretion, are likely to be involved. In conclusion, this is the first study to report the in vivo effects of CBX in dogs with PDH. The findings suggest that CBX inhibits ACTH secretion from canine pituitary tumors, resulting in lower cortisol concentrations.

Quercetin improves postpartum hypogalactia in milk-deficient mice via stimulating prolactin production in pituitary gland.

PubMed

Lin, Man; Wang, Na; Yao, Bei; Zhong, Yao; Lin, Yan; You, Tianhui

2018-04-19

Postpartum dysgalactia is a common clinical problem for lactating women. Seeking out the safe and efficient phytoestrogens will be a promising strategy for postpartum dysgalactia therapy. In this study, the postpartum mice within four groups, including control group, the model group, and the treatment groups intragastrically administrated with normal saline, bromocriptine, bromocriptine plus 17α-ethinyl estradiol, and bromocriptine plus quercetin, respectively, were used. The results showed that quercetin, a kind of natural phytoestrogen, could efficiently promote lactation yield and mammary gland development in the agalactosis mice produced by bromocriptine administration. Mechanically, quercetin, such as 17α-ethinyl estradiol, significantly stimulated prolactin (PRL) production and deposition in the mammary gland in the agalactosis mice determined by western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Furthermore, quercetin could increase the expression of β-casein, stearoyl-CoA desaturase, fatty acid synthase, and α-lactalbumin in the breast tissues that are responsible for the production of fatty acid, lactose, and galactose in the milk at the transcriptional level determined by quantitative polymerase chain reaction. Specifically, quercetin promoted primary mammary epithelial cell proliferation and stimulated prolactin receptor (PRLR) expression probably via AKT activation in vitro. In conclusion, this study indicates that estrogen-like quercetin promotes mammary gland development and lactation yield in milk-deficient mice, probably via stimulating PRL expression and release from the pituitary gland, as well as induces PRLR expression in primary mammary epithelial cells. Copyright © 2018 John Wiley & Sons, Ltd.

Establishment and culture optimization of a new type of pituitary immortalized cell line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kokubu, Yuko; Asashima, Makoto; Life Science Center of TARA, The University of Tsukuba, Ibaraki-ken 305-8577

The pituitary gland is a center of the endocrine system that controls homeostasis in an organism by secreting various hormones. The glandular anterior pituitary consists of five different cell types, each expressing specific hormones. However, their regulation and the appropriate conditions for their in vitro culture are not well defined. Here, we report the immortalization of mouse pituitary cells by introducing TERT, E6, and E7 transgenes. The immortalized cell lines mainly expressed a thyrotroph-specific thyroid stimulating hormone beta (Tshb). After optimization of the culture conditions, these immortalized cells proliferated and maintained morphological characteristics similar to those of primary pituitary cells undermore » sphere culture conditions in DMEM/F12 medium supplemented with N2, B27, basic FGF, and EGF. These cell lines responded to PKA or PKC pathway activators and induced the expression of Tshb mRNA. Moreover, transplantation of the immortalized cell line into subcutaneous regions and kidney capsules of mice further increased Tshb expression. These results suggest that immortalization of pituitary cells with TERT, E6, and E7 transgenes is a useful method for generating proliferating cells for the in vitro analysis of pituitary regulatory mechanisms. - Highlights: • Mouse pituitary cell lines were immortalized by introducing TERT, E6, and E7. • The immortalized cell lines mainly expressed thyroid stimulating hormone beta. • The cell lines responded to PKA or PKC pathway activators, and induced Tshb.« less

Molecular Cloning of Pituitary Glycoprotein α-Subunit and Follicle Stimulating Hormone and Chorionic Gonadotropin β-Subunits from New World Squirrel Monkey and Owl Monkey

PubMed Central

Scammell, Jonathan G.; Funkhouser, Jane D.; Moyer, Felricia S.; Gibson, Susan V.; Willis, Donna L.

2008-01-01

The goal of this study was to characterize the gonadotropins expressed in pituitary glands of the New World squirrel monkey (Saimiri sp.) and owl monkey (Aotus sp.). The various subunits were amplified from total RNA from squirrel monkey and owl monkey pituitary glands by reverse transcription-polymerase chain reaction and the deduced amino acid sequences compared to those of other species. Mature squirrel monkey and owl monkey glycoprotein hormone α-polypeptides (96 amino acids in length) were determined to be 80% homologous to the human sequence. The sequences of mature β subunits of follicle stimulating hormone (FSHβ) from squirrel monkey and owl monkey (111 amino acids in length) are 92% homologous to human FSHβ. New World primate glycoprotein hormone α-polypeptides and FSHβ subunits showed conservation of all cysteine residues and consensus N-linked glycosylation sites. Attempts to amplify the β-subunit of luteinizing hormone from squirrel monkey and owl monkey pituitary glands were unsuccessful. Rather, the β-subunit of chorionic gonadotropin (CG) was amplified from pituitaries of both New World primates. Squirrel monkey and owl monkey CGβ are 143 and 144 amino acids in length and 77% homologous with human CGβ. The greatest divergence is in the C terminus, where all four sites for O-linked glycosylation in human CGβ, responsible for delayed metabolic clearance, are predicted to be absent in New World primate CGβs. It is likely that CG secreted from pituitary of New World primates exhibits a relatively short half-life compared to human CG. PMID:17897645

Molecular cloning of pituitary glycoprotein alpha-subunit and follicle stimulating hormone and chorionic gonadotropin beta-subunits from New World squirrel monkey and owl monkey.

PubMed

Scammell, Jonathan G; Funkhouser, Jane D; Moyer, Felricia S; Gibson, Susan V; Willis, Donna L

2008-02-01

The goal of this study was to characterize the gonadotropins expressed in pituitary glands of the New World squirrel monkey (Saimiri sp.) and owl monkey (Aotus sp.). The various subunits were amplified from total RNA from squirrel monkey and owl monkey pituitary glands by reverse transcription-polymerase chain reaction and the deduced amino acid sequences compared to those of other species. Mature squirrel monkey and owl monkey glycoprotein hormone alpha-polypeptides (96 amino acids in length) were determined to be 80% homologous to the human sequence. The sequences of mature beta subunits of follicle stimulating hormone (FSHbeta) from squirrel monkey and owl monkey (111 amino acids in length) are 92% homologous to human FSHbeta. New World primate glycoprotein hormone alpha-polypeptides and FSHbeta subunits showed conservation of all cysteine residues and consensus N-linked glycosylation sites. Attempts to amplify the beta-subunit of luteinizing hormone from squirrel monkey and owl monkey pituitary glands were unsuccessful. Rather, the beta-subunit of chorionic gonadotropin (CG) was amplified from pituitaries of both New World primates. Squirrel monkey and owl monkey CGbeta are 143 and 144 amino acids in length and 77% homologous with human CGbeta. The greatest divergence is in the C terminus, where all four sites for O-linked glycosylation in human CGbeta, responsible for delayed metabolic clearance, are predicted to be absent in New World primate CGbetas. It is likely that CG secreted from pituitary of New World primates exhibits a relatively short half-life compared to human CG.

Pituitary response to thyrotropin releasing hormone in children with overweight and obesity.

PubMed

Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

2016-08-03

Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9-5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r(2) = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r(2) = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies.

Pituitary response to thyrotropin releasing hormone in children with overweight and obesity

PubMed Central

Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

2016-01-01

Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9–5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r2 = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r2 = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies. PMID:27485208

Comparing models of the combined-stimulation advantage for speech recognition.

PubMed

Micheyl, Christophe; Oxenham, Andrew J

2012-05-01

The "combined-stimulation advantage" refers to an improvement in speech recognition when cochlear-implant or vocoded stimulation is supplemented by low-frequency acoustic information. Previous studies have been interpreted as evidence for "super-additive" or "synergistic" effects in the combination of low-frequency and electric or vocoded speech information by human listeners. However, this conclusion was based on predictions of performance obtained using a suboptimal high-threshold model of information combination. The present study shows that a different model, based on Gaussian signal detection theory, can predict surprisingly large combined-stimulation advantages, even when performance with either information source alone is close to chance, without involving any synergistic interaction. A reanalysis of published data using this model reveals that previous results, which have been interpreted as evidence for super-additive effects in perception of combined speech stimuli, are actually consistent with a more parsimonious explanation, according to which the combined-stimulation advantage reflects an optimal combination of two independent sources of information. The present results do not rule out the possible existence of synergistic effects in combined stimulation; however, they emphasize the possibility that the combined-stimulation advantages observed in some studies can be explained simply by non-interactive combination of two information sources.

Mechanisms for pituitary tumorigenesis: the plastic pituitary

PubMed Central

Melmed, Shlomo

2003-01-01

The anterior pituitary gland integrates the repertoire of hormonal signals controlling thyroid, adrenal, reproductive, and growth functions. The gland responds to complex central and peripheral signals by trophic hormone secretion and by undergoing reversible plastic changes in cell growth leading to hyperplasia, involution, or benign adenomas arising from functional pituitary cells. Discussed herein are the mechanisms underlying hereditary pituitary hypoplasia, reversible pituitary hyperplasia, excess hormone production, and tumor initiation and promotion associated with normal and abnormal pituitary differentiation in health and disease. PMID:14660734

Novel Mutations in HESX1 and PROP1 Genes in Combined Pituitary Hormone Deficiency.

PubMed

Avbelj Stefanija, Magdalena; Kotnik, Primož; Bratanič, Nina; Žerjav Tanšek, Mojca; Bertok, Sara; Bratina, Nataša; Battelino, Tadej; Trebušak Podkrajšek, Katarina

2015-01-01

The HESX1 gene is essential in forebrain development and pituitary organogenesis, and its mutations are the most commonly identified genetic cause of septo-optic dysplasia (SOD). The PROP1 gene is involved in anterior pituitary cell lineage specification and is commonly implicated in non-syndromic combined pituitary hormone deficiency (CPHD). We aimed to assess the involvement of HESX1 and PROP1 mutations in a cohort of patients with SOD and CPHD. Six patients with sporadic SOD and 16 patients with CPHD from 14 pedigrees were screened for mutations in HESX1 and PROP1 genes by exon sequencing. Half of the CPHD patients had variable associated clinical characteristics, such as hearing loss, orofacial cleft, kidney disorder or developmental delay. Novel variants were evaluated in silico and verified in SNP databases. A novel heterozygous p.Glu102Gly mutation in the HESX1 gene and a novel homozygous p.Arg121Thr mutation in the PROP1 gene were detected in 2 pedigrees with CPHD. A small previously reported deletion in PROP1 c.301_302delAG was detected in a separate patient with CPHD, in heterozygous state. No mutations were identified in patients with SOD. Our results expand the spectrum of mutations implicated in CPHD. The frequency of 15% of the PROP1 mutations in CPHD was low, likely due to the clinical heterogeneity of the cohort. © 2015 S. Karger AG, Basel.

Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cronin, M.J.; Evans, W.S.; Rogol, A.D.

1986-08-01

Bordetella pertussis synthesis a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changes the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplifiedmore » the secretory response to hypophysiotrophic hormones. The authors conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is the response that explains the subsequent acceleration of hormone release.« less

[Molecular pathology of congenital pituitary hypothyroidism--discovery of new clinical entities].

PubMed

Tatsumi, K; Amino, N; Miyai, K

1993-05-01

Congenital pituitary hypothyroidism (pituitary cretinism) results in severe mental and growth retardation when it is not treated soon after birth. Since the introduction of neonatal mass screening of thyrotropin (TSH), most congenital hypothyroidism has been detected except for pituitary and hypothalamic hypothyroidism. In 1971, we reported the first familial case of congenital isolated TSH deficiency and thereafter began intensively investigating the molecular pathology of congenital pituitary hypothyroidism. After determining the entire structure of the human TSH beta gene, we identified the molecular pathology in this patient. Recently, we reported a familial case of congenital combined pituitary hormone deficiency (PIT1 abnormality). To examine the PIT1 gene, which encodes pituitary specific transcription factor, Pit-1/GHF-1, we determined its genomic structure. Sequence comparisons using PCR amplified PIT1 gene sequences revealed only one nonsense mutation in the patient, and established that this alteration caused the combined deficiencies of TSH, GH and PRL. We also discuss other recent progress in molecular pathology of congenital pituitary hypothyroidism.

Massive pleural and pericardial effusion due to hypothyroidism in a patient with a surgically treated thyroid-stimulating hormone-producing pituitary adenoma.

PubMed

Lee, Ji-Hoon; Park, MinA; Park, Myung Jae; Jo, Yong Suk

2018-05-14

Hypothyroidism is relatively rare etiology of serositis with effusion, but massive pleural effusion is very unusual. This is a report of massive pleural effusion in patient taking methimazole after surgical resection of thyroid-stimulating hormone (TSH)-producing pituitary adenoma (TSHoma). The patient was clinically and biochemically hypothyroid and responded well to discontinuation of methimazole and thyroid hormone replacement therapy. When assessing patients with pleural effusion, we should not rely on laboratory test results alone, as a detailed medical history and thorough physical examination could be more useful.

Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency.

PubMed

Breitfeld, Jana; Martens, Susanne; Klammt, Jürgen; Schlicke, Marina; Pfäffle, Roland; Krause, Kerstin; Weidle, Kerstin; Schleinitz, Dorit; Stumvoll, Michael; Führer, Dagmar; Kovacs, Peter; Tönjes, Anke

2013-12-01

The complex process of development of the pituitary gland is regulated by a number of signalling molecules and transcription factors. Mutations in these factors have been identified in rare cases of congenital hypopituitarism but for most subjects with combined pituitary hormone deficiency (CPHD) genetic causes are unknown. Bone morphogenetic proteins (BMPs) affect induction and growth of the pituitary primordium and thus represent plausible candidates for mutational screening of patients with CPHD. We sequenced BMP2, 4 and 7 in 19 subjects with CPHD. For validation purposes, novel genetic variants were genotyped in 1046 healthy subjects. Additionally, potential functional relevance for most promising variants has been assessed by phylogenetic analyses and prediction of effects on protein structure. Sequencing revealed two novel variants and confirmed 30 previously known polymorphisms and mutations in BMP2, 4 and 7. Although phylogenetic analyses indicated that these variants map within strongly conserved gene regions, there was no direct support for their impact on protein structure when applying predictive bioinformatics tools. A mutation in the BMP4 coding region resulting in an amino acid exchange (p.Arg300Pro) appeared most interesting among the identified variants. Further functional analyses are required to ultimately map the relevance of these novel variants in CPHD.

Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency

PubMed Central

2013-01-01

Background The complex process of development of the pituitary gland is regulated by a number of signalling molecules and transcription factors. Mutations in these factors have been identified in rare cases of congenital hypopituitarism but for most subjects with combined pituitary hormone deficiency (CPHD) genetic causes are unknown. Bone morphogenetic proteins (BMPs) affect induction and growth of the pituitary primordium and thus represent plausible candidates for mutational screening of patients with CPHD. Methods We sequenced BMP2, 4 and 7 in 19 subjects with CPHD. For validation purposes, novel genetic variants were genotyped in 1046 healthy subjects. Additionally, potential functional relevance for most promising variants has been assessed by phylogenetic analyses and prediction of effects on protein structure. Results Sequencing revealed two novel variants and confirmed 30 previously known polymorphisms and mutations in BMP2, 4 and 7. Although phylogenetic analyses indicated that these variants map within strongly conserved gene regions, there was no direct support for their impact on protein structure when applying predictive bioinformatics tools. Conclusions A mutation in the BMP4 coding region resulting in an amino acid exchange (p.Arg300Pro) appeared most interesting among the identified variants. Further functional analyses are required to ultimately map the relevance of these novel variants in CPHD. PMID:24289245

Pituitary Androgen Receptor Signalling Regulates Prolactin but Not Gonadotrophins in the Male Mouse

PubMed Central

O’Hara, Laura; Curley, Michael; Tedim Ferreira, Maria; Cruickshanks, Lyndsey; Milne, Laura; Smith, Lee B.

2015-01-01

Production of the androgen testosterone is controlled by a negative feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. Stimulation of testicular Leydig cells by pituitary luteinising hormone (LH) is under the control of hypothalamic gonadotrophin releasing hormone (GnRH), while suppression of LH secretion by the pituitary is controlled by circulating testosterone. Exactly how androgens exert their feedback control of gonadotrophin secretion (and whether this is at the level of the pituitary), as well as the role of AR in other pituitary cell types remains unclear. To investigate these questions, we exploited a transgenic mouse line (Foxg1Cre/+; ARfl/y) which lacks androgen receptor in the pituitary gland. Both circulating testosterone and gonadotrophins are unchanged in adulthood, demonstrating that AR signalling is dispensable in the male mouse pituitary for testosterone-dependent regulation of LH secretion. In contrast, Foxg1Cre/+; ARfl/y males have a significant increase in circulating prolactin, suggesting that, rather than controlling gonadotrophins, AR-signalling in the pituitary acts to suppress aberrant prolactin production in males. PMID:25799562

Effects of forced swimming stress on thyroid function, pituitary thyroid-stimulating hormone and hypothalamus thyrotropin releasing hormone expression in adrenalectomy Wistar rats.

PubMed

Sun, Qiuyan; Liu, Aihua; Ma, Yanan; Wang, Anyi; Guo, Xinhong; Teng, Weiping; Jiang, Yaqiu

2016-11-01

In order to study the impact that is imposed on the hypothalamic-pituitary-thyroid (HPT) axis of adrenalectomy male Wistar rats by stress caused by swimming, the blood level of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH), the expression of TSHβ mRNA at the pituitary and thyrotropin releasing hormone (TRH) expression at the paraventricular nucleus (PVN) were measured. A total of 50 male Wistar rats of 6-8 weeks of age and with an average weight of 190-210 grams were randomly divided into the following two groups: The surgical (without adrenal glands) and non-surgical (adrenalectomy) group. These two groups were then divided into the following five groups, according to the time delay of sacrifice following forced swim (10 min, 2 h, 12 h and 24 h) and control (not subjected to swimming) groups. A bilateral adrenalectomy animal model was established. Serum TSH in the blood was measurement by chemiluminescent immunoassay, and cerebrum tissue were excised for the measurement of TRH expression using an immunohistochemistry assay. In addition, pituitaries were excised for the extraction of total RNA. Finally, reverse transcription-quantitative polymerase chain reaction was performed for quantitation of TSHβ. Following swimming, the serum T3, T4 and TSH, the TSHβ mRNA expression levels in the pituitary and the TRH expression in the PVN of the surgical group were gradually increased. In the non-surgical group, no significant differences were observed in the serum T3, T4 and TSH levels compared with the control group. The TSHβ mRNA expression at the pituitary showed a similar result. Furthermore, the TRH expression at PVN was gradually increased and stress from swimming could increase the blood T4, T3 and TSH levels, TSHβ mRNA expression at the pituitary and TRH expression at the PVN in adrenalectomy Wistar rats. Moreover, the index in the surgical group changed significantly compared with the non-surgical group. In conclusion, the results

Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary

PubMed Central

Mathioudakis, Nestoras; Sundaresh, Ram; Larsen, Alexandra; Ruff, William; Schiller, Jennifer; Cázares, Hugo Guerrero; Burger, Peter; Salvatori, Roberto; Quiñones-Hinojosa, Alfredo

2014-01-01

Purpose Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary. Methods The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially. Results GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (P <0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (P <0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (P<0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke’s remnant, the putative pituitary stem cell niche, and in corticotropes. Conclusion Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis. PMID:24402129

The pituitary gland under infrared light - in search of a representative spectrum for homogeneous regions.

PubMed

Banas, A; Banas, K; Furgal-Borzych, A; Kwiatek, W M; Pawlicki, B; Breese, M B H

2015-04-07

The pituitary gland is a small but vital organ in the human body. It is located at the base of the brain and is often described as the master gland due to its multiple functions. The pituitary gland secretes and stores hormones, such as the thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), growth hormone (hGH), prolactin, gonadotropins, and luteinizing hormones, as well as the antidiuretic hormone (ADH). A proper diagnosis of pituitary disorders is of utmost importance as this organ participates in regulating a variety of body functions. Typical histopathological analysis provides much valuable information, but it gives no insight into the biochemical background of the changes that occur within the gland. One approach that could be used to evaluate the biochemistry of tissue sections obtained from pituitary disorders is Fourier Transform Infra-Red (FTIR) spectromicroscopy. In order to collect diagnostically valuable information large areas of tissue must be investigated. This work focuses on obtaining a unique and representative FTIR spectrum characteristic of one type of cell architecture within a sample. The idea presented is based on using hierarchical cluster analysis (HCA) for data evaluation to search for uniform patterns within samples from the perspective of FTIR spectra. The results obtained demonstrate that FTIR spectromicroscopy, combined with proper statistical evaluation, can be treated as a complementary method for histopathological analysis and ipso facto can increase the sensitivity and specificity for detecting various disorders not only for the pituitary gland, but also for other human tissues.

Endoscopic endonasal transsphenoidal surgery: surgical results of 228 pituitary adenomas treated in a pituitary center.

PubMed

Gondim, Jackson A; Schops, Michele; de Almeida, João Paulo C; de Albuquerque, Lucas Alverne F; Gomes, Erika; Ferraz, Tânia; Barroso, Francisca Andréa C

2010-01-01

Pituitary tumors are challenging tumors in the sellar region. Surgical approaches to the pituitary have undergone numerous refinements over the last 100 years. The introduction of the endoscope have revolutionized pituitary surgery. The aim of this study is to report the results of a consecutive series of patients undergoing pituitary surgery using a pure endoscopic endonasal approach and to evaluate the efficacy and safety of this procedure. We reviewed the data of 228 consecutive patients who underwent endonasal transsphenoidal adenoma removal over an 10-year period. Pre- and post-operative hormonal status (at least 3 months after surgery) were analyzed and compared with clinical parameters presented by the patients. Tumor removal rate, endocrinological outcomes, and complications were retrospectively assessed in 228 patients with pituitary adenomas who underwent 251 procedures between December 1998 and December 2007. There were 93 nonfunctioning adenomas, 58 growth hormone-secreting, 41 prolactin-secreting, 28 adrenocorticotropin hormone secreting, 7 FSH-LH secreting and 1 thyroid-stimulating hormone-secreting adenomas. Gross total removal was achieved in 79.3% of the cases after a median follow-up of 61.5 months. The remission results for patients with nonfunctioning adenomas was 83% and for functioning adenomas were 76.3% (70.6% for GH hormone-secreting, 85.3% for prolactin hormone-secreting, 71.4% for ACTH hormone-secreting, 85.7% for FSH-LH hormone-secreting and 100% for TSH hormone-secreting), with no recurrence at the time of the last follow-up. Post-operative complications were present in 35 (13.9%) cases. The most frequent complications were temporary and permanent diabetes insipidus (six and two cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (two cases) and CSF leaks (eight cases). There was no death related to the procedure in this series. The endoscopic endonasal approach for resection of pituitary adenomas, provides

Gonadotrophin-inhibitory hormone receptor expression in the chicken pituitary gland: potential influence of sexual maturation and ovarian steroids.

PubMed

Maddineni, S; Ocón-Grove, O M; Krzysik-Walker, S M; Hendricks, G L; Proudman, J A; Ramachandran, R

2008-09-01

Gonadotrophin-inhibitory hormone (GnIH), a hypothalamic RFamide, has been found to inhibit gonadotrophin secretion from the anterior pituitary gland originally in birds and, subsequently, in mammalian species. The gene encoding a transmembrane receptor for GnIH (GnIHR) was recently identified in the brain, pituitary gland and gonads of song bird, chicken and Japanese quail. The objectives of the present study are to characterise the expression of GnIHR mRNA and protein in the chicken pituitary gland, and to determine whether sexual maturation and gonadal steroids influence pituitary GnIHR mRNA abundance. GnIHR mRNA quantity was found to be significantly higher in diencephalon compared to either anterior pituitary gland or ovaries. GnIHR mRNA quantity was significantly higher in the pituitaries of sexually immature chickens relative to sexually mature chickens. Oestradiol or a combination of oestradiol and progesterone treatment caused a significant decrease in pituitary GnIHR mRNA quantity relative to vehicle controls. GnIHR-immunoreactive (ir) cells were identified in the chicken pituitary gland cephalic and caudal lobes. Furthermore, GnIHR-ir cells were found to be colocalised with luteinising hormone (LH)beta mRNA-, or follicle-stimulating hormone (FSH)beta mRNA-containing cells. GnIH treatment significantly decreased LH release from anterior pituitary gland slices collected from sexually immature, but not from sexually mature chickens. Taken together, GnIHR gene expression is possibly down regulated in response to a surge in circulating oestradiol and progesterone levels as the chicken undergoes sexual maturation to allow gonadotrophin secretion. Furthermore, GnIHR protein expressed in FSHbeta or LHbeta mRNA-containing cells is likely to mediate the inhibitory effect of GnIH on LH and FSH secretion.

Does the CRH binding protein shield the anterior pituitary from placental CRH?

PubMed

Thomson, M

1998-12-01

Corticotropin releasing factor (CRH) is released from the hypothalamus and travels to the anterior pituitary where it stimulates the release of adrenocorticotropin (ACTH). In turn, ACTH travels through the blood and stimulates the release of cortisol from the adrenal. The placenta is also a source of CRH and is responsible for the dramatic rises in CRH plasma levels in the third trimester of pregnancy. A CRH binding protein may stop placental CRH from overstimulating the pituitary and may contribute to the reason that pregnant women show only mildly elevated levels of ACTH in the blood. There is evidence to suggest, however, that the CRH binding protein does not completely shield the corticotrope from placental CRH.

Stimulation of in vitro steroidogenesis by pituitary hormones in a turtle (Trachemys scripta) within the temperature-sensitive period for sex determination.

PubMed

White, R B; Thomas, P

1992-12-01

To investigate the possible involvement of pituitary hormones in the regulation of steroidogenesis during reptilian sexual differentiation, we tested the ability of gonadotropin (ovine FSH), adrenocorticotropin (porcine ACTH), and growth hormone (bovine GH) to stimulate in vitro steroidogenesis in embryonic adrenal-kidney-gonad complexes (AKGs) of a turtle, Trachemys scripta, during and after the temperature-sensitive period for sex determination (TSP). Radioimmunoassays were used to measure progesterone, testosterone, estradiol, and corticosterone in incubation media; additionally, immunoreactive ACTH was measured in plasma. Presumptive male and female AKGs were stimulated by both FSH and ACTH at each stage investigated. Secretion of progesterone and corticosterone was usually far greater than that of testosterone or estradiol in both basal and hormone-stimulated incubations. In general, AKGs from presumptive males secreted more progesterone and corticosterone than AKGs from presumptive females. Progesterone and estradiol secretions were stimulated by both FSH and ACTH, but testosterone secretion was stimulated only by ACTH. Corticosterone secretion was strongly stimulated by ACTH. GH failed to significantly stimulate steroid secretion. Plasma ACTH levels were significantly higher in males than in females, and both sexes had significantly higher plasma levels of ACTH after the TSP compared to during the TSP. Our data demonstrate that during the temperature-sensitive period AKGs are responsive to both gonadotropin and ACTH, and that there are significant sex differences in steroidogenesis, sensitivity to gonadotropin and ACTH, and plasma ACTH levels.

Pituitary stalk interruption syndrome presenting as short stature: a case report.

PubMed

Ram, Nanik; Ali, Syed Ahsan; Hussain, Syed Zubair

2014-12-19

Pituitary stalk interruption syndrome is a rare congenital abnormality of the pituitary that is responsible for anterior pituitary deficiency. It is characterized by a classic triad of interrupted pituitary stalk, absent or ectopic posterior pituitary, and anterior pituitary hypoplasia or aplasia. Clinical presentation varies according to age. In adults it presents as short stature and anterior pituitary deficiency. Without early diagnosis and treatment, mortality and morbidity in these patients is high. Early diagnosis and treatment of this rare disease can prevent permanent short statue of the patient. We report the first case of pituitary stalk interruption syndrome from Pakistan. A 17-year-old Pakistani young man presented with short stature and underdeveloped secondary sexual characters. His siblings and parents were healthy, with normal height. An examination showed his blood pressure was 90/60 mmHg, and his height, weight, and body mass index were 142 cm, 34.5 kg, and 17.10 kg/m2, respectively. He had no hair growth on his face, axilla, or pubis. His testes were between 1 and 2 mL in size, with a 4 cm-at-stretch micropenis. His lab investigations showed that his thyroid stimulating hormone (TSH) was 8.58 uIU/mL (0.4 to 4.2), his free thyroid hormone level FT4 was 0.46 ng/dL (0.89 to 1.76), his prolactin was 21.1 ng/mL (3.0 to 14.7), and his baseline cortisol was 0.30 ug/dL (4.3 to 22.4). His cortisol level after 60 minutes of cosyntropin injection was 3.5 ug/dL (4.3 to 22.4), his insulin like growth factor IGF-1 was 31.56 ng/mL (247.3 to 481.7), his testosterone level was under 2.5 ng/dL (2 to 800), his follicle stimulating hormone FSH was 0.41 uIU/mL (0.0 to 10.0), and his leutinizing hormone LH was under 0.1 uIU/mL (1.2 to 7.8). His bone age was 10 years according to the Greulich and Pyle method, as shown by X-rays. The results from his pituitary magnetic resonance imaging scan were consistent with pituitary stalk interruption syndrome. We describe a young

Sexually dimorphic expression of gonadotropin subunits in the pituitary of protogynous honeycomb grouper (Epinephelus merra): evidence that follicle-stimulating hormone (FSH) induces gonadal sex change.

PubMed

Kobayashi, Yasuhisa; Alam, Mohammad Ashraful; Horiguchi, Ryo; Shimizu, Akio; Nakamura, Masaru

2010-06-01

Recent studies have suggested that the hypothalamic-pituitary-gonadal axis is involved in gonadal sex change in sex-changing teleosts. However, its underlying mechanism remains largely unknown. In this study, we focused on the distinct roles of two gonadotropins (GTHs), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), in the protogynous hermaphrodite teleost, honeycomb grouper (Epinephelus merra). First, we investigated the expression pattern of mRNAs for GTH subunits (cga, fshb, and lhb) in the pituitaries from fish at the different sexual phases. Real-time RT-PCR analyses showed that fhsb mRNA levels in the female pituitary were low. However, fshb transcripts increased dramatically in association with testis development. In contrast, levels of cga and lhb mRNAs did not significantly vary during sex change. In addition, immunohistochemical observations of Fshb- and Lhb-producing cells in the pituitary, through the use of specific antibodies for detections of teleost GTH subunits, were consistent with sexually dimorphic expression of Fshb. In order to identify the role of GTH in gonad of honeycomb grouper, we treated females with bovine FSH (50 or 500 ng/fish) or LH (500 ng/fish) in vivo. After 3 wk, FSH treatments induced female-to-male sex change and up-regulated endogenous androgen levels and fshb transcripts, whereas LH treatment had no effect on sex change. These results suggest that FSH may trigger the female-to-male sex change in honeycomb grouper.

Pituitary gene mutations and the growth hormone pathway.

PubMed

Moseley, C T; Phillips, J A

2000-01-01

Hereditary forms of pituitary insufficiency not associated with anatomic defects of the central nervous system, hypothalamus, or pituitary are a heterogeneous group of disorders that result from interruptions at different points in the hypothalamic-pituitary-somatomedin-peripheral tissue axis. These different types of pituitary dwarfism can be classified on the level of the defect; mode of inheritance; whether the phenotype is isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD); whether the hormone is absent, deficient, or abnormal; and, in patients with GH resistance, whether insulin-like growth factor 1 (IGF1) is deficient due to GH receptor or IGF1 defects. Information on each disorder is summarized. More detailed information can be obtained through the electronic database Online Mendelian Inheritance in Man which is available at http://www3.ncbi.nlm.nih.gov/Omim/.

Biological role of pituitary estrogen receptors ERalpha and ERbeta on progesterone receptor expression and action and on gonadotropin and prolactin secretion in the rat.

PubMed

Sánchez-Criado, José E; Martín De Las Mulas, Juana; Bellido, Carmina; Tena-Sempere, Manuel; Aguilar, Rafaela; Blanco, Alfonso

2004-01-01

Estrogen (E) is a key regulator of the synthesis and secretion of pituitary reproductive hormones [luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL)]. Until recently, it was thought that all biological actions of E at the pituitary were manifested through a single E receptor (R). The pituitary, like many other reproductive tissues, expresses two isoforms of ER, alpha and beta, both activated by E. The relative contribution of alpha and beta forms in E regulatory actions is largely unknown. To this end, 2-week-old ovariectomized (OVX) rats were injected over 3 days with 25 microg estradiol benzoate (EB), 1.5 mg of propylpyrazole triol (PPT), a selective ERalpha agonist, 1.5 mg of the selective ERbeta agonist diarylpropionitrile (DPN) or a combination of PPT and DPN. Controls were injected with 0.2 ml oil. At 10:00 h on the day after treatment, trunk blood was collected to determine serum concentration of LH, FSH and PRL, and pituitaries were processed for RT-PCR analysis of total (A+B) progesterone receptor (PR) mRNA, immunocytochemistry of PR and incubation. Pituitaries from each of the five groups were incubated in DMEM, with or without 20 nM of the antiprogestin at the receptor ZK299, for 3 h with: 10(-8)M 17beta-estradiol, 10(-6)M PPT, 10(-6)M DPN, PPT+DPN or medium alone, respectively, to determine LH, FSH and PRL secretion, and, when challenged with two pulses of 15 min 1 h apart of 10(-8)M gonadotropin-releasing hormone (GnRH) (GnRH self-priming). EB, PPT and PPT+DPN treatments increased PR mRNA and the number and intensity of nuclei immunoreactive (IR) for PR in gonadotropes, and reduced the number of gonadectomy cells. Like E, PPT alone or in combination with DPN stimulated PRL secretion, increased basal and GnRH-stimulated LH and FSH secretion and induced GnRH self-priming in the absence of ZK299 in the incubation medium. DPN alone had only a significant E-like effect on gonadectomy cells and IR-PR, but not on GnRH self

Outcome of endoscopic transsphenoidal surgery in combination with somatostatin analogues in patients with growth hormone producing pituitary adenoma.

PubMed

Zhou, Tao; Wang, Fuyu; Meng, Xianghui; Ba, Jianmin; Wei, Shaobo; Xu, Bainan

2014-11-01

To determine the efficacy of endoscopic surgery in combination with long-acting somatostatin analogues (SSAs) in treating patients with growth hormone (GH)-secreting pituitary tumor. We performed retrospective analysis of 133 patients with GH producing pituitary adenoma who underwent pure endoscopic transsphenoidal surgery in our center from January 2007 to July 2012. Patients were followed up for a range of 3-48 months. The radiological remission, biochemical remission and complication were evaluated. A total of 110 (82.7%) patients achieved radiological complete resection, 11 (8.2%) subtotal resection, and 12 (9.0%) partial resection. Eighty-eight (66.2%) patients showed nadir GH level less than 1 ng/mL after oral glucose administration. No mortality or severe disability was observed during follow up. Preoperative long-acting SSA successfully improved left ventricle ejection fraction (LVEF) and blood glucose in three patients who subsequently underwent success operation. Long-acting SSA (20 mg every 30 days) achieved biochemical remission in 19 out 23 (82.6%) patients who showed persistent high GH level after surgery. Endoscopic transsphenoidal surgery can biochemically cure the majority of GH producing pituitary adenoma. Post-operative use of SSA can improve biochemical remission.

Outcome of Endoscopic Transsphenoidal Surgery in Combination with Somatostatin Analogues in Patients with Growth Hormone Producing Pituitary Adenoma

PubMed Central

Zhou, Tao; Wang, Fuyu; Meng, Xianghui; Ba, Jianmin; Wei, Shaobo

2014-01-01

Objective To determine the efficacy of endoscopic surgery in combination with long-acting somatostatin analogues (SSAs) in treating patients with growth hormone (GH)-secreting pituitary tumor. Methods We performed retrospective analysis of 133 patients with GH producing pituitary adenoma who underwent pure endoscopic transsphenoidal surgery in our center from January 2007 to July 2012. Patients were followed up for a range of 3-48 months. The radiological remission, biochemical remission and complication were evaluated. Results A total of 110 (82.7%) patients achieved radiological complete resection, 11 (8.2%) subtotal resection, and 12 (9.0%) partial resection. Eighty-eight (66.2%) patients showed nadir GH level less than 1 ng/mL after oral glucose administration. No mortality or severe disability was observed during follow up. Preoperative long-acting SSA successfully improved left ventricle ejection fraction (LVEF) and blood glucose in three patients who subsequently underwent success operation. Long-acting SSA (20 mg every 30 days) achieved biochemical remission in 19 out 23 (82.6%) patients who showed persistent high GH level after surgery. Conclusion Endoscopic transsphenoidal surgery can biochemically cure the majority of GH producing pituitary adenoma. Post-operative use of SSA can improve biochemical remission. PMID:25535518

Effects of osmotic swelling on voltage-gated calcium channel currents in rat anterior pituitary cells.

PubMed

Ben-Tabou De-Leon, Shlomo; Blotnick, Edna; Nussinovitch, Itzhak

2003-10-01

Decrease in extracellular osmolarity ([Os]e) results in stimulation of hormone secretion from pituitary cells. Different mechanisms can account for this stimulation of hormone secretion. In this study we examined the possibility that hyposmolarity directly modulates voltage-gated calcium influx in pituitary cells. The effects of hyposmolarity on L-type (IL) and T-type (IT) calcium currents in pituitary cells were investigated by using two hyposmotic stimuli, moderate (18-22% decrease in [Os]e) and strong (31-32% decrease in [Os]e). Exposure to moderate hyposmotic stimuli resulted in three response types in IL (a decrease, a biphasic effect, and an increase in IL) and in increase in IT. Exposure to strong hyposmotic stimuli resulted only in increases in both IL and IT. Similarly, in intact pituitary cells (perforated patch method), exposure to either moderate or strong hyposmotic stimuli resulted only in increases in both IL and IT. Thus it appears that the main effect of decrease in [Os]e is increase in calcium channel currents. This increase was differential (IL were more sensitive than IT) and voltage independent. In addition, we show that these hyposmotic effects cannot be explained by activation of an anionic conductance or by an increase in cell membrane surface area. In conclusion, this study shows that hyposmotic swelling of pituitary cells can directly modulate voltage-gated calcium influx. This hyposmotic modulation of IL and IT may contribute to the previously reported hyposmotic stimulation of hormone secretion. The mechanisms underlying these hyposmotic effects and their possible physiological relevance are discussed.

DNA synthesis in the pituitary gland of the rat: effect of sulpiride and clomiphene.

PubMed

Burdman, J A; Szijan, I; Jahn, G A; Machiavelli, G; Kalbermann, L E

1979-09-15

Sulpiride administration to rats releases prolactin and increases DNA replication in the anterior pituitary gland. Clomiphene prevents the stimulation of DNA synthesis produced by sulpiride, but does not affect prolactin release from the gland. These findings suggest that the intracellular prolactin content of the anterior pituitary gland plays a role in the regulation of DNA synthesis through a mechanism mediated by oestrogens.

Responsiveness of pituitary to galanin throughout the reproductive cycle of male European sea bass (Dicentrarchus labrax).

PubMed

Pinto, P; Velez, Z; Sousa, C; Santos, S; Andrade, A; Alvarado, M V; Felip, A; Zanuy, S; Canário, A V M

2017-09-01

The neuropeptide galanin (Gal) is a putative factor regulating puberty onset and reproduction through its actions on the pituitary. The present study investigated the pituitary responsiveness to galanin and the patterns of galanin receptors (Galrs) expression throughout the reproductive cycle of two years old male European sea bass (Dicentrarchus labrax), an important aquaculture species. Quantitative analysis of pituitary and hypothalamus transcript expression of four galr subtypes revealed differential regulation according to the testicular developmental stage, with an overall decrease in expression from the immature stage to the mid-recrudescence stage. Incubation of pituitary cells with mammalian 1-29Gal peptide induced significant changes in cAMP concentration, with sensitivities that varied according to the testicular development stages. Furthermore 1-29Gal was able to stimulate both follicle stimulating hormone (Fsh) and luteinizing hormone (Lh) release from pituitary cell suspensions. The magnitude of the effects and effective concentrations varied according to reproductive stage, with generalized induction of Fsh and Lh release in animals sampled in January (full spermiation). The differential expression of galrs in pituitary and hypothalamus across the reproductive season, together with the differential effects of Gal on gonadotropins release in vitro strongly suggests the involvement of the galaninergic system in the regulation the hypothalamus-pituitary-gonad axis of male sea bass. This is to our knowledge the first clear evidence for the involvement of galanin in the regulation of reproduction in non-mammalian vertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

PubMed Central

Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

2014-01-01

Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature

PubMed Central

PU, JIUJUN; WANG, ZHIMING; ZHOU, HUI; ZHONG, AILING; JIN, KAI; RUAN, LUNLIANG; YANG, GANG

2016-01-01

Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas. PMID:27347184

Dual control of pituitary thyroid stimulating hormone secretion by thyroxine and triiodothyronine in athyreotic patients

PubMed Central

Hoermann, Rudolf; Midgley, John E. M.; Dietrich, Johannes W.; Larisch, Rolf

2017-01-01

Background: Patient responses to levothyroxine (LT4) monotherapy vary considerably. We sought to differentiate contributions of FT4 and FT3 in controlling pituitary thyroid stimulating hormone (TSH) secretion. Methods: We retrospectively assessed the relationships between TSH and thyroid hormones in 319 patients with thyroid carcinoma through 2914 visits on various LT4 doses during follow-up for 5.5 years (median, IQR 4.2, 6.9). We also associated patient complaints with the relationships. Results: Under varying dose requirements (median 1.84 µg/kg, IQR 1.62, 2.11), patients reached TSH targets below 0.4, 0.1 or 0.01 mIU/l at 73%, 54% and 27% of visits. While intercept, slope and fit of linearity of the relationships between lnTSH and FT4/FT3 varied between individuals, gender, age, LT4 dose and deiodinase activity influenced the relationships in the cohort (all p < 0.001). Deiodinase activity impaired by LT4 dose significantly affected the lnTSH–FT4 relationship. Dose increase and reduced conversion efficiency displaced FT3–TSH equilibria. In LT4-treated patients, FT4 and FT3 contributed on average 52% versus 38%, and by interaction 10% towards TSH suppression. Symptomatic presentations (11%) accompanied reduced FT3 concentrations (–0.23 pmol/l, p = 0.001) adjusted for gender, age and BMI, their relationships being shifted towards higher TSH values at comparable FT3/FT4 levels. Conclusions: Variation in deiodinase activity and resulting FT3 levels shape the TSH–FT4 relationship in LT4-treated athyreotic patients, suggesting cascade control of pituitary TSH production by the two hormones. Consequently, measurement of FT3 and calculation of conversion efficiency may identify patients with impaired biochemistry and a resulting lack of symptomatic control. PMID:28794850

Single-nucleotide variants in two Hedgehog genes, SHH and HHIP, as genetic cause of combined pituitary hormone deficiency.

PubMed

Gorbenko del Blanco, Darya; de Graaff, Laura C G; Visser, Theo J; Hokken-Koelega, Anita C S

2013-03-01

Combined pituitary hormone deficiency (CPHD) is characterized by deficiencies of two or more anterior pituitary hormones. Its genetic cause is unknown in the majority of cases. The Hedgehog (Hh) signalling pathway has been implicated in disorders associated with pituitary development. Mutations in Sonic Hedgehog (SHH) have been described in patients with holoprosencephaly (with or without pituitary involvement). Hedgehog interacting protein (HHIP) has been associated with variations in adult height in genome wide association studies. We investigated whether mutations in these two genes of the Hh pathway, SHH and HHIP, could result in 'idiopathic' CPHD. We directly sequenced the coding regions and exon - intron boundaries of SHH and HHIP in 93 CPHD patients of the Dutch HYPOPIT study in whom mutations in the classical CPHD genes PROP1, POU1F1, HESX1, LHX3 and LHX4 had been ruled out. We compared the expression of Hh genes in Hep3B transfected cells between wild-type proteins and mutants. We identified three single-nucleotide variants (p.Ala226Thr, c.1078C>T and c.*8G>T) in SHH. The function of the latter was severely affected in our in vitro assay. In HHIP, we detected a new activating variant c.-1G>C, which increases HHIP's inhibiting function on the Hh pathway. Our results suggest involvement of the Hedgehog pathway in CPHD. We suggest that both SHH and HHIP are investigated as a second screening in CPHD, after mutations in the classical CPHD genes have been ruled out. © 2012 Blackwell Publishing Ltd.

An unusual case of hypopituitarism and transient thyrotoxicosis following asymptomatic pituitary apoplexy.

PubMed

Yoshida, Masanori; Murakami, Miho; Ueda, Harumi; Miyata, Misaki; Takahashi, Norio; Oiso, Yutaka

2014-01-01

Although pituitary function is often impaired in pituitary apoplexy, the development of thyrotoxicosis is rare. We describe an unusual case of hypopituitarism due to pituitary apoplexy coexisting with transient hyperthyroidism. A 74-year-old woman presented with severe fatigue, palpitation, appetite loss, hypotension, and hyponatremia. Endocrine studies showed hyperthyroidism and anterior pituitary hormone deficiencies. A magnetic resonance imaging suggested recent-onset pituitary apoplexy in a pituitary tumor, although the patient had no apoplectic symptoms such as headache and visual disturbance. Thyrotoxicosis and adrenal insufficiency worsened her general condition. Glucocorticoid supplementation improved her clinical symptoms and hyponatremia. Serum anti-thyrotropin receptor and thyroid-stimulating antibody titers were negative, and her thyroid function was spontaneously normalized without antithyroid medication, suggesting painless thyroiditis. Thereafter, her thyroid function decreased because of central hypothyroidism and 75 µg of levothyroxine was needed to maintain thyroid function at the euthyroid stage. The pituitary mass was surgically removed and an old hematoma was detected in the specimen. Considering that painless thyroiditis develops as a result of an autoimmune process, an immune rebound mechanism due to adrenal insufficiency probably caused painless thyroiditis. Although the most common type of thyroid disorder in pituitary apoplexy is central hypothyroidism, thyrotoxicosis caused by painless thyroiditis should be considered even if the patient has pituitary deficiencies. Because thyrotoxicosis with adrenal insufficiency poses a high risk for a life-threatening adrenal crisis, prompt diagnosis and treatment are critical.

Immunohistochemical localization of anterior pituitary hormones in S-100 protein-positive cells in the rat pituitary gland.

PubMed

Kikuchi, Motoshi; Yatabe, Megumi; Tando, Yukiko; Yashiro, Takashi

2011-09-01

In the anterior and intermediate lobes of the rat pituitary gland, non-hormone-producing cells that express S-100 protein coexist with various types of hormone-producing cells and are believed to function as phagocytes, supporting and paracrine-controlling cells of hormone-producing cells and stem cells, among other functions; however, their cytological characteristics are not yet fully understood. Using a transgenic rat that expresses green fluorescent protein under the promoter of the S100β protein gene, we immunohistochemically detected expression of the luteinizing hormone, thyroid-stimulating hormone, prolactin, growth hormone and proopiomelanocortin by S-100 protein-positive cells located between clusters of hormone-producing cells in the intermediate lobe. These findings lend support to the hypothesis that S-100 protein-positive cells are capable of differentiating into hormone-producing cells in the adult rat pituitary gland.

Growth hormone (GH) secretion and pituitary size in children with short stature. Efficacy of GH therapy in GH-deficient children, depending on the pituitary size.

PubMed

Hilczer, Maciej; Szalecki, Mieczysław; Smyczynska, Joanna; Stawerska, Renata; Kaniewska, Danuta; Lewinski, Andrzej

2005-10-01

Certain relationships between pituitary size and growth hormone (GH) secretion have previously been observed, however they are still a matter of controversy. Organic abnormalities of the hypothalamic-hypophyseal region are important for predicting growth response to GH therapy. Evaluation of relations between GH secretion and the pituitary size in short children and estimation of the efficacy of GH therapy in children with GH deficiency (GHD). The analysis comprised 216 short children (159 boys). Two GH stimulation tests, as well as magnetic resonance image (MRI) examination, were performed in each patient. All the patients with GHD were treated with GH for, at least, one year. Significant correlations were found between pituitary height and GH secretion (p < 0.05). Patients were classified into three (3) groups: 1) pituitary hypoplasia (HP) for height age; 2) HP for the chronological age but not for the height age; 3) normal pituitary size. Significant differences in GH secretion were observed among the groups (6.1+/-5.3 vs. 8.1+/-4.4 vs. 12.3+/-9.1 ng/mL, respectively). There was a negative correlation between GH peak and height gain during GH therapy (r = -0.34). The highest growth improvement was noticed in patients with HP for the height age. Pituitary hypoplasia for the height age is related to more severe GH deficiency and the best response to GH therapy.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

PubMed

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T 4 ) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy

PubMed Central

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Abstract. Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T4) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts. PMID:29026274

Ghrelin increases intracellular Ca²⁺ concentration in the various hormone-producing cell types of the rat pituitary gland.

PubMed

Yamazaki, Mami; Aizawa, Sayaka; Tanaka, Toru; Sakai, Takafumi; Sakata, Ichiro

2012-09-20

Ghrelin, isolated from the stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), has potent growth hormone release ability in vivo and in vitro. Although GHS-R is abundantly expressed in the pituitary gland, there is no direct evidence of a relationship between hormone-producing cells and functional GHS-R in the pituitary gland. The aim of this study was to determine which anterior pituitary cells respond to ghrelin stimulation in male rats. We performed Fura-2 Ca(2+) imaging analysis using isolated pituitary cells, and performed immunocytochemistry to identify the type of pituitary hormone-producing cells. In Fura-2 Ca(2+) imaging analysis, ghrelin administration increased the intracellular Ca(2+) concentration in approximately 50% of total isolated anterior pituitary cells, and 20% of these cells strongly responded to ghrelin. Immunocytochemical analysis revealed that 82.9 ± 1.3% of cells that responded to ghrelin stimulation were GH-immunopositive. On the other hand, PRL-, LH-, and ACTH-immunopositive cells constituted 2.0 ± 0.3%, 12.6 ± 0.3%, and 2.5 ± 0.8% of ghrelin-responding pituitary cells, respectively. TSH-immunopositive cells did not respond to ghrelin treatment. These results suggest that ghrelin directly acts not only on somatotrophs, but also on mammotrophs, gonadotrophs, and corticotrophs in the rat pituitary gland. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Does the Pituitary Gland Volume Change in Polycystic Ovary Syndrome?

PubMed

Bozkurt Koseoglu, Sezen; Dinc Elibol, Funda

2018-05-15

Polycystic ovary syndrome (PCOS) is the commonest cause of menstrual irregularity and hirsutism during reproductive age. We hypothesized in the alterations in the pituitary gland in PCOS. We measured the volume of the pituitary gland in 39 PCOS patients and 42 age-matched healthy controls using 0.35 mm thick T1-weighted sagittal cranial images. Serum levels of estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured on days 3-5 of the menstrual cycle of the participants. There was a significant difference in terms of LH, FSH, and LH/FSH ratio (p < 0.05) between groups. Mean pituitary gland volume (PGV) was 4.1 ± 1.36 mm3 for the study group and 3.4 ± 0.77 mm3 for the control group. PGV was statistically significantly higher in PCOS group than the control group (p < 0.05). There was no correlation between hormone levels and PGVs in groups. Enlarged pituitary volume in PCOS may be due to excessive LH release. © 2018 S. Karger AG, Basel.

Growth hormone-releasing hormone stimulates and somatostatin inhibits the release of a novel protein by cultured rat pituitary cells.

PubMed

Tachibana, K; Marquardt, H; Yokoya, S; Friesen, H G

1988-10-01

We have reported that the secretion of at least 17 distinct peptides [including rat (rGH)] GH by cultured rat pituitary cells was stimulated by GH-releasing hormone and inhibited by somatostatin, when analyzed by two-dimensional polyacrylamide gel electrophoresis. Three of these peptides (no. 23, 24, and 25) were not rGH immunoreactive. In order to determine whether these three peptides are fragments, degradation products or posttranscriptionally modified forms of rGH, rGH and peptide no. 23 were characterized structurally. From partial peptide maps of rGH and peptide no. 23 by V8 protease or chymotrypsin, it appeared that these peptides were not related to each other. By N-terminal microsequencing of two-dimensional polyacrylamide gel electrophoresis purified peptide, we have obtained the sequence of 24 N-terminal amino acid residues of peptide no. 23. This sequence has no significant homology with rGH or any other reported protein sequence. Antiserum was generated against a synthetic oligopeptide corresponding to amino acid residues 3-24 of peptide no. 23. The antiserum cross-reacted with peptides no. 23, 24, and 25 upon Western blot analysis. These results indicate that peptide no. 23 has a novel structure unrelated to other pituitary hormones. Since its secretion is influenced by GH-releasing hormone and somatostatin, peptide no. 23 may represent a previously unrecognized structurally unique growth factor.

Testosterone replacement therapy: role of pituitary and thyroid in diagnosis and treatment

PubMed Central

Crawford, Megan

2016-01-01

Crosstalk among hormones characterizes endocrine function, and assessment of the hypogonadal man should take that into consideration. In men for whom testosterone deficiency is a concern, initial evaluation should include a thorough history and physical exam in which other endocrinopathies are being considered. Hypogonadism can be associated with both pituitary and thyroid dysfunction, for which appropriate biochemical evaluation should be undertaken in certain clinical scenarios. If low serum testosterone is confirmed measurement of luteinizing and follicle stimulating hormones (LH and FSH respectively) is essential to establish whether the hypogonadism is primary or secondary. In secondary hypogonadism measurement of prolactin is always necessary, and measurement of other pituitary hormones, along with pituitary imaging, may be indicated. Checking thyroid function may also be enlightening, and can raise additional therapeutic considerations. Correction of other pituitary axes may attenuate the need for testosterone replacement therapy in some cases. PMID:28078216

Stem cells in the canine pituitary gland and in pituitary adenomas.

PubMed

van Rijn, Sarah J; Tryfonidou, Marianna A; Hanson, Jeanette M; Penning, Louis C; Meij, Björn P

2013-12-01

Cushing's disease (CD) or pituitary-dependent hypercortisolism is a common endocrinopathy in dogs, with an estimated prevalence of 1 or 2 in 1000 dogs per year. It is caused by an adrenocorticotropic hormone secreting adenoma in the pars distalis or pars intermedia of the pituitary gland. The pituitary gland is a small endocrine gland located in the pituitary fossa. In the postnatal individual, the hypothalamus-pituitary axis plays a central role in maintaining homeostatic functions, like control of metabolism, reproduction, and growth. Stem cells are suggested to play a role in the homeostatic adaptations of the adult pituitary gland, such as the rapid specific cell-type expansion in response to pregnancy or lactation. Several cell populations have been suggested as pituitary stem cells, such as Side Population cells and cells expressing Sox2 or Nestin. These cell populations are discussed in this review. Also, stem and progenitor cells are thought to play a role in pituitary tumorigenesis, such as the development of pituitary adenomas in dogs. There are limited reports on the role of stem cells in pituitary adenomas, especially in dogs. Further studies are needed to identify and characterize this cell population and to develop specific cell targeting therapeutic strategies as a new way of treating canine CD.

Functional and morphological changes in the adenohypophysis of dogs with induced primary hypothyroidism: loss of TSH hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with transdifferentiation.

PubMed

Diaz-Espiñeira, M M; Mol, J A; van den Ingh, T S G A M; van der Vlugt-Meijer, R H; Rijnberk, A; Kooistra, H S

2008-07-01

From case studies in humans it is known that primary hypothyroidism (PH) may be associated with morphological and functional changes of the pituitary. There is no insight into the time scale of these changes. In this study, seven beagle dogs were followed up for 3 years after the induction of primary hypothyroidism. Three of these dogs were followed up for another 1.5 years while receiving l-thyroxine. Adenohypophyseal function was investigated at 2-month intervals with the combined intravenous injection of CRH, GHRH, GnRH, and TRH, and measurement of the plasma concentrations of ACTH, GH, LH, PRL, and TSH. In addition, after 2 years of hypothyroidism a single TRH-stimulation test and a somatostatin test were performed, with measurements of the same pituitary hormones. Every 6 months the pituitary gland was visualized by computed tomography (CT). Induction of PH led to high plasma TSH concentrations for a few months, where after concentrations gradually declined to values no longer significantly different from pre-PH values. A blunted response to stimulation of TSH release preceded this decline. Basal plasma GH concentrations increased during PH and there was a paradoxical hyperresponsiveness to TRH stimulation. Basal GH concentrations remained elevated and returned only to low values during l-thyroxine treatment. Basal PRL concentrations decreased significantly during PH and normalized after several months of l-thyroxine treatment. The pituitary gland became enlarged in all dogs. Histomorphology and immunohistochemical studies in 4 dogs, after 3 years of PH, revealed thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and decreased numbers of mammotrophs. Several cells stained for both GH and TSH. In conclusion, with time PH led to a loss of the TSH response to low T4 concentrations, hypersecretion of GH, and hyposecretion of PRL. The enlarged pituitaries were characterized by thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and

Investigation of pituitary functions in patients with acute meningitis: a pilot study.

PubMed

Tanriverdi, F; Alp, E; Demiraslan, H; Dokmetas, H S; Unluhizarci, K; Doganay, M; Casanueva, F F; Kelestimur, F

2008-06-01

Although long-term pituitary consequences of tuberculous meningitis are well documented in the literature, there have been few case reports of pituitary dysfunction after acute bacterial or viral meningitis. In this preliminary study, we have assessed the pituitary functions in adult patients who had acute bacterial or viral meningitis. Fourteen patients (8 men, 6 women; mean age 35.3+/-13.3) were included in the study. The diagnosis of bacterial and viral meningitis was proven by clinical findings, cerebrospinal fluid (CSF) examination, gram staining, and blood and CSF cultures. Pituitary functions were evaluated ranging from 6 to 48 months (mean 20 months) after acute meningitis. GH deficiency was investigated by the GHRH+arginine stimulation test. Four of 14 patients (28.6%) had isolated GH deficiency. In GH-deficient patients, the earliest duration was 6 months and the latest duration was 48 months after the diagnosis of acute meningitis. Three of the GH-deficient patients had acute bacterial meningitis and 1 patient had acute viral meningitis. Pituitary magnetic resonance imaging revealed normal pituitary gland in the patients with GH deficiency. This is the first systematic study evaluating the anterior pituitary function long term after the diagnosis of acute meningitis. Based on the present study, it is tempting to speculate that pituitary dysfunction is a more common sequel of acute bacterial or viral meningitis than hitherto reported. Studies with high numbers of patients are warranted to ascertain the prevalence of meningitis-induced hypopituitarism.

The role of hypothalamic inflammation, the hypothalamic-pituitary-adrenal axis and serotonin in the cancer anorexia-cachexia syndrome.

PubMed

van Norren, Klaske; Dwarkasing, Jvalini T; Witkamp, Renger F

2017-09-01

In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia-cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin. The anorexia-cachexia syndrome is directly associated with higher mortality in cancer patients. Recent reports confirm its severe impact on the quality of life of patients and their families.Hypothalamic inflammation has been shown to contribute to muscle and adipose tissue loss in cancer via central hypothalamic interleukine (IL)1β-induced activation of the hypothalamic-pituitary-adrenal axis. The resulting release of glucocorticoids directly stimulates catabolic processes in these tissues via activation of the ubiquitin-proteosome pathway. Next to this, hypothalamic inflammation has been shown to reduce food intake in cancer by triggering changes in orexigenic and anorexigenic responses via upregulation of serotonin availability and stimulation of its signalling pathways in hypothalamic tissues. This combination of reduced food intake and stimulation of tissue catabolism represents a dual mechanism by which hypothalamic inflammation contributes to the development and maintenance of anorexia and cachexia in cancer. Hypothalamic inflammation is a driving force in the development of the anorexia-cachexia syndrome via hypothalamic-pituitary-adrenal axis and serotonin pathway activation.

Relationship between release of LH and incorporation of tritiated thymidine in the anterior pituitary gland of the castrated female rat.

PubMed

Machiavelli, G A; Romano, M I; Burdman, J A

1985-06-01

Castration of female rats during diestrus increases the concentration of circulating LH from days 3 and the incorporation of 3H thymidine into pituitary DNA from day 5. Both effects are completely abolished by the administration of dihydrotestosterone. Although the i.v. injection of LHRH markedly enhances the concentration of LH in serum, it does not modify the incorporation of 3H thymidine into pituitary DNA. Castration might produce a maximal stimulation in 3H thymidine incorporation and a further stimulation of LH release with LHRH is unable to enhance the incorporation of the radioactive precursor. The results suggest a relationship between LH secretion and DNA synthesis in the pituitary gland of the rat.

Female orgasm but not male ejaculation activates the pituitary. A PET-neuro-imaging study.

PubMed

Huynh, Hieu Kim; Willemsen, Antoon T M; Holstege, Gert

2013-08-01

The pituitary gland plays an important role in basic survival mechanisms by releasing fluctuating amounts of hormones into the bloodstream, depending on the circumstances the individual finds itself. However, despite these changes in pituitary hormonal production, neuroimaging studies have never been able to demonstrate changes in the activation level of the pituitary. The most apparent reason is the much higher blood flow rate in the pituitary than in the brain. However, the present PET-scanning study demonstrates for the first time that neuroimaging techniques can identify increased pituitary activity. In a study with 11 healthy women sexual orgasm compared to rest caused an increased blood supply to the pituitary. We assume that this increase signifies elevated pituitary activation in order to produce higher plasma concentrations of oxytocin and prolactin. These hormones induce vaginal and uterus movements, ovulation and enhancement of sperm and egg transport. No increased blood supply was observed comparing clitoral stimulation, orgasm attempt, and faked orgasm with rest. In a study with 11 healthy men comparing ejaculation with rest did not reveal increased pituitary activation, probably because ejaculation causes a much lower increase of oxytocin and prolactin plasma concentration than female orgasm. Copyright © 2013 Elsevier Inc. All rights reserved.

2,3,7,8-tetrachlorodibenzo-p-dioxin potentially attenuates the gene expression of pituitary gonadotropin β-subunits in a fetal age-specific fashion: a comparative study using cultured pituitaries.

PubMed

Takeda, Tomoki; Yamamoto, Midori; Himeno, Masaru; Takechi, Shinji; Yamaguchi, Tadatoshi; Ishida, Takumi; Ishii, Yuji; Yamada, Hideyuki

2011-04-01

Our previous studies have demonstrated that maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a reduction in gonadotropin biosynthesis in the fetal pituitary, resulting in the attenuated expression of steroidogenic proteins in the fetal gonads and the impairment of sexual behaviors in adulthood. However, the mechanism of the attenuation remains unknown. To address this issue, we investigated whether TCDD affects the pituitary production of gonadotropins, using cultured pituitary. In the absence of gonadotropin-releasing hormone (GnRH), a regulator of gonadotropin biosynthesis, TCDD did not affect the expression of gonadotropin mRNAs both in fetal and postnatal pituitaries. On the other hand, in the presence of GnRH, TCDD interfered with the synthesis of gonadotropin β-subunit mRNAs only in the fetal pituitary. A protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate) and a PKA activator (8-bromoadenosine-3' 5'-cyclic monophosphate) induced the expression of gonadotropin mRNAs in the fetal pituitary. Among the subunits, only the induction of β-subunit was reduced by TCDD treatment. These results suggest that TCDD reduces gonadotropin biosynthesis via damage to GnRH-stimulated PKC and PKA signaling in a β-subunit- and fetal age-specific manner.

Stem/progenitor cells in pituitary organ homeostasis and tumourigenesis

PubMed Central

Manshaei, Saba

2018-01-01

Evidence for the presence of pituitary gland stem cells has been provided over the last decade using a combination of approaches including in vitro clonogenicity assays, flow cytometric side population analysis, immunohistochemical analysis and genetic approaches. These cells have been demonstrated to be able to self-renew and undergo multipotent differentiation to give rise to all hormonal lineages of the anterior pituitary. Furthermore, evidence exists for their contribution to regeneration of the organ and plastic responses to changing physiological demand. Recently, stem-like cells have been isolated from pituitary neoplasms raising the possibility that a cytological hierarchy exists, in keeping with the cancer stem cell paradigm. In this manuscript, we review the evidence for the existence of pituitary stem cells, their role in maintaining organ homeostasis and the regulation of their differentiation. Furthermore, we explore the emerging concept of stem cells in pituitary tumours and their potential roles in these diseases. PMID:28855316

Prolactin release, oestrogens and proliferation of prolactin-secreting cells in the anterior pituitary gland of adult male rats.

PubMed

Pérez, R L; Machiavelli, G A; Romano, M I; Burdman, J A

1986-03-01

Relationships among the release of prolactin, the effect of oestrogens and the proliferation of prolactin-secreting cells were studied under several experimental conditions. Administration of sulpiride or oestradiol released prolactin and stimulated cell proliferation in the anterior pituitary gland of adult male rats. Clomiphene completely abolished the rise in cell proliferation, but did not interfere with the sulpiride-induced release of prolactin. Treatment with oestradiol plus sulpiride significantly increased serum prolactin concentrations and the mitotic index compared with the sum of the stimulation produced by both drugs separately. Bromocriptine abolished the stimulatory effect of oestradiol on the serum prolactin concentration and on cell proliferation. In oestradiol- and/or sulpiride-treated rats, 80% of the cells in mitoses were lactotrophs. The remaining 20% did not stain with antisera against any of the pituitary hormones. The number of prolactin-secreting cells in the anterior pituitary gland significantly increased after the administration of oestradiol or sulpiride. The results demonstrate that treatment with sulpiride and/or oestradiol increases the proliferation and the number of lactotrophs in the anterior pituitary gland of the rat.

Combined Growth Hormone and Thyroid-Stimulating Hormone Deficiency in a Japanese Patient with a Novel Frameshift Mutation in IGSF1.

PubMed

Asakura, Yumi; Abe, Kiyomi; Muroya, Koji; Hanakawa, Junko; Oto, Yuji; Narumi, Satoshi; Hasegawa, Tomonobu; Adachi, Masanori

2015-01-01

Recent reports have indicated that loss-of-function mutations in the immunoglobulin superfamily member 1 gene (IGSF1, OMIM 300888) cause congenital central hypothyroidism with macroorchidism. We conducted a next-generation sequencing-based comprehensive mutation screening for pituitary hormone deficiencies to elucidate molecular mechanisms other than anatomical abnormalities of the pituitary that might be responsible for multiple anterior hormone deficiency in a male patient who originally visited our institute complaining of short stature. He was born large for gestational age (4,370 g, +3.0 SD) after an obstructed labour. Endocrinological evaluation revealed growth hormone and thyroid-stimulating hormone deficiency. Magnetic resonance imaging showed a discontinuity of the pituitary stalk with an ectopic posterior lobe and a hypoplastic anterior lobe, likely explaining multiple anterior pituitary hormone deficiency. We identified a novel hemizygous IGSF1 mutation (c.1137_1138delCA, p.Asn380Glnfs*6) in the patient. In reviewing the literature, we noticed that all reported Japanese male IGSF1 mutation carriers were born larger than mean standards for gestational age (mean birth weight SD score of +2.0, 95% confidence interval 1.0-3.0). This case suggests that more attention should be paid to intrauterine growth and birth history when patients are suspected of having an IGSF1 mutation. © 2015 S. Karger AG, Basel.

The effects of combined repetitive transcranial magnetic stimulation and transcranial direct current stimulation on motor function in patients with stroke.

PubMed

Kwon, Tae Gun; Park, Eunhee; Kang, Chung; Chang, Won Hyuk; Kim, Yun-Hee

2016-11-22

Both transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), when provided to stroke patients in combination with motor training, enhance therapeutic efficacy and motor function. However, the majority of previous studies have only examined a single treatment modality. The authors investigated the modulating influence of combination dual-mode brain stimulation upon bihemispheric stimulation with motor training in stroke patients. Twenty stroke patients with hemiparesis underwent five randomly arranged sessions of diverse combinations of rTMS and tDCS. We applied cathodal or anodal tDCS over the contralesional primary motor cortex (cM1) and 10 Hz rTMS over the ipsilesional primary motor cortex (iM1) in a simultaneous or preconditioning method including sham stimulation. Immediately after dual-mode stimulation, sequential hand motor training was performed for 5 minutes. The total pulses of rTMS and the duration of tDCS and motor training were the same for all sessions. Cortical excitability and sequential motor performance were evaluated before and after each session. Motor function and corticomotor excitability following simultaneous stimulation via cathodal tDCS over the cM1 combined with 10 Hz rTMS over the iM1 were significantly increased after the intervention, with significantly greater motor improvement than seen with other treatment conditions (P < 0.05). For the combination of bihemispheric rTMS and tDCS, simultaneous stimulation of cathodal tDCS and 10 Hz rTMS results in better motor performance in stroke patients than other combination methods. This result seemed to be related to effective modulation of interhemispheric imbalance of cortical excitability by dual-mode stimulation.

Pituitary Tumors—Patient Version

Cancer.gov

Pituitary tumors are usually not cancer and are called pituitary adenomas. They grow slowly and do not spread. Rarely, pituitary tumors are cancer and they can spread to distant parts of the body. Start here to find information on pituitary tumors treatment.

Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency.

PubMed

Turton, J P; Strom, M; Langham, S; Dattani, M T; Le Tissier, P

2012-03-01

  Mutations in the POU1F1 gene severely affect the development and function of the anterior pituitary gland and lead to combined pituitary hormone deficiency (CPHD).   The clinical and genetic analysis of a patient presenting with CPHD and functional characterization of identified mutations.   We describe a male patient with extreme short stature, learning difficulties, anterior pituitary hypoplasia, secondary hypothyroidism and undetectable prolactin, growth hormone (GH) and insulin-like growth factor 1 (IGF1), with normal random cortisol.   The POU1F1 coding region was amplified by PCR and sequenced; the functional consequence of the mutations was analysed by cell transfection and in vitro assays.   Genetic analysis revealed compound heterozygosity for two novel putative loss of function mutations in POU1F1: a transition at position +3 of intron 1 [IVS1+3nt(A>G)] and a point mutation in exon 6 resulting in a substitution of arginine by tryptophan (R265W). Functional analysis revealed that IVS1+3nt(A>G) results in a reduction in the correctly spliced POU1F1 mRNA, which could be corrected by mutations of the +4, +5 and +6 nucleotides. Analysis of POU1F1(R265W) revealed complete loss of function resulting from severely reduced protein stability.   Combined pituitary hormone deficiency in this patient is caused by loss of POU1F1 function by two novel mechanisms, namely aberrant splicing (IVS1+3nt (A>G) and protein instability (R265W). Identification of the genetic basis of CPHD enabled the cessation of hydrocortisone therapy without the need for further assessment for evolving endocrinopathy. © 2012 Blackwell Publishing Ltd.

Effects of Insufficient Sleep on Pituitary-Adrenocortical Response to CRH Stimulation in Healthy Men.

PubMed

Guyon, Aurore; Morselli, Lisa L; Balbo, Marcella L; Tasali, Esra; Leproult, Rachel; L'Hermite-Balériaux, Mireille; Van Cauter, Eve; Spiegel, Karine

2017-06-01

Severe sleep restriction results in elevated evening cortisol levels. We examined whether this relative hypercortisolism is associated with alterations in the pituitary-adrenocortical response to evening corticotropin-releasing hormone (CRH) stimulation. Eleven subjects participated in 2 sessions (2 nights of 10 hours vs. 4 hours in bed) in randomized order. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 09:00 to 24:00 for adrenocorticotropic hormone (ACTH) and cortisol measurements, and perceived stress was assessed hourly. Ovine CRH was injected at 18:00 (1 µg/kg body weight). Prior to CRH injection, baseline ACTH, but not cortisol, levels were elevated after sleep restriction. Relative to the well-rested condition, sleep restriction resulted in a 27% decrease in overall ACTH response to CRH (estimated by the incremental area under the curve from 18:00 to 24:00; p = .002) while the cortisol response was decreased by 21% (p = .083). Further, the magnitude of these decreases was correlated with the individual amount of sleep loss (ACTH: rSp = -0.65, p = .032; cortisol: rSp = -0.71, p = .015). The acute post-CRH increment of cortisol was reduced (p = .002) without changes in ACTH reactivity, suggesting decreased adrenal sensitivity. The rate of decline from peak post-injection levels was reduced for cortisol (p = .032), but not for ACTH. Scores of perceived stress were unaffected by CRH injection and were low and similar under both sleep conditions. Sleep restriction is associated with a reduction of the overall ACTH and cortisol responses to evening CRH stimulation, and a reduced reactivity and slower recovery of the cortisol response. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS

PubMed Central

Cardoso, Rodolfo C.; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C.

2016-01-01

Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype. PMID:27792406

Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS.

PubMed

Cardoso, Rodolfo C; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C; Padmanabhan, Vasantha

2016-12-01

Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype.

Occurrence of pituitary dysfunction following traumatic brain injury.

PubMed

Bondanelli, Marta; De Marinis, Laura; Ambrosio, Maria Rosaria; Monesi, Marcello; Valle, Domenico; Zatelli, Maria Chiara; Fusco, Alessandra; Bianchi, Antonio; Farneti, Marco; degli Uberti, Ettore C I

2004-06-01

Traumatic brain injury (TBI) may be associated with impairment of pituitary hormone secretion, which may contribute to long-term physical, cognitive, and psychological disability. We studied the occurrence and risk factors of pituitary dysfunction, including growth hormone deficiency (GHD) in 50 patients (mean age 37.6 +/- 2.4 years; 40 males, age 20-60 years; 10 females, age 23-87 years) with TBI over 5 years. Cranial or facial fractures were documented in 12 patients, and neurosurgery was performed in 14. According to the Glasgow Coma Scale (GCS), 16 patients had suffered from mild, 7 moderate, and 27 severe TBI. Glasgow Outcome Scale (GOS) indicated severe disability in 5, moderate disability in 11, and good recovery in 34 cases. Basal pituitary hormone evaluation, performed once at times variable from 12 to 64 months after TBI, showed hypogonadotrophic hypogonadism in 7 (14%), central hypothyroidism in 5 (10%), low prolactin (PRL) levels in 4 (8%), and high PRL levels in 4 (8%) cases. All subjects had normal corticotrophic and posterior pituitary function. Seven patients showed low insulin-like growth factor-I (IGF-I) levels for age and sex. Results of GHRH plus arginine testing indicated partial GHD in 10 (20%) and severe GHD in 4 (8%) cases. Patients with GHD were older (p <0.05) than patients with normal GH secretion. Magnetic resonance imaging demonstrated pituitary abnormalities in 2 patients; altogether pituitary dysfunction was observed in 27 (54%) patients. Six patients (12%) showed a combination of multiple abnormalities. Occurrence of pituitary dysfunction was 37.5%, 57.1%, and 59.3% in the patients with mild, moderate, and severe TBI, respectively. GCS scores were significantly (p <0.02) lower in patients with pituitary dysfunction compared to those with normal pituitary function (8.3 +/- 0.5 vs. 10.2 +/- 0.6). No relationship was detected between pituitary dysfunction and years since TBI, type of injury, and outcome from TBI. In conclusion, subjects

Establishment and culture optimization of a new type of pituitary immortalized cell line.

PubMed

Kokubu, Yuko; Asashima, Makoto; Kurisaki, Akira

2015-08-07

The pituitary gland is a center of the endocrine system that controls homeostasis in an organism by secreting various hormones. The glandular anterior pituitary consists of five different cell types, each expressing specific hormones. However, their regulation and the appropriate conditions for their in vitro culture are not well defined. Here, we report the immortalization of mouse pituitary cells by introducing TERT, E6, and E7 transgenes. The immortalized cell lines mainly expressed a thyrotroph-specific thyroid stimulating hormone beta (Tshb). After optimization of the culture conditions, these immortalized cells proliferated and maintained morphological characteristics similar to those of primary pituitary cells under sphere culture conditions in DMEM/F12 medium supplemented with N2, B27, basic FGF, and EGF. These cell lines responded to PKA or PKC pathway activators and induced the expression of Tshb mRNA. Moreover, transplantation of the immortalized cell line into subcutaneous regions and kidney capsules of mice further increased Tshb expression. These results suggest that immortalization of pituitary cells with TERT, E6, and E7 transgenes is a useful method for generating proliferating cells for the in vitro analysis of pituitary regulatory mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Acromegaly due to a Macroinvasive Plurihormonal Pituitary Adenoma and a Rectal Carcinoid Tumor

PubMed Central

Chin, Sang Ouk; Hwang, Jin-Kyung; Rhee, Sang Youl; Chon, Suk; Oh, Seungjoon; Lee, Misu; Pellegata, Natalia S.

2015-01-01

A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific transcription factor-1 (Pit-1) was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor. PMID:25559714

Detection of Pituitary Antibodies by Immunofluorescence: Approach and Results in Patients With Pituitary Diseases

PubMed Central

Ricciuti, Adriana; De Remigis, Alessandra; Landek-Salgado, Melissa A.; De Vincentiis, Ludovica; Guaraldi, Federica; Lupi, Isabella; Iwama, Shintaro; Wand, Gary S.; Salvatori, Roberto

2014-01-01

Context: Pituitary antibodies have been measured mainly to identify patients whose disease is caused or sustained by pituitary-specific autoimmunity. Although reported in over 100 publications, they have yielded variable results and are thus considered of limited clinical utility. Objectives: Our objectives were to analyze all publications reporting pituitary antibodies by immunofluorescence for detecting the major sources of variability, to experimentally test these sources and devise an optimized immunofluorescence protocol, and to assess prevalence and significance of pituitary antibodies in patients with pituitary diseases. Study Design and Outcome Measures: We first evaluated the effect of pituitary gland species, section fixation, autofluorescence quenching, blockade of unwanted antibody binding, and use of purified IgG on the performance of this antibody assay. We then measured cross-sectionally the prevalence of pituitary antibodies in 390 pituitary cases and 60 healthy controls, expressing results as present or absent and according to the (granular, diffuse, perinuclear, or mixed) staining pattern. Results: Human pituitary was the best substrate to detect pituitary antibodies and yielded an optimal signal-to-noise ratio when treated with Sudan black B to reduce autofluorescence. Pituitary antibodies were more common in cases (95 of 390, 24%) than controls (3 of 60, 5%, P = .001) but did not discriminate among pituitary diseases when reported dichotomously. However, when expressed according to their cytosolic staining, a granular pattern was highly predictive of pituitary autoimmunity (P < .0001). Conclusion: We report a comprehensive study of pituitary antibodies by immunofluorescence and provide a method and an interpretation scheme that should be useful for identifying and monitoring patients with pituitary autoimmunity. PMID:24606106

[Influence of hyperprolactinemia and tumoral size in the postoperative pituitary function in clinically nonfunctioning pituitary macroadenomas].

PubMed

Fonseca, Ana Luiza Vidal; Chimelli, Leila; Santos, Mario José C Felippe; Santos, Alair Augusto S M Damas dos; Violante, Alice Helena Dutra

2002-09-01

To study the influence of hyperprolactinemia and tumoral size in the pituitary function in clinically nonfunctioning pituitary macroadenomas. Twenty three patients with clinically nonfunctioning pituitary macroadenomas were evaluated by image studies (computed tomography or magnetic resonance) and basal hormonal level; 16 had preoperative hypothalamus-hypophysial function tests (megatests). All tumors had histological diagnosis and in seventeen immunohistochemical study for adenohypophysial hormones was also performed. Student's t test, chi square test, exact test of Fisher and Mc Neman test were used for the statistics analysis. The level of significance adopted was 5% (p<0.05). Tumoral diameter varied of 1.1 to 4.7 cm (average=2.99 cm +/- 1.04). In the preoperative, 5 (21.7%) patients did not show laboratorial hormonal deficit, 9 (39.1%) developed hyperprolactinemia, 13 (56,5%) normal levels of prolactin (PRL) and 1 (4.3%) subnormal; 18 (78.3%) patients developed hypopituitarism (4 pan-hypopituitarism). Nineteen patients (82.6%) underwent transsfenoidal approach, 3 (13%) craniotomy and 1 (4.4%) combined access. Only 6 patients had total tumoral resection. Of the 17 immunohistochemical studies, 5 tumours were immunonegatives, 1 compound, 1 LH+, 1 FSH +, 1 alpha sub-unit and 8 focal or isolated immunorreactivity for one of the pituitary hormones or sub-units; of the other six tumours, 5 were chromophobe and 1 chromophobe/acidophile. No significant statistic difference was noted between tumoral size and preoperative PRL levels (p=0.82), nor between tumoral size and postoperative hormonal state, except in the GH and gonadal axis. Significant statistic was noted: between tumoral size and preoperative hormonal state (except in the gonadal axis); between normal PRL levels, associated to none or little preoperative hypophysial disfunction, and recovery of postoperative pituitary function. Isolated preoperative hyperprolactinemia and tumoral size have not been predictable

Two novel LHX3 mutations in patients with combined pituitary hormone deficiency including cervical rigidity and sensorineural hearing loss.

PubMed

Ramzan, Khushnooda; Bin-Abbas, Bassam; Al-Jomaa, Lolwa; Allam, Rabab; Al-Owain, Mohammed; Imtiaz, Faiqa

2017-03-16

Congenital combined pituitary hormone deficiency (CPHD) is a rare heterogeneous group of conditions. CPHD-type 3 (CPHD3; MIM# 221750) is caused by recessive mutations in LHX3, a LIM-homeodomain transcription factor gene. The isoforms of LHX3 are critical for pituitary gland formation and specification of the anterior pituitary hormone-secreting cell types. They also play distinct roles in the development of neuroendocrine and auditory systems. Here, we summarize the clinical, endocrinological, radiological and molecular features of three patients from two unrelated families. Clinical evaluation revealed severe CPHD coupled with cervical vertebral malformations (rigid neck, scoliosis), mild developmental delay and moderate sensorineural hearing loss (SNHL). The patients were diagnosed with CPHD3 based on the array of hormone deficiencies and other associated syndromic symptoms, suggestive of targeted LHX3 gene sequencing. A novel missense mutation c.437G > T (p. Cys146Phe) and a novel nonsense mutation c.466C > T (p. Arg156Ter), both in homozygous forms, were found. The altered Cys146 resides in the LIM2 domain of the encoded protein and is a phylogenetically conserved residue, which mediates LHX3 transcription factor binding with a zinc cation. The p. Arg156Ter is predicted to result in a severely truncated protein, lacking the DNA binding homeodomain. Considering genotype/phenotype correlation, we suggest that the presence of SNHL and limited neck rotation should be considered in the differential diagnosis of CPHD3 to facilitate molecular diagnosis. This report describes the first LHX3 mutations from Saudi patients and highlights the importance of combining molecular diagnosis with the clinical findings. In addition, it also expands the knowledge of LHX3-related CPHD3 phenotype and the allelic spectrum for this gene.

Pituitary iron and volume predict hypogonadism in transfusional iron overload.

PubMed

Noetzli, Leila J; Panigrahy, Ashok; Mittelman, Steven D; Hyderi, Aleya; Dongelyan, Ani; Coates, Thomas D; Wood, John C

2012-02-01

Hypogonadism is the most common morbidity in patients with transfusion-dependent anemias such as thalassemia major. We used magnetic resonance imaging (MRI) to measure pituitary R2 (iron) and volume to determine at what age these patients develop pituitary iron overload and volume loss. We recruited 56 patients (47 with thalassemia major, five with chronically transfused thalassemia intermedia and four with Blackfan-Diamond syndrome) to have pituitary MRIs to measure pituitary R2 and volume. Hypogonadism was defined clinically based on the timing of secondary sexual characteristics or the need for sex hormone replacement therapy. Patients with transfusional iron overload begin to develop pituitary iron overload in the first decade of life; however, clinically significant volume loss was not observed until the second decade of life. Severe pituitary iron deposition (Z > 5) and volume loss (Z < -2.5) were independently predictive of hypogonadism. Pituitary R2 correlated significantly with serum ferritin as well as liver, pancreatic, and cardiac iron deposition by MRI. Log pancreas R2* was the best single predictor for pituitary iron, with an area under the receiving operator characteristic curve of 0.88, but log cardiac R2* and ferritin were retained on multivariate regression with a combined r(2) of 0.71. Pituitary iron overload and volume loss were independently predictive of hypogonadism. Many patients with moderate-to-severe pituitary iron overload retained normal gland volume and function, representing a potential therapeutic window. The subset of hypogonadal patients having preserved gland volumes may also explain improvements in pituitary function observed following intensive chelation therapy. Copyright © 2011 Wiley Periodicals, Inc.

Pituitary Tumors

MedlinePlus

... Organizations Publications Definition The pituitary is a small, bean-sized gland that is below the hypothalamus, a ... common diseases. × Definition The pituitary is a small, bean-sized gland that is below the hypothalamus, a ...

Effect of haloperidol on the synthesis of DNA in the pituitary gland of the rat.

PubMed

Machiavelli, G A; Jahn, G A; Kalbermann, L E; Szijan, I; Alonso, G E; Burdman, J A

1982-03-01

The administration of haloperidol increased serum prolactin and decreased the pituitary concentration of prolactin 15 min after its administration. Concomitantly there was a stimulation in the synthesis of DNA and the activity of DNA polymerase alpha in the anterior pituitary gland that was greater in oestrogenized than in non-oestrogenized male rats. Both these effects were greatly reduced by clomiphene in the oestrogenized male rats, although it did not affect the release of prolactin produced by haloperidol. In non-oestrogenized animals clomiphene abolished the stimulatory effect of haloperidol on the synthesis of DNA. These results suggest that the reduction in the intracellular levels of prolactin are a primary event in the oestrogen mediated stimulation of cell proliferation by prolactin releasing agents.

V3 vasopressin receptor and corticotropic phenotype in pituitary and nonpituitary tumors.

PubMed

de Keyzer, Y; René, P; Lenne, F; Auzan, C; Clauser, E; Bertagna, X

1997-01-01

Pituitary corticotropic cells express a specific vasopressin receptor, called V1b or V3, through which vasopressin stimulates corticotropin secretion. We recently cloned a cDNA coding for this receptor and showed that it belongs to the G protein-coupled receptor family. V3 mRNA is readily detected by RT-PCR in normal human pituitaries and corticotropic pituitary adenomas but not in PRL or GH-secreting adenomas, thus demonstrating that, like POMC itself and the CRH receptor, V3 is a marker of the corticotropic phenotype. Nuclease protection experiments suggest that V3 is overexpressed in some corticotropic adenomas, and thus may play a role in tumor development by activating the phospholipase C-signalling pathway. In addition analysis of its expression in nonpituitary neuroendocrine tumors showed a striking association with carcinoids of the lung responsible for the ectopic ACTH syndrome.

Submicroscopic deletion involving the fibroblast growth factor receptor 1 gene in a patient with combined pituitary hormone deficiency.

PubMed

Fukami, Maki; Iso, Manami; Sato, Naoko; Igarashi, Maki; Seo, Misuzu; Kazukawa, Itsuro; Kinoshita, Eiichi; Dateki, Sumito; Ogata, Tsutomu

2013-01-01

Combined pituitary hormone deficiency (CPHD), isolated hypogonadotropic hypogonadism (IHH), Kallmann syndrome (KS), and septo-optic dysplasia (SOD) are genetically related conditions caused by abnormal development of the anterior midline in the forebrain. Although mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been implicated in the development of IHH, KS, and SOD, the relevance of FGFR1 abnormalities to CPHD remains to be elucidated. Here, we report a Japanese female patient with CPHD and FGFR1 haploinsufficiency. The patient was identified through copy-number analyses and direct sequencing of FGFR1 performed for 69 patients with CPHD. The patient presented with a combined deficiency of GH, LH and FSH, and multiple neurological abnormalities. In addition, normal TSH values along with a low free T4 level indicated the presence of central hypothyroidism. Molecular analyses identified a heterozygous ~ 8.5 Mb deletion involving 56 genes and pseudogenes. None of these genes except FGFR1 have been associated with brain development. No FGFR1 abnormalities were identified in the remaining 68 patients, although two patients carried nucleotide substitutions (p.V102I and p.S107L) that were assessed as benign polymorphism by in vitro functional assays. These results indicate a possible role of FGFR1 in anterior pituitary function and the rarity of FGFR1 abnormalities in patients with CPHD.

Two coexisting heterozygous frameshift mutations in PROP1 are responsible for a different phenotype of combined pituitary hormone deficiency.

PubMed

Ziemnicka, K; Budny, B; Drobnik, K; Baszko-Błaszyk, D; Stajgis, M; Katulska, K; Waśko, R; Wrotkowska, E; Słomski, R; Ruchała, M

2016-08-01

The role of genetic background in childhood-onset combined pituitary hormone deficiency (CPHD) has been extensively studied. The major contributors are the PROP1, POU1F1, LHX3, LHX4 and HESX1 genes coding transcription factors implicated in pituitary organogenesis. The clinical consequences of mutations encompass impaired synthesis of a growth hormone (GH) and one or more concurrent pituitary hormones (i.e. LH, FSH, TSH, PRL). Manifestation of the disorder may vary due to various mutation impacts on the final gene products or an influence of environmental factors during pituitary organogenesis. We describe the clinical and molecular characteristics of two brothers aged 47 and 39 years presenting an uncommon manifestation of congenital hypopituitarism. Sequencing of the PROP1, POU1F1, LHX3, LHX4 and HESX1 genes was performed to confirm the genetic origin of the disorder. A compound heterozygosity in the PROP1 gene has been identified for both probands. The first change represents a mutational hot spot (c.150delA, p.R53fsX164), whereas the second is a novel alteration (p.R112X) that leads to protein disruption. Based on precise genetic diagnosis, an in silico prediction of a p.R112X mutation on protein architecture was performed. The resulting clinical phenotype was surprisingly distinct compared to most patients with genetic alterations in PROP1 reported in the current literature. This may be caused by a residual activity of a newly identified p.R112X protein that preserves over 70 % of the homeodomain structure. This examination may confirm a key role of a DNA-binding homeodomain in maintaining PROP1 functionality and suggests a conceivable explanation of an unusual phenotype.

Pituitary gigantism: a case report.

PubMed

Bhattacharjee, Rana; Roy, Ajitesh; Goswami, Soumik; Selvan, Chitra; Chakraborty, Partha P; Ghosh, Sujoy; Biswas, Dibakar; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2012-12-01

To present a rare case of gigantism. A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years. She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory. Blood pressure was normal. Height 221 cm, weight 138 kg, body mass index (BMI)28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1) was 703 ng/ml with all glucose suppressedgrowth hormone (GH)values of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH), follicle stimulating Hormone (FSH) was low. Oral glucose tolerance test (OGTT), liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH) were normal. Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment.

Pituitary Gigantism: A Case Report

PubMed Central

Bhattacharjee, Rana; Roy, Ajitesh; Goswami, Soumik; Selvan, Chitra; Chakraborty, Partha P.; Ghosh, Sujoy; Biswas, Dibakar; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2012-01-01

Objective: To present a rare case of gigantism. Case Report: A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years. She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory. Blood pressure was normal. Height 221 cm, weight 138 kg, body mass index (BMI)28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1) was 703 ng/ml with all glucose suppressedgrowth hormone (GH)values of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH), follicle stimulating Hormone (FSH) was low. Oral glucose tolerance test (OGTT), liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH) were normal. Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment. PMID:23565401

Transcriptome-Wide Identification of Preferentially Expressed Genes in the Hypothalamus and Pituitary Gland

PubMed Central

St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

2012-01-01

To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12–15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland. PMID:22649398

Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland.

PubMed

St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

2011-01-01

To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12-15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

Pituitary Imaging.

PubMed

Pressman, Barry D

2017-09-01

Modern pituitary imaging is MRI. However, computed tomography (CT) still has limited usefulness. In addition, because CT offers much better bone detail and calcium detection, there are some cases in which such additional information is necessary. Before the advent of CT, plain radiography, pneumoencephalography, and angiography were used to diagnose pituitary masses. More recently, CT, and then especially MRI, made it possible to primarily delineate lesions within and around the pituitary gland rather than depend on secondary information that could only suggest their presence. Copyright © 2017 Elsevier Inc. All rights reserved.

Pituitary tumor

MedlinePlus

... during the person's lifetime. The pituitary is part of the endocrine system. The pituitary helps control the release of hormones ... Hollander AB, Alonso-Basanta M, et al. Cancer of the central nervous system. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan ...

Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene.

PubMed

Burton, F H; Hasel, K W; Bloom, F E; Sutcliffe, J G

1991-03-07

Cyclic AMP is thought to act as an intracellular second messenger, mediating the physiological response of many cell types to extracellular signals. In the pituitary, growth hormone (GH)-producing cells (somatotrophs) proliferate and produce GH in response to hypothalamic GH-releasing factor, which binds a receptor that stimulates Gs protein activation of adenylyl cyclase. We have now determined whether somatotroph proliferation and GH production are stimulated by cAMP alone, or require concurrent, non-Gs-mediated induction of other regulatory molecules by designing a transgene to induce chronic supraphysiological concentrations of cAMP in somatotrophs. The rat GH promoter was used to express an intracellular form of cholera toxin, a non-cytotoxic and irreversible activator of Gs. Introduction of this transgene into mice caused gigantism, elevated serum GH levels, somatotroph proliferation and pituitary hyperplasia. These results support the direct triggering of these events by cAMP, and illustrate the utility of cholera toxin transgenes as a tool for physiological engineering.

Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism.

PubMed

De Bellis, A; Dello Iacovo, A; Bellastella, G; Savoia, A; Cozzolino, D; Sinisi, A A; Bizzarro, A; Bellastella, A; Giugliano, D

2014-10-01

Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.

ROLE OF THE PITUITARY GLAND IN MELANIZATION IN THE SKIN OF THE GOLDFISH, CARASSIUS AURATUS, INDUCED BY X-RAY IRRADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Egami, N.; Etoh, H.; Tachi, C.

1962-01-01

The role of the pituitary gland in the melanogenesis caused by x irradiation in the goldfish, Carassius auratus, was studied. It was concluded that the secretion of adrenocorticotropic hormone from the pituitary is stimulated by exposing goldfish to x radiation and that melanophores in the skin are produced by the overexcretion of the hormone. (C.H.)

Abnormalities of tooth development in pituitary dwarfism.

PubMed

Kosowicz, J; Rzymski, K

1977-12-01

Roentgenographic studies of the jaws and teeth in a group of forty-eight pituitary dwarfs showed the following abnormalities in the development of the teeth: 1. Delayed shedding of the deciduous teeth. 2. Absence of resorption of the roots of the deciduous teeth at the usual time. 3. Marked delay in eruption of the permanent teeth. 4. Retention of permanent teeth in the maxillary and mandibular shafts. 5. Development of the apical parts of roots of the retained permanent teeth and their growth toward the lower mandibular edge. 6. Displacement of the first molars from the mandibular shaft to rami. 7. Tilting of some of the retained teeth. 8. Small size of the maxilla and mandible with overcrowding of the teeth in these bones. 9. Complete absence of buds of the wisdom teeth, even in patients in the fourth decade of life. 10. Stimulation of development and eruption of the teeth after administration of anabolic drugs. These abnormalities when present in combination depend on growth hormone deficiency since they do not occur in other types of dwarfism.

Diagnostic Usefulness of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor Binding Protein 3 in Children with Suspected Pituitary Dwarfism.

PubMed

Zelazowska-Rutkowska, Beata; Trusiak, Marta; Bossowski, Artur; Cylwik, Bogdan

2018-05-01

Pituitary dwarfism (also known as short stature) is a medical condition in which the pituitary gland does not produce enough growth hormone (GH). To confirm the diagnosis of growth hormone deficiency the overnight profile of GH secretion and GH provocative tests are usually performed; however, due to wide GH fluctuations throughout the day and night and the invasiveness of stimulation tests, their clinical utility is limited. Therefore, screening for IGF-1 (insulin-like growth factor 1) and IGFBP-3 (insulin-like growth factor binding protein type 3) is proposed, suggesting that these tests provide a more accurate reflection of the mean plasma GH level, although the results of these tests are still problematic. In this context, the aim of this study was to assess the diagnostic usefulness of IGF-1 and IGFBP-3 in children with suspected pituitary dwarfism. Studies were carried out in 127 children with abnormal growth and low spontaneous 24-hour plasma GH profiles and abnormal results of GH stimulation tests. Fasting serum IGF-1 and IGFBP-3 were determined by chemiluminescent quantitative measurement using the IMMULITE 1000 IGF-1 and IGFBP-3 kits (Siemens Healthcare Diagnostics, United Kingdom) on the IMMULITE 1000 analyzer (Siemens Healthcare Diagnostics, USA). Results were compared to the normal range by children's age. Mean serum IGF-1 concentrations were within the lower normal range (41.7% cases), and 58.3% results were below the normal reference range in the study group. The average serum IGFBP-3 levels were within the lower normal range. We conclude that IGF-1 test can be a useful tool in the diagnosis of pituitary dwarfism in children suspected of this condition, but due to relatively poor sensitivity the testing cannot be performed alone, but in combination with other tests. The IGFBP-3 test is not useful for the diagnosis of this disease.

Alteration in G Proteins and Prolactin Levels in Pituitary After Ethanol and Estrogen Treatment

PubMed Central

Chaturvedi, Kirti; Sarkar, Dipak K.

2010-01-01

Background Chronic administration of ethanol increases plasma prolactin levels and enhances estradiol’s mitogenic action on the lactotropes of the pituitary gland. The present study was conducted to determine the changes in the pituitary levels of G proteins during the tumor development following alcohol and ethanol treatments. Methods Using ovariectomized Fischer-344 female rats, we have determined ethanol and estradiol actions at 2 and 4 weeks on pituitary weight and pituitary cell contents of prolactin, Gs. Gq11, Gi1, Gi2, and Gi3 proteins. Western blots were employed to measure protein contents. Results Ethanol increased basal and estradiol-enhanced wet weight and the prolactin content in the pituitary in a time-dependent manner. Chronic exposure of estradiol increased the levels of Gs protein in the pituitary. Unlike estradiol, ethanol exposure did not show significant effect on the basal level of Gs protein, but moderately increased the estradiol-induced levels of this protein. Estradiol exposure enhanced Gq11 protein levels in the pituitary after 2 and 4 weeks, while ethanol treatment failed to alter these protein levels in the pituitary in control-treated or estradioltreated ovariectomized rats. In the case of Gi1, estradiol but not ethanol increased the level of this protein at 4 weeks of treatment. However, estradiol and ethanol alone reduced the levels of both Gi2 and Gi3 proteins at 2 and 4 weeks of treatment. Ethanol also significantly reduced the estradiol-induced Gi2 levels at 4 weeks and Gi3 level at 2 and 4 weeks. Conclusions These results confirm ethanol’s and estradiol’s growth-promoting and prolactin stimulating actions on lactotropes of the pituitary and further provide evidence that ethanol and estradiol may control lactotropic cell functions by altering expression of specific group of G proteins in the pituitary. PMID:18336630

METHOXYCHLOR-INDUCED ALTERATIONS IN THE HISTOLOGICAL EXPRESSION OF ANGIOGENIC FACTORS IN PITUITARY AND UTERUS

EPA Science Inventory

Within the reproductive system, estrogenic stimulation of uterine and pituitary tissue typically causes a proliferative response accompanied by an angiogenic induction of new blood vessels from existing ones, thereby providing nutrients and oxygen to the growing tissue. The proes...

STRESS IN THE CLASSIFICATION OF PITUITARY TUMORS. FOCUS ON AGGRESSIVE PITUITARY ADENOMAS.

PubMed

Kovács, Kálmán; Rotondo, Fabio; Horváth, Eva; Syro, Luis V

2014-03-30

After a brief summary of the stress concept and the contribution of Dr. Hans Selye, this publication focuses on the classification of pituitary neoplasms and the difficulties to provide conclusive information on the prognosis of various pituitary tumor types. The term "aggressive pituitary tumors" was introduced. These tumors have a rapid cell proliferation rate. At present, the assessment of Ki-67 nuclear labeling index appears to be the simplest and most reliable method to evaluate tumor cell multiplication. Further studies on pituitary tumor biomarkers are needed.

Steroidogenic Factor 1, Pit-1, and Adrenocorticotropic Hormone: A Rational Starting Place for the Immunohistochemical Characterization of Pituitary Adenoma.

PubMed

McDonald, William C; Banerji, Nilanjana; McDonald, Kelsey N; Ho, Bridget; Macias, Virgilia; Kajdacsy-Balla, Andre

2017-01-01

-Pituitary adenoma classification is complex, and diagnostic strategies vary greatly from laboratory to laboratory. No optimal diagnostic algorithm has been defined. -To develop a panel of immunohistochemical (IHC) stains that provides the optimal combination of cost, accuracy, and ease of use. -We examined 136 pituitary adenomas with stains of steroidogenic factor 1 (SF-1), Pit-1, anterior pituitary hormones, cytokeratin CAM5.2, and α subunit of human chorionic gonadotropin. Immunohistochemical staining was scored using the Allred system. Adenomas were assigned to a gold standard class based on IHC results and available clinical and serologic information. Correlation and cluster analyses were used to develop an algorithm for parsimoniously classifying adenomas. -The algorithm entailed a 1- or 2-step process: (1) a screening step consisting of IHC stains for SF-1, Pit-1, and adrenocorticotropic hormone; and (2) when screening IHC pattern and clinical history were not clearly gonadotrophic (SF-1 positive only), corticotrophic (adrenocorticotropic hormone positive only), or IHC null cell (negative-screening IHC), we subsequently used IHC for prolactin, growth hormone, thyroid-stimulating hormone, and cytokeratin CAM5.2. -Comparison between diagnoses generated by our algorithm and the gold standard diagnoses showed excellent agreement. When compared with a commonly used panel using 6 IHC for anterior pituitary hormones plus IHC for a low-molecular-weight cytokeratin in certain tumors, our algorithm uses approximately one-third fewer IHC stains and detects gonadotroph adenomas with greater sensitivity.

Effects of cytokines on the pituitary-adrenal axis in cancer patients.

PubMed

Nolten, W E; Goldstein, D; Lindstrom, M; McKenna, M V; Carlson, I H; Trump, D L; Schiller, J; Borden, E C; Ehrlich, E N

1993-10-01

Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-beta (IFN-beta ser), 90 or 450 x 10(6) IU, IFN-gamma, 0.1-100 x 10(6) IU, or TNF 125-275 micrograms/m2. Sixty to 120 min after IFN-beta ser injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-beta ser administration. IFN-gamma > or = 30 x 10(6) IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.

Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes.

PubMed

Bertko, Eleonore; Klammt, Jürgen; Dusatkova, Petra; Bahceci, Mithat; Gonc, Nazli; Ten Have, Louise; Kandemir, Nurgun; Mansmann, Georg; Obermannova, Barbora; Oostdijk, Wilma; Pfäffle, Heike; Rockstroh-Lippold, Denise; Schlicke, Marina; Tuzcu, Alpaslan Kemal; Pfäffle, Roland

2017-08-01

Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of pituitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients.

Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes

PubMed Central

Bertko, Eleonore; Klammt, Jürgen; Dusatkova, Petra; Bahceci, Mithat; Gonc, Nazli; ten Have, Louise; Kandemir, Nurgun; Mansmann, Georg; Obermannova, Barbora; Oostdijk, Wilma; Pfäffle, Heike; Rockstroh-Lippold, Denise; Schlicke, Marina; Tuzcu, Alpaslan Kemal; Pfäffle, Roland

2017-01-01

Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of pituitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients. PMID:28356564

Follicular thyroid carcinoma with metastases to the pituitary causing pituitary insufficiency.

PubMed

Vianello, Federica; Mazzarotto, Renzo; Taccaliti, Augusto; Lora, Ornella; Basso, Michela; Servodio, Oscar; Mian, Caterina; Sotti, Guido

2011-08-01

Pituitary metastases are found in about 1% of all pituitary resections. They often derive from breast, lung, and gastroenteric tract adenocarcinomas, very rarely from thyroid carcinoma. Presenting symptoms of thyroid carcinoma metastatic to the pituitary gland are usually chiasmatic with central neurological impairment due to space-occupying expansion in the parasellar region. Hypopituitarism is more often associated with papillary and medullary rather than follicular thyroid carcinoma (FTC). Here we describe a patient with pituitary metastasis from FTC who had hypopituitarism with thyrotropin (TSH) deficiency. A 61-year-old woman, who presented with visual deficits and pain to the right orbit, was found on magnetic resonance imaging to have a large mass involving the pituitary gland. She was found to have pituitary insufficiency based on corticotropin-releasing hormone and TSH-releasing hormone testing. Transnasopharyngeal biopsy of the mass revealed metastases from FTC. After total thyroidectomy, which confirmed widely invasive FTC, the patient underwent external beam radiation therapy of the metastases for progressive neurological symptoms and an increase in orbit pain. Since endogenous TSH production was insufficient, we used recombinant human TSH (rhTSH) as preparation for a series of radioiodine treatments. rhTSH administration, followed by 7.4 GBq of (131)I, was repeated seven times over a 10-year period. This was associated with a marked decrease in serum thyroglobulin levels accompanied by substantial clinical improvement, but after 7 years disease progression occurred. Seven patients with pituitary metastases from FTC have been reported. In all cases, some neurological signs and symptoms related to mass effect were reported, but no pituitary insufficiency was described. This may be the first case of FTC with metastases to the pituitary causing hypopituitarism. It seems likely that management of such cases could be limited to biopsy to confirm thyroid

Diagnosis and treatment of pituitary adenomas.

PubMed

Chanson, P; Salenave, S

2004-12-01

Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). All patients with pituitary tumors should be evaluated for gonadal, thyroid and adrenal function as well as PRL and GH secretion. Specific stimulation and suppression tests for pituitary hormones are performed in selected situations for detecting the type of hypersecretion or the response to treatment. Imaging procedures (mainly magnetic resonance imaging, MRI, nowadays) determine the presence, size and extent of the lesion. The classification of pituitary tumors is based on the staining properties of the cell cytoplasm viewed by light microscopy and immunocytochemistry revealing the secretory pattern of the adenoma. Treatment of pituitary adenomas consists of surgery (performed in more than 99% of cases via a transphenoidal route) and radiotherapy, generally fractionated or, in selected cases, using stereotactic techniques such as gamma-knife. The availability of medical treatment (dopamine, DA, agonists, somatostatin analogs, GH-receptor antagonists...) has profoundly modified the indications of radiotherapy, drugs being now generally used as a second-line treatment, after surgery (or even as first-line treatment). Based on the results of the different treatment modalities for each type of pituitary adenoma, recommendations will be proposed. They may be summarized as follows. For treatment of GH-secreting adenomas, trans-sphenoidal surgery is the first-line therapy except when the macroadenoma is giant or if surgery is contra-indicated; postoperative radiation therapy (fractionated, or by gamma-knife) is

Pituitary gigantism.

PubMed Central

Lu, P W; Silink, M; Johnston, I; Cowell, C T; Jimenez, M

1992-01-01

A case of pituitary gigantism resulting from a pituitary adenoma which secreted growth hormone is described. The patient was successfully treated by surgery, which led to the normalisation of endogenous growth hormone secretion. An acceptable final height was achieved with high dose intramuscular testosterone treatment. Images Figure 1 PMID:1520009

Triangular stimulation method utilizing combination spinal cord stimulation with peripheral subcutaneous field stimulation for chronic pain patients: a retrospective study.

PubMed

Navarro, Rosa M; Vercimak, Danika C

2012-01-01

This retrospective data collection study aims to evaluate the responses of patients who have been implanted with a neuromodulation system using a combination of spinal cord stimulation (SCS) and peripheral subcutaneous field stimulation (PSFS) leads for chronic intractable pain. Forty patients with chronic, intractable pain implanted with both SCS and PSFS leads were enrolled in a retrospective data collection study. Pre-implant data (demographics, pain levels, pain location, and medication use) and post-implant data (pain levels, medication use, and device programming reports) were compared to measure short- and long-term improvements in pain for a period of approximately six months. Device system use and parameter data were collected. The majority of patients experienced immediate and short-term pain relief and reduction in oral pain medications as a result of combination SCS/PSFS therapy. The improvements were maintained for some, but not all patients by six months. Patients cycled through multiple programs over follow-up; the use of triangular stimulation was consistent over time, and by six months, patients preferred this program over others. Limitations of the retrospective chart review included missing data and variable follow-up times, and may have made determinations of long-term efficacy difficult. This study demonstrates that combination SCS and PSFS therapy is potentially a beneficial treatment option for reducing pain levels and oral pain medication compared with baseline in previously resistive chronic pain patients. There is a need for further study of this therapy in a greater number of subjects and in a prospective, controlled setting. In the author's general experience, triangular stimulation is very effective for treating isolated low back pain, because it covers larger topographic areas of the lower back than flow or field stimulation. An investigational device exemption study will be necessary for subcutaneous field stimulation indicated for

Double separate versus contiguous pituitary adenomas: MRI features and endocrinological follow up.

PubMed

Roberts, Sammie; Borges, Manuel Thomas; Lillehei, Kevin O; Kleinschmidt-DeMasters, B K

2016-10-01

Double pituitary adenomas are defined as two adenomas within a gland. These have distinct light microscopic and immunohistochemical features and may be clearly-separate or contiguous. Most reports have focused on the various hormonal combinations in double tumors rather than on any potential increased risk for residual mass or endocrinopathy. Departmental files were searched to identify all double adenomas from 1/1/2000 to 3/1/2016, with review of magnetic resonance imaging (MRI) to determine if the dual nature of the lesions could be discerned retrospectively after histologic diagnosis of double adenoma. All cases were immunostained for standard anterior pituitary hormones. Eight cases were identified: 2 follicle-stimulating hormone (FSH)/alpha subunit (ASU) + prolactinoma (PRL); 1 PRL + corticotroph (ACTH); 1 hormone-negative + PRL; 1 ACTH + ASU/growth hormone (GH)/PRL; 1 GH/PR + PRL; 1 FSH/ASU, + ACTH; 1 GH + luteinizing hormone (LH). One patient had clearly-separate lesions identified preoperatively and required two surgical procedures for gross total resection. A second patient had 2 lesions recognized at surgery and afterwards on retrospective neuroimaging. The remaining 6 patients had double adenomas discovered at the time of histologic examination that were not resolvable at surgery or on retrospective neuroimaging. Four patients, 2 with clearly-separate and 2 with contiguous double adenomas, had persistent MRI abnormalities, and one had continued endocrine abnormalities. Double contiguous pituitary adenomas are difficult to anticipate preoperatively or to resolve intraoperatively. Although double contiguous adenomas are much more common than double separate lesions, both have a risk for subtotal resection and, thus, residual mass and/or endocrinopathy may ensue.

Combined motor point associative stimulation (MPAS) and transcranial direct current stimulation (tDCS) improves plateaued manual dexterity performance.

PubMed

Hoseini, Najmeh; Munoz-Rubke, Felipe; Wan, Hsuan-Yu; Block, Hannah J

2016-10-28

Motor point associative stimulation (MPAS) in hand muscles is known to modify motor cortex excitability and improve learning rate, but not plateau of performance, in manual dexterity tasks. Central stimulation of motor cortex, such as transcranial direct current stimulation (tDCS), can have similar effects if accompanied by motor practice, which can be difficult and tiring for patients. Here we asked whether adding tDCS to MPAS could improve manual dexterity in healthy individuals who are already performing at their plateau, with no motor practice during stimulation. We hypothesized that MPAS could provide enough coordinated muscle activity to make motor practice unnecessary, and that this combination of stimulation techniques could yield improvements even in subjects at or near their peak. If so, this approach could have a substantial effect on patients with impaired dexterity, who are far from their peak. MPAS was applied for 30min to two right hand muscles important for manual dexterity. tDCS was simultaneously applied over left sensorimotor cortex. The motor cortex input/output (I/O) curve was assessed with transcranial magnetic stimulation (TMS), and manual dexterity was assessed with the Purdue Pegboard Test. Compared to sham or cathodal tDCS combined with MPAS, anodal tDCS combined with MPAS significantly increased the plateau of manual dexterity. This result suggests that MPAS has the potential to substitute for motor practice in mediating a beneficial effect of tDCS on manual dexterity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study.

PubMed

Deal, Cheri; Hasselmann, Caroline; Pfäffle, Roland W; Zimmermann, Alan G; Quigley, Charmian A; Child, Christopher J; Shavrikova, Elena P; Cutler, Gordon B; Blum, Werner F

2013-01-01

Magnetic resonance imaging (MRI) is used to investigate the etiology of growth hormone deficiency (GHD). This study examined relationships between MRI findings and clinical/hormonal phenotypes in children with GHD in the observational Genetics and Neuroendocrinology of Short Stature International Study, GeNeSIS. Clinical presentation, hormonal status and first-year GH response were compared between patients with pituitary imaging abnormalities (n = 1,071), patients with mutations in genes involved in pituitary development/GH secretion (n = 120) and patients with idiopathic GHD (n = 7,039). Patients with hypothalamic-pituitary abnormalities had more severe phenotypes than patients with idiopathic GHD. Additional hormonal deficiencies were found in 35% of patients with structural abnormalities (thyroid-stimulating hormone > adrenocorticotropic hormone > luteinizing hormone/follicle-stimulating hormone > antidiuretic hormone), most frequently in patients with septo-optic dysplasia (SOD). Patients with the triad [ectopic posterior pituitary (EPP), pituitary aplasia/hypoplasia and stalk defects] had a more severe phenotype and better response to GH treatment than patients with isolated abnormalities. The sex ratio was approximately equal for patients with SOD, but there was a significantly higher proportion of males (approximately 70%) in the EPP, pituitary hypoplasia, stalk defects, and triad categories. This large, international database demonstrates the value of classification of GH-deficient patients by the presence and type of hypothalamic-pituitary imaging abnormalities. This information may assist family counseling and patient management. Copyright © 2013 S. Karger AG, Basel.

Effects of combined mechanical stimulation on the proliferation and differentiation of pre-osteoblasts

PubMed Central

Kang, Kyung Shin; Lee, Seung-Jae; Lee, Haksue; Moon, Wonkyu

2011-01-01

We observed how combined mechanical stimuli affect the proliferation and differentiation of pre-osteoblasts. For this research, a bioreactor system was developed that can simultaneously stimulate cells with cyclic strain and ultrasound, each of which is known to effectively stimulate bone tissue regeneration. MC3T3-E1 pre-osteoblasts were chosen for bone tissue engineering due to their osteoblast-like characteristics. 3-D scaffolds were fabricated with polycaprolactone and poly-L-lactic acid using the salt leaching method. The cells were stimulated by the bioreactor with cyclic strain and ultrasound. The bioreactor was set at a frequency of 1.0 Hz and 10% strain for cyclic strain and 1.0 MHz and 30 mW/cm2 for ultrasound. Three experimental groups (ultrasound, cyclic strain, and combined stimulation) and a control group were examined. Each group was stimulated for 20 min/day. Mechanical stimuli did not affect MC3T3-E1 cell proliferation significantly up to 10 days when measured with the cell counting kit-8. However, gene expression analysis of collagen type-I, osteocalcin, RUNX2, and osterix revealed that the combined mechanical stimulation accelerated the matrix maturation of MC3T3-E1 cells. These results indicate that the combined mechanical stimulation can enhance the differentiation of pre-osteoblasts more efficiently than simple stimuli, in spite of no effect on cell proliferation. PMID:21532314

MRI assessment of pituitary iron accumulation by using pituitary-R2 in β-thalassemia patients.

PubMed

Bozdağ, Mustafa; Bayraktaroğlu, Selen; Aydınok, Yeşim; Çallı, Mehmet Cem

2018-06-01

Background Patients with thalassemia major (TM) require repeated blood transfusions, which leads to accumulation of iron in a wide variety of tissues. Accumulation of iron in the pituitary gland can lead to irreversible hypogonadotropic hypogonadism (HH) in this group of patients. Purpose To investigate the reliability of pituitary-R2 as a marker to estimate the extent of pituitary iron load by comparing the pituitary magnetic resonance imaging (MRI) findings with hepatic iron load and serum ferritin levels. Material and Methods A total of 38 β-TM patients were classified into HH (group A, n = 18) and non-HH (group B, n = 17) groups. A third group, group C, consisted of 17 healthy participants. Each participant underwent 1.5-T MRI examinations. Pituitary gland heights (PGH), pituitary-R2 values, and liver-R2 values were measured by using multi-echo spin-echo sequences. Results Pituitary-R2 values were significantly higher in group A compared with group B ( P < 0.05). A positive correlation was detected between the pituitary-R2 values and serum ferritin levels in TM patients ( P < 0.01). A threshold value of 14.1 Hz for pituitary-R2 was found to give a high specificity and sensitivity in distinguishing the TM patients with HH from those with normal pituitary functions. PGH measurements were significantly lower in group A compared with group B ( P < 0.05). Conclusion MRI-assessed pituitary-R2 seems to be a reliable marker for differentiating the TM patients with normal pituitary function from those with secondary hypogonadism due to iron toxicity.

Notch Signaling in Postnatal Pituitary Expansion: Proliferation, Progenitors, and Cell Specification

PubMed Central

Nantie, Leah B.; Himes, Ashley D.; Getz, Dan R.

2014-01-01

Mutations in PROP1 account for up to half of the cases of combined pituitary hormone deficiency that result from known causes. Despite this, few signaling molecules and pathways that influence PROP1 expression have been identified. Notch signaling has been linked to Prop1 expression, but the developmental periods during which Notch signaling influences Prop1 and overall pituitary development remain unclear. To test the requirement for Notch signaling in establishing the normal pituitary hormone milieu, we generated mice with early embryonic conditional loss of Notch2 (conditional knockout) and examined the consequences of chemical Notch inhibition during early postnatal pituitary maturation. We show that loss of Notch2 has little influence on early embryonic pituitary proliferation but is crucial for postnatal progenitor maintenance and proliferation. In addition, we show that Notch signaling is necessary embryonically and postnatally for Prop1 expression and robust Pit1 lineage hormone cell expansion, as well as repression of the corticotrope lineage. Taken together, our studies identify temporal and cell type–specific roles for Notch signaling and highlight the importance of this pathway throughout pituitary development. PMID:24673559

[Pituitary gland tumors].

PubMed

Jesser, J; Schlamp, K; Bendszus, M

2014-10-01

This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15% of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65% of pituitary gland adenomas secrete hormones whereby approximately 50% secrete prolactin, 10% secrete growth hormone (somatotropin) and 6% secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10% of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland.

Pituitary disorders in pregnancy.

PubMed

Chrisoulidou, Alexandra; Boudina, Maria; Karavitaki, Niki; Bili, Eleni; Wass, John

2015-01-01

The pituitary gland is significantly affected during gestation in terms of both size and function. Due to this physiologic adaptation, endocrine evaluation and interpretation of imaging is far more complex than in the non-pregnant state. Pituitary disorders are rare in pregnancy, as they are usually associated with gonadal dysfunction, thereby posing difficulties with fertility. This review will focus on pituitary adenomas (prolactinomas, GH-secreting and ACTH-secreting), their diagnostic handicaps and the recommendations for treatment. We will also discuss the two pituitary disorders encountered in pregnancy, Sheehan's syndrome and lymphocytic hypophysitis.

Hypothalamic-pituitary cytokine network.

PubMed

Kariagina, Anastasia; Romanenko, Dmitry; Ren, Song-Guang; Chesnokova, Vera

2004-01-01

Cytokines expressed in the brain and involved in regulating the hypothalamus-pituitary-adrenal (HPA) axis contribute to the neuroendocrine interface. Leukemia inhibitory factor (LIF) and LIF receptors are expressed in human pituitary cells and murine hypothalamus and pituitary. LIF potently induces pituitary proopiomelanocortin (POMC) gene transcription and ACTH secretion and potentiates CRH induction of POMC. In vivo, LIF, along with CRH, enhances POMC expression and ACTH secretion in response to emotional and inflammatory stress. To further elucidate specific roles for both CRH and LIF in activating the inflammatory HPA response, double-knockout mice (CRH/LIFKO) were generated by breeding the null mutants for each respective single gene. Inflammation produced by ip injection of lipopolysaccharide (1 microg/mouse) to double CRH and LIF-deficient mice elicited pituitary POMC induction similar to wild type and markedly higher than in single null animals (P<0.0.01). Double-knockout mice also demonstrated robust corticosterone response to inflammation. High pituitary POMC mRNA levels may reflect abundant TNFalpha, IL-1beta, and IL-6 activation observed in the hypothalamus and pituitary of these animals. Our results suggest that increased central proinflammatory cytokine expression can compensate for the impaired HPA axis function and activates inflammatory ACTH and corticosterone responses in mice-deficient in both CRH and LIF.

Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis.

PubMed

Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Nakamura, Yumi; Koyama, Hidekazu

2015-01-01

Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD), which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1), which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2), which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX), an 11HSD inhibitor, on the healthy dog's pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH), and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing's disease.

Clinical characteristics of patients with thyrotropin-secreting pituitary adenoma.

PubMed

Wu, Yung-Yen; Chang, Hung-Yu; Lin, Jen-Der; Chen, Kwang-Wen; Huang, Yu-Yao; Jung, Shih-Ming

2003-03-01

Thyroid-stimulating hormone (thyrotropin, TSH)-secreting pituitary adenoma is a very rare cause of hyperthyroidism. Diagnosis of this condition is often delayed due to lack of availability of TSH radioimmunoassay (RIA), the failure to recognize the utility of RIA and the incorrect attribution of the condition to other causes of thyrotoxicosis. This retrospective study analyzed the clinical characteristics of patients with this disorder treated from 1991 to 2002. Seven patients (6 females, 1 male; mean age, 48 years; range, 33 to 72 years) with a diagnosis of TSHsecreting pituitary adenoma based on detectable TSH levels with high serum free thyroid hormone or triiodothyronine concentrations and pituitary lesions found on neuroimaging were included in this study. Patient records including clinical features, endocrine studies, immunohistochemistry studies, and response to treatment were reviewed. All 7 patients had hyperthyroidism, elevated free thyroxine or triiodothyronine levels, and unsuppressed levels of TSH. Imaging studies demonstrated a pituitary mass or lesion in all patients. Six patients had macroadenomas and 1 patient had a microadenoma. One of the patients had coexisting acromegalic features and hypersecretion of growth hormone was diagnosed. All of the patients had been treated with thionamides or thyroidectomy for presumed primary hyperthyroidism. Serum alpha-subunit level was uncharacteristically normal in 2 patients and elevated in 1 patient. Alpha-subunit/TSH molar ratios were elevated in 3 patients. Five patients underwent transsphenoidal adenomectomy but only one of them remained well-controlled at follow-up. Three patients received administration of somatostatin analogs and they achieved normalization of serum TSH and free thyroid hormones during the period of therapy. TSH immunoassay has an important role in the evaluation of hyperthyroid patients to determine the presence of inappropriate secretion. TSH-secreting pituitary adenoma exhibits

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing.

PubMed

Jomaa, Barae; Aarts, Jac M M J G; de Haan, Laura H J; Peijnenburg, Ad A C M; Bovee, Toine F H; Murk, Albertinka J; Rietjens, Ivonne M C M

2013-01-01

This study investigates the in vitro effect of eleven thyroid-active compounds known to affect pituitary and/or thyroid weights in vivo, using the proliferation of GH3 rat pituitary cells in the so-called "T-screen," and of FRTL-5 rat thyroid cells in a newly developed test denoted "TSH-screen" to gain insight into the relative value of these in vitro proliferation tests for an integrated testing strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen was stimulated by three out of eleven tested compounds, namely thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three compounds, only T4 causes an increase in relative pituitary weight, and thus T4 was the only compound for which the effect in the in vitro assay correlated with a reported in vivo effect. As to the newly developed TSH-screen, two compounds had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4 antagonized FRTL-5 cell proliferation. These effects correlated with in vivo changes induced by these compounds on thyroid weight. Altogether, the results indicate that most of the selected compounds affect pituitary and thyroid weights by modes of action different from a direct thyroid hormone receptor (THR) or TSH receptor (TSHR)-mediated effect, and point to the need for additional in vitro tests for an ITS. Additional analysis of the T-screen revealed a positive correlation between the THR-mediated effects of the tested compounds in vitro and their effects on relative heart weight in vivo, suggesting that the T-screen may directly predict this THR-mediated in vivo adverse effect.

Contemporary indications for transsphenoidal pituitary surgery.

PubMed

Miller, Brandon A; Ioachimescu, Adriana G; Oyesiku, Nelson M

2014-12-01

To analyze current indications for transsphenoidal pituitary surgery. The current literature regarding transsphenoidal surgery for all subtypes of pituitary adenomas and other sellar lesions was examined. Alternate approaches for pituitary surgery were also reviewed. Transsphenoidal surgery continues to be the mainstay of surgical treatment for pituitary tumors, and has good outcomes in experienced hands. Pre- and postoperative management of pituitary tumors remains an important part of the treatment of patients with pituitary tumors. Even as medical and surgical treatment for pituitary tumors evolves, transsphenoidal surgery remains a mainstay of treatment. Outcomes after transshenoidal surgery have improved over time. Neurosurgeons must be aware of the indications, risks and alternatives to transsphenoidal pituitary surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

Treatment of Pituitary Carcinomas and Atypical Pituitary Adenomas: A Review

PubMed Central

HIROHATA, Toshio; ISHII, Yudo; MATSUNO, Akira

2014-01-01

Atypical pituitary adenomas (APAs) are aggressive tumors, harboring a Ki-67 (MIB-1) staining index of 3% or more, and positive immunohistochemical staining for p53 protein, according to the World Health Organization (WHO) classification in 2004. Pituitary carcinomas (PC) usually develop from progressive APAs and predominantly consist of hormone-generating tumors, defined by the presence of disseminations in the cerebrospinal system or systemic metastases. Most of the cases with these malignant pituitary adenomas underwent surgeries, irradiations and adjuvant medical treatments, nevertheless, the therapies are mainly palliative. Recently, the efficacy of temozolomide (TMZ), an orally administered alkylating agent, has been reported as an alternative medical treatment. However, some recent studies have demonstrated a significant recurrence rate after effective response to TMZ. Further clinical and pathological researches of malignant pituitary adenomas will be required to improve the outcome of patients with these tumors. PMID:25446382

The de novo Q167K mutation in the POU1F1 gene leads to combined pituitary hormone deficiency in an Italian patient.

PubMed

Malvagia, Sabrina; Poggi, Giovanni Maria; Pasquini, Elisabetta; Donati, Maria Alice; Pela, Ivana; Morrone, Amelia; Zammarchi, Enrico

2003-11-01

The POU1F1 gene encodes a transcription factor that is important for the development and differentiation of the cells producing GH, prolactin, and TSH in the anterior pituitary gland. Patients with POU1F1 mutations show a combined pituitary hormone deficiency with low or absent levels of GH, prolactin, and TSH. Fourteen mutations have been reported in the POU1F1 gene up to now. These genetic lesions can be inherited either in an autosomal dominant or an autosomal recessive mode. We report on the first Italian patient, a girl, affected by combined pituitary hormone deficiency. The patient was found to be positive for congenital hypothyroidism (with low TSH levels) at neonatal screening. Substitutive therapy was started, but subsequent growth was very poor, although psychomotor development was substantially normal. Hospitalized at 10 mo she showed hypotonic crises, growth retardation, delayed bone age, and facial dysmorphism. In addition to congenital hypothyroidism, GH and prolactin deficiencies were found. Mutation DNA analysis of the patient's POU1F1 gene identified the novel Q167K amino acid change at the heterozygous level. The highly conserved Q167 residue is located in the POU-specific domain. No mutation was detected in the other allele. DNA analysis in the proband's parents did not identify this amino acid substitution, suggesting a de novo genetic lesion. From these data it can be hypothesized that the Q167K mutation has a dominant negative effect.

Central regulation of the hypothalamo-pituitary-thyroid (HPT) axis: focus on clinical aspects.

PubMed

Fliers, E; Boelen, A; van Trotsenburg, A S P

2014-01-01

The hypothalamus is the most prominent brain region involved in setpoint regulation of the thyroid axis. It generates the diurnal thyroid-stimulating hormone (TSH) rhythm, and it plays a central role in the adaptation of the thyroid axis to environmental factors such as caloric deprivation or infection. Many studies, including studies in human post-mortem tissue samples, have confirmed a key role for the thyrotropin-releasing hormone (TRH) neuron in the hypothalamic paraventricular nucleus (PVN) in thyroid axis regulation. In addition to their negative feedback action on TRH neurons in the hypothalamus, intrahypothalamic thyroid hormones can also modulate metabolism in adipose tissue and the liver via the autonomic nervous system. Congenital or acquired dysfunction of the hypothalamus or pituitary gland may result in central hypothyroidism (CeH). In the Netherlands, the prevalence of permanent congenital CeH as detected by neonatal screening is approximately 1 in 18000. In most neonates congenital CeH is accompanied by additional anterior pituitary hormone deficiencies, and many show clear morphological abnormalities such as a small anterior gland, a thin or absent pituitary stalk, or an ectopic posterior pituitary gland. Recently, a mutation in the immunoglobulin superfamily member 1 (IGSF1) gene was reported as a novel cause of X-linked, apparently isolated CeH occurring in neonates, children and adults. In adults, the most frequent cause of acquired CeH is a pituitary macroadenoma, usually accompanied by other pituitary hormone deficiencies. Central hyperthyroidism is a rare disorder, especially in children. In adults, it is mostly caused by a TSH-secreting pituitary adenoma. © 2014 Elsevier B.V. All rights reserved.

Cellular distribution and regulation of ghrelin messenger ribonucleic acid in the rat pituitary gland.

PubMed

Caminos, J E; Nogueiras, R; Blanco, M; Seoane, L M; Bravo, S; Alvarez, C V; García-Caballero, T; Casanueva, F F; Diéguez, C

2003-11-01

Ghrelin, a 28-amino-acid acylated peptide, strongly stimulates GH release and food intake. In the present study, we found that ghrelin is expressed in somatotrophs, lactotrophs, and thyrotrophs but not in corticotrophs or gonadotrophs of rat pituitary. Persistent expression of the ghrelin gene is found during postnatal development in male and female rats, although the levels significantly decrease in both cases from pituitaries of 20-d-old rats onward, but at 60 d old, the levels were higher in male than female rats. This sexually dimorphic pattern appears to be mediated by estrogens because ovariectomy, but not orchidectomy, increases pituitary ghrelin mRNA levels. Taking into account that somatotroph cell function is markedly influenced by thyroid hormones, glucocorticoids, GH, and metabolic status, we also assessed such influence. We found that ghrelin mRNA levels decrease in hypothyroid- and glucocorticoid-treated rats, increase in GH-deficient rats (dwarf rats), and remain unaffected by food deprivation. In conclusion, we have defined the specific cell types that express ghrelin in the rat anterior pituitary gland. These data provide direct morphological evidence that ghrelin may well be acting in a paracrine-like fashion in the regulation of anterior pituitary cell function. In addition, we clearly demonstrate that pituitary ghrelin mRNA levels are age and gender dependent. Finally, we show that pituitary ghrelin mRNA levels are influenced by alteration on thyroid hormone, glucocorticoids, and GH levels but not by fasting, which indicates that the regulation of ghrelin gene expression is tissue specific.

Transient pituitary enlargement with central hypogonadism secondary to bilateral cavernous sinus thrombosis: pituitary oedema?

PubMed

Joubert, Michael; Verdon, Renaud; Reznik, Yves

2009-05-01

Design We report the case of an incidental pituitary mass discovered in the context of bilateral cavernous sinus thrombosis due to a bacterial pansinusitis. Conclusions Magnetic resonance imaging features of the pituitary lesion, together with transient central hypogonadism and total regression of the mass after anticoagulation and antimicrobial therapy, suggest that this lesion is a pituitary oedema of vascular mechanism. Other possible causes of pituitary mass in such a situation are also discussed.

Pituitary Tumors—Health Professional Version

Cancer.gov

Pituitary tumors represent from 10% to 25% of all intracranial neoplasms. Pituitary tumors can be classified into three groups: benign adenoma, invasive adenoma, and carcinoma. Find evidence-based information on pituitary tumors treatment.

Testosterone Combined with Electrical Stimulation and Standing: Effect on Muscle and Bone

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-2-0190 TITLE: Testosterone Combined with Electrical Stimulation and Standing: Effect on Muscle and Bone PRINCIPAL...including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and...2015 - 29 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Testosterone Combined with Electrical Stimulation and Standing: Effect on Muscle and Bone

Probing phase- and frequency-dependent characteristics of cortical interneurons using combined transcranial alternating current stimulation and transcranial magnetic stimulation.

PubMed

Hussain, Sara J; Thirugnanasambandam, Nivethida

2017-06-01

Paired-pulse transcranial magnetic stimulation (TMS) and peripheral stimulation combined with TMS can be used to study cortical interneuronal circuitry. By combining these procedures with concurrent transcranial alternating current stimulation (tACS), Guerra and colleagues recently showed that different cortical interneuronal populations are differentially modulated by the phase and frequency of tACS-imposed oscillations (Guerra A, Pogosyan A, Nowak M, Tan H, Ferreri F, Di Lazzaro V, Brown P. Cerebral Cortex 26: 3977-2990, 2016). This work suggests that different cortical interneuronal populations can be characterized by their phase and frequency dependency. Here we discuss how combining TMS and tACS can reveal the frequency at which cortical interneuronal populations oscillate, the neuronal origins of behaviorally relevant cortical oscillations, and how entraining cortical oscillations could potentially treat brain disorders. Copyright © 2017 the American Physiological Society.

Pituitary Tumors Treatment (PDQ®)—Health Professional Version

Cancer.gov

Pituitary tumors treatment can include surgery, radiation therapy, and medical therapy, either alone or in combination. Treatment is individualized and is dictated by the type of tumor, its location, and hormonal expression. Get detailed treatment information in ths summary for clinicians.

ICA Occlusion by an ACTH-secreting pituitary adenoma post-TSS and irradiation

PubMed Central

El-Zammar, Diala; Akagami, Ryojo

2011-01-01

Occlusion of intracranial arteries by a pituitary adenoma with ensuing infarction is a rare occurrence. In this case study, we show the instance of a pituitary macroadenoma and apoplexy causing mechanical obstruction of the internal carotid artery with consequent infarction following transphenoidal surgery (TSS) and radiation therapy in a patient with Cushing's disease. We report a 44-year-old woman presented with amenorrhea and headaches. Necessary investigations, resection by TSS, and microscopic examination revealed an adenocorticotropin (ACTH)-secreting pituitary macroadenoma. The pituitary tumour recurred in subsequent years, resulting in the development of Cushing's disease and syndrome. Despite two more transphenoidal surgeries, radiotherapy, and medical suppressive therapy, the pituitary adenoma continued to enlarge, and the hypercortisolemia and Cushingoid symptoms persisted. A craniotomy was arranged as the next step in the treatment strategy. Only hours prior to the scheduled surgery, the patient developed left-sided hemiplegia, was diagnosed with acute occlusion of the right ICA and underwent an emergency bifrontal craniotomy with evacuation of the tumour and decompression. Pathological examination revealed evidence of apoplexy in the ACTH-secreting pituitary adenoma. This case demonstrates the vast scope of complications that can arise from pituitary adenomas despite combination therapy and forewarns clinicians to be prepared to manage these infrequent but conceivable occurrences. PMID:22399870

Transsphenoidal Surgery for Mixed Pituitary Gangliocytoma-Adenomas.

PubMed

Shepard, Matthew J; Elzoghby, Mohamed A; Ghanim, Daffer; Lopes, M Beatriz S; Jane, John A

2017-12-01

Most sellar gangliocytomas are discovered with a concurrent pituitary adenoma, also known as a mixed gangliocytoma-adenoma (MGA). MGAs are rare, with fewer than 100 cases reported in the literature to date and only 1 previously documented surgical series. Because MGAs are radiologically indistinguishable from pituitary adenomas, they are often diagnosed after surgery. Combined with the paucity of clinical outcome data for these tumors, this makes their diagnosis and management challenging. Here we describe the clinical presentation and outcomes of 10 individuals who were diagnosed with a MGA at a single institution. This retrospective case series study included patients diagnosed with a combined sellar MGA between 1993 and 2016. This series comprised 10 patients, mean age of 44 years (range, 28-63 years) diagnosed with an MGA. The mean tumor size was 1.6 cm (range, 0.4-2.4 cm). Five patients presented with acromegaly, and 1 patient had recurrent Cushing disease. Transsphenoidal surgery was performed in all cases, and gross total resection was achieved in 7 patients (70%). Histologically, 9 of the 10 MGAs were identified as mixed somatotroph adenoma-gangliocytomas. The median duration of follow-up was 74 months (range, 2-180 months). Following adjuvant treatment (n = 3), all patients with acromegaly (n = 4) achieved biochemical remission, and no patient experienced recurrence of the pituitary tumor with a median radiographic follow-up of 48 months. MGAs are often associated with a hypersecretory adenoma. Transsphenoidal surgery is well tolerated by most patients, and when performed in combination with adjuvant therapy, a low rate of recurrence and reversal of preoperative endocrinopathy can be expected. Copyright © 2017 Elsevier Inc. All rights reserved.

Pituitary gland imaging and outcome.

PubMed

Di Iorgi, Natascia; Morana, Giovanni; Gallizia, Anna Lisa; Maghnie, Mohamad

2012-01-01

Magnetic resonance imaging (MRI) allows a detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. The identification of posterior pituitary hyperintensity, now considered a marker of neurohypophyseal functional integrity, has been the most striking advance for the diagnosis and understanding of anterior and posterior pituitary diseases. The advent of MRI has in fact led to a significant improvement in the understanding of the pathogenesis of disorders that affect the hypothalamo-pituitary area. Today, there is convincing evidence to support the hypothesis that marked MRI differences in pituitary morphology indicate a diverse range of disorders which affect the organogenesis and function of the anterior pituitary gland with different prognoses. Furthermore, the association of extrapituitary malformations accurately defined by MRI has supported a better definition of several conditions linked to pituitary hormone deficiencies and midline defects. MRI is a very informative procedure that should be used to support a diagnosis of hypopituitarism. It is useful in clinical management, because it helps endocrinologists determine which patients to target for further molecular studies and genetic counselling, which ones to screen for additional hormone deficits, and which ones may need growth hormone replacement into adult life. Copyright © 2012 S. Karger AG, Basel.

Pyrethroid Insecticide Cypermethrin Accelerates Pubertal Onset in Male Mice via Disrupting Hypothalamic-Pituitary-Gonadal Axis.

PubMed

Ye, Xiaoqing; Li, Feixue; Zhang, Jianyun; Ma, Huihui; Ji, Dapeng; Huang, Xin; Curry, Thomas E; Liu, Weiping; Liu, Jing

2017-09-05

Pyrethroids, a class of insecticides that are widely used worldwide, have been identified as endocrine-disrupting chemicals (EDCs). Our recent epidemiological study reported on an association of increased pyrethroids exposure with elevated gonadotropins levels and earlier pubertal development in Chinese boys. In this study, we further investigated the effects of cypermethrin (CP), one of the most ubiquitous pyrethroid insecticides, on hypothalamic-pituitary-gonadal (HPG) axis and pubertal onset in male animal models. Early postnatal exposure to CP at environmentally relevant doses (0.5, 5, and 50 μg/kg CP) significantly accelerated the age of puberty onset in male mice. Administration of CP induced a dose-dependent increase in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in male mice. CP did not affect gonadotropin-releasing hormone (GnRH) gene expression in the hypothalamus, but CP at higher concentrations stimulated GnRH pulse frequency. CP could induce the secretion of LH and FSH, as well as the expression of gonadotropin subunit genes [chorionic gonadotropin α (CGα), LHβ, and FSHβ] in pituitary gonadotropes. CP stimulated testosterone production and the expression of steroidogenesis-related genes [steroidogenic acute regulatory (StAR) and Cytochrome p 450, family 11, subfamily A, polypeptide 1 (CYP11A1)] in testicular Leydig cells. The interference with hypothalamic sodium channels as well as calcium channels in pituitary gonadotropes and testicular Leydig cells was responsible for CP-induced HPG axis maturation. Our findings established in animal models provide further evidence for the biological plausibility of pyrethroid exposure as a potentially environmental contributor to earlier puberty in males.

The Calcium-Sensing Receptor Couples to Gαs and Regulates PTHrP and ACTH Secretion in Pituitary Cells

PubMed Central

Mamillapalli, Ramanaiah; Wysolmerski, John

2013-01-01

The calcium-sensing receptor (CaR) is a G-protein-coupled receptor (GPCR) that binds and signals in response to extracellular calcium and other polycations. It is highly expressed on parathyroid and kidney cells, where it participates in the regulation of systemic calcium homeostasis. It is also expressed on many other cell types and is involved in a wide array of biological functions such as cell growth and differentiation, ion transport and hormone secretion. It has been described to couple to several different G-proteins including Gαi/0, Gαq/11 and Gα12/13. Recently, it has also been shown to stimulate cAMP production by coupling to Gαs in immortalized or malignant breast cells. The CaR is expressed on cells in the anterior pituitary and had previously been described to stimulate cAMP production in these cells. In this report, we examined signaling from the CaR in murine pituitary corticotroph-derived, AtT-20 cells. We found that CaR activation led to the stimulation of cAMP production, and PTHrP and ACTH secretion from these cells. Furthermore, manipulation of cAMP levels was able to modulate PTHrP and ACTH secretion independent of changes in extracellular calcium. Finally, we demonstrated that the CaR couples to Gαs in AtT-20 cells. Therefore, in pituitary corticotroph-like cells, as in breast cancer cells, the CaR utilizes Gαs and activates cAMP production to stimulate hormone secretion. PMID:20032198

Long-Term Outcomes, Genetics, and Pituitary Morphology in Patients with Isolated Growth Hormone Deficiency and Multiple Pituitary Hormone Deficiencies: A Single-Centre Experience of Four Decades of Growth Hormone Replacement.

PubMed

Rohayem, Julia; Drechsel, Hendrik; Tittel, Bettina; Hahn, Gabriele; Pfaeffle, Roland; Huebner, Angela

2016-01-01

Growth hormone (GH) has been used to treat children with GH deficiency (GHD) since 1966. Using a combined retrospective and cross-sectional approach, we explored the long-term outcomes of patients with GHD, analysed factors influencing therapeutic response, determined persistence into adulthood, investigated pituitary morphology, and screened for mutations in causative genes. The files of 96 GH-deficient children were reviewed. In a subset of 50 patients, re-assessment in adulthood was performed, including GHRH-arginine testing, pituitary magnetic resonance imaging (MRI), and mutational screening for the growth hormone-1 gene (GH1) and the GHRH receptor gene (GHRHR) in isolated GHD (IGHD), and HESX1, PROP1, POU1F1, LHX3, LHX4, and GLI2 in multiple pituitary hormone deficiency (MPHD) patients. GH was started at a height SDS of -3.2 ± 1.4 in IGHD patients and of -4.1 ± 2.1 in MPHD patients. Relative height gain was 0.3 SDS/year, absolute gain 1.6 SDS, and 1.2/2.6 SDS in IGHD/MPHD, respectively. Mid-parental target height was reached in 77%. Initial height SDS, bone age retardation and duration of GH replacement were correlated with height SDS gain. GHD persisted into adulthood in 19 and 89% of subjects with IGHD and MPHD, respectively. In 1/42 IGHD patients a GH1 mutation was detected; PROP1 mutations were found in 3/7 MPHD subjects. Anterior pituitary hypoplasia, combined with posterior pituitary ectopy and pituitary stalk invisibility on MRI, was an exclusive finding in MPHD patients. GH replacement successfully corrects the growth deficit in children with GHD. While the genetic aetiology remains undefined in most cases of IGHD, PROP1 mutations constitute a major cause for MPHD. Persistence of GHD into adulthood is related to abnormal pituitary morphology. © 2016 S. Karger AG, Basel.

Pituitary Dysfunction from an Unruptured Ophthalmic Internal Carotid Artery Aneurysm with Improved 2-year Follow-up Results: A Case Report.

PubMed

Qi, Meng; Ye, Ming; Li, Meng; Zhang, Peng

2018-01-01

Internal carotid artery (ICA) supraclinoid segment aneurysms extending into the sellar region and leading to pituitary dysfunction are a rare occurrence. To date, long-term follow up of pituitary function 2 years post-treatment has never been reported. Herein, we present a case of pituitary dysfunction due to an unruptured ophthalmic segment internal carotid artery aneurysm and report improved 2-year follow-up results. A 76-year-old male presented with disturbed consciousness due to hyponatremia, which was caused by hypoadrenocorticism resulting from pituitary dysfunction complicated by hypogonadism and hypothyroidism. Computed tomography angiography revealed an intracranial aneurysm of the ophthalmic segment of the right ICA with an intrasellar extension. Thus, digital subtraction angiography and coil embolization were performed, followed by hormone replacement therapy. A 2-year follow-up revealed a partial improvement in the pituitary function, including complete restoration of thyroid-stimulating hormone level and other thyroid hormones levels, and partial restoration of testosterone levels, followed by discontinuation of thyroid hormone replacement therapy. However, the mechanisms of such pituitary dysfunction and the effects of various treatments, including clipping and coiling, on different hormones of pituitary function recovery remain unclear. A long-term follow-up of >2 years may elucidate the pituitary function recovery post-treatment and provide a medication adjustment for hormone replacement therapy.

A novel heterozygous intronic mutation in POU1F1 is associated with combined pituitary hormone deficiency.

PubMed

Takagi, Masaki; Kamasaki, Hotaka; Yagi, Hiroko; Fukuzawa, Ryuji; Narumi, Satoshi; Hasegawa, Tomonobu

2017-02-27

POU class 1 homeobox 1 (POU1F1) regulates pituitary cell-specific gene expression of somatotropes, lactotropes, and thyrotropes. In humans, two POU1F1 isoforms (long and short isoform), which are generated by the alternative use of the splice acceptor site for exon 2, have been identified. To date, more than 30 POU1F1 mutations in patients with combined pituitary hormone deficiency (CPHD) have been described. All POU1F1 variants reported to date affect both the short and long isoforms of the POU1F1 protein; therefore, it is unclear at present whether a decrease in the function of only one of these two isoforms is sufficient for disease onset in humans. Here, we described a sibling case of CPHD carrying a heterozygous mutation in intron 1 of POU1F1. In vitro experiments showed that this mutation resulted in exon 2-skipping of only in the short isoform of POU1F1, while the long isoform remained intact. This result strongly suggests the possibility, for the first time, that isolated mutations in the short isoform of POU1F1 could be sufficient for induction of POU1F1-related CPHD. This finding improves our understanding of the molecular mechanisms, and developmental course associated with mutations in POU1F1.

Adult pituitary stem cells: from pituitary plasticity to adenoma development.

PubMed

Florio, Tullio

2011-01-01

The pituitary needs high plasticity of the hormone-producing cell compartment to generate the continuously changing hormonal signals that govern the key physiological processes it is involved in, as well as homeostatic cell turnover. However, the underlying mechanisms are still poorly understood. It was proposed that adult stem cells direct the generation of newborn cells with a hormonal phenotype according to the physiological requirements. However, only in recent years adult pituitary stem cells have begun to be phenotypically characterized in several studies that identified multiple stem/progenitor cell candidates. Also considering the incompletely defined features of this cell subpopulation, some discrepancies among the different reports are clearly apparent and long-term self-renewal remains to be unequivocally demonstrated. Here, all the recently published evidence is analyzed, trying, when possible, to reconcile the results of the different studies. Finally, with the perspective of shedding light on pituitary tumorigenesis and the development of potentially new pharmacological approaches directed against these cells, very recent evidence on the presence of putative cancer stem cells in human pituitary adenomas is discussed. Copyright © 2011 S. Karger AG, Basel.

Combined Dextroamphetamine and Transcranial Direct Current Stimulation in Poststroke Aphasia.

PubMed

Keser, Zafer; Dehgan, Michelle Weber; Shadravan, Shaparak; Yozbatiran, Nuray; Maher, Lynn M; Francisco, Gerard E

2017-10-01

There is a growing need for various effective adjunctive treatment options for speech recovery after stroke. A pharmacological agent combined with noninvasive brain stimulation has not been previously reported for poststroke aphasia recovery. In this "proof of concept" study, we aimed to test the safety of a combined intervention consisting of dextroamphetamine, transcranial direct current stimulation, and speech and language therapy in subjects with nonfluent aphasia. Ten subjects with chronic nonfluent aphasia underwent two experiments where they received dextroamphetamine or placebo along with transcranial direct current stimulation and speech and language therapy on two separate days. The Western Aphasia Battery-Revised was used to monitor changes in speech performance. No serious adverse events were observed. There was no significant increase in blood pressure with amphetamine or deterioration in speech and language performance. Western Aphasia Battery-Revised aphasia quotient and language quotient showed a statistically significant increase in the active experiment. Comparison of proportional changes of aphasia quotient and language quotient in active experiment with those in placebo experiment showed significant difference. We showed that the triple combination therapy is safe and implementable and seems to induce positive changes in speech and language performance in the patients with chronic nonfluent aphasia due to stroke.

Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and pituitary glands in radiotherapy of nasopharyngeal cancer patients.

PubMed

Lin, Zhixiong; Wang, Xiaoyan; Xie, Wenjia; Yang, Zhining; Che, Kaijun; Wu, Vincent W C

2013-12-01

Radiation-induced thyroid dysfunction after radiotherapy for nasopharyngeal cancer (NPC) has been reported. This study investigated the radiation effects of the thyroid and pituitary glands on thyroid function after radiotherapy for NPC. Sixty-five NPC patients treated with radiotherapy were recruited. Baseline thyroid hormone levels comprising free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were taken before treatment and at 3, 6, 12 and 18 months. A seven-beam intensity-modulated radiotherapy plan was generated for each patient. Thyroid and pituitary gland dose volume histograms were generated, dividing the patients into four groups: high (>50 Gy) thyroid and pituitary doses (HTHP group); high thyroid and low pituitary doses (HTLP group); low thyroid and high pituitary doses; and low thyroid and pituitary doses. Incidence of hypothyroidism was analysed. Twenty-two (34%) and 17 patients (26%) received high mean thyroid and pituitary doses, respectively. At 18 months, 23.1% of patients manifested various types of hypothyroidism. The HTHP group showed the highest incidence (83.3%) of hypothyroidism, followed by the HTLP group (50%). NPC patients with high thyroid and pituitary gland doses carried the highest risk of abnormal thyroid physiology. The dose to the thyroid was more influential than the pituitary dose at 18 months after radiotherapy, and therefore more attention should be given to the thyroid gland in radiotherapy planning. © 2013 The Royal Australian and New Zealand College of Radiologists.

Imaging of pediatric pituitary endocrinopathies

PubMed Central

Chaudhary, Vikas; Bano, Shahina

2012-01-01

Accurate investigation of the hypothalamic-pituitary area is required in pediatric patients for diagnosis of endocrine-related disorders. These disorders include hypopituitarism, growth failure, diencephalic syndrome, delayed puberty, precocious puberty, diabetes insipidus, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and hyperpituitarism. Magnetic resonance imaging (MRI) is the modality of choice to visualize hypothalamic-pituitary axis and associated endocrinopathies. Neuroimaging can be normal or disclose abnormalities related to pituitary-hypothalamic axis like (i) congenital and developmental malformations; (ii) tumors; (iii) cystic lesions; and (iv) infectious and inflammatory conditions. Classical midline anomalies like septo-optic dysplasias or corpus callosum agenesis are commonly associated with pituitary endocrinopathies and also need careful evaluation. In this radiological review, we will discuss neuroendocrine disorders related to hypothalamic pituitary-axis. PMID:23087850

Direct and indirect requirements of Shh/Gli signaling in early pituitary development.

PubMed

Wang, Yiwei; Martin, James F; Bai, C Brian

2010-12-15

Induction of early pituitary progenitors is achieved through combined activities of signals from adjacent embryonic tissues. Previous studies have identified a requirement for oral ectoderm derived Sonic Hedgehog (Shh) in specification and/or proliferation of early pituitary progenitors, however how different Gli genes mediate Shh signaling to control pituitary progenitor development has not yet been determined. Here we show that Gli2, which encodes a major Gli activator, is required for proliferation of specific groups of pituitary progenitors but not for initial dorsoventral patterning. We further show that the action of Gli2 occurs prior to the closure of Rathke' pouch. Lastly, we show that Shh/Gli2 signaling controls the diencephalic expression of Bone morphogenetic protein 4 (Bmp4) and Fibroblast growth factor 8 (Fgf8), two genes that are known to play critical roles in patterning and growth of Rathke's pouch. Our results therefore suggest both cell-autonomous and non-cell-autonomous requirements for Gli2 in regulation of pituitary progenitor specification, proliferation and differentiation. Copyright © 2010 Elsevier Inc. All rights reserved.

Developmental analysis and influence of genetic background on the Lhx3 W227ter mouse model of combined pituitary hormone deficiency disease.

PubMed

Prince, Kelly L; Colvin, Stephanie C; Park, Soyoung; Lai, Xianyin; Witzmann, Frank A; Rhodes, Simon J

2013-02-01

Combined pituitary hormone deficiency (CPHD) diseases result in severe outcomes for patients including short stature, developmental delays, and reproductive deficiencies. Little is known about their etiology, especially the developmental profiles and the influences of genetic background on disease progression. Animal models for CPHD provide valuable tools to investigate disease mechanisms and inform diagnostic and treatment protocols. Here we examined hormone production during pituitary development and the influence of genetic background on phenotypic severity in the Lhx3(W227ter/W227ter) mouse model. Lhx3(W227ter/W227ter) embryos have deficiencies of ACTH, α-glycoprotein subunit, GH, PRL, TSHβ, and LHβ during prenatal development. Furthermore, mutant mice have significant reduction in the critical pituitary transcriptional activator-1 (PIT1). Through breeding, the Lhx3(W227ter/W227ter) genotype was placed onto the 129/Sv and C57BL/6 backgrounds. Intriguingly, the genetic background significantly affected viability: whereas Lhx3(W227ter/W227ter) animals were found in the expected frequencies in C57BL/6, homozygous animals were not viable in the 129/Sv genetic environment. The hormone marker and PIT1 reductions observed in Lhx3(W227ter/W227ter) mice on a mixed background were also seen in the separate strains but in some cases were more severe in 129/Sv. To further characterize the molecular changes in diseased mice, we conducted a quantitative proteomic analysis of pituitary proteins. This showed significantly lower levels of PRL, pro-opiomelanocortin (ACTH), and α-glycoprotein subunit proteins in Lhx3(W227ter/W227ter) mice. Together, these data show that hormone deficiency disease is apparent in early prenatal stages in this CPHD model system. Furthermore, as is noted in human disease, genetic background significantly impacts the phenotypic outcome of these monogenic endocrine diseases.

Developmental Analysis and Influence of Genetic Background on the Lhx3 W227ter Mouse Model of Combined Pituitary Hormone Deficiency Disease

PubMed Central

Prince, Kelly L.; Colvin, Stephanie C.; Park, Soyoung; Lai, Xianyin; Witzmann, Frank A.

2013-01-01

Combined pituitary hormone deficiency (CPHD) diseases result in severe outcomes for patients including short stature, developmental delays, and reproductive deficiencies. Little is known about their etiology, especially the developmental profiles and the influences of genetic background on disease progression. Animal models for CPHD provide valuable tools to investigate disease mechanisms and inform diagnostic and treatment protocols. Here we examined hormone production during pituitary development and the influence of genetic background on phenotypic severity in the Lhx3W227ter/W227ter mouse model. Lhx3W227ter/W227ter embryos have deficiencies of ACTH, α-glycoprotein subunit, GH, PRL, TSHβ, and LHβ during prenatal development. Furthermore, mutant mice have significant reduction in the critical pituitary transcriptional activator-1 (PIT1). Through breeding, the Lhx3W227ter/W227ter genotype was placed onto the 129/Sv and C57BL/6 backgrounds. Intriguingly, the genetic background significantly affected viability: whereas Lhx3W227ter/W227ter animals were found in the expected frequencies in C57BL/6, homozygous animals were not viable in the 129/Sv genetic environment. The hormone marker and PIT1 reductions observed in Lhx3W227ter/W227ter mice on a mixed background were also seen in the separate strains but in some cases were more severe in 129/Sv. To further characterize the molecular changes in diseased mice, we conducted a quantitative proteomic analysis of pituitary proteins. This showed significantly lower levels of PRL, pro-opiomelanocortin (ACTH), and α-glycoprotein subunit proteins in Lhx3W227ter/W227ter mice. Together, these data show that hormone deficiency disease is apparent in early prenatal stages in this CPHD model system. Furthermore, as is noted in human disease, genetic background significantly impacts the phenotypic outcome of these monogenic endocrine diseases. PMID:23288907

Development of pituitary adenoma in women with hyperprolactinaemia: clinical, endocrine, and radiological characteristics.

PubMed Central

Pontiroli, A E; Falsetti, L

1984-01-01

Sixty eight women referred for treatment of hyperprolactinaemia entered a three year follow up study to determine the clinical and endocrine course of the disease and its association with microadenoma of the pituitary. Details recorded before treatment included medical history, gonadotrophin and ovarian hormonal concentrations, and release of prolactin in response to protirelin (thyrotrophin releasing hormone), benserazide, cimetidine, and nomifensine. Sellar tomography was then performed yearly for three years in all women, 54 of them also undergoing computed coronal and sagittal tomography. At baseline evaluation 27 women showed radiological evidence of pituitary adenoma; at the end of the follow up period the number had increased to 41. Amenorrhoea, steady and raised serum prolactin concentrations, a low ratio of luteinising hormone to follicle stimulating hormone, a longer duration of disease, and low serum progesterone concentrations were more common in women with a final diagnosis of pituitary adenoma than in those whose sella remained normal. Tests for release of prolactin had yielded abnormal results from the outset in all 41 women with radiological evidence of pituitary adenoma and in about half of those whose sella had remained radiologically normal. Response to medical treatment (metergoline in 20 patients, bromocriptine in 21) was similar and showed no difference between patients with tumorous and non-tumorous hyperprolactinaemia. These findings suggest that a large proportion of women with hyperprolactinaemia may harbour a prolactin secreting pituitary adenoma which becomes apparent over a relatively short period. Amenorrhoea and steady and raised serum prolactin concentrations are more common in these women. Tests for release of prolactin are of predictive value in identifying women who will develop a pituitary adenoma. PMID:6421360

Structural studies of α-melanocyte-stimulating hormone and a novel β-melanocyte-stimulating hormone from the neurointermediate lobe of the pituitary of the dogfish Squalus acanthias

PubMed Central

Bennett, Hugh P. J.; Lowry, Philip J.; McMartin, Colin; Scott, Alexander P.

1974-01-01

A melanocyte-stimulating hormone (MSH) has been isolated from extracts of the neurointermediate lobe of the pituitary of the dogfish Squalus acanthias by gel-filtration and ion-exchange chromatography. It had approximately 1% of the potency of mammalian α-MSH on bioassays in vitro on frog skin and dogfish skin. Sequence analysis revealed it to be a hexadecapeptide with the following primary structure: Asp-Gly-Asp-Asp-Tyr-Lys-Phe-Gly-His-Phe-Arg-Trp-Ser-Val-Pro-Leu. It appears to be related to the β-MSH species of mammalian species but has only the sequence -His-Phe-Arg-Trp- in common with the heptapeptide core -Met-Glu-His-Phe-Arg-Trp-Gly- which is characteristic not only of the MSH peptides but also of the adrenocorticotrophins and lipotrophins studied so far. An α-MSH was also isolated, 50% of which was amidated at the C-terminus group. Sequence data from this study taken in conjunction with those from a previous study (Lowry & Chadwick, 1970b) revealed it to be a tridecapeptide which is identical with the N-terminal sequence of dogfish adrenocorticotrophin. PMID:4375978

The pituitary-skin connection in amphibians. Reciprocal regulation of melanotrope cells and dermal melanocytes.

PubMed

Vaudry, H; Chartrel, N; Desrues, L; Galas, L; Kikuyama, S; Mor, A; Nicolas, P; Tonon, M C

1999-10-20

In amphibians, alpha-MSH secreted by the pars intermedia of the pituitary plays a pivotal role in the process of skin color adaptation. Reciprocally, the skin of amphibians contains a number of regulatory peptides, some of which have been found to regulate the activity of pituitary melanotrope cells. In particular, the skin of certain species of amphibians harbours considerable amounts of thyrotropin-releasing hormone, a highly potent stimulator of alpha-MSH release. Recently, we have isolated and sequenced from the skin of the frog Phyllomedusa bicolor--a novel peptide named skin peptide tyrosine tyrosine (SPYY), which exhibits 94% similarity with PYY from the frog Rana ridibunda. For concentrations ranging from 5 x 10(-10) to 10(-7) M, SPYY induces a dose-related inhibition of alpha-MSH secretion. At a dose of 10(-7) M, SPYY totally abolished alpha-MSH release. These data strongly suggest the existence of a regulatory loop between the pars intermedia of the pituitary and the skin in amphibians.

Extreme elevation of intrasellar pressure in patients with pituitary tumor apoplexy: relation to pituitary function.

PubMed

Zayour, Dany H; Selman, Warren R; Arafah, Baha M

2004-11-01

The dominant mechanism for hypopituitarism and hyperprolactinemia commonly observed in patients with pituitary macroadenomas was postulated to be increased intrasellar pressure (ISP) caused by the slow and gradual expansion of adenomas within the sella turcica. Hemorrhagic infarction of adenomas (pituitary tumor apoplexy) is associated with a rapid, rather than gradual, increase in intrasellar contents. The impacts of the sudden increase in intrasellar contents on ISP and pituitary function are unknown. ISP and pituitary function were determined in 13 patients with pituitary tumor apoplexy who had surgical decompression within 1 wk of symptoms' onset. ISP measurements were remarkably high (median, 47 mm Hg), whereas serum prolactin (PRL) concentrations were generally low (median, 3.5 microg/liter). There was an inverse correlation (r = -0.76; P < 0.01) between ISP measurements and serum PRL concentrations. Postoperatively, partial recovery or maintenance of pituitary function was noted in seven of 13 patients. These seven patients had higher (P = 0.013) serum PRL levels (9.3 +/- 7.4 microg/liter) and lower (P < 0.001) ISP measurements (35.9 +/- 7.3 mm Hg) than the respective values in the remaining six with persistent postoperative hypopituitarism (1.6 +/- 0.6 microg/liter and 55.9 +/- 2.4 mm Hg, respectively). The low serum PRL levels in patients with tumor apoplexy suggested that ischemic necrosis of the anterior pituitary resulting from sudden and extreme elevation of ISP was commonly observed in this setting. A normal or elevated serum PRL level in patients with non-PRL-secreting macroadenomas indicates the presence of viable pituitary cells and the high likelihood of postoperative recovery of pituitary function.

A pediatric case of pituitary macroadenoma presenting with pituitary apoplexy and cranial nerve involvement: case report

PubMed Central

Özçetin, Mustafa; Karacı, Mehmet; Toroslu, Ertuğ; Edebali, Nurullah

2016-01-01

Pituitary adenomas usually arise from the anterior lobe of the pituitary gland and are manifested with hormonal disorders or mass effect. Mass effect usually occurs in nonfunctional tumors. Pituitary adenomas may be manifested with visual field defects or rarely in the form of total oculomotor palsy. Visual field defect is most frequently in the form of bitemporal hemianopsia and superior temporal defect. Sudden loss of vision, papilledema and ophthalmoplegia may be observed. Pituitary apoplexy is defined as an acute clinical syndrome characterized with headache, vomiting, loss of vision, ophthalmoplegia and clouding of consciousness. The problem leading to pituitary apoplexy may be decreased blood supply in the adenoma and hemorrhage following this decrease or hemorrhage alone. In this article, we present a patient who presented with fever, vomiting and sudden loss of vision and limited outward gaze in the left eye following trauma and who was found to have pituitary macroadenoma causing compression of the optic chiasma and optic nerve on the left side on cranial and pituitary magnetic resonance imaging. PMID:27738402

The acute salinity changes activate the dual pathways of endocrine responses in the brain and pituitary of tilapia.

PubMed

Aruna, Adimoolam; Nagarajan, Ganesan; Chang, Ching-Fong

2015-01-15

To analyze and compare the stress and osmoregulatory hormones and receptors in pituitary during acute salinity changes, the expression patterns of corticotropin releasing hormone (crh) in hypothalamus, prolactin (prl) releasing peptide (pRrp) in telencephalon and diencephalon, glucocorticoid receptors 2 (gr2), and mineralocorticoid receptor (mr), crh-r, pro-opiomelanocorticotropin (pomc), pRrp, prl, dopamine 2 receptor (d2-r), growth hormone (gh), gh-receptor (gh-r) and insulin-like growth hormone (igf-1) transcripts in pituitary were characterized in euryhaline tilapia. The results indicate that the crh transcripts increased in the hypothalamus and rostral pars distalis of the pituitary after the transfer of fish to SW. Similarly, the pRrp transcripts were more abundant in SW acclimated tilapia forebrain and hypothalamus. The crh-r, gr2 and mr transcripts were more expressed in rostral pars distalis and pars intermedia of pituitary at SW than FW tilapia. The data indicate that the SW acclimation stimulates these transcripts in the specific regions of the brain and pituitary which may be related to the activation of the hypothalamic-pituitary-interrenal (HPI)-axis. The results of dual in situ hybridization reveal that the transcripts of crh-r, gr2 and mr with pomc are highly co-localized in corticotrophs of pituitary. Furthermore, we demonstrate high expression of pRrp in the brain and low expression of pRrp and prl transcripts in the pituitary of SW fish. No crh-r and corticosteroid receptors were co-localized with prl transcripts in the pituitary. The gh-r and igf-1 mRNA levels were significantly increased in SW acclimated tilapia pituitary whereas there was no difference in the gh mRNA levels. The data suggest that the locally produced pRrp and d2-r may control and regulate the expression of prl mRNA in pituitary. Therefore, the dual roles of pRrp are involved in the stress (via brain-pituitary) and osmoregulatory (via pituitary) pathways in tilapia exposed to

Developmental abnormalities of the posterior pituitary gland.

PubMed

di Iorgi, Natascia; Secco, Andrea; Napoli, Flavia; Calandra, Erika; Rossi, Andrea; Maghnie, Mohamad

2009-01-01

While the molecular mechanisms of anterior pituitary development are now better understood than in the past, both in animals and in humans, little is known about the mechanisms regulating posterior pituitary development. The posterior pituitary gland is formed by the evagination of neural tissue from the floor of the third ventricle. It consists of the distal axons of the hypothalamic magnocellular neurones that shape the neurohypophysis. After its downward migration, it is encapsulated together with the ascending ectodermal cells of Rathke's pouch which form the anterior pituitary. By the end of the first trimester, this development is completed and vasopressin and oxytocin can be detected in neurohypophyseal tissue. Abnormal posterior pituitary migration such as the ectopic posterior pituitary lobe appearing at the level of median eminence or along the pituitary stalk have been reported in idiopathic GH deficiency or in subjects with HESX1, LHX4 and SOX3 gene mutations. Another intriguing feature of abnormal posterior pituitary development involves genetic forms of posterior pituitary neurodegeneration that have been reported in autosomal-dominant central diabetes insipidus and Wolfram disease. Defining the phenotype of the posterior pituitary gland can have significant clinical implications for management and counseling, as well as providing considerable insight into normal and abnormal mechanisms of posterior pituitary development in humans.

Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation.

PubMed

Ille, Sebastian; Sollmann, Nico; Hauck, Theresa; Maurer, Stefanie; Tanigawa, Noriko; Obermueller, Thomas; Negwer, Chiara; Droese, Doris; Zimmer, Claus; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

2015-07-01

Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods. The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery. The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%. In comparison with fMRI, rTMS is a more sensitive but less specific

Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era

PubMed Central

Fang, Qing; George, Akima S.; Brinkmeier, Michelle L.; Mortensen, Amanda H.; Gergics, Peter; Cheung, Leonard Y. M.; Daly, Alexandre Z.; Ajmal, Adnan; Pérez Millán, María Ines; Ozel, A. Bilge; Kitzman, Jacob O.; Mills, Ryan E.; Li, Jun Z.

2016-01-01

The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD. PMID:27828722

Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.

PubMed

Fang, Qing; George, Akima S; Brinkmeier, Michelle L; Mortensen, Amanda H; Gergics, Peter; Cheung, Leonard Y M; Daly, Alexandre Z; Ajmal, Adnan; Pérez Millán, María Ines; Ozel, A Bilge; Kitzman, Jacob O; Mills, Ryan E; Li, Jun Z; Camper, Sally A

2016-12-01

The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD.

Pituitary gland volumes in bipolar disorder.

PubMed

Clark, Ian A; Mackay, Clare E; Goodwin, Guy M

2014-12-01

Bipolar disorder has been associated with increased Hypothalamic-Pituitary-Adrenal axis function. The mechanism is not well understood, but there may be associated increases in pituitary gland volume (PGV) and these small increases may be functionally significant. However, research investigating PGV in bipolar disorder reports mixed results. The aim of the current study was twofold. First, to assess PGV in two novel samples of patients with bipolar disorder and matched healthy controls. Second, to perform a meta-analysis comparing PGV across a larger sample of patients and matched controls. Sample 1 consisted of 23 established patients and 32 matched controls. Sample 2 consisted of 39 medication-naïve patients and 42 matched controls. PGV was measured on structural MRI scans. Seven further studies were identified comparing PGV between patients and matched controls (total n; 244 patients, 308 controls). Both novel samples showed a small (approximately 20mm(3) or 4%), but non-significant, increase in PGV in patients. Combining the two novel samples showed a significant association of age and PGV. Meta-analysis showed a trend towards a larger pituitary gland in patients (effect size: .23, CI: -.14, .59). While results suggest a possible small difference in pituitary gland volume between patients and matched controls, larger mega-analyses with sample sizes greater even than those used in the current meta-analysis are still required. There is a small but potentially functionally significant increase in PGV in patients with bipolar disorder compared to controls. Results demonstrate the difficulty of finding potentially important but small effects in functional brain disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing's Disease to Pituitary Carcinoma.

PubMed

Borba, Clarissa Groberio; Batista, Rafael Loch; Musolino, Nina Rosa de Castro; Machado, Vanielle Carvalho; Alcantara, Ana Elisa Evangelista; da Silva, Gilberto Ochman; Sperling Cescato, Valter Angelo; da Cunha Neto, Malebranche Berardo Carneiro

2015-01-01

Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH). It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing's disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15%) and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

Localization of amylin-like immunoreactivity in melanocyte-stimulating hormone-containing cells of the pars intermedia but not those of the pars distalis in the axolotl (Ambystoma mexicanum) pituitary.

PubMed

Suzuki, Hirohumi; Yamamoto, Toshiharu

2016-04-01

Immunohistochemical techniques were employed to investigate the distribution of amylin-like immunoreactivity in the axolotl (Ambystoma mexicanum) pituitary. Amylin-immunoreactive cells were observed in the pars intermedia, and these cells were found to be immunoreactive for α-melanocyte-stimulating hormone (αMSH) as well. In contrast, αMSH-immunoreactive cells in the pars distalis were immuno-negaitive for amylin. These light microscopic findings were confirmed by immunoelectron microscopy. Amylin-immunoreactive signals were located on the haloes of presumable secretory granules in association with αMSH-immunoreactive signals in the amylin-positive cells. However, in the pars distalis, the αMSH-positive cells did not contain amylin-immunoreactive secretory granules. Western blot analysis of axolotl pituitary extracts revealed the labeling of a protein band at approximately 10.5-kDa by the anti-rat amylin serum, which was not labeled by the anti-αMSH antibody. These findings indicate that amylin secreted from MSH-producing cells in the pars intermedia may modulate MSH secretion in an autocrine fashion and may participate in MSH functions such as fatty homeostasis together with MSH. Copyright © 2016 Elsevier GmbH. All rights reserved.

Nelfinavir induces radiation sensitization in pituitary adenoma cells

PubMed Central

Zeng, Jing; See, Alfred P.; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P.; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K.; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T.; Lim, Michael

2017-01-01

Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir’s effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 d, 17 d with nelfinavir treatment, 27 d with radiation 6 Gy, and 41 d with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on protein gel blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies. PMID:21811091

Nelfinavir induces radiation sensitization in pituitary adenoma cells.

PubMed

Zeng, Jing; See, Alfred P; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T; Lim, Michael

2011-10-01

Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution, and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir's effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 days, 17 days with nelfinavir treatment, 27 days with radiation 6 Gy, and 41 days with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on Western blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies.

Molecular analysis of brazilian patients with combined pituitary hormone deficiency and orthotopic posterior pituitary lobe reveals eight different PROP1 alterations with three novel mutations.

PubMed

Madeira, Joao Lo; Nishi, Mirian Y; Nakaguma, Marilena; Benedetti, Anna F; Biscotto, Isabela Peixoto; Fernandes, Thamiris; Pequeno, Thiago; Figueiredo, Thalita; Franca, Marcela M; Correa, Fernanda A; Otto, Aline P; Abrão, Milena; Miras, Mirta B; Santos, Silvana; Jorge, Alexander Al; Costalonga, Everlayny F; Mendonca, Berenice B; Arnhold, Ivo Jp; Carvalho, Luciani R

2017-12-01

Mutations in PROP1, HESX1 and LHX3 are associated with combined pituitary hormone deficiency (CPHD) and orthotopic posterior pituitary lobe (OPP). To identify mutations in PROP1, HESX1 and LHX3 in a large cohort of patients with CPHD and OPP (35 Brazilian, two Argentinian). We studied 23 index patients with CPHD and OPP (six familial and 17 sporadic) as well as 14 relatives. PROP1 was sequenced by the Sanger method in all except one sporadic case studied using a candidate gene panel. Multiplex ligation-dependent probe amplification (MLPA) was applied to one familial case in whom PROP1 failed to amplify by PCR. In the 13 patients without PROP1 mutations, HESX1 and LHX3 were sequenced by the Sanger method. We identified PROP1 mutations in 10 index cases. Three mutations were novel: one affecting the initiation codon (c.1A>G) and two affecting splicing sites, c.109+1G>A and c.342+1G>C. The known mutations, c.150delA (p.Arg53Aspfs*112), c.218G>A (p.Arg73His), c.263T>C (p.Phe88Ser) and c.301_302delAG (p.Leu102Cysfs*8), were also detected. MLPA confirmed complete PROP1 deletion in one family. We did not identify HESX1 and LHX3 mutations by Sanger. PROP1 mutations are a prevalent cause of congenital CPHD with OPP, and therefore, PROP1 sequencing must be the first step of molecular investigation in patients with CPHD and OPP, especially in populations with a high frequency of PROP1 mutations. In the absence of mutations, massively parallel sequencing is a promising approach. The high prevalence and diversity of PROP1 mutations is associated with the ethnic background of this cohort. © 2017 John Wiley & Sons Ltd.

Case report of a pituitary thyrotropin-secreting macroadenoma with Hashimoto thyroiditis and infertility.

PubMed

Li, Jiaqi; Li, Jianwei; Jiang, Shu; Yu, Ruichao; Yu, Yerong

2018-01-01

Thyrotropin-secreting adenoma (TSHoma) is rare, diagnosis and treatment are often delayed if the condition coexists with Hashimoto thyroiditis. The enlarged pituitary adenoma may eventually induce panhypopituitarism, infertility, or the compression of optic nerves and optic chiasma. This patient was a 36-year-old man who had been referred to the pituitary disease multidisciplinary team (MDT) of the West China Hospital, due to infertility. Examinations revealed pituitary thyrotropin-secreting macroadenoma. We conducted trans-sphenoidal surgery. Human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) were used for reproductive reconstruction after surgery. This patient successfully fathered a child. To date, the multidisciplinary team treatment of TSHoma was rare, TSHomas are often misdiagnosed as macroadenomas, because the clinical features are varied and it often takes a long time to be diagnosed. So the purpose of this case report is to attract attention to the manifestation of increased thyroid stimulating hormone (TSH) concentration and discuss MDT treatment for TSH-secreting adenoma. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Regulation of Thyroid-stimulating Hormone Release from the Pituitary by Thyroxine during Metamorphosis in Xenopus laevis

EPA Science Inventory

Environmentally-relevant chemicals such as perchlorate have the ability to disrupt the hypothalamo-pituitary-thyroid (HPT) axis of exposed individuals. Larval anurans are a particularly suitable model species for studying the effects of thyroid-disrupting chemicals (TDCs) becaus...

A Recessive Mutation Resulting in a Disabling Amino Acid Substitution (T194R) in the LHX3 Homeodomain Causes Combined Pituitary Hormone Deficiency

PubMed Central

Bechtold-Dalla Pozza, Susanne; Hiedl, Stefan; Roeb, Julia; Lohse, Peter; Malik, Raleigh E.; Park, Soyoung; Durán-Prado, Mario; Rhodes, Simon J.

2012-01-01

Background/Aims Recessive mutations in the LHX3 ho-meodomain transcription factor gene are associated with developmental disorders affecting the pituitary and nervous system. We describe pediatric patients with combined pituitary hormone deficiency (CPHD) who harbor a novel mutation in LHX3. Methods Two female siblings from related parents were examined. Both patients had neonatal complications. The index patient had CPHD featuring deficiencies of GH, LH, FSH, PRL, and TSH, with later onset of ACTH deficiency. She also had a hypoplastic anterior pituitary, respiratory distress, hearing impairment, and limited neck rotation. The LHX3 gene was sequenced and the biochemical properties of the predicted altered proteins were characterized. Results A novel homozygous mutation predicted to change amino acid 194 from threonine to arginine (T194R) was detected in both patients. This amino acid is conserved in the DNA-binding homeodomain. Computer modeling predicted that the T194R change would alter the homeodomain structure. The T194R protein did not bind tested LHX3 DNA recognition sites and did not activate the α-glycoprotein and PRL target genes. Conclusion The T194R mutation affects a critical residue in the LHX3 protein. This study extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in the LHX3 gene. PMID:22286346

Fetal Hypothalamus-Pituitary-Adrenal Responses to Estradiol Sulfate

PubMed Central

2011-01-01

Estradiol (E2) is an important modifier of the activity of the fetal hypothalamus-pituitary-adrenal axis. We have reported that estradiol-3-sulfate (E2SO4) circulates in fetal blood in far higher concentrations than E2 and that the fetal brain expresses steroid sulfatase, required for local deconjugation of E2SO4. We performed the present study to test the hypothesis that chronic infusion of E2SO4 chronically increases ACTH and cortisol secretion and that it shortens gestation. Chronically catheterized fetal sheep were treated with E2SO4 intracerebroventricular (n = 5), E2SO4 iv (n = 4), or no steroid infusion (control group, n = 5). Fetuses were subjected to arterial blood sampling every other day until spontaneous birth for plasma hormone analysis. Treatment with E2SO4 attenuated preparturient increases in ACTH secretion near term without affecting the ontogenetic rise in plasma cortisol. Infusion of E2SO4 intracerebroventricularly significantly increased plasma E2, plasma E2SO4, and plasma progesterone and shortened gestation compared with all other groups. These results are consistent with the conclusion that E2SO4: 1) interacts with the hypothalamus-pituitary-adrenal axis primarily by stimulating cortisol secretion and inhibiting ACTH and pro-ACTH secretion by negative feedback; and 2) stimulates the secretion of E2 and E2SO4. We conclude that the endocrine response to E2SO4 in the fetus is not identical with the response to E2. PMID:21952234

Hereditary pituitary hyperplasia with infantile gigantism.

PubMed

Gläsker, Sven; Vortmeyer, Alexander O; Lafferty, Antony R A; Hofman, Paul L; Li, Jie; Weil, Robert J; Zhuang, Zhengping; Oldfield, Edward H

2011-12-01

We report hereditary pituitary hyperplasia. The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. The study is a retrospective analysis of three cases from one family. The study was conducted at the National Institutes of Health, a tertiary referral center. A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. The condition was treated by total hypophysectomy. We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

Electrical stimulation of acupoint combinations against deep venous thrombosis in elderly bedridden patients after major surgery.

PubMed

Hou, Lili; Chen, Cuiping; Xu, Lei; Yin, Peihao; Peng, Wen

2013-04-01

To compare the effects of electrical stimulation of different acupoint combinations among postoperative bedridden elderly patients on hemorheology and deep venous blood flow velocity and investigate the.role of electrical stimulation against deep vein thrombosis (DVT). From November 2010 to October 2011, a total of 160 elderly bedridden patients after major surgery were divided into the conventional care group, invigorating and promoting Qi group, blood-activating and damp-eliminating group, and acupoint-combination stimulation group. Whole blood viscosity, plasma viscosity, D-dimer levels, lower limb skin temperature, lower limb circumference, and flow velocities of the external iliac vein, femoral vein, popliteal vein, and deep calf veins in all patients were documented and compared among the four groups. Whole blood viscosity, plasma viscosity, D-dimer levels, and lower limb circumference were significantly reduced in the blood-activating and damp-eliminating group compared with the conventional care group (P < 0.05) and were almost equal to those in the acupoint-combination stimulation group (P > 0.05). Lower limb venous flow velocities were accelerated in the invigorating and promoting Qi group compared with the other groups, excluding the acupoint-combination stimulation group (P < 0.05). Hemorheological indices in postoperative bedridden elderly patients were improved after combined electrical stimulation at Yinlingquan (SP 9) and Sanyinjiao (SP 6). Combined electrical stimulation at Zusanli (ST 36) and Taichong (LR 3), on the other hand, accelerated lower limb venous flow.

Pituitary gigantism: Causes and clinical characteristics.

PubMed

Rostomyan, Liliya; Daly, Adrian F; Beckers, Albert

2015-12-01

Acromegaly and pituitary gigantism are very rare conditions resulting from excessive secretion of growth hormone (GH), usually by a pituitary adenoma. Pituitary gigantism occurs when GH excess overlaps with the period of rapid linear growth during childhood and adolescence. Until recently, its etiology and clinical characteristics have been poorly understood. Genetic and genomic causes have been identified in recent years that explain about half of cases of pituitary gigantism. We describe these recent discoveries and focus on some important settings in which gigantism can occur, including familial isolated pituitary adenomas (FIPA) and the newly described X-linked acrogigantism (X-LAG) syndrome. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Pituitary Adenoma Apoplexy in an Adolescent: A Case Report and Review of the Literature

PubMed Central

Zijlker, Hero; Schagen, Sebastian; Wit, Jan Maarten; Biermasz, Nienke; van Furth, Wouter; Oostdijk, Wilma

2017-01-01

We present a 13-year-old boy who was admitted with complaints of a state of progressive sleepiness and a sudden headache with vomiting and fever. Laboratory testing showed hypoglycemia, multiple pituitary hormonal deficiencies, and an elevated C-reactive protein level. A cranial magnetic resonance imaging (MRI) showed an opaque sphenoid sinus and an intrasellar mass suggesting hemorrhage, so that we suspected pituitary apoplexy (PA) originating from a non-functioning adenoma, although a pituitary abscess could not completely be excluded. The boy was treated with antibiotics, hydrocortisone, and levothyroxine. Due to his rapid clinical improvement, no surgery was performed and we considered the diagnosis of PA as confirmed. At follow-up, the MRI scan showed a small residual lesion. Pituitary deficiencies of growth hormone, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, and vasopressin persisted. A literature search of all well-documented cases of PA in children or adolescents (n=30, 13 boys and 17 girls) indicated that this condition is rare below 20 years of age but must be considered when a patient experiences headache with or without visual disturbances, even in the presence of clinical and laboratory signals suggestive of pituitary abscess. MRI neuroimaging is helpful in the differential diagnosis. In both conditions, the possibility of ACTH deficiency should always be considered, investigated, and treated. In cases without severe neuro-ophthalmological deficits and/or with a rapid and positive response to acute medical management, one can abstain from surgical treatment. PMID:28588003

The effects of high-frequency transcranial magnetic stimulation combined with transcutaneous electrical stimulation in a severe stroke patient.

PubMed

Koyama, Soichiro; Tanabe, Shigeo; Takeda, Kazuya; Warashina, Hiroaki; Sakurai, Hiroaki; Kanada, Yoshikiyo; Okumura, Ryuji; Shinoda, Jun; Nagata, Junji; Kanno, Tetsuo

2012-10-12

The case report describes the effects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) combined with transcutaneous electrical stimulation (TES) in a patient with severe stroke. The patient was a 69-year-old male who was affected by a left middle cerebral artery infarction. The patient had no movement in his right hand. To assess the effects, cerebral blood flow and motor function were measured before and after treatment. This treatment delivered rTMS over the affected M1 with TES at the paretic wrist extensor muscles for 10 days. The regional cerebral blood flow (rCBF) in the entire brain was measured by positronemission tomography. To evaluate the motor function, the Fugl-Meyer assessment (FMA) was used. After treatment, the rCBF was increased (except for the stimulated region), and the FMA score was slightly improved. These results suggest the potential therapeutic use of rTMS combined with TES for recovery in severe stroke.

Combination of Foot Stimulation and Tramadol Treatment Reverses Irritation Induced Bladder Overactivity in Cats

PubMed Central

Mally, Abhijith D.; Zhang, Fan; Matsuta, Yosuke; Shen, Bing; Wang, Jicheng; Roppolo, James R.; de Groat, William C.; Tai, Changfeng

2013-01-01

Purpose We determined whether transcutaneous electrical foot stimulation combined with a low dose of tramadol (Sigma-Aldrich®) could completely suppress bladder overactivity. Materials and Methods Repeat cystometrograms were performed in 18 α-chloralose anesthetized cats by infusing the bladder with saline or 0.25% acetic acid. Transcutaneous electrical stimulation (5 Hz) of the cat hind foot at 2 to 4 times the threshold intensity needed to induce observable toe movement was applied to suppress acetic acid induced bladder overactivity. Tramadol (1 to 3 mg/kg intravenously) was administered to enhance foot inhibition. Results Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE of 26% ± 5% of saline control capacity (p <0.01). Without tramadol, foot stimulation at 2 and 4 threshold intensity applied during acetic acid cystometrograms significantly increased bladder capacity to a mean of 47% ± 5% and 62% ± 6% of saline control capacity, respectively (p <0.05). Without foot stimulation, tramadol (1 mg/kg) only slightly changed bladder capacity to a mean of 39% ± 2% of saline control capacity (p >0.05), while 3 mg/kg significantly increased capacity to 85% ± 14% that of control (p <0.05). However, 1 mg/kg tramadol combined with foot stimulation increased bladder capacity to a mean of 71% ± 18% (2 threshold intensity) and 84% ± 14% (4 threshold intensity), respectively, which did not significantly differ from saline control capacity. In addition, long lasting (greater than 1.5 to 2 hours) post-stimulation inhibition was induced by foot stimulation combined with 3 mg/kg tramadol treatment. Conclusions This study suggests a new treatment strategy for overactive bladder by combining foot stimulation with a low dose of tramadol, which is noninvasive and has potentially high efficacy and fewer adverse effects. PMID:23088991

Diagnostic Accuracy of Perioperative Measurement of Basal Anterior Pituitary and Target Gland Hormones in Predicting Adrenal Insufficiency After Pituitary Surgery.

PubMed

Cerina, Vatroslav; Kruljac, Ivan; Radosevic, Jelena Marinkovic; Kirigin, Lora Stanka; Stipic, Darko; Pecina, Hrvoje Ivan; Vrkljan, Milan

2016-03-01

The insulin tolerance test (ITT) is the gold standard for diagnosing adrenal insufficiency (AI) after pituitary surgery. The ITT is unpleasant for patients, requires close medical supervision and is contraindicated in several comorbidities. The aim of this study was to analyze whether tumor size, remission rate, preoperative, and early postoperative baseline hormone concentrations could serve as predictors of AI in order to increase the diagnostic accuracy of morning serum cortisol. This prospective study enrolled 70 consecutive patients with newly diagnosed pituitary adenomas. Thirty-seven patients had nonfunctioning pituitary adenomas (NPA), 28 had prolactinomas and 5 had somatotropinomas. Thyroxin (T4), thyrotropin (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and insulin-like growth factor 1 (IGF-I) were measured preoperatively and on the sixth postoperative day. Serum morning cortisol was measured on the third postoperative day (CORT3) as well as the sixth postoperative day (CORT6). Tumor mass was measured preoperatively and remission was assessed 3 months after surgery. An ITT was performed 3 to 6 months postoperatively. Remission was achieved in 48% of patients and AI occurred in 51%. Remission rates and tumor type were not associated with AI. CORT3 had the best predictive value for AI (area under the curve (AUC) 0.868, sensitivity 82.4%, specificity 83.3%). Tumor size, preoperative T4, postoperative T4, and TSH were also associated with AI in a multivariate regression model. A combination of all preoperative and postoperative variables (excluding serum cortisol) had a sensitivity of 75.0% and specificity of 77.8%. The predictive power of CORT3 substantially improved by adding those variables into the model (AUC 0.921, sensitivity 94.1%, specificity 78.3%, PPV 81.9%, NPV of 92.7%). In a subgroup analysis that included only female patients with NPA, LH had exactly the same predictive value as CORT3. The addition

Correlation between LH secretion in castrated rats with cellular proliferation and synthesis of DNA in the anterior pituitary gland.

PubMed

Romano, M I; Machiavelli, G A; Pérez, R L; Carricarte, V; Burdman, J A

1984-07-01

The relationship between the release of LH and the synthesis of DNA was studied in the anterior pituitary gland of castrated rats. Cell types were characterized immunocytochemically. Castration significantly (P less than 0.01) increased the concentration of LH in serum (1326%) and the incorporation of [3H]thymidine into pituitary DNA (72%). This was accompanied by an increment in the activity of the enzyme DNA polymerase-alpha (58%) and in the number of mitoses (from 2 +/- 0.1/mm2 in intact rats to 21 +/- 0.8/mm2 15 days after castration). Only 20% of the mitoses found in the pituitary gland of castrated rats were positively stained with the antiserum against the beta-subunit of LH. The other 80% did not stain either with LH antiserum or with antisera against the other pituitary hormones. There was a significant (P less than 0.01) increase in the number of LH cells in castrated rats (48%). All the changes produced in the anterior pituitary gland after castration were prevented by the administration of dihydrotestosterone. The results demonstrate that a stimulation of LH release is followed by an increase of DNA synthesis and cell proliferation of gonadotrophs in the anterior pituitary gland.

A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report.

PubMed

Lim, Joo Hee; Kim, Soo Jung; Jung, Mo Kyung; Kim, Ki Eun; Kwon, Ah Reum; Chae, Hyun Wook; Kim, Duk Hee; Kim, Ho-Seong

2016-03-01

A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.

Pituitary apoplexy: pathophysiology, diagnosis and management.

PubMed

Glezer, Andrea; Bronstein, Marcello D

2015-06-01

Pituitary apoplexy is characterized by sudden increase in pituitary gland volume secondary to ischemia and/or necrosis, usually in a pituitary adenoma. Most cases occur during the 5th decade of life, predominantly in males and in previously unknown clinically non-functioning pituitary adenomas. There are some predisposing factors as arterial hypertension, anticoagulant therapy and major surgery. Clinical picture comprises headache, visual impairment, cranial nerve palsies and hypopituitarism. Most cases improve with both surgical and expectant management and the best approach in the acute phase is still controversial. Surgery, usually by transsphenoidal route, is indicated if consciousness and/or vision are impaired, despite glucocorticoid replacement and electrolyte support. Pituitary function is impaired in most patients before apoplexy and ACTH deficiency is common, which makes glucocorticoid replacement needed in most cases. Pituitary deficiencies, once established, usually do not recover, regardless the treatment. Sellar imaging and endocrinological function must be periodic reevaluated.

Follicular development and hormonal levels following highly purified or recombinant follicle-stimulating hormone administration in ovulatory women undergoing ovarian stimulation after pituitary suppression for in vitro fertilization: implications for implantation potential.

PubMed

Balasch, J; Fábregues, F; Creus, M; Peñarrubia, J; Vidal, E; Carmona, F; Puerto, B; Vanrell, J A

2000-01-01

The main goal in the present study was to compare follicular development and estradiol levels after ovarian stimulation in pituitary suppressed normally ovulating women undergoing IVF, using highly purified urinary follicle stimulating hormone (FSH) (u-FSH-HP) and recombinant FSH (rec-FSH). A secondary variable in our study was embryo implantation potential, which is closely related to appropriate follicular development and oocyte competence. For the main purpose of this study, 30 IVF patients (group 1) were treated during IVF consecutive cycles, using the same stimulation protocol, with u-FSH-HP in the first treatment study cycle and rec-FSH in the second one. As a control group (group 2) for implantation rates obtained in cycles treated with rec-FSH, 30 additional IVF patients were included who underwent a second IVF attempt again with u-FSH-HP. The total dose of FSH used and ovarian response obtained in terms of estradiol plasma levels and the total number of growing follicles on the day of human chronic gonadotropin (HCG) injection were similar in both treatment cycles in group 1 but better follicular dynamics and oocyte maturity were obtained with rec-FSH. The implantation rate was significantly higher in rec-FSH treated cycles in patients in group 1 than in control women (group 2). rec-FSH is more efficacious than u-FSH-HP when used in the same patient in inducing multiple follicular development in down-regulated cycles as indicated by ovarian performance and oocyte maturity. In addition, rec-FSH yields significantly higher implantation rates than u-FSH-HP when used in patients undergoing their second IVF attempt.

Prevalence of hypopituitarism after intracranial operations not directly associated with the pituitary gland

PubMed Central

2013-01-01

Background Over the last few years, awareness and detection rates of hypopituitarism following traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) has steadily increased. Moreover, recent studies have found that a clinically relevant number of patients develop pituitary insufficiency after intracranial operations and radiation treatment for non-pituitary tumors. But, in a substantial portion of more than 40%, the hypopituitarism already exists before surgery. We sought to determine the frequency, pattern, and severity of endocrine disturbances using basal and advanced dynamic pituitary testing following non-pituitary intracranial procedures. Methods 51 patients (29 women, 22 men) with a mean age of 55 years (range of 20 to 75 years) underwent prospective evaluation of basal parameters and pituitary function testing (combined growth hormone releasing hormone (GHRH)/arginine test, insulin tolerance test (ITT), low dose adrenocorticotropic hormone (ACTH) test), performed 5 to 168 months (median 47.2 months) after intracranial operation (4 patients had additional radiation and 2 patients received additional radiation combined with chemotherapy). Results We discovered an overall rate of hypopituitarism with distinct magnitude in 64.7% (solitary in 45.1%, multiple in 19.6%, complete in 0%). Adrenocorticotropic hormone insufficiency was found in 51.0% (partial in 41.2%, complete in 9.8%) and growth hormone deficiency (GHD) occurred in 31.4% (partial in 25.5%, severe in 5.9%). Thyrotropic hormone deficiency was not identified. The frequency of hypogonadism was 9.1% in men. Pituitary deficits were associated with operations both in close proximity to the sella turcica and more distant regions (p = 0.91). Age (p = 0.76) and gender (p = 0.24) did not significantly differ across patients with versus those without hormonal deficiencies. Groups did not significantly differ across pathology and operation type (p = 0.07). Conclusion Hypopituitarism

Prevalence of hypopituitarism after intracranial operations not directly associated with the pituitary gland.

PubMed

Fleck, Steffen Kristian; Wallaschofski, Henri; Rosenstengel, Christian; Matthes, Marc; Kohlmann, Thomas; Nauck, Matthias; Schroeder, Henry Werner Siegfried; Spielhagen, Christin

2013-11-04

Over the last few years, awareness and detection rates of hypopituitarism following traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) has steadily increased. Moreover, recent studies have found that a clinically relevant number of patients develop pituitary insufficiency after intracranial operations and radiation treatment for non-pituitary tumors. But, in a substantial portion of more than 40%, the hypopituitarism already exists before surgery. We sought to determine the frequency, pattern, and severity of endocrine disturbances using basal and advanced dynamic pituitary testing following non-pituitary intracranial procedures. 51 patients (29 women, 22 men) with a mean age of 55 years (range of 20 to 75 years) underwent prospective evaluation of basal parameters and pituitary function testing (combined growth hormone releasing hormone (GHRH)/arginine test, insulin tolerance test (ITT), low dose adrenocorticotropic hormone (ACTH) test), performed 5 to 168 months (median 47.2 months) after intracranial operation (4 patients had additional radiation and 2 patients received additional radiation combined with chemotherapy). We discovered an overall rate of hypopituitarism with distinct magnitude in 64.7% (solitary in 45.1%, multiple in 19.6%, complete in 0%). Adrenocorticotropic hormone insufficiency was found in 51.0% (partial in 41.2%, complete in 9.8%) and growth hormone deficiency (GHD) occurred in 31.4% (partial in 25.5%, severe in 5.9%). Thyrotropic hormone deficiency was not identified. The frequency of hypogonadism was 9.1% in men. Pituitary deficits were associated with operations both in close proximity to the sella turcica and more distant regions (p = 0.91). Age (p = 0.76) and gender (p = 0.24) did not significantly differ across patients with versus those without hormonal deficiencies. Groups did not significantly differ across pathology and operation type (p = 0.07). Hypopituitarism occurs more frequently than expected in

Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement.

PubMed

Casanueva, Felipe F; Barkan, Ariel L; Buchfelder, Michael; Klibanski, Anne; Laws, Edward R; Loeffler, Jay S; Melmed, Shlomo; Mortini, Pietro; Wass, John; Giustina, Andrea

2017-10-01

With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.

Hereditary Pituitary Hyperplasia with Infantile Gigantism

PubMed Central

Gläsker, Sven; Vortmeyer, Alexander O.; Lafferty, Antony R. A.; Hofman, Paul L.; Li, Jie; Weil, Robert J.; Zhuang, Zhengping

2011-01-01

Context: We report hereditary pituitary hyperplasia. Objective: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. Design: The study is a retrospective analysis of three cases from one family. Setting: The study was conducted at the National Institutes of Health, a tertiary referral center. Patients: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. Interventions: The condition was treated by total hypophysectomy. Main Outcome Measure(s): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. Results: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. Conclusions: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development. PMID:21976722

Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone. A new syndrome of "inappropriate secretion of TSH".

PubMed Central

Gershengorn, M C; Weintraub, B D

1975-01-01

An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed. PMID:1159077

Pituitary Medicine From Discovery to Patient-Focused Outcomes

PubMed Central

2016-01-01

Context: This perspective traces a pipeline of discovery in pituitary medicine over the past 75 years. Objective: To place in context past advances and predict future changes in understanding pituitary pathophysiology and clinical care. Design: Author's perspective on reports of pituitary advances in the published literature. Setting: Clinical and translational Endocrinology. Outcomes: Discovery of the hypothalamic-pituitary axis and mechanisms for pituitary control, have culminated in exquisite understanding of anterior pituitary cell function and dysfunction. Challenges facing the discipline include fundamental understanding of pituitary adenoma pathogenesis leading to more effective treatments of inexorably growing and debilitating hormone secreting pituitary tumors as well as medical management of non-secreting pituitary adenomas. Newly emerging pituitary syndromes include those associated with immune-targeted cancer therapies and head trauma. Conclusions: Novel diagnostic techniques including imaging genomic, proteomic, and biochemical analyses will yield further knowledge to enable diagnosis of heretofore cryptic syndromes, as well as sub classifications of pituitary syndromes for personalized treatment approaches. Cost effective personalized approaches to precision therapy must demonstrate value, and will be empowered by multidisciplinary approaches to integrating complex subcellular information to identify therapeutic targets for enabling maximal outcomes. These goals will be challenging to attain given the rarity of pituitary disorders and the difficulty in conducting appropriately powered prospective trials. PMID:26908107

Ghrelin receptor expression and colocalization with anterior pituitary hormones using a GHSR-GFP mouse line.

PubMed

Reichenbach, Alex; Steyn, Frederik J; Sleeman, Mark W; Andrews, Zane B

2012-11-01

Ghrelin is the endogenous ligand for the GH secretagogue receptor (GHSR) and robustly stimulates GH release from the anterior pituitary gland. Ghrelin also regulates the secretion of anterior pituitary hormones including TSH, LH, prolactin (PRL), and ACTH. However, the relative contribution of a direct action at the GHSR in the anterior pituitary gland vs. an indirect action at the GHSR in the hypothalamus remains undefined. We used a novel GHSR-enhanced green fluorescent protein (eGFP) reporter mouse to quantify GHSR coexpression with GH, TSH, LH, PRL, and ACTH anterior pituitary cells in males vs. females and in chow-fed or calorie-restricted (CR) mice. GHSR-eGFP-expressing cells were only observed in anterior pituitary. The number of GHSR-eGFP-expressing cells was higher in male compared with females, and CR did not affect the GHSR-eGFP cell number. Double staining revealed 77% of somatotrophs expressed GHSR-eGFP in both males and females. Nineteen percent and 12.6% of corticotrophs, 21% and 9% of lactotrophs, 18% and 19% of gonadotrophs, and 3% and 9% of males and females, respectively, expressed GHSR-eGFP. CR increased the number of TSH cells, but suppressed the number of lactotrophs and gonadotrophs, expressing GHSR-eGFP compared with controls. These studies support a robust stimulatory action of ghrelin via the GHSR on GH secretion and identify a previously unknown sexual dimorphism in the GHSR expression in the anterior pituitary. CR affects GHSR-eGFP expression on lactotrophs, gonadotrophs, and thyrotrophs, which may mediate reproductive function and energy metabolism during periods of negative energy balance. The low to moderate expression of GHSR-eGFP suggests that ghrelin plays a minor direct role on remaining anterior pituitary cells.

Pituitary gland and pregnancy.

PubMed

Foyouzi, Nastaran; Frisbaek, Yr; Norwitz, Errol R

2004-12-01

The hypothalamic-pituitary-adrenal axis is central to mammalian reproductive function, including conception, pregnancy maintenance, parturition, and breastfeeding. Pregnancy is associated with substantial physiologic changes within this endocrine axis to meet the demands of pregnancy, which include support of the fetus (volume support, nutritional and oxygen supply, clearance of fetal waste), protection of the fetus (from starvation, drugs, toxins), preparation of the uterus for labor, and protection of the mother from potential cardiovascular injury at delivery. This article reviews the anatomy, embryology, and physiology of the pituitary. The effect of pregnancy on pituitary structure and function, in health and disease, also is discussed.

Estradiol and corticosterone stimulate the proliferation of a GH cell line, MtT/S: Proliferation of growth hormone cells.

PubMed

Nogami, Haruo; Hiraoka, Yoshiki; Aiso, Sadakazu

2016-08-01

Estrogens are known as a potent growth-stimulator of the anterior pituitary cells such as prolactin cells and somatomammotroph cell lines, while glucocorticoids often inhibit cellular proliferation in the pituitary gland as well as in the extra-pituitary tissues. In this study, the involvement of these steroid hormones in the regulation of proliferation was examined in the MtT/S cells, secreting growth hormone (GH). Effects of estrogens and glucocorticoids were examined in MtT/S cells grown in the medium containing dextran-coated charcoal treated serum. The relative cell density after culture was estimated by the Cell Titer-Glo Luminescent Cell Viability Assay System, and the proliferation rate was determined by the BrdU incorporation method. The mRNA levels were determined by real-time PCR. Estradiol and the specific agonist for both estrogen receptor (ER) α and ERβ stimulated MtT/S growth at a dose dependent manner. The membrane impermeable estrogen, 17β-estradiol-bovine serum albumin conjugate also stimulated the MtT/S proliferation. The effects of all estrogens were inhibited by an estrogen receptor antagonist, ICI182780. Corticosterone stimulated the proliferation of MtT/S cells at doses lower than 10nM without stimulating GH gene transcription, whereas it did not change the proliferation rate at 1μM. The effects of corticosterone were inhibited by glucocorticoid receptor inhibitor, RU486, but not by the mineralocorticoid receptor antagonist, spironolactone. Both estrogens and glucocorticoids were found to stimulate the proliferation of MtT/S, increasing the mRNA expression of cyclins D1, D3, and E. The results suggest that estrogens and glucocorticoids may be involved in the mechanisms responsible for the proliferation of GH cells in the course of pituitary development, to maintain the population of GH cells in the adult pituitary gland, and also in the promotion of GH cell tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of gender, body weight, and blood glucose dynamics on the growth hormone response to the glucagon stimulation test in patients with pituitary disease.

PubMed

Wilson, Jessica R; Utz, Andrea L; Devin, Jessica K

2016-02-01

Body weight blunts the growth hormone (GH) response to provocative stimuli. The appropriate GH cut-off to confirm GH deficiency in obese and overweight patients undergoing the glucagon stimulation test (GST) has recently been questioned. We hypothesized that the peak GH would be inversely related to the nadir blood glucose (BG) after glucagon and that this may be a mechanism influencing peak GH in overweight patients. This retrospective study examined effects of gender, body weight, and BG dynamics on GH response to GST in patients evaluated in our Pituitary Center. Adult patients who underwent GST from September 2009-2014 were included. Continuous variable comparisons were analyzed using the Mann-Whitney U-test and categorical data by Fisher's Exact Test. Spearman correlation was used to determine associations between continuous variables. 42 patients (N=28, 66.7% female) had sufficient data for analysis. Obese patients (N=26) had a reduced GH response, summarized as GH area under the curve (AUC) (p=0.03 vs. non-obese patients) and higher BG during GST, summarized as AUC (p<0.01 vs. non-obese patients). Obese women (N=19), in particular, stimulated lower (p=0.03 vs. non-obese women) and had a higher nadir BG (p=0.03 vs. non-obese women). While weight correlated with extent (rs=0.35; p=0.02) and timing (rs=0.31; p=0.05) of nadir BG reached, there was no significant correlation between BG dynamics and the GH response in the total population (N=42). Ten patients (7 with pan anterior hypopituitarism, defined as 3 anterior pituitary deficiencies) had a peak GH≤0.1ng/mL during GST. When these subjects with a negligible peak GH response were excluded from the analysis, weight was associated with GH AUC (rs=-0.45; p=0.01), peak GH response (rs=-0.42; p=0.02) and nadir BG (rs=0.48; p<0.01). Furthermore, the nadir BG achieved during GST was inversely related to GH AUC (rs=-0.38; p=0.03) and peak GH (rs=-0.37; p=0.04) such that patients (N=32) with higher nadir BG had

Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes.

PubMed

Child, Christopher J; Blum, Werner F; Deal, Cheri; Zimmermann, Alan G; Quigley, Charmian A; Drop, Stenvert L S; Cutler, Gordon B; Rosenfeld, Ron G

2016-05-01

To determine characteristics of children initially diagnosed with isolated growth hormone deficiency (IGHD) of organic aetiology, who later developed multiple pituitary hormone deficiencies (MPHD). Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naïve at baseline in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study. Development of MPHD was ascertained from investigator-provided diagnoses, adverse events and concomitant medications. Analyses were performed for all patients and separately for those who developed MPHD within 4.5 years or had >3.5 years follow-up and continued to have IGHD (4-year cohort). MPHD developed in 71/716 (9.9%) children overall, and in 60/290 (20.7%) in the 4-year cohort. The most frequent additional deficiencies were thyroid-stimulating hormone (47 patients) and gonadotropins (23 patients). Compared with those who remained with IGHD, children who developed MPHD had more severe GHD at study entry, significantly lower baseline insulin-like growth factor1, peak stimulated growth hormone, and more frequent diagnosis of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Multivariate logistic regression analyses identified female gender, longer follow-up, higher baseline age and lower peak stimulated growth hormone as predictors of MPHD development. MPHD is more likely to develop in patients with severe organic IGHD, especially those with history of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Older baseline age, female gender and longer follow-up duration were also associated with higher incidence of MPHD. Long-term monitoring of pituitary function is recommended, irrespective of the aetiology of GHD. © 2016 European Society of Endocrinology.

MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency.

PubMed

Castinetti, Frederic; Reynaud, Rachel; Saveanu, Alexandru; Jullien, Nicolas; Quentien, Marie Helene; Rochette, Claire; Barlier, Anne; Enjalbert, Alain; Brue, Thierry

2016-06-01

Over the last 5 years, new actors involved in the pathogenesis of combined pituitary hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily glycoprotein and ciliary G protein-coupled receptors, as well as new transcription factors and signalling molecules. New modes of inheritance for alterations of genes encoding transcription factors have also been described. Finally, actors known to be involved in a very specific phenotype (hypogonadotroph hypogonadism for instance) have been identified in a wider range of phenotypes. These data thus suggest that new mechanisms could explain the low rate of aetiological identification in this heterogeneous group of diseases. Taking into account the fact that several reviews have been published in recent years on classical aetiologies of CPHD such as mutations of POU1F1 or PROP1, we focused the present overview on the data published in the last 5 years, to provide the reader with an updated review on this rapidly evolving field of knowledge. © 2016 European Society of Endocrinology.

Genetically Engineered Mouse Models of Pituitary Tumors

PubMed Central

Cano, David A.; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso

2014-01-01

Animal models constitute valuable tools for investigating the pathogenesis of cancer as well as for preclinical testing of novel therapeutics approaches. However, the pathogenic mechanisms of pituitary-tumor formation remain poorly understood, particularly in sporadic adenomas, thus, making it a challenge to model pituitary tumors in mice. Nevertheless, genetically engineered mouse models (GEMMs) of pituitary tumors have provided important insight into pituitary tumor biology. In this paper, we review various GEMMs of pituitary tumors, highlighting their contributions and limitations, and discuss opportunities for research in the field. PMID:25136513

Multiple-scale neuroendocrine signals connect brain and pituitary hormone rhythms

PubMed Central

Romanò, Nicola; Guillou, Anne; Martin, Agnès O; Mollard, Patrice

2017-01-01

Small assemblies of hypothalamic “parvocellular” neurons release their neuroendocrine signals at the median eminence (ME) to control long-lasting pituitary hormone rhythms essential for homeostasis. How such rapid hypothalamic neurotransmission leads to slowly evolving hormonal signals remains unknown. Here, we show that the temporal organization of dopamine (DA) release events in freely behaving animals relies on a set of characteristic features that are adapted to the dynamic dopaminergic control of pituitary prolactin secretion, a key reproductive hormone. First, locally generated DA release signals are organized over more than four orders of magnitude (0.001 Hz–10 Hz). Second, these DA events are finely tuned within and between frequency domains as building blocks that recur over days to weeks. Third, an integration time window is detected across the ME and consists of high-frequency DA discharges that are coordinated within the minutes range. Thus, a hierarchical combination of time-scaled neuroendocrine signals displays local–global integration to connect brain–pituitary rhythms and pace hormone secretion. PMID:28193889

Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.

PubMed

Pivonello, Rosario; Waaijers, Marlijn; Kros, Johan M; Pivonello, Claudia; de Angelis, Cristina; Cozzolino, Alessia; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

2017-08-01

The dopamine D 2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D 2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D 2 receptor. D 2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D 2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D 2 receptors. D 2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

Hyperthyroidism secondary to a pituitary adenoma secreting TSH, FSH, alpha-subunit and GH.

PubMed

Patrick, A W; Atkin, S L; MacKenzie, J; Foy, P M; White, M C; MacFarlane, I A

1994-02-01

A 51-year-old man had been treated for hyperthyroidism with antithyroid drugs for 8 years. He was then found to have a large pituitary adenoma with biochemical evidence of overproduction of TSH, FSH and alpha-subunit. Subsequent immunocytochemical and tissue culture studies confirmed secretion of these hormones. In addition, the tumour stained for GH and was capable of GH production in vitro. This combination of hormones produced by a pituitary adenoma has not been previously reported.

Expression of leukemia inhibitory factor and leukemia inhibitory factor receptor in the canine pituitary gland and corticotrope adenomas.

PubMed

Hanson, J M; Mol, J A; Meij, B P

2010-05-01

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the IL-6 family that activates the hypothalamic-pituitary-adrenal axis and promotes corticotrope cell differentiation during development. The aim of this study was to investigate the expression of LIF and its receptor (LIFR) in the canine pituitary gland and in corticotrope adenomas, and to perform a mutation analysis of LIFR. Using immunohistochemistry, immunofluorescence, and quantitative expression analysis, LIF and LIFR expression were studied in pituitary glands of control dogs and in specimens of corticotrope adenoma tissue collected through hypophysectomy in dogs with pituitary-dependent hypercortisolism (PDH, Cushing's disease). Using sequence analysis, cDNA was screened for mutations in the LIFR. In the control pituitary tissues and corticotrope adenomas, there was a low magnitude of LIF expression. The LIFR, however, was highly expressed and co-localized with ACTH(1-24) expression. Cytoplasmatic immunoreactivity of LIFR was preserved in corticotrope adenomas and adjacent nontumorous cells of pars intermedia. No mutation was found on mutation analysis of the complete LIFR cDNA. Surprisingly, nuclear to perinuclear immunoreactivity for LIFR was present in nontumorous pituitary cells of the pars distalis in 10 of 12 tissue specimens from PDH dogs. These data show that LIFR is highly co-expressed with adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in the canine pituitary gland and in corticotrope adenomas. Nuclear immunoreactivity for LIFR in nontumorous cells of the pars distalis may indicate the presence of a corticotrope adenoma. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome.

PubMed

McCormack, Shana E; Li, Dong; Kim, Yeon Joo; Lee, Ji Young; Kim, Soo-Hyun; Rapaport, Robert; Levine, Michael A

2017-07-01

Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized. The objective of this study was to identify a genetic cause of PSIS in an affected child. Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus. WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered. Copyright © 2017 Endocrine Society

Genetic regulation of pituitary gland development in human and mouse.

PubMed

Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C A F; Dattani, Mehul T

2009-12-01

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke's pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans.

Genetic Regulation of Pituitary Gland Development in Human and Mouse

PubMed Central

Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C. A. F.; Dattani, Mehul T.

2009-01-01

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans. PMID:19837867

The tripeptide aldehyde, Boc-DPhe-Phe-Lysinal, is a novel Ca2+ channel inhibitor in pituitary cells.

PubMed

Makara, G B; Rappay, G; Garamvölgyi, V; Nagy, I; Dankó, S; Bajusz, S

1988-06-22

The effect of Boc-DPhe-Phe-Lysinal (Boc-DPPL) on the 45Ca2+ uptake of rat anterior pituitary monolayer cultures was investigated. The compound decreased the basal Ca2+ uptake at 3 x 10(-4) mol/l. The 45Ca2+ uptake stimulated by potassium-induced depolarization was more sensitive to Boc-DPPL inhibition, a slight decrease was seen with 3 x 10(-6) mol/l and there was a half maximal inhibition at 3 x 10(-5) mol/l. Boc-DPPL is known to inhibit pituitary hormone release in similar concentrations, an effect might also be due to its calcium antagonist property.

LH-RH binding to purified pituitary plasma membranes: absence of adenylate cyclase activation.

PubMed

Clayton, R N; Shakespear, R A; Marshall, J C

1978-06-01

Purified bovine pituitary plasma membranes possess two specific LH-RH binding sites. The high affinity site (2.5 X 10(9) l/mol) has low capacity (9 X 10(-15) mol/mg membrane protein) while the low affinity site 6.1 X 10(5) l/mol) has a much higher capacity (1.1 X 10(-10) mol/mg). Specific LH-RH binding to plasma membranes is increased 8.5-fold during purification from homogenate whilst adenylate cyclase activity is enriched 7--8-fold. Distribution of specific LH-RH binding to sucrose density gradient interface fractions parallels that of adenylate cyclase activity. Mg2+ and Ca2+ inhibit specific [125I]LH-RH binding at micromolar concentrations. Synthetic LH-RH, up to 250 microgram/ml, failed to stimulate adenylase cyclase activity of the purified bovine membranes. Using a crude 10,800 g rat pituitary membrane preparation, LH-RH similarly failed to activate adenylate cyclase even in the presence of guanyl nucleotides. These data confirm the presence of LH-RH receptor sites on pituitary plasma membranes and suggest that LH-RH-induced gonadotrophin release may be mediated by mechanisms other than activation of adenylate cyclase.

Genetic forms of pituitary dwarfism.

PubMed

Rimoin, D L

1971-05-01

Pituitary dwarfism represents a genetically heterogeneous group of disorders which may be classified on the basis of: associated developmental anomalies or degenerative disease; deficiency of, or peripheral insensitivity to HGH; the number of deficient hormones; the associated metabolic disturbances; and the mode of inheritance. Hereditary forms of pituitary dwarfism include: congenital absence of the pituitary, panhypopituitary dwarfism (autosomal and X-linked recessive forms), isolated HGH deficiency (Types I and II), Laron type of dwarfism, and peripheral unresponsiveness to HGH (the African Pygmies).

Pituitary stem cells drop their mask.

PubMed

Vankelecom, Hugo

2012-01-01

The pituitary gland represents the organism's endocrine hub, integrating central and peripheral inputs to generate the appropriate hormonal signals that govern key physiological processes. To meet the changing endocrine demands, the gland has to flexibly remodel its hormone-producing cell compartment. Mechanisms underlying pituitary cellular plasticity, as well as homeostatic turnover, are poorly understood. Similar to other tissues, resident stem cells may participate in the generation of newborn cells. Although in the past recurrently postulated to exist, pituitary stem cells remained obscure until the quest recently regained momentum, resulting in a surge of studies that designated very strong candidates for the stem/progenitor cell position. The cells identified express stem cell-associated markers and signaling factors, as well as transcriptional regulators that play essential roles during pituitary embryogenesis. They exhibit the stem cell properties of multilineage differentiation and prominent efflux capacity ("side population" phenotype), and display a topographical pattern reminiscent of niche-like configurations. Yet, the stem cell tenet of long-term self-renewal remains to be unequivocally demonstrated. Taken together, pituitary stem cells commence to drop their mask. While their "face gradually becomes visible, the "character" they play in the pituitary awaits further disclosure. The aim of this review is to highlight the recent progress in pituitary stem/progenitor cell identification by sketching the historical context, describing the new findings with inclusion of critical and cautionary reflections, proposing a tentative stem/progenitor cell model, and pointing out remaining gaps and challenges. The recent acceleration in pituitary stem cell research may announce an exciting era in this endocrine field.

Response of Indian growth hormone deficient children to growth hormone therapy: association with pituitary size.

PubMed

Khadilkar, Vaman V; Prasad, Hemchand Krishna; Ekbote, Veena H; Rustagi, Vaishakhi T; Singh, Joshita; Chiplonkar, Shashi A; Khadilkar, Anuradha V

2015-05-01

To ascertain the impact of pituitary size as judged by Magnetic Resonance Imaging (MRI), on response to Growth Hormone (GH) therapy in GH deficient children. Thirty nine children (9.1 ± 2.7 y, 22 boys) with non-acquired GH deficiency (21 Isolated GH deficiency and 18 Combined pituitary hormone deficiency) were consecutively recruited and followed up for one year. Clinical, radiological (bone age and MRI) and biochemical parameters were studied. Children with hypoplastic pituitary (pituitary height < 3 mm) had more severe height deficit (height for age Z-score -6.0 vs. -5.0) and retardation of skeletal maturation (bone age chronological age ratio of 0.59 vs. 0.48) at baseline as compared to children with normal pituitary heights (p < 0.05 for both). After one year of GH therapy, height for age Z scores and percentage change in height for age Z scores were significantly higher in children with hypoplastic pituitaries (13.8 ± 3.6 and 28.7 % vs. 11.2 ± 4.1 and 21.4 %). Significant co-relation was observed between pituitary height and height for age Z-scores at baseline (r = 0.39, p < 0.05). The predicted adult height using Tanner Whitehouse-2 equations improved from 140.8 to 152.3 cm in children with hypoplastic pituitary when compared to an increase from 145.8 to 153.5 cm observed in children with normal pituitary height (p < 0.05). Indian growth hormone deficient children with hypoplastic pituitary respond better to therapy with GH in short term.

Roles of the locus coeruleus and adrenergic receptors in brain-mediated hypothalamic-pituitary-adrenal axis responses to intracerebroventricular alcohol.

PubMed

Selvage, Dan

2012-06-01

Alcohol activates the hypothalamic-pituitary-adrenal (HPA) axis through its actions in both the periphery and the central nervous system (CNS). The studies presented here were designed to test the CNS-specific noradrenergic mechanisms by which alcohol stimulates HPA activity in the male rat. We used an experimental paradigm in which a small, nontoxic amount (5 μl) of alcohol was slowly microinfused intracerebroventricularly (icv). Alcohol was administered icv to animals with lesions of the locus coeruleus (LC) or in animals pretreated with α- or β-adrenergic receptor antagonists. Hormonal HPA activation was determined by measuring secretion of the pituitary stress hormone adrenocorticotropin (ACTH). Neuronal activation was determined by quantification of the expression of the transcription factor c-fos (Fos). As expected, icv alcohol stimulated ACTH secretion from the pituitary and Fos expression in the paraventricular nucleus of the hypothalamus (PVN). Bilateral electrolytic LC lesions blocked the ability of icv alcohol to stimulate ACTH secretion. Pretreatment with icv propranolol increased basal ACTH secretion levels, but icv alcohol did not increase this effect. Propranolol also blunted icv alcohol-induced PVN Fos expression. A low dose of phenoxybenzamine, an α-adrenergic receptor antagonist, did not affect the ability of icv alcohol to stimulate ACTH release. However, a higher dose of the drug was able to block the ACTH response to icv alcohol. Despite this, phenoxybenzamine did not inhibit alcohol-induced Fos expression. Icv pretreatment with corynanthine, a selective α-1 adrenergic receptor antagonist, modestly raised basal ACTH levels and blocked the icv alcohol-induced secretion of this hormone. These results indicate that the LC and norepinephrine play important roles in HPA activation caused by icv alcohol administration, but that the specific adrenergic receptor subtypes involved in this phenomenon still need to be identified. Copyright © 2012

beta. -lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant. beta. -endorphin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liotta, A.S.; Suda, T.; Krieger, D.T.

1978-06-01

..beta..-Lipotropin is the predominant opioid peptide of the human pituitary and rat pars distalis and is present in concentrations essentially equimolar with corticotropin. When freshly obtained nonfrozen rat anterior pituitaries were homogenized with 0.2 M HCl, approximately 98% of the immunoreactivity detected utilizing an antiserum that crossreacts equally with ..beta..-lipotropin and ..beta..-endorphin coeluted with /sup 125/I-labeled human ..beta..-lipotropin upon molecular sieve chromatography. The remainder of the activity eluted with synthetic human ..beta..-endorphin. Similar results were obtained for human pituitary. HCl homogenization of thawed tissue or homogenization of fresh tissue with acetic acid yielded substantially greater concentrations of ..beta..-endorphin and decreasedmore » concentrations of ..beta..-lipotropin. In human subjects, acute anterior pituitary stimulation using either insulin-induced hypoglycemia or vasopressin administration was associated with increased plasma ..beta..-lipotropin and corticotropin levels. At the time of peak concentrations, no significant levels of ..beta..-endorphin were detectable. These data indicate the lack of significant amounts of ..beta..-endorphin in human pituitary. Additionally, there appears to be no specific intrapituitary conversion of ..beta..-lipotropin to ..beta..-endorphin.« less

Isolation and Characterization of Rat Pituitary Endothelial Cells

PubMed Central

Chaturvedi, Kirti; Sarkar, Dipak K.

2010-01-01

Most previous studies that determined the effect of estradiol on angiogenesis used endothelial cells from nonpituitary sources. Because pituitary tumor tissue receives its blood supply via portal and arterial circulation, it is important to use pituitary-derived endothelial cells in studying pituitary angiogenesis. We have developed a magnetic separation technique to isolate endothelial cells from pituitary tissues and have characterized these cells in primary cultures. Endothelial cells of the pituitary showed the existence of endothelial cell marker, CD31, and of von Willebrand factor protein. These cells in cultures also showed immunore-activity of estrogen receptors alpha and beta. The angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, significantly increased proliferation and migration of the pituitary-derived endothelial cells in primary cultures. These results suggest that a magnetic separation technique can be used for enrichment of pituitary-derived endothelial cells for determination of cellular mechanisms governing the vascularization in the pituitary. PMID:17028416

Speech Perception With Combined Electric-Acoustic Stimulation: A Simulation and Model Comparison.

PubMed

Rader, Tobias; Adel, Youssef; Fastl, Hugo; Baumann, Uwe

2015-01-01

The aim of this study is to simulate speech perception with combined electric-acoustic stimulation (EAS), verify the advantage of combined stimulation in normal-hearing (NH) subjects, and then compare it with cochlear implant (CI) and EAS user results from the authors' previous study. Furthermore, an automatic speech recognition (ASR) system was built to examine the impact of low-frequency information and is proposed as an applied model to study different hypotheses of the combined-stimulation advantage. Signal-detection-theory (SDT) models were applied to assess predictions of subject performance without the need to assume any synergistic effects. Speech perception was tested using a closed-set matrix test (Oldenburg sentence test), and its speech material was processed to simulate CI and EAS hearing. A total of 43 NH subjects and a customized ASR system were tested. CI hearing was simulated by an aurally adequate signal spectrum analysis and representation, the part-tone-time-pattern, which was vocoded at 12 center frequencies according to the MED-EL DUET speech processor. Residual acoustic hearing was simulated by low-pass (LP)-filtered speech with cutoff frequencies 200 and 500 Hz for NH subjects and in the range from 100 to 500 Hz for the ASR system. Speech reception thresholds were determined in amplitude-modulated noise and in pseudocontinuous noise. Previously proposed SDT models were lastly applied to predict NH subject performance with EAS simulations. NH subjects tested with EAS simulations demonstrated the combined-stimulation advantage. Increasing the LP cutoff frequency from 200 to 500 Hz significantly improved speech reception thresholds in both noise conditions. In continuous noise, CI and EAS users showed generally better performance than NH subjects tested with simulations. In modulated noise, performance was comparable except for the EAS at cutoff frequency 500 Hz where NH subject performance was superior. The ASR system showed similar behavior

Double pituitary adenomas: six surgical cases.

PubMed

Sano, T; Horiguchi, H; Xu, B; Li, C; Hino, A; Sakaki, M; Kannuki, S; Yamada, S

1999-05-01

While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.

A distal modular enhancer complex acts to control pituitary- and nervous system-specific expression of the LHX3 regulatory gene.

PubMed

Mullen, Rachel D; Park, Soyoung; Rhodes, Simon J

2012-02-01

Lin-11, Isl-1, and Mec-3 (LIM)-homeodomain (HD)-class transcription factors are critical for many aspects of mammalian organogenesis. Of these, LHX3 is essential for pituitary gland and nervous system development. Pediatric patients with mutations in coding regions of the LHX3 gene have complex syndromes, including combined pituitary hormone deficiency and nervous system defects resulting in symptoms such as dwarfism, thyroid insufficiency, infertility, and developmental delay. The pathways underlying early pituitary development are poorly understood, and the mechanisms by which the LHX3 gene is regulated in vivo are not known. Using bioinformatic and transgenic mouse approaches, we show that multiple conserved enhancers downstream of the human LHX3 gene direct expression to the developing pituitary and spinal cord in a pattern consistent with endogenous LHX3 expression. Several transferable cis elements can individually guide nervous system expression. However, a single 180-bp minimal enhancer is sufficient to confer specific expression in the developing pituitary. Within this sequence, tandem binding sites recognized by the islet-1 (ISL1) LIM-HD protein are essential for enhancer activity in the pituitary and spine, and a pituitary homeobox 1 (PITX1) bicoid class HD element is required for spatial patterning in the developing pituitary. This study establishes ISL1 as a novel transcriptional regulator of LHX3 and describes a potential mechanism for regulation by PITX1. Moreover, these studies suggest models for analyses of the transcriptional pathways coordinating the expression of other LIM-HD genes and provide tools for the molecular analysis and genetic counseling of pediatric patients with combined pituitary hormone deficiency.

A Distal Modular Enhancer Complex Acts to Control Pituitary- and Nervous System-Specific Expression of the LHX3 Regulatory Gene

PubMed Central

Mullen, Rachel D.; Park, Soyoung

2012-01-01

Lin-11, Isl-1, and Mec-3 (LIM)-homeodomain (HD)-class transcription factors are critical for many aspects of mammalian organogenesis. Of these, LHX3 is essential for pituitary gland and nervous system development. Pediatric patients with mutations in coding regions of the LHX3 gene have complex syndromes, including combined pituitary hormone deficiency and nervous system defects resulting in symptoms such as dwarfism, thyroid insufficiency, infertility, and developmental delay. The pathways underlying early pituitary development are poorly understood, and the mechanisms by which the LHX3 gene is regulated in vivo are not known. Using bioinformatic and transgenic mouse approaches, we show that multiple conserved enhancers downstream of the human LHX3 gene direct expression to the developing pituitary and spinal cord in a pattern consistent with endogenous LHX3 expression. Several transferable cis elements can individually guide nervous system expression. However, a single 180-bp minimal enhancer is sufficient to confer specific expression in the developing pituitary. Within this sequence, tandem binding sites recognized by the islet-1 (ISL1) LIM-HD protein are essential for enhancer activity in the pituitary and spine, and a pituitary homeobox 1 (PITX1) bicoid class HD element is required for spatial patterning in the developing pituitary. This study establishes ISL1 as a novel transcriptional regulator of LHX3 and describes a potential mechanism for regulation by PITX1. Moreover, these studies suggest models for analyses of the transcriptional pathways coordinating the expression of other LIM-HD genes and provide tools for the molecular analysis and genetic counseling of pediatric patients with combined pituitary hormone deficiency. PMID:22194342

The Influence of Pituitary Size on Outcome After Transsphenoidal Hypophysectomy in a Large Cohort of Dogs with Pituitary-Dependent Hypercortisolism.

PubMed

van Rijn, S J; Galac, S; Tryfonidou, M A; Hesselink, J W; Penning, L C; Kooistra, H S; Meij, B P

2016-07-01

Transsphenoidal hypophysectomy is one of the treatment strategies in the comprehensive management of dogs with pituitary-dependent hypercortisolism (PDH). To describe the influence of pituitary size at time of pituitary gland surgery on long-term outcome. Three-hundred-and-six dogs with PDH. Survival and disease-free fractions were analyzed and related to pituitary size; dogs with and without recurrence were compared. Four weeks after surgery, 91% of dogs were alive and remission was confirmed in 92% of these dogs. The median survival time was 781 days, median disease-free interval was 951 days. Over time, 27% of dogs developed recurrence of hypercortisolism after a median period of 555 days. Dogs with recurrence had significantly higher pituitary height/brain area (P/B) ratio and pre-operative basal urinary corticoid-to-creatinine ratio (UCCR) than dogs without recurrence. Survival time and disease-free interval of dogs with enlarged pituitary glands was significantly shorter than that of dogs with a non-enlarged pituitary gland. Pituitary size at the time of surgery significantly increased over the 20-year period. Although larger tumors have a less favorable prognosis, outcome in larger tumors improved over time. Transsphenoidal hypophysectomy is an effective treatment for PDH in dogs, with an acceptable long-term outcome. Survival time and disease-free fractions are correlated negatively with pituitary gland size, making the P/B ratio an important pre-operative prognosticator. However, with increasing experience, and for large tumors, pituitary gland surgery remains an option to control the pituitary mass and hypercortisolism. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles

PubMed Central

Alsop, Derek; Ings, Jennifer S.; Vijayan, Mathilakath M.

2009-01-01

While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity. PMID:19649243

Thyroid storm induced by TSH-secreting pituitary adenoma: a case report.

PubMed

Fujio, Shingo; Ashari; Habu, Mika; Yamahata, Hitoshi; Moinuddin, F M; Bohara, Manoj; Arimura, Hiroshi; Nishijima, Yui; Arita, Kazunori

2014-01-01

Thyroid stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon tumors of the anterior pituitary gland. Patients with TSHomas may present with hyperthyroidism, but the incidence of thyroid storm due to TSHomas has yet to be determined. We report a rare case of thyroid storm caused by TSHoma in a 54-year-old woman. Preoperatively she had symptoms of excessive sweating and palpitation. Blood tests showed inappropriate secretion of TSH with blood TSH 6.86 μ U/mL, fT3 19.8 pg/mL, and fT4 5.95 ng/dL. Magnetic resonance imaging (MRI) revealed a pituitary tumor with maximum diameter of 13 mm that was extirpated through transsphenoidal route. After operation the patient was stuporous and thyroid storm occurred presenting with hyperthermia, hypertension, and tachycardia. It was well managed with nicardipine, midazolam, steroids, and potassium iodide. Immunohistochemical staining of tumor specimen was positive for TSH and growth hormone (GH). One year after operation, fT3 and fT4 levels were still high. As her tumor was diagnosed to be GH- and TSH-producing adenoma, octreotide injection therapy was started, which normalized thyroid hormone levels. This is the second reported case with thyroid storm due to TSHoma and emphasizes the importance of strategies with interdisciplinary cooperation for prevention of such emergency conditions.

Nocturnal pituitary hormone and renin profiles during chronic heat exposure.

PubMed

Saini, J; Brandenberger, G; Libert, J P; Follenius, M

1993-07-01

To establish the principal endocrine systems involved in the initial adaptation to chronic passive heat exposure, responses of the hydromineral and pituitary systems were compared. Nocturnal plasma profiles of growth hormone, prolactin, thyrotropin, and plasma renin activity were determined during a period of prolonged heat exposure designed to simulate a hot climate. Two groups of six male subjects (G1 and G2) were kept for 11 days in a climatically controlled apartment. The G1 group was exposed to 20 degrees C throughout the study, and the G2 group was exposed to 20 degrees C for 5 days and to 35 degrees C for the following 6 days. Blood was collected continuously during the 1st and 10th nights from 2300 to 0700 h and was sampled in 10-min aliquots for hormone analysis. Heat exposure increased the nocturnal mean core temperature (P < 0.02) and stimulated plasma renin activity (P < 0.01) but had little effect on the pituitary hormones except for a small increase in prolactin (P < 0.05). For the G1 group there was no change in hormone profiles. These results demonstrate that the principal initial endocrine system involved in acclimatization to passive heat exposure is the renin-angiotensin system, reflecting counteractive measures against salt and water losses. In contrast, 5 days of continuous heat exposure does not provoke metabolic changes, indicated by the small effect on pituitary hormone profiles.

Improvements in Attention and Decision-Making Following Combined Behavioral Training and Brain Stimulation.

PubMed

Filmer, Hannah L; Varghese, Elizabeth; Hawkins, Guy E; Mattingley, Jason B; Dux, Paul E

2017-07-01

In recent years there has been a significant commercial interest in 'brain training' - massed or spaced practice on a small set of tasks to boost cognitive performance. Recently, researchers have combined cognitive training regimes with brain stimulation to try and maximize training benefits, leading to task-specific cognitive enhancement. It remains unclear, however, whether the performance gains afforded by such regimes can transfer to untrained tasks, or how training and stimulation affect the brain's latent information processing dynamics. To examine these issues, we applied transcranial direct current stimulation (tDCS) over the prefrontal cortex while participants undertook decision-making training over several days. Anodal, relative to cathodal/sham tDCS, increased performance gains from training. Critically, these gains were reliable for both trained and untrained tasks. The benefit of anodal tDCS occurred for left, but not right, prefrontal stimulation, and was absent for stimulation delivered without concurrent training. Modeling revealed left anodal stimulation combined with training caused an increase in the brain's rate of evidence accumulation for both tasks. Thus tDCS applied during training has the potential to modulate training gains and give rise to transferable performance benefits for distinct cognitive operations through an increase in the rate at which the brain acquires information. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center.

PubMed

Otto, Aline P; França, Marcela M; Correa, Fernanda A; Costalonga, Everlayny F; Leite, Claudia C; Mendonca, Berenice B; Arnhold, Ivo J P; Carvalho, Luciani R S; Jorge, Alexander A L

2015-08-01

Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up. To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time. We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time. From 83 patients initially with IGHD, 37 (45%) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38%) deficiencies developed followed by TSH (31%), ACTH (12%) and ADH deficiency (5%). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002). Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.

Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene

PubMed Central

Aaltonen, Lauri A.; Daly, Adrian F.

2013-01-01

Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses

Three endocrine neoplasms: an unusual combination of pheochromocytoma, pituitary adenoma, and papillary thyroid carcinoma.

PubMed

Sisson, James C; Giordano, Thomas J; Avram, Anca M

2012-04-01

Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid-occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and (131)I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.

Response of Combined Electrical Stimulation and Biodegradable Ceramics.

DTIC Science & Technology

1982-06-01

C 5044 /1/2 N ANC A~DF’N 1111111.01=L6 MICROCOP REOUIO" ET HR NAIOA BREUOFSTN 193 A’’ Report Number 7 RESPOSE OF COMBINED ELECTRICAL STIMULATION AND...past ten years. U In most all reports, the TCP has demonstrated good biocompatibility, which has resulted in these types of compounds being introduced...the same for all soecimens and the compound was not osteooenic. Some concerns have develooed about residues of TCP within bone lesion sites when large

Secretion of Growth Hormone in Response to Muscle Sensory Nerve Stimulation

NASA Technical Reports Server (NTRS)

Grindeland, Richard E.; Roy, R. R.; Edgerton, V. R.; Gosselink, K. L.; Grossman, E. J.; Sawchenko, P. E.; Wade, Charles E. (Technical Monitor)

1994-01-01

Growth hormone (GH) secretion is stimulated by aerobic and resistive exercise and inhibited by exposure to actual or simulated (bedrest, hindlimb suspension) microgravity. Moreover, hypothalamic growth hormone-releasing factor (GRF) and preproGRF mRNA are markedly decreased in spaceflight rats. These observations suggest that reduced sensory input from inactive muscles may contribute to the reduced secretion of GH seen in "0 G". Thus, the aim of this study was to determine the effect of muscle sensory nerve stimulation on secretion of GH. Fed male Wistar rats (304 +/- 23 g) were anesthetized (pentobarbital) and the right peroneal (Pe), tibial (T), and sural (S) nerves were cut. Electrical stimulation of the distal (D) or proximal (P) ends of the nerves was implemented for 15 min. to mimic the EMG activity patterns of ankle extensor muscles of a rat walking 1.5 mph. The rats were bled by cardiac puncture and their anterior pituitaries collected. Pituitary and plasma bioactive (BGH) and immunoactive (IGH) GH were measured by bioassay and RIA.

Changes in thrombospondin-1 levels in the endothelial cells of the anterior pituitary during estrogen-induced prolactin-secreting pituitary tumors

PubMed Central

Sarkar, Abby J; Chaturvedi, Kirti; Chen, Cui Ping; Sarkar, Dipak K

2010-01-01

Thrombospondin-1 (TSP-1), a multifunctional matrix glycoprotein, has been shown to control tumor growth by inhibiting angiogenesis in various tissues. However, the role of this glycoprotein in pituitary angiogenesis is not well studied. In this report, we determined the changes in the production and action of TSP-1 on endothelial cells in anterior pituitary following estradiol treatment, which is known to increase prolactin-secreting tumor growth and vascularization in this tissue. We showed that TSP-1 immunoreactive protein is distributed in the anterior pituitary, particularly in the endothelial cells. Estradiol treatment for 2 and 4 weeks decreased the total tissue immunoreactive level of TSP-1 as well as the endothelial cell-specific immunoreactive level of this protein in the anterior pituitary. The steroid treatment also decreased the protein levels of TSP-1 in anterior pituitary tissues and in purified pituitary endothelial cells in primary cultures. Determination of the effects of TSP-1 on proliferation and migration of pituitary-derived endothelial cells in primary cultures elucidated an inhibitory action of TSP-1 on these vascular cell functions. These results suggest that locally produced TSP-1 may regulate estrogen angiogenic action on the pituitary. PMID:17283240

Effects of growth hormone treatment on the pituitary expression of GHRH receptor mRNA in uremic rats.

PubMed

Ferrando, Susana; Rodríguez, Julián; Santos, Fernando; Weruaga, Ana; Fernández, Marta; Carbajo, Eduardo; García, Enrique

2002-09-01

A decreased ability of pituitary cells to secrete growth hormone (GH) in response to growth hormone releasing hormone (GHRH) stimulation has been shown in young uremic rats. The aim of the current study was to examine the effect of uremia and GH treatment on pituitary GHRH receptor expression. Pituitary GHRH receptor mRNA levels were analyzed by RNase protection assay in young female rats made uremic by subtotal nephrectomy, either untreated (UREM) or treated with 10 IU/kg/day of GH (UREM-GH), and normal renal function animals fed ad libitum (SAL) or pair-fed with the UREM group (SPF). Rats were sacrificed 14 days after the second stage nephrectomy. Renal failure was confirmed by concentrations (X +/- SEM) of serum urea nitrogen (mmol/L) and creatinine (micromol/L) in UREM (20 +/- 1 and 89.4 +/- 4.5) and UREM-GH (16 +/- 1 and 91.4 +/- 6.9) that were much higher (P < 0.001) than those of sham animals (SAL, 3 +/- 0 and 26.5 +/- 2.2; SPF, 4 +/- 0 and 26.5 +/- 2.1). UREM rats became growth retarded as shown by a daily longitudinal tibia growth rate below (P < 0.05) that observed in SAL animals (156 +/- 3 vs. 220 +/- 5 microm/day). GH treatment resulted in significant growth rate acceleration (213 +/- 6 microm/day). GHRH receptor mRNA levels were no different among the SAL (0.43 +/- 0.03), SPF (0.43 +/- 0.08) and UREM (0.44 +/- 0.04) groups, whereas UREM-GH rats had significantly higher values (0.72 +/- 0.07). The status of pituitary GHRH receptor is not modified by nutritional deficit or by severe uremia causing growth retardation. By contrast, the growth promoting effect of GH administration is associated with stimulated GHRH receptor gene expression.

Pituitary apoplexy.

PubMed

Bi, Wenya Linda; Dunn, Ian F; Laws, Edward R

2015-02-01

Pituitary apoplexy is a clinical syndrome of sudden headache and visual decline associated with acute hemorrhagic or ischemic change of an intrasellar mass, and comprises only a subset of hemorrhagic pituitary lesions. The most common presenting symptoms include headache, nausea, diminished visual acuity or visual field, ophthalmoplegia/paresis, and impaired mental status. Multiple risk factors have been reported, although the majority of cases have no identifiable precipitants. MRI is the most sensitive diagnostic modality, with specific imaging findings dependent on the timing post-hemorrhage. Early clinical suspicion is imperative to allow for corticosteroid replacement and hemodynamic stabilization when indicated. Transsphenoidal surgical decompression improves outcome in a majority of cases, although conservative management may be appropriate in select scenarios.

In Vivo and In Vitro Arsenic Exposition Induces Oxidative Stress in Anterior Pituitary Gland.

PubMed

Ronchetti, Sonia A; Bianchi, María S; Duvilanski, Beatriz H; Cabilla, Jimena P

2016-07-01

Inorganic arsenic (iAs) is at the top of toxic metalloids. Inorganic arsenic-contaminated water consumption is one of the greatest environmental health threats worldwide. Human iAs exposure has been associated with cancers of several organs, neurological disorders, and reproductive problems. Nevertheless, there are no reports describing how iAs affects the anterior pituitary gland. The aim of this study was to investigate the mechanisms involved in iAs-mediated anterior pituitary toxicity both in vivo and in vitro. We showed that iAs administration (from 5 to 100 ppm) to male rats through drinking water increased messenger RNA expression of several oxidative stress-responsive genes in the anterior pituitary gland. Serum prolactin levels diminished, whereas luteinizing hormone (LH) levels were only affected at the higher dose tested. In anterior pituitary cells in culture, 25 µmol/L iAs significantly decreased prolactin release in a time-dependent fashion, whereas LH levels remained unaltered. Cell viability was significantly reduced mainly by apoptosis evidenced by morphological and phosphatidylserine externalization studies. This process is characterized by early depolarization of mitochondrial membrane potential and increased levels of reactive oxygen species. Expression of some key oxidative stress-responsive genes, such as heme oxygenase-1 and metallothionein-1, was also stimulated by iAs exposure. The antioxidant N-acetyl cysteine prevented iAs-induced effects on the expression of oxidative stress markers, prolactin release, and apoptosis. In summary, the present work demonstrates for the first time that iAs reduces prolactin release both in vivo and in vitro and induces apoptosis in anterior pituitary cells, possibly resulting from imbalanced cellular redox status. © The Author(s) 2016.

Cranial electrotherapy stimulation affects mood state but not levels of peripheral neurotrophic factors or hypothalamic- pituitary-adrenal axis regulation.

PubMed

Roh, Hee-Tae; So, Wi-Young

2017-01-01

Cranial electrotherapy stimulation (CES) is reported to aid in relieving symptoms of depression and anxiety, though the mechanism underlying this effect remains unclear. Therefore, the present study aimed to evaluate changes in the hypothalamic-pituitary-adrenal (HPA) axis response and levels of neurotrophic factors, as well as changes in mood state, in patients undergoing CES therapy. Fifty healthy postmenopausal women were randomly assigned to either a Sham CES group (n = 25) or an Active CES group (n = 25). CES treatment was conducted in 20-minute sessions, three times per week for 8 weeks, using a micro current cranial electrotherapy stimulator. Blood samples were collected prior to and following the 8-week treatment period for measurement of cortisol, adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) levels. Changes in mood state were also examined at the time of blood collection using the Profile of Mood States (POMS). No significant differences in cortisol, ACTH, BDNF, or NGF were observed between the two participant groups (p > 0.05) following the treatment period. However, those in the Active CES group exhibited significantly decreased Tension-Anxiety and Depression-Dejection scores on the POMS relative to pre-treatment scores (p < 0.05). Furthermore, Depression-Dejection scores following treatment were significantly lower in the Active CES group than in the Sham CES group (p < 0.05). No significant differences were observed in any other POMS scores such as Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment (p > 0.05). These results suggest that 8 weeks of CES treatment does not induce changes in blood levels of neurotrophic factors or HPA-axis-related hormones, though such treatment may be effective in treating symptoms of anxiety and depression.

Giant pituitary adenoma: histological types, clinical features and therapeutic approaches.

PubMed

Iglesias, Pedro; Rodríguez Berrocal, Víctor; Díez, Juan José

2018-06-16

Giant pituitary adenomas comprise about 6-10% of all pituitary tumors. They are mostly clinically non-functioning adenomas and occur predominantly in males. The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarism. Functioning adenomas give rise to specific symptoms of hormonal hypersecretion. The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients. Neurosurgical treatment, either through transsphenoidal or transcranial surgery, continues to be the treatment of choice in the majority of patients with giant pituitary adenomas. The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients.

Genetic disorders of the anterior pituitary gland.

PubMed

Teller, W M

1985-01-01

This survey deals with disorders caused by genetically disturbed function of the anterior pituitary gland. Genetic Dwarfism may be caused by isolated growth hormone deficiency (IGHD) or panpituitary diseases, such as congenital absence of the pituitary or familial panhypopituitarism. Genetic disturbances of isolated pituitary hormone secretion without dwarfism may occur as isolated gonadotropin deficiency (IGD), isolated luteinizing hormone deficiency ("fertile eunuch"), Kallmann syndrome (olfactogenital dysplasia), isolated thyrotropin deficiency (ITD) and isolated corticotropin deficiency (ICD). Pituitary dysfunction may also be associated with other genetic disease entities.

Hypophysopexy technique for radiosurgical treatment of cavernous sinus pituitary adenoma.

PubMed

Couldwell, William T; Rosenow, Joshua M; Rovit, Richard L; Benzil, Deborah L

2002-01-01

Stereotactic radiosurgery is being used with increased frequency in the treatment of residual or recurrent pituitary adenomas. The major risk associated with radiosurgical treatment of residual or recurrent pituitary tumor adjacent to normal functional pituitary gland is radiation of the pituitary, which frequently leads to the development of hypopituitarism. The authors describe a technique of pituitary transposition to reduce the radiation dose to the normal pituitary gland in cases of planned radiosurgical treatment of residual pituitary adenoma within the cavernous sinus. A sellar exploration for tumor resection is performed, the pituitary gland is transposed from the region of the cavernous sinus, and a fat and fascia graft is interposed between the normal pituitary gland and the residual tumor in the cavernous sinus. The residual tumor may then be treated with stereotactic radiosurgery. The increased distance between the normal pituitary gland and the residual tumor facilitates treatment of the tumor with radiosurgery and reduces the radiation to the normal pituitary gland. An illustrative case of a young female with recurrent acromegaly and a pituitary adenoma invading the cavernous sinus is described.

The Infundibular Recess Passes through the Entire Pituitary Stalk.

PubMed

Tsutsumi, S; Hori, M; Ono, H; Tabuchi, T; Aoki, S; Yasumoto, Y

2016-12-01

The infundibular recess (IR), commonly illustrated as a V-shaped hollow in the sagittal view, is recognized as a small extension of the third ventricle into the pituitary stalk. The precise morphology of the human IR is unknown. The present study sought to delineate the morphology of the IR using magnetic resonance imaging. Subjects included 100 patients without acute cerebral infarcts, intracranial hemorrhage, intrasellar or suprasellar cysts, hydrocephalus, inflammatory disease, or brain tumors. Patients with symptoms of increased intracranial pressure, intracranial hypotension, or pituitary dysfunction were excluded. Thin-sliced, seamless T2-weighted sequences involving the optic chiasm, entire pituitary stalk, and pituitary gland were performed in axial and sagittal planes for each patient. The numbers of slices delineating the pituitary stalk and IR were recorded from the axial images and quantified as ratios. The pituitary stalk consistently appeared as a styloid- or cone-shaped structure with variable inclinations toward the third ventricle floor. The IR was delineated as a smoothly tapering, tubular extension of the third ventricle located in the central portion of the pituitary stalk. In 81 % of patients, the IR passed through the entire length of the pituitary stalk and reached the upper surface of the pituitary gland, which was identified in 40 % of the midsagittal images. The IR is a cerebrospinal fluid-filled canal passing through the center of the pituitary stalk and connects the third ventricle to the pituitary gland. It may function in conjunction with the pituitary gland.

Thyroid-stimulating Hormone (TSH): Measurement of Intracellular, Secreted, and Circulating Hormone in Xenopus laevis and Xenopus tropicalis.

EPA Science Inventory

Thyroid Stimulating Hormone (TSH) is a hormone produced in the pituitary that stimulates the thyroid gland to grow and produce thyroid hormone (TH). The concentration of TH controls developmental changes that take place in a wide variety of organisms. Many use the metaphoric ch...

From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

PubMed

Asa, S L; Casar-Borota, O; Chanson, P; Delgrange, E; Earls, P; Ezzat, S; Grossman, A; Ikeda, H; Inoshita, N; Karavitaki, N; Korbonits, M; Laws, E R; Lopes, M B; Maartens, N; McCutcheon, I E; Mete, O; Nishioka, H; Raverot, G; Roncaroli, F; Saeger, W; Syro, L V; Vasiljevic, A; Villa, C; Wierinckx, A; Trouillas, J

2017-04-01

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients. © 2017 Society for Endocrinology.

Pituitary Dysfunction after Blast Traumatic Brain Injury: The UK BIOSAP Study

PubMed Central

Baxter, David; Sharp, David J; Feeney, Claire; Papadopoulou, Debbie; Ham, Timothy E; Jilka, Sagar; Hellyer, Peter J; Patel, Maneesh C; Bennett, Alexander N; Mistlin, Alan; McGilloway, Emer; Midwinter, Mark; Goldstone, Anthony P

2013-01-01

Objective Pituitary dysfunction is a recognized consequence of traumatic brain injury (TBI) that causes cognitive, psychological, and metabolic impairment. Hormone replacement offers a therapeutic opportunity. Blast TBI (bTBI) from improvised explosive devices is commonly seen in soldiers returning from recent conflicts. We investigated: (1) the prevalence and consequences of pituitary dysfunction following moderate to severe bTBI and (2) whether it is associated with particular patterns of brain injury. Methods Nineteen male soldiers with moderate to severe bTBI (median age = 28.3 years) and 39 male controls with moderate to severe nonblast TBI (nbTBI; median age = 32.3 years) underwent full dynamic endocrine assessment between 2 and 48 months after injury. In addition, soldiers had structural brain magnetic resonance imaging, including diffusion tensor imaging (DTI), and cognitive assessment. Results Six of 19 (32.0%) soldiers with bTBI, but only 1 of 39 (2.6%) nbTBI controls, had anterior pituitary dysfunction (p = 0.004). Two soldiers had hyperprolactinemia, 2 had growth hormone (GH) deficiency, 1 had adrenocorticotropic hormone (ACTH) deficiency, and 1 had combined GH/ACTH/gonadotrophin deficiency. DTI measures of white matter structure showed greater traumatic axonal injury in the cerebellum and corpus callosum in those soldiers with pituitary dysfunction than in those without. Soldiers with pituitary dysfunction after bTBI also had a higher prevalence of skull/facial fractures and worse cognitive function. Four soldiers (21.1%) commenced hormone replacement(s) for hypopituitarism. Interpretation We reveal a high prevalence of anterior pituitary dysfunction in soldiers suffering moderate to severe bTBI, which was more frequent than in a matched group of civilian moderate to severe nbTBI subjects. We recommend that all patients with moderate to severe bTBI should routinely have comprehensive assessment of endocrine function. Ann Neurol 2013;74:527–536 PMID

Animal models of pituitary neoplasia

PubMed Central

Lines, K.E.; Stevenson, M.; Thakker, R.V.

2016-01-01

Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

Gigantism associated with a pituitary tumour secreting growth hormone and prolactin and cured by transsphenoidal hypophysectomy.

PubMed

Favre, L; Rogers, L M; Cobb, C A; Rabin, D

1979-06-01

An 18-year old male is reported who presented with a history of a growtn spurt over the year preceding his admission. His height was above the 97th percentile, and he had incompletely developed secondary sexual characters. Pituitary evaluation demonstrated a moderately elevated level of growth hormone (hGH) not suppressible by a glucose load and not stimulable by TRH or by L-DOPA. Serum prolactin (PRL) concentration was also increased while gonadotrophin, thyroid and adrenal function were all subnormal. There was clear radiological evidence of a large pituitary tumour with suprasellar extension and transsphenoidal total hypophysectomy was performed. A mixed chromophobe and acidophilic adenoma was found and both growth hormone and prolactin were demonstrable in different cells of the tumour by the immunoperoxidase technique. Post-operatively the patient has hypopituitarism and levels of growth hormone and prolactin have remained low or undetectable after 6 months. Thus early diagnosis and surgical treatment of gigantism of this mixed hGH-PRL secreting pituitary tumour was associated with a cure, which contrasts with the unfavourable outcome of many of the patients previously reported.

Stimulation of the hypothalamo-pituitary-adrenal axis in the rat by three selective type-4 phosphodiesterase inhibitors: in vitro and in vivo studies

PubMed Central

Kumari, Meena; Cover, Patricia O; Poyser, Robert H; Buckingham, Julia C

1997-01-01

releasing hormone (ir-CRH-41) but lower concentrations of the drugs were without effect as also was BRL 61063 at 100 μM (P>0.05); the rank order of potency was thus BRL 61063>rolipram>denbufylline. The adenylyl cyclase activator forskolin (100 μM, P<0.01) also stimulated the release of ir-CRH-41, producing effects which were additive with those of rolipram and denbufylline but not with those of BRL 61063. The secretory responses to forskolin (100 μM) were accompanied by a highly significant increase in the cyclic AMP content of the hypothalamic tissue (P<0.005). Rolipram (10 μM) also significantly (P<0.05) elevated the hypothalamic cyclic AMP but denbufylline (10 mM) and BRL 61063 (10 μM) did not. However, all three PDE-inhibitors potentiated the rise in cyclic AMP induced by forskolin (P<0.05). None of the drugs tested, alone or in combination, modified the release of arginine vasopressin (ir-AVP) from the hypothalamus. Rolipram (100 μM), denbufylline (100 μM) and BRL 61063 (100 μM) stimulated the release of corticotrophin (ir-ACTH) from pituitary tissue in vitro (P<0.05) but in lower concentrations they were without significant effect. In addition, rolipram (10 μM, P<0.05), denbufylline (0.1 μM, P<0.05) and BRL 61063 (10 μM, P<0.05) potentiated the significant (P<0.05) rises in ir-ACTH secretion induced by forskolin (100 μM). Forskolin (100 μM) also produced a highly significant increase (P<0.01) in the tissue cyclic AMP content which was further potentiated by rolipram (10 μM), denbufylline (10 μM) and BRL 61063 (10 μM) which, alone did not affect the cyclic AMP content of the tissue. Since both denbufylline and BRL 61063 possess significant adenosine A1 receptor blocking activity, further studies examined the potential influence of these receptors on the secretion in vitro of CRH-41, AVP and ACTH. The release of ir-CRH-41 was increased significantly by adenosine deaminase (ADA, 5 u ml−1, P<0.05) and the A1-receptor

Plasticity of the reproductive axis caused by social status change in an african cichlid fish: I. Pituitary gonadotropins.

PubMed

Maruska, Karen P; Levavi-Sivan, Berta; Biran, Jakob; Fernald, Russell D

2011-01-01

Social position in a dominance hierarchy is often tightly coupled with fertility. Consequently, an animal that can recognize and rapidly take advantage of an opportunity to rise in rank will have a reproductive advantage. Reproduction in all vertebrates is controlled by the brain-pituitary-gonad axis, and in males of the African cichlid fish Astatotilapia burtoni, GnRH1 neurons at the apex of this axis are under social control. However, little is known about how quickly social information is transformed into functional reproductive change, or about how socially controlled changes in GnRH1 neurons influence downstream actions of the brain-pituitary-gonad axis. We created an opportunity for reproductively suppressed males to ascend in status and then measured how quickly the perception of this opportunity caused changes in mRNA and protein levels of the pituitary gonadotropins. mRNA levels of the β-subunits of LH and FSH rose rapidly in the pituitary 30 min after suppressed males perceived an opportunity to ascend. In contrast, mRNA levels of GnRH receptor-1 remained unchanged during social transition but were higher in stable dominant compared with subordinate males. In the circulation, levels of both LH and FSH were also quickly elevated. There was a positive correlation between mRNA in the pituitary and circulating protein levels for LH and FSH, and both gonadotropins were positively correlated with plasma 11-ketotestosterone. Our results show that the pituitary is stimulated extremely rapidly after perception of social opportunity, probably to allow suppressed males to quickly achieve reproductive success in a dynamic social environment.

Surgical Management of Carney Complex-Associated Pituitary Pathology.

PubMed

Lonser, Russell R; Mehta, Gautam U; Kindzelski, Bogdan A; Ray-Chaudhury, Abhik; Vortmeyer, Alexander O; Dickerman, Robert; Oldfield, Edward H

2017-05-01

Carney complex (CNC) is a familial neoplasia syndrome that is associated with pituitary-associated hypersecretion of growth hormone (GH) (acromegaly). The underlying cause of pituitary GH hypersecretion and its management have been incompletely defined. To provide biological insight into CNC-associated pituitary pathology and improve management, we analyzed findings in CNC patients who underwent transsphenoidal surgery. Consecutive CNC patients at the National Institutes of Health with acromegaly and imaging evidence of a pituitary adenoma(s) who underwent transsphenoidal resection of tumor(s) were included. Prospectively acquired magnetic resonance imaging and biochemical, surgical, and histological data were analyzed. Seven acromegalic CNC patients (2 male, 5 female) were included. The mean age at surgery was 29.7 years (range, 18-44 years). The mean follow-up was 4.7 years (range, 0.2-129 months). Magnetic resonance imaging revealed a single pituitary adenoma in 4 patients and multiple pituitary adenomas in 3 patients. Whereas patients with single discrete pituitary adenomas underwent selective adenomectomy, patients with multiple adenomas underwent selective adenomectomy of multiple tumors, as well as partial or total hypophysectomy. All adenomas were either GH and prolactin positive or exclusively prolactin positive. Pituitary tissue surrounding the adenomas in patients with multiple adenomas revealed hyperplastic GH- and prolactin-positive tissue. CNC-associated acromegaly results from variable pituitary pathology, including a single GH-secreting adenoma or multiple GH-secreting adenomas and/or GH hypersecretion of the pituitary gland surrounding multiple adenomas. Although selective adenomectomy is the preferred treatment for cases of GH-secreting adenomas, multiple adenomas with associated pituitary gland GH hypersecretion may require partial or complete hypophysectomy to achieve biochemical remission. Copyright © 2017 by the Congress of Neurological

Surgical Management of Carney Complex–Associated Pituitary Pathology

PubMed Central

Mehta, Gautam U.; Kindzelski, Bogdan A.; Ray-Chaudhury, Abhik; Vortmeyer, Alexander O.; Dickerman, Robert; Oldfield, Edward H.

2017-01-01

Abstract BACKGROUND: Carney complex (CNC) is a familial neoplasia syndrome that is associated with pituitary-associated hypersecretion of growth hormone (GH) (acromegaly). The underlying cause of pituitary GH hypersecretion and its management have been incompletely defined. OBJECTIVE: To provide biological insight into CNC-associated pituitary pathology and improve management, we analyzed findings in CNC patients who underwent transsphenoidal surgery. METHODS: Consecutive CNC patients at the National Institutes of Health with acromegaly and imaging evidence of a pituitary adenoma(s) who underwent transsphenoidal resection of tumor(s) were included. Prospectively acquired magnetic resonance imaging and biochemical, surgical, and histological data were analyzed. RESULTS: Seven acromegalic CNC patients (2 male, 5 female) were included. The mean age at surgery was 29.7 years (range, 18-44 years). The mean follow-up was 4.7 years (range, 0.2-129 months). Magnetic resonance imaging revealed a single pituitary adenoma in 4 patients and multiple pituitary adenomas in 3 patients. Whereas patients with single discrete pituitary adenomas underwent selective adenomectomy, patients with multiple adenomas underwent selective adenomectomy of multiple tumors, as well as partial or total hypophysectomy. All adenomas were either GH and prolactin positive or exclusively prolactin positive. Pituitary tissue surrounding the adenomas in patients with multiple adenomas revealed hyperplastic GH- and prolactin-positive tissue. CONCLUSION: CNC-associated acromegaly results from variable pituitary pathology, including a single GH-secreting adenoma or multiple GH-secreting adenomas and/or GH hypersecretion of the pituitary gland surrounding multiple adenomas. Although selective adenomectomy is the preferred treatment for cases of GH-secreting adenomas, multiple adenomas with associated pituitary gland GH hypersecretion may require partial or complete hypophysectomy to achieve biochemical

Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH.

PubMed

Acampora, D; Mazan, S; Tuorto, F; Avantaggiato, V; Tremblay, J J; Lazzaro, D; di Carlo, A; Mariano, A; Macchia, P E; Corte, G; Macchia, V; Drouin, J; Brûlet, P; Simeone, A

1998-04-01

Genetic and molecular approaches have enabled the identification of regulatory genes critically involved in determining cell types in the pituitary gland and/or in the hypothalamus. Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland. Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (betaFSH), luteinizing hormone (betaLH) and alpha-glycoprotein subunit (alphaGSU) genes. Analysis of Otx1 null mice indicates that, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism due to low levels of pituitary GH, FSH and LH hormones which, in turn, dramatically affect downstream molecular and organ targets. Nevertheless, Otx1-/- mice gradually recover from most of these abnormalities, showing normal levels of pituitary hormones with restored growth and gonadal function at 4 months of age. Expression patterns of related hypothalamic and pituitary cell type restricted genes, growth hormone releasing hormone (GRH), gonadotropin releasing hormone (GnRH) and their pituitary receptors (GRHR and GnRHR) suggest that, in Otx1-/- mice, hypothalamic and pituitary cells of the somatotropic and gonadotropic lineages appear unaltered and that the ability to synthesize GH, FSH and LH, rather than the number of cells producing these hormones, is affected. Our data indicate that Otx1 is a new pituitary transcription factor involved at the prepubescent stage in the control of GH, FSH and LH hormone levels and suggest that a complex regulatory mechanism might exist to control the physiological need for pituitary hormones at specific postnatal stages.

Cortical changes after mental imagery training combined with electromyography-triggered electrical stimulation in patients with chronic stroke.

PubMed

Hong, Il Ki; Choi, Jong Bae; Lee, Jong Ha

2012-09-01

Paresis of the upper extremity after stroke is not effectively solved by existing therapies. We investigated whether mental imagery training combined with electromyogram-triggered electric stimulation improved motor function of the paretic upper extremity in patients with chronic stroke and induced cortical changes. Fourteen subjects with chronic stroke (≥12 months) were randomly allocated to receive mental imagery training combined with electromyogram-triggered electric stimulation (n=7) or generalized functional electric stimulation (n=7) on the forearm extensor muscles of the paretic extremity in 2 20-minute daily sessions 5 days a week for 4 weeks. The upper extremity component of the Fugl-Meyer Motor Assessment, the Motor Activity Log, the modified Barthel Index, and (18)F-fluorodeoxyglucose brain positron emission tomography were measured before and after the intervention. The group receiving mental imagery training combined with electromyogram-triggered electric stimulation exhibited significant improvements in the upper extremity component of the Fugl-Meyer Motor Assessment after intervention (median, 7; interquartile range, 5-8; P<0.05), but the group receiving functional electric stimulation did not (median, 0; interquartile range, 0-3). Differences in score changes between the 2 groups were significant. The mental imagery training combined with electromyogram-triggered electric stimulation group showed significantly increased metabolism in the contralesional supplementary motor, precentral, and postcentral gyri (P(uncorrected)<0.001) after the intervention, but the functional electric stimulation group showed no significant differences. Mental imagery training combined with electromyogram-triggered electric stimulation improved motor function of the paretic extremity in patients with chronic stroke. The intervention increased metabolism in the contralesional motor-sensory cortex. Clinical Trial Registration- URL: https

Prospective investigation of the hypothalamo-pituitary-adrenal axis in patients with tularemia.

PubMed

Demiraslan, Hayati; Şimşek, Yasin; Tanriverdi, Fatih; Doğanay, Mehmet; Keleştemur, Hasan Fahrettin

2015-01-01

To investigate prospectively the hypothalamo-pituitary-adrenal (HPA) axis by adrenocorticotropic hormone (ACTH) stimulation test. Tularemia was diagnosed according to guidelines. An ACTH stimulation test (1 µg) and a dexamethasone suppression test (DST; 1 mg) were performed in patients in the acute phase of tularemia before antibiotic treatment and in the chronic phase. Nineteen patients (mean age: 41.0 ± 13.2 years; 57.9% female) with tularemia were enrolled in the study in 2011 and 2012. Cortisol response to ACTH stimulation test was sufficient in all patients during the acute phase. After the DST, the cortisol was not suppressed during the acute phase in only one patient. The median control time of 11 patients after acute tularemia was 13 months. During the chronic phase, cortisol response to ACTH stimulation was normal in all patients, and after DST cortisol was suppressed in all patients. The peak cortisol level after the ACTH stimulation test in the acute phase was higher than that in the chronic phase, but the difference was not statistically significant. The HPA axis of patients with tularemia was not significantly affected in the acute and chronic phases.

Localization of the aromatase enzyme expression in the human pituitary gland and its effect on growth hormone, prolactin, and thyroid stimulating hormone axis.

PubMed

Caglar, Asli Sezgin; Kapucu, Aysegul; Dar, Kadriye Akgun; Ozkaya, Hande Mefkure; Caglar, Erkan; Ince, Haluk; Kadioglu, Pinar

2015-08-01

The aim of this study is to evaluate aromatase expression in prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) secreting cells. Nontumoral human pituitary specimens were obtained from autopsy samples. Aromatase co-expression was determined by double immunohistochemical staining and assessed using H scores. H scores for GH-aromatase co-expression (GH-aromatase), TSH-aromatase co-expression (TSH-aromatase), and PRL-aromatase co-expression (PRL-aromatase) were 83.1 ± 13.1, 95.6 ± 16.1, and 83.7 ± 14.5, respectively. TSH producing cells exhibited the highest H score for co-expression of aromatase (p < 0.001). There was no gender difference in terms of H scores for aromatase expression and double immunohistochemical staining results (p > 0.05 for all). There was a negative correlation between the H scores for aromatase and PRL-aromatase, GH-aromatase and TSH-aromatase, respectively (r = -0.592, p < 0.001; r = -0.593, p < 0.001; r = -0.650, p < 0.001, respectively). Also, H scores for aromatase co-expression of each hormone were negatively correlated with the H scores for the corresponding hormone (r = -0.503, p < 0.001 for PRL-aromatase and PRL; r = -0.470, p < 0.001 for GH-aromatase, and GH; r = -0.641, p < 0.001 for TSH-aromatase and TSH). H scores for mean aromatase, GH-aromatase, TSH-aromatase were invariant of age (p > 0.05 for all). Age was negatively correlated with PRL-aromatase H score (r = -0.373, p = 0.008). Our study demonstrated significant aromatase co-expression in PRL, GH, and TSH secreting cells of the human anterior pituitary gland. The mutual paracrinal regulation between aromatase and three adenohypophyseal hormones indicates that aromatase may have a regulatory role on the synthesis and secretion of these hormones.

Doppler of the uterine arteries combined with endometrial thickness correlate well with the degree of pituitary suppression in women treated with long-acting GnRH agonists.

PubMed

Geber, Selmo; Vaintraub, Marco Túlio; Rotschild, Gisele; Sampaio, Marcos

2013-02-01

The aim of this study was to evaluate the use of Doppler velocimetry of the uterine arteries and its association to endometrial thickness as a method to confirm pituitary suppression after administration of gonadotropin-releasing hormone analogues in assisted reproduction treatment cycles. A total of 70 patients using gonadotropin-releasing hormone analogues for pituitary suppression for in vitro fertilization treatment were studied. To confirm down-regulation, serum estradiol levels and endometrial thickness were evaluated 10 days after gonadotropin-releasing hormone analogues administration. When estradiol was <30 pg/ml and endometrial thickness was <3 mm, pituitary suppression was confirmed. Doppler velocimetric measurements were performed at the same day to study the pulsatility index of the uterine arteries, until pituitary suppression was confirmed. All 70 patients had normal ovarian morphology. For the patients who had estradiol levels ≤30 pg/ml, the mean pulsatility index of the uterine arteries was 2.95 ± 0.79 and for those who had levels >30 pg/ml the mean PI was 2.22 ± 0.8 (p = 0.005). For the patients who had endometrial thickness ≤5 mm the mean PI was 2.86 ± 0.82 and for those with endometrial thickness >5 mm the mean PI was 2.17 ± 0.79 (p = 0.004). Using a cut-off point of 2.51 for the pulsatility index, to compare to estradiol levels, we observed a sensitivity of 72.7 % and specificity of 71 %. The combination of Doppler velocimetric and endometrial thickness showed a sensitivity of 94 % and specificity of 82.3 %. Doppler velocimetric analysis of the uterine arteries can be an important tool in the diagnosis of the down-regulation after the use of gonadotropin-releasing hormone analogues and might help simplify assisted reproduction programmes.

Constitution and behavior of follicular structures in the human anterior pituitary gland.

PubMed Central

Ciocca, D. R.; Puy, L. A.; Stati, A. O.

1984-01-01

The follicular structures present in the human pituitary gland were studied, at the light-microscopic level, using histochemical and immunocytochemical techniques. The antisera applied in the peroxidase-antiperoxidase procedure were anti-hFSH beta, anti-hLH beta, anti-hPRL, anti-hGH, anti-hTSH beta, anti-hLPH beta, anti-pACTH, and anti-hACTH. In the 10 normal pituitaries examined, follicles were always found in the three areas of the adenohypophysis. The wall of the pars distalis follicles showed the seven immunoreactive cell types studied, while follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells were the only ones present in the wall of the pars tuberalis follicles. Most of the cell types studied were also present in the wall of the intermediate area follicles, but these follicles had characteristics not found in the other two areas. They were very large, with frequent interconnections forming a three-dimensional network of anastomotic cavities, and the colloid had different histochemical affinity. None of the hormones studied could be detected by immunocytochemistry within the follicular colloid. Three of the ten pituitary adenomas examined showed numerous follicular structures. Some of the follicles in the adenomatous pituitaries were similar to those found in the normal adenohypophysis, but there were also follicles filled with only traces of colloid and numerous blood cells in the cavity, and follicles filled with neoformed connective tissue. In one of these cases, FSH/LH immunoreactive adenoma cells were seen in the wall of the follicles. The results obtained suggest that the finding of pituitary adenomas with follicular structures is not uncommon and that the follicles originate from the tumor cells. In addition, the follicles seem to have several functional stages, explaining the finding of different types of follicular formation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11

The low-dose combination preparation Vertigoheel activates cyclic nucleotide pathways and stimulates vasorelaxation.

PubMed

Heinle, H; Tober, C; Zhang, D; Jäggi, R; Kuebler, W M

2010-01-01

Vertigo of various and often unknown aetiologies has been associated with and attributed to impaired microvascular perfusion in the inner ear or the vertebrobasilar system. Vertigoheel is a low-dose combination preparation of proven value in the symptomatic treatment of vertigo. In the present study we tested the hypothesis that Vertigoheel's anti-vertiginous properties may in part be due to a vasodilatory effect exerted via stimulation of the adenylate and/or guanylate cyclase pathways. Thus, the influence of Vertigoheel or its single constituents on synthesis and degradation of cyclic nucleotides was measured. Furthermore, vessel myography was used to observe the effect of Vertigoheel on the vasoreactivity of rat carotid arteries. Vertigoheel and one of its constituents, Anamirta cocculus, stimulated adenylate cyclase activity, while another constituent, Conium maculatum, inhibited phosphodiesterase 5, suggesting that the individual constituents of Vertigoheel contribute differentially to a synergistic stimulation of cyclic nucleotide signalling pathways. In rat carotid artery rings, Vertigoheel counteracted phenylephrine-induced tonic vasoconstriction. The present data demonstrate a vasorelaxant effect of Vertigoheel that goes along with a synergistic stimulation of cyclic nucleotide pathways and may provide a mechanistic basis for the documented anti-vertiginous effects of this combination preparation.

[Old phenotype and new genotypes. Pituitary adenomas].

PubMed

Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A

2015-11-01

Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively.

p21, an important mediator of quiescence during pituitary tumor formation, is dispensable for normal pituitary development during embryogenesis.

PubMed Central

Monahan, Pamela; Himes, Ashley D.; Parfieniuk, Agata; Raetzman, Lori T.

2011-01-01

A delicate balance between proliferation and differentiation must be maintained in the developing pituitary to ensure the formation of the appropriate number of hormone producing cells. In the adult, proliferation is actively restrained to prevent tumor formation. The cyclin dependent kinase inhibitors (CDKIs) of the CIP/KIP family, p21, p27 and p57, mediate cell cycle inhibition. Although p21 is induced in the pituitary upon loss of Notch signaling or initiation of tumor formation to halt cell cycle progression, its role in normal pituitary organogenesis has not been explored. In wildtype pituitaries, expression of p21 is limited to a subset of cells embryonically as well as during the postnatal proliferative phase. Mice lacking p21 do not have altered cell proliferation during early embryogenesis, but do show a slight delay in separation of proliferating progenitors from the oral ectoderm. By embryonic day 16.5, p21 mutants have an alteration in the spatial distribution of proliferating pituitary progenitors, however there is no overall change in proliferation. At postnatal day 21, there appears to be no change in proliferation, as assessed by cells expressing Ki67 protein. However, p21 mutant pituitaries have significantly less mRNA of Myc and the cyclins Ccnb1, Ccnd1, Ccnd2 and Ccne1 than wildtype pituitaries. Interestingly, unlike the redundant role in cell cycle inhibition uncovered in p27/p57 double mutants, the pituitary of p21/p27 double mutants has a similar proliferation profile to p27 single mutants at the time points examined. Taken together, these studies demonstrate that unlike p27 or p57, p21 does not play a major role in control of progenitor proliferation in the developing pituitary. However, p21 may be required to maintain normal levels of cell cycle components. PMID:22154697

Pathology of the human pituitary adenomas

PubMed Central

Kajiya, Hanako; Takei, Mao; Egashira, Noboru; Tobita, Maya; Takekoshi, Susumu; Teramoto, Akira

2008-01-01

This article describes pertinent aspects of histochemical and molecular changes of the human pituitary adenomas. The article outlines individual tumor groups with general, specific and molecular findings. The discussion further extends to the unusual adenomas or carcinomas. The description in this article are pertinent not only for the practicing pathologists who are in the position of making proper diagnosis, but also for the pituitary research scientists who engage in solving basic problems in pituitary neoplasms by histochemistry and molecular biology. PMID:18688636

Preoperative preparation of patients with pituitary gland disorders.

PubMed

Malenković, Vesna; Gvozdenović, Ljiljana; Milaković, Branko; Sabljak, Vera; Ladjević, Nebojsa; Zivaljević, Vladan

2011-01-01

This paper presents the most common disorders of pituitary function: acromegaly, hypopituitarism, diabetes insipidus and syndrome similar to diabetes insipidus, in terms of their importance in preoperative preparation of patients. Pituitary function manages almost the entire endocrine system using the negative feedback mechanism that is impaired by these diseases. The cause of acromegaly is a pituitary adenoma, which produces growth hormone in adults. Primary therapy of acromegaly is surgical, with or without associated radiotherapy. If a patient with acromegaly as comorbidity prepares for non-elective neurosurgical operation, then it requires consultation with brain surgeons for possible delays of that operation and primary surgical treatment of pituitary gland. If operative treatment of pituitary gland is carried out, the preoperative preparation (for other surgical interventions) should consider the need for perioperative glucocorticoid supplementation. Panhypopituitarism consequences are different in children and adults and the first step in diagnosis is to assess the function of target organs. Change of electrolytes and water occurs in the case of pituitary lesions in the form of central or nephrogenic diabetes insipidus as a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Preoperative preparation of patients with pituitary dysfunction should be multidisciplinary, whether it is a neurosurgical or some other surgical intervention. The aim is to evaluate the result of insufficient production of pituitary hormones (hypopituitarism), excessive production of adenohypophysis hormones (acromegaly, Cushing's disease and hyperprolactinemia) and the influence of pituitary tumours in surrounding structures (compression syndrome) and to determine the level of perioperative risk. Pharmacological suppressive therapy of the hyperfunctional pituitary disorders can have significant interactions with drugs used in the perioperative period.

Pituitary apoplexy in a teenager--case report.

PubMed

Chao, Chen-Cheng; Lin, Chun-Ju

2014-06-01

Pituitary apoplexy is a rare clinical emergency which results from hemorrhage or infarction in the pituitary gland. We present a 14-year-old girl with pituitary apoplexy and review the literature. Our patient experienced blurred vision, nausea, and headache. Her best-corrected visual acuity was 20/200 and 20/20. Confrontation test visual field testing revealed bitemporal hemianopsia. Brain imaging demonstrated a suprasellar mass. The microscopic endonasal transsphenoidal approach only found 5-10 mL brownish fluid-like material. Pathology confirmed no malignancy. Pituitary apoplexy was diagnosed. Her nausea and headache gradually improved. Six months after operation, her best-corrected visual acuity had improved to 20/30 and 20/20. Although pituitary apoplexy is rare in pediatric patients, prompt evaluation including detailed ophthalmic examination, biochemical evaluation, endocrine workup, and image study are very important. Copyright © 2014 Elsevier Inc. All rights reserved.

Pituitary abscess: a case report and review of the literature

PubMed Central

Karagiannis, Apostolos K A; Dimitropoulou, Fotini; Papatheodorou, Athanasios; Lyra, Stavroula; Seretis, Andreas

2016-01-01

Summary Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34-year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively. Learning points Pituitary abscess is a rare disease and the reported clinical features vary mimicking other pituitary lesions. The diagnosis of pituitary abscess is often very difficult to make and rarely included in the differential. The histological findings of acute inflammatory infiltration confirm the diagnosis of pituitary abscess. Medical and surgical treatment is usually recommended upon diagnosis of a pituitary abscess. PMID:27274845

A patient with thyrotropinoma cosecreting growth hormone and follicle-stimulating hormone with low alpha-glycoprotein: a new subentity?

PubMed

Elhadd, Tarik A; Ghosh, Sujoy; Teoh, Wei Leng; Trevethick, Katy Ann; Hanzely, Zoltan; Dunn, Laurence T; Malik, Iqbal A; Collier, Andrew

2009-08-01

Thyrotropinomas are rare pituitary tumors. In 25 percent of cases there is autonomous secretion of a second pituitary hormone, adding to the clinical complexity. We report a patient with thyrotropin (TSH)-dependant hyperthyroidism along with growth hormone (GH) and follicle-stimulating hormone (FSH) hypersecretion but low alpha-glycoprotein (alpha-subunit) concentrations, a hitherto unique constellation of findings. A 67-year-old Scottish lady presented with longstanding ankle edema, paroxysmal atrial fibrillation, uncontrolled hypertension, fine tremors, warm peripheries, and agitation. Initial findings were a small goiter, elevated serum TSH of 7.37 mU/L (normal range, 0.30-6.0 mU/L), a free-thyroxine concentration of 34.9 pmol/L (normal range, 9.0-24.0 pmol/L), a flat TSH response to TSH-releasing hormone, and serum alpha-subunit of 3.1 IU/L (normal, <3.0 IU/L). There was no evidence of an abnormal thyroid hormone beta receptor by genotyping. Serum FSH was 56.8 U/L, but the luteinizing hormone (LH) was 23.6 U/L (postmenopausal FSH and LH reference ranges both >30 U/L) Basal insulin-like growth factor I was elevated to 487 microg/L with the concomitant serum GH being 14.1 mU/L, and subsequent serum GH values 30 minutes after 75 g oral glucose being 19.1 mU/L and 150 minutes later being 13.7 mU/L. An magnetic resonance imaging pituitary revealed a macroadenoma. Pituitary adenomectomy was performed with the histology confirming a pituitary adenoma, and the immunohistochemistry staining showed positive reactivity for FSH with scattered cells staining for GH and TSH. Staining for other anterior pituitary hormones was negative. After pituitary surgery she became clinically and biochemically euthyroid, the serum IFG-1 became normal, but the pattern of serum FSH and LH did not change. This case of plurihormonal thyrotropinoma is unique in having hypersecretion of TSH, GH, and FSH with low alpha-subunit. Such a combination may represent a new subentity of TSHomas.

Stimulation of synthesis and release of brain-derived neurotropic factor from intestinal smooth muscle cells by substance P and pituitary adenylate cyclase-activating peptide.

PubMed

Al-Qudah, M; Alkahtani, R; Akbarali, H I; Murthy, K S; Grider, J R

2015-08-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin present in the intestine where it participates in survival and growth of enteric neurons, augmentation of enteric circuits, and stimulation of intestinal peristalsis and propulsion. Previous studies largely focused on the role of neural and mucosal BDNF. The expression and release of BDNF from intestinal smooth muscle and the interaction with enteric neuropeptides has not been studied in gut. The expression and secretion of BDNF from smooth muscle cultured from the rabbit intestinal longitudinal muscle layer in response to substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP) was measured by western blot and enzyme-linked immunosorbent assay. BDNF mRNA was measured by reverse-transcription polymerase chain reaction. The expression of BNDF protein and mRNA was greater in smooth muscle cells (SMCs) from the longitudinal muscle than from circular muscle layer. PACAP and SP increased the expression of BDNF protein and mRNA in cultured longitudinal SMCs. PACAP and SP also stimulated the secretion of BDNF from cultured longitudinal SMCs. Chelation of intracellular calcium with BAPTA (1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) prevented SP-induced increase in BDNF mRNA and protein expression and SP-induced secretion of BDNF. Neuropeptides known to be present in enteric neurons innervating the longitudinal layer increase the expression of BDNF mRNA and protein in SMCs and stimulate the release of BDNF. Considering the ability of BDNF to enhance smooth muscle contraction, this autocrine loop may partially explain the characteristic hypercontractility of longitudinal muscle in inflammatory bowel disease. © 2015 John Wiley & Sons Ltd.

Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo

Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophsmore » taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of

Different degrees of somatotroph ablation compromise pituitary growth hormone cell network structure and other pituitary endocrine cell types.

PubMed

Waite, Eleanor; Lafont, Chrystel; Carmignac, Danielle; Chauvet, Norbert; Coutry, Nathalie; Christian, Helen; Robinson, Iain; Mollard, Patrice; Le Tissier, Paul

2010-01-01

We have generated transgenic mice with somatotroph-specific expression of a modified influenza virus ion channel, (H37A)M2, leading to ablation of GH cells with three levels of severity, dependent on transgene copy number. GH-M2(low) mice grow normally and have normal-size pituitaries but 40-50% reduction in pituitary GH content in adult animals. GH-M2(med) mice have male-specific transient growth retardation and a reduction in pituitary GH content by 75% at 42 d and 97% by 100 d. GH-M2(high) mice are severely dwarfed with undetectable pituitary GH. The GH secretory response of GH-M2(low) and GH-M2(med) mice to GH-releasing peptide-6 and GHRH was markedly attenuated. The content of other pituitary hormones was affected depending on transgene copy number: no effect in GH-M2(low) mice, prolactin and TSH reduced in GH-M2(med) mice, and all hormones reduced in GH-M2(high) mice. The effect on non-GH hormone content was associated with increased macrophage invasion of the pituitary. Somatotroph ablation affected GH cell network organization with limited disruption in GH-M2(low) mice but more severe disruption in GH-M2(med) mice. The remaining somatotrophs formed tight clusters after puberty, which contrasts with GHRH-M2 mice with a secondary reduction in somatotrophs that do not form clusters. A reduction in pituitary beta-catenin staining was correlated with GH-M2 transgene copy number, suggesting M2 expression has an effect on cell-cell communication in somatotrophs and other pituitary cell types. GH-M2 transgenic mice demonstrate that differing degrees of somatotroph ablation lead to correlated secondary effects on cell populations and cellular network organization.

Trophic and neurotrophic factors in human pituitary adenomas (Review).

PubMed

Spoletini, Marialuisa; Taurone, Samanta; Tombolini, Mario; Minni, Antonio; Altissimi, Giancarlo; Wierzbicki, Venceslao; Giangaspero, Felice; Parnigotto, Pier Paolo; Artico, Marco; Bardella, Lia; Agostinelli, Enzo; Pastore, Francesco Saverio

2017-10-01

The pituitary gland is an organ that functionally connects the hypothalamus with the peripheral organs. The pituitary gland is an important regulator of body homeostasis during development, stress, and other processes. Pituitary adenomas are a group of tumors arising from the pituitary gland: they may be subdivided in functional or non-functional, depending on their hormonal activity. Some trophic and neurotrophic factors seem to play a key role in the development and maintenance of the pituitary function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. Several lines of evidence suggest that trophic and neurotrophic factors may be involved in pituitary function, thus suggesting a possible role of the trophic and neurotrophic factors in the normal development of pituitary gland and in the progression of pituitary adenomas. Additional studies might be necessary to better explain the biological role of these molecules in the development and progression of this type of tumor. In this review, in light of the available literature, data on the following neurotrophic factors are discussed: ciliary neurotrophic factor (CNTF), transforming growth factors β (TGF‑β), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), vascular endothelial growth inhibitor (VEGI), fibroblast growth factors (FGFs) and epidermal growth factor (EGF) which influence the proliferation and growth of pituitary adenomas.

Pituitary gland

MedlinePlus Videos and Cool Tools

... should release by sending it either hormonal or electrical messages. In response to hormonal messages from the ... have properties similar to steroids In response to electrical messages from the hypothalamus, the pituitary gland releases ...

Production of recombinant rat proopiomelanocortin1-74 and characterization of its mitogenic action on pituitary lactotrophs.

PubMed

Bert, C; Vande Vijver, V; Andries, M; Verhaert, P; Proost, P; De Vreese, B; Van Beeumen, J; Vankelecom, H; Denef, C

1999-08-20

We report the production of biologically active recombinant rat Gly-2-Ser-1-POMC1-74 (rrPOMC1-74) in a prokaryotic expression system. The polypeptide was produced as a fusion protein with glutathione-S-transferase (GST), using the pGEX-4T-1 vector and subsequently cleaved by thrombin. Amino acid sequencing, up to residue 45, showed a correct primary structure including the two additional amino acids at the N-terminus, Gly and Ser, derived from the thrombin cleavage site. Electrospray ionization mass spectrometry showed a Mr of 8358.5 Da which was 14-16 Da heavier (oxidation or methylation) than the calculated mass. Combined digestion with trypsin and endoproteinase Glu-C followed by MALDI-TOF mass spectrometry and N-terminal sequencing of the separated fragments showed a correct disulphide bridge configuration. In reaggregate cell cultures of immature rat pituitary, rrPOMC1-74 displayed biological activity similar to that of natural human (h) POMC1-76 or rat POMC1-74: it stimulated DNA replication in lactotrophs but not in other pituitary cell types. However, its efficacy was significantly lower than that of the natural product. Gamma3-MSH, a peptide that can be generated from POMC1-74 and a typical ligand of the melanocortin-3 (MC-3) receptor, also stimulated DNA replication in lactotrophs and, in contrast to rrPOMC1-74, also in somatotrophs and thyrotrophs. rrPOMC1-74 increased cAMP levels in 293HEK cells stably transfected with the MC-3 receptor with an intrinsic activity and potency similar to that of gamma3-MSH. However, natural hPOMC1-76 was inactive in the latter test system. These data show that rrPOMC1-74 mimics the selective mitogenic action of natural POMC1-74 on lactotrophs. Since natural POMC1-74 is N- and O-glycosylated and rrPOMC1-74 is not, glycosylation does not seem to determine the selectivity for lactotrophs. In spite of the feature that rrPOMC1-74 is an agonist at the MC-3 receptor and the reported evidence that the MC-3 receptor is expressed

Posttransplantation lymphoproliferative disease involving the pituitary gland.

PubMed

Meriden, Zina; Bullock, Grant C; Bagg, Adam; Bonatti, Hugo; Cousar, John B; Lopes, M Beatriz; Robbins, Mark K; Cathro, Helen P

2010-11-01

Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus-negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD. Copyright © 2010 Elsevier Inc. All rights reserved.

The association of pituitary tumors and headache.

PubMed

Levy, Miles J

2011-04-01

Pituitary tumors may give rise to headache via numerous mechanisms. The traditional explanation for headache is dural stretch and cavernous sinus invasion, although this is not borne out by clinical studies. Certain functional pituitary tumors are associated with headache, notably growth hormone and prolactin-secreting tumors. The observation that somatostatin analogues can have a dramatic analgesic effect in acromegaly suggests that biochemical properties of the tumor may be important. The genetic predisposition of the patient to primary headache also determines whether headache occurs with pituitary tumors. This article attempts to outline the clinical features, management strategies, and key academic questions regarding the subject of pituitary tumors and headache.

Pituitary iron and volume imaging in healthy controls.

PubMed

Noetzli, L J; Panigrahy, A; Hyderi, A; Dongelyan, A; Coates, T D; Wood, J C

2012-02-01

Patients with transfusional iron overload develop iron deposits in the pituitary gland, which are associated with volume loss and HH. The purpose of this study was to characterize R2 and volumetric data in a healthy population for diagnostic use in patients with transfusional iron overload. One hundred healthy controls without iron overload between the ages of 2 and 48 were recruited to have MR imaging of the brain to assess their pituitary R2 and volume. Pituitary R2 was assessed with a 8-echo spin-echo sequence, and pituitary volumes, by a 3D spoiled gradient-echo sequence with 1-mm(3) resolution. A 2-component continuous piecewise linear approximation was used for creating volumetric and R2 nomograms. Equations were generated from regression relationships for convenient z-score calculation. Pituitary R2 rose weakly with age (r(2) = 0.19, P < .0001). Anterior and total pituitary volumes increased steadily up to 18 years of age, after which volume slightly decreased. Females had larger pituitary glands, most likely representing their larger lactotroph population. From these data, a clinician can calculate the z scores for R2 and pituitary volume in patients with iron overload. Normal ranges are well-differentiated from values previously associated with endocrine disease in transfusional siderosis; this finding suggests that preclinical iron overload can be recognized and appropriately treated.

Immunoreactive dynorphin in pituitary and brain.

PubMed Central

Goldstein, A; Ghazarossian, V E

1980-01-01

Distribution of the potent opioid peptide dynorphin has been determined in pituitary gland (pig, beef, rat), in the various regions of rat brain, and in rat spinal cord, by using a highly specific antiserum. By gel permeation chromatography in 4 M guanidine, the porcine pituitary immunoreactivity is found in a major peak of apparent molecular weight about 1700 and a minor peak of about 3400. Similar peaks are found in rat pituitary extracts, whereas rat brain contains, in addition, two peaks of larger apparent molecular weight. In the pituitary, immunoreactive dynorphin is found predominantly in pars nervosa. In the central nervous system, it is distributed widely, with highest concentrations in hypothalamus, medulla-pons, midbrain, and spinal cord. Although dynorphin contains leucine-enkephalin, the regional distribution of dynorphin is different from that of enkephalin or of any other known opioid peptide. PMID:6108564

Pituitary estrogen receptor alpha is involved in luteinizing hormone pulsatility at mid-gestation in the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha).

PubMed

Proietto, Sofía; Yankelevich, Lorena; Villarreal, Federico Martín; Inserra, Pablo Ignacio Felipe; Charif, Santiago Elías; Schmidt, Alejandro Raúl; Cortasa, Santiago Andrés; Corso, María Clara; Di Giorgio, Noelia Paula; Lux-Lantos, Victoria; Vitullo, Alfredo Daniel; Halperin, Julia; Dorfman, Verónica Berta

2018-04-12

The South American plains vizcacha, Lagostomus maximus, is a caviomorph rodent native from Argentina, Bolivia and Paraguay. It shows peculiar reproductive features like pre-ovulatory follicle recruitment during pregnancy with an ovulatory process at around mid-gestation. We have described the activation of the hypothalamic - pituitary - ovarian (HPO) axis during pregnancy. A progressive decrease of progesterone (P4) at mid-pregnancy elicits the delivery of gonadotropin-releasing hormone (GnRH) with the consequent secretion of follicle stimulating hormone (FSH) and estradiol (E 2 ) followed by luteinizing hormone (LH) release resulting in follicular luteinization and the P4 concentration recover. Pituitary gland is the central regulator of the HPO axis being E 2 a key hormone involved in the regulation of its activity. In this work we analyzed the action of E 2 on the pituitary response to the GnRH wave as well as its involvement on LH secretion at mid-gestation in L. maximus. The expression of GnRHR at the pituitary pars distalis showed a significant decrease at mid-pregnancy compared to early- and term-gestating females. ERα showed a significant increment from mid-gestation whereas ERβ did not show variations throughout pregnancy; whereas the LH expression in the pituitary pars distalis showed a significant increase at mid-gestation, concordantly with serum LH, which was followed by a decrease at term-gestation with similar values than at early-pregnancy. The number of cells with co-localization of ERα and GnRHR showed a decline at mid-pregnancy related to early- and term-gestation, whereas the cells with co-localization of ERα and LH increased at mid- and term-pregnancy. On the other hand, ex vivo measuring of LH pulsatility showed a significant increment in the total mass of LH delivered at mid-pregnancy followed by a decrease at term-gestation. The stimulation of ERα with the PPT specific agonist induced a significant increment in the total mass of LH

How to deal with giant pituitary adenomas: transsphenoidal or transcranial, simultaneous or two-staged?

PubMed

Han, Sheng; Gao, Wei; Jing, Zhitao; Wang, Yunjie; Wu, Anhua

2017-04-01

Giant pituitary adenomas (diameter >4 cm) are a challenge to treat, and there is no consensus on the optimal surgical strategy. We report here our experience in surgical management of these lesions. Adult patients with giant pituitary adenomas (n = 62; 54 non-functioning and eight hormone-secreting adenomas) who underwent surgical resection at our hospital from 2009 to 2015 were retrospectively reviewed. Surgical and clinical outcomes were analyzed. Single transsphenoidal and transcranial approaches were used in 43 (69.4%) and four (6.5%) patients, respectively. A combined transsphenoidal and transcranial approach was used in 13 patients (20.9%) and in two patients (3.2%), a transcranial procedure was followed 3 months later by a transsphenoidal approach. Greater than 90% resection was achieved in 47 cases (75.8%). During a mean follow-up period of 46.9 months, 49 patients (79%) showed improved visual impairment scores, while none experienced visual deterioration. There was no post-operative hemorrhage or mortality. A total of 27 patients (43.5%) received adjuvant medical and/or radiation therapy. At last follow-up, eight patients (12.9%) had recurrence. For giant pituitary adenoma, the transsphenoidal and transcranial approaches should be combined flexibly based on the characteristics of the tumor. In certain cases, a simultaneous combined approach can maximize tumor extirpation and lower the risk of swelling and bleeding of the residual tumor.

In Situ Hybridization Method Reveals (Pro)renin Receptor Expressing Cells in the Pituitary Gland of Rats: Correlation with Anterior Pituitary Hormones.

PubMed

Takahashi, Kazuhiro; Yatabe, Megumi; Fujiwara, Ken; Hirose, Takuo; Totsune, Kazuhito; Yashiro, Takashi

2013-02-28

Expression of (pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, was studied in rat pituitary gland. In situ hybridization showed that cells expressing (P)RR mRNA were widely distributed in the anterior lobe and intermediate lobe of the pituitary gland. Double-staining using in situ hybridization for (P)RR mRNA and immunohistochemistry for the pituitary hormones showed that (P)RR mRNA was expressed in most of the GH cells and ACTH cells in the anterior lobe. (P)RR mRNA was also expressed in a few prolactin cells and TSH cells, but not in LH cells. The present study has shown for the first time the distribution of (P)RR mRNA expressing cells in the rat pituitary gland. These findings suggest that (P)RR plays physiological roles in the pituitary gland, such as the modulation of the pituitary hormone secretion.

Expression of Hsp27 and Hsp70 and vacuolization in the pituitary glands in cases of fatal hypothermia.

PubMed

Doberentz, Elke; Markwerth, Philipp; Wagner, Rebecca; Madea, Burkhard

2017-09-01

Hypothermia causes systemic cellular stress. The pituitary gland is an endocrine gland and plays an important role in thermoregulation. When the core body temperature drops, the pituitary gland is activated by stimulation of hypothalamic hormones. In this study, we investigated morphological alterations of the pituitary gland in cases of fatal hypothermia. Several morphological alterations of the anterior lobe of the pituitary gland, such as hemorrhage, vacuolization, and hyperemia, have been previously described in fatal hypothermia. However, the diagnostic value of these findings is controversial. We compared 11 cases of fatal hypothermia with 10 cases lacking antemortem hypothermic influences. In the presence of thermal cellular stress, the expression of heat shock proteins increases to protect cellular structures. Therefore, we immunohistochemically analyzed Hsp27 and Hsp70. Hsp27 expression was detected in 27.3% of the cases of fatal hypothermia and in 10.0% of the control cases, whereas Hsp70 expression was not detected in any case. Additionally, Sudan staining was performed to quantify fatty degeneration. A positive reaction was found in 45.5% of the study group and in 10.0% of the control group. This indicates that fatty degeneration might be a valuable marker when other macroscopic signs of hypothermia are absent.

Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism.

PubMed

Hirsch, Dania; Benbassat, Carlos; Toledano, Yoel; S'chigol, Irena; Tsvetov, Gloria; Shraga-Slutzky, Ilana; Eizenberg, Yoav; Shimon, Ilan

2015-08-01

Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce. To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia. A historical prospective cohort of males with HH. Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels <10.4 nmol/L (300 ng/mL), normal LH and FSH levels and no known pituitary disease. Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m2, respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41-347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3%) men pituitary imaging was normal. Microadenoma was found in 8 (10.7%), empty sella and thickened pituitary stalk in one patient (1.3%) each. In other four patients (5.3%) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies. This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.

The Molecular Registry of Pituitary Adenomas (REMAH): A bet of Spanish Endocrinology for the future of individualized medicine and translational research.

PubMed

Luque, Raúl M; Ibáñez-Costa, Alejandro; Sánchez-Tejada, Laura; Rivero-Cortés, Esther; Robledo, Mercedes; Madrazo-Atutxa, Ainara; Mora, Mireia; Álvarez, Clara V; Lucas-Morante, Tomás; Álvarez-Escolá, Cristina; Fajardo, Carmen; Castaño, Luis; Gaztambide, Sonia; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Gálvez, María Ángeles; Salvador, Javier; Valassi, Elena; Webb, Susan M; Picó, Antonio; Puig-Domingo, Manel; Gilabert, Montserrat; Bernabéu, Ignacio; Marazuela, Mónica; Leal-Cerro, Alfonso; Castaño, Justo P

2016-01-01

Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples. Copyright © 2016 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

The synthetic gestagen levonorgestrel directly affects gene expression in thyroid and pituitary glands of Xenopus laevis tadpoles.

PubMed

Lorenz, Claudia; Opitz, Robert; Trubiroha, Achim; Lutz, Ilka; Zikova, Andrea; Kloas, Werner

2016-08-01

The synthetic gestagen levonorgestrel (LNG) was previously shown to perturb thyroid hormone-dependent metamorphosis in Xenopus laevis. However, so far the mechanisms underlying the anti-metamorphic effects of LNG remained unknown. Therefore, a series of in vivo and ex vivo experiments was performed to identify potential target sites of LNG action along the pituitary-thyroid axis of X. laevis tadpoles. Prometamorphic tadpoles were treated in vivo with LNG (0.01-10nM) for 72h and brain-pituitary and thyroid tissue was analyzed for marker gene expression. While no treatment-related changes were observed in brain-pituitary tissue, LNG treatment readily affected thyroidal gene expression in tadpoles including decreased slc5a5 and iyd mRNA expression and a strong induction of dio2 and dio3 expression. When using an ex vivo organ explant culture approach, direct effects of LNG on both pituitary and thyroid gland gene expression were detecTable Specifically, treatment of pituitary explants with 10nM LNG strongly stimulated dio2 expression and concurrently suppressed tshb expression. In thyroid glands, ex vivo LNG treatment induced dio2 and dio3 mRNA expression in a thyrotropin-independent manner. When thyroid explants were cultured in thyrotropin-containing media, LNG caused similar gene expression changes as seen after 72h in vivo treatment including a very strong repression of thyrotropin-induced slc5a5 expression. Concerning the anti-thyroidal activity of LNG as seen under in vivo conditions, our ex vivo data provide clear evidence that LNG directly affects expression of genes important for thyroidal iodide handling as well as genes involved in negative feedback regulation of pituitary tshb expression. Copyright © 2016 Elsevier B.V. All rights reserved.

Dynamic interactions between Pit-1 and C/EBPalpha in the pituitary cell nucleus.

PubMed

Demarco, Ignacio A; Voss, Ty C; Booker, Cynthia F; Day, Richard N

2006-11-01

The homeodomain (HD) transcription factors are a structurally conserved family of proteins that, through networks of interactions with other nuclear proteins, control patterns of gene expression during development. For example, the network interactions of the pituitary-specific HD protein Pit-1 control the development of anterior pituitary cells and regulate the expression of the hormone products in the adult cells. Inactivating mutations in Pit-1 disrupt these processes, giving rise to the syndrome of combined pituitary hormone deficiency. Pit-1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to regulate prolactin transcription. Here, we used the combination of biochemical analysis and live-cell microscopy to show that two different point mutations in Pit-1, which disrupted distinct activities, affected the dynamic interactions between Pit-1 and C/EBPalpha in different ways. The results showed that the first alpha-helix of the POU-S domain is critical for the assembly of Pit-1 with C/EBPalpha, and they showed that DNA-binding activity conferred by the HD is critical for the final intranuclear positioning of the metastable complex. This likely reflects more general mechanisms that govern cell-type-specific transcriptional control, and the results from the analysis of the point mutations could indicate an important link between the mislocalization of transcriptional complexes and disease processes.

Pituitary Tumors

MedlinePlus

... hormones in your body. This can cause endocrine diseases such as Cushing's syndrome and hyperthyroidism. Symptoms of pituitary tumors include Headaches Vision problems Nausea and vomiting Problems caused ... the tumor. Other options include medicines, radiation therapy, and chemotherapy.

Pituitary Tumors

MedlinePlus

... or milk production), sex hormones (control the menstrual cycle and other sexual functions), thyroid gland hormones (control the thyroid gland), adrenal gland hormones, and vasopressin (a hormone involved in water and electrolyte balance). Symptoms of pituitary adenoma and ...

Pituitary volumes are changed in patients with conversion disorder.

PubMed

Atmaca, Murad; Baykara, Sema; Mermi, Osman; Yildirim, Hanefi; Akaslan, Unsal

2016-03-01

Our study group previously measured pituitary volumes and found a relationship between somatoform disoders and pituitary volumes. Therefore, in conversion disorder, another somatoform disorder, we hypothesized that pituitary gland volumes would be reduced. Twenty female patients and healthy controls were recruited to the present investigation. The volumes of the pituitary gland were determined by using a 1.5 Tesla magnetic resonance scanner. We found that the pituitary gland volumes of the patients with conversion disorder were significantly smaller than those of healthy control subjects. In the patients with conversion disorder but not in the healthy control group, a significant negative correlation between the duration of illness and pituitary gland volume was determined. In summary, in the present study, we suggest that the patients with conversion disorder have smaller pituitary volumes compared to those of healthy control subjects. Further studies should confirm our data and ascertain whether volumetric alterations determined in the patients with conversion disorder can be changed with treatment or if they change over time.

Stimulation of Synthesis and Release of Brain-Derived Neurotropic Factor (BDNF) from Intestinal Smooth Muscle Cells by Substance P and Pituitary Adenylate Cyclase-Activating Peptide (PACAP)

PubMed Central

Al-Qudah, M.; Alkahtani, R.; Akbarali, H.I.; Murthy, K.S.; Grider, J.R.

2015-01-01

Background Brain-derived neurotrophic factor (BDNF) is a neurotrophin present in the intestine where it participates in survival and growth of enteric neurons, augmentation of enteric circuits, and stimulation of intestinal peristalsis and propulsion. Previous studies largely focused on the role of neural and mucosal BDNF. The expression and release of BDNF from intestinal smooth muscle and the interaction with enteric neuropeptides has not been studied in gut. Methods The expression and secretion of BDNF from smooth muscle cultured from rabbit longitudinal intestinal muscle in response to substance P and pituitary adenylate cyclase activating peptide (PACAP) was measured by western blot and ELISA. BDNF mRNA was measured by rt-PCR. Key Results The expression of BNDF protein and mRNA was greater in smooth muscle cells from the longitudinal muscle than from circular muscle layer. PACAP and substance P increased the expression of BDNF protein and mRNA in cultured longitudinal smooth muscle cells. PACAP and substance P also stimulated the secretion of BDNF from cultured longitudinal smooth muscle cells. Chelation of intracellular calcium with BAPTA prevented substance P-induced increase in BDNF mRNA and protein expression as well as substance P-induced secretion of BDNF. Conclusions & Inferences Neuropeptides known to be present in enteric neurons innervating the longitudinal layer increase the expression of BDNF mRNA and protein in smooth muscle cells and stimulate the release of BDNF. Considering the ability of BDNF to enhance smooth muscle contraction, this autocrine loop may partially explain the characteristic hypercontractility of longitudinal muscle in inflammatory bowel disease. PMID:26088546

Pit-1/growth hormone factor 1 splice variant expression in the rhesus monkey pituitary gland and the rhesus and human placenta.

PubMed

Schanke, J T; Conwell, C M; Durning, M; Fisher, J M; Golos, T G

1997-03-01

We have examined the expression of Pit-1 messenger RNA (mRNA) splice variants in the nonhuman primate pituitary and in rhesus and human placenta. Full-length complementary DNAs (cDNAs) representing Pit-1 and the Pit-1 beta splice variants were cloned from a rhesus monkey pituitary cDNA library and were readily detectable by RT-PCR with rhesus pituitary gland RNA. The Pit-1T variant previously reported in mouse pituitary tumor cell lines was not detectable in normal rhesus pituitary tissue, although two novel splice variants were detected. A cDNA approximating the rat Pit-1 delta 4 variant was cloned but coded for a truncated and presumably nonfunctional protein. Only by using a nested RT-PCR approach were Pit-1 and Pit-1 beta variants consistently detectable in both human and rhesus placental tissue. The Pit-1 beta variant mRNA was not detectable in JEG-3 choriocarcinoma cells unless the cells were stimulated with 8-Br-cAMP. Immunoblot studies with nuclear extracts from primary rhesus syncytiotrophoblast cultures or JEG-3 choriocarcinoma cells indicated that although mRNA levels were very low, Pit-1 protein was detectable in differentiated cytotrophoblasts, and levels increased after treatment with 8-Br-cAMP. Two major species of Pit-1 protein were detected that corresponded to the two major bands in rat pituitary GH3 cell nuclear extracts. Low levels of slightly larger bands also were seen, which may represent Pit-1 beta protein or phosphorylated species. We conclude that Pit-1 splice variants expressed in the primate pituitary gland differ from those in the rodent gland and that the Pit-1 and Pit-1 beta mRNAs expressed in the placenta give rise to a pattern of protein expression similar to that seen in pituitary cells, which is inducible by treatment with 8-Br-cAMP.

Exploration and Modulation of Brain Network Interactions with Noninvasive Brain Stimulation in Combination with Neuroimaging

PubMed Central

Shafi, Mouhsin M.; Westover, M. Brandon; Fox, Michael D.; Pascual-Leone, Alvaro

2012-01-01

Much recent work in systems neuroscience has focused on how dynamic interactions between different cortical regions underlie complex brain functions such as motor coordination, language, and emotional regulation. Various studies using neuroimaging and neurophysiologic techniques have suggested that in many neuropsychiatric disorders, these dynamic brain networks are dysregulated. Here we review the utility of combined noninvasive brain stimulation and neuroimaging approaches towards greater understanding of dynamic brain networks in health and disease. Brain stimulation techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation, use electromagnetic principles to noninvasively alter brain activity, and induce focal but also network effects beyond the stimulation site. When combined with brain imaging techniques such as functional MRI, PET and EEG, these brain stimulation techniques enable a causal assessment of the interaction between different network components, and their respective functional roles. The same techniques can also be applied to explore hypotheses regarding the changes in functional connectivity that occur during task performance and in various disease states such as stroke, depression and schizophrenia. Finally, in diseases characterized by pathologic alterations in either the excitability within a single region or in the activity of distributed networks, such techniques provide a potential mechanism to alter cortical network function and architectures in a beneficial manner. PMID:22429242

Development and sexual dimorphism of the pituitary gland.

PubMed

MacMaster, Frank P; Keshavan, Matcheri; Mirza, Yousha; Carrey, Normand; Upadhyaya, Ameet R; El-Sheikh, Rhonda; Buhagiar, Christian J; Taormina, S Preeya; Boyd, Courtney; Lynch, Michelle; Rose, Michelle; Ivey, Jennifer; Moore, Gregory J; Rosenberg, David R

2007-02-13

The pituitary gland plays a central role in sexual development and brain function. Therefore, we examined the effect of age and gender on pituitary volume in a large sample of healthy children and adults. Volumetric magnetic resonance imaging (MRI) was conducted in one hundred and fifty four (77 males and 77 females) healthy participants. Males were between the ages of 7 to 35 years (16.91+/-5.89 years) and females were 7 to 35 years of age (16.75+/-5.75 years). Subjects were divided into subgroups of age (7 to 9, 10 to 13, 14 to 17, 18 to 21, 22 and older) and sex (male/female). Pituitary gland volume differed between sexes when comparing the age groups (F=3.55, df=2, 143, p=0.03). Females demonstrated larger pituitary glands than males in the age 14 to 17 year old groups (p=0.04). Young (19 years and under) and old (20 years and older) females demonstrated a correlation between pituitary volume and age. Males did not show this relationship. These findings provide additional evidence for gender differences in the normative anatomy of the pituitary and may have relevance for the study of various childhood onset neuropsychiatric disorders in which pituitary dysfunction has been implicated.

Combination Pharmacotherapies for Stimulant Use Disorder: A Review of Clinical Findings and Recommendations for Future Research

PubMed Central

Stoops, William W.; Rush, Craig R.

2014-01-01

Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. Innovative strategies are necessary to develop successful pharmacotherapies for stimulant use disorders. This manuscript reviews human laboratory studies and clinical trials to determine whether one such strategy, use of combination pharmacotherapies, holds promise. The extant literature shows that combination pharmacotherapy produced results that were better than placebo treatment, especially with medications shown to have efficacy as monotherapies. However, many studies did not compare individual constituents to the combination treatment, making it impossible to determine whether combination treatment is more effective than monotherapy. Future research should systematically compare combined treatments with individual agents using medications showing some efficacy when tested alone. PMID:24716825

Assessment of pituitary micro-lesions using 3D sampling perfection with application-optimized contrasts using different flip-angle evolutions.

PubMed

Wang, Jing; Wu, Yue; Yao, Zhenwei; Yang, Zhong

2014-12-01

The aim of this study was to explore the value of three-dimensional sampling perfection with application-optimized contrasts using different flip-angle evolutions (3D-SPACE) sequence in assessment of pituitary micro-lesions. Coronal 3D-SPACE as well as routine T1- and dynamic contrast-enhanced (DCE) T1-weighted images of the pituitary gland were acquired in 52 patients (48 women and four men; mean age, 32 years; age range, 17-50 years) with clinically suspected pituitary abnormality at 3.0 T, retrospectively. The interobserver agreement of assessment results was analyzed with K-statistics. Qualitative analyses were compared using Wilcoxon signed-rank test. There was good interobserver agreement of the independent evaluations for 3D-SPACE images (k = 0.892), fair for routine MR images (k = 0.649). At 3.0 T, 3D-SPACE provided significantly better images than routine MR images in terms of the boundary of pituitary gland, definition of pituitary lesions, and overall image quality. The evaluation of pituitary micro-lesions using combined routine and 3D-SPACE MR imaging was superior to that using only routine or 3D-SPACE imaging. The 3D-SPACE sequence can be used for appropriate and successful evaluation of the pituitary gland. We suggest 3D-SPACE sequence to be a powerful supplemental sequence in MR examinations with suspected pituitary micro-lesions.

[Study on the early detection of Sclerotinia of Brassica napus based on combinational-stimulated bands].

PubMed

Liu, Fei; Feng, Lei; Lou, Bing-gan; Sun, Guang-ming; Wang, Lian-ping; He, Yong

2010-07-01

The combinational-stimulated bands were used to develop linear and nonlinear calibrations for the early detection of sclerotinia of oilseed rape (Brassica napus L.). Eighty healthy and 100 Sclerotinia leaf samples were scanned, and different preprocessing methods combined with successive projections algorithm (SPA) were applied to develop partial least squares (PLS) discriminant models, multiple linear regression (MLR) and least squares-support vector machine (LS-SVM) models. The results indicated that the optimal full-spectrum PLS model was achieved by direct orthogonal signal correction (DOSC), then De-trending and Raw spectra with correct recognition ratio of 100%, 95.7% and 95.7%, respectively. When using combinational-stimulated bands, the optimal linear models were SPA-MLR (DOSC) and SPA-PLS (DOSC) with correct recognition ratio of 100%. All SPA-LSSVM models using DOSC, De-trending and Raw spectra achieved perfect results with recognition of 100%. The overall results demonstrated that it was feasible to use combinational-stimulated bands for the early detection of Sclerotinia of oilseed rape, and DOSC-SPA was a powerful way for informative wavelength selection. This method supplied a new approach to the early detection and portable monitoring instrument of sclerotinia.

Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder

PubMed Central

Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

2017-01-01

Objectives: Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Design: Prospective controlled study in an outpatient clinic. Methods: Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Results: Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. Conclusions: The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches. PMID:29264511

Whole brain-pituitary in vitro preparation of the transgenic medaka (Oryzias latipes) as a tool for analyzing the differential regulatory mechanisms of LH and FSH release.

PubMed

Karigo, Tomomi; Aikawa, Masato; Kondo, Chika; Abe, Hideki; Kanda, Shinji; Oka, Yoshitaka

2014-02-01

Two types of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), are important pituitary hormones for sexual maturation and reproduction, and both of them are centrally regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In mammals, these two gonadotropins are secreted from a single type of gonadotrope. The mechanisms of differential regulation by GnRH of the release of two types of gonadotropins with different secretory profiles are still unknown. In teleosts, however, LH and FSH are secreted from separate cellular populations, unlike in mammals. This feature makes them useful for studying the regulatory mechanisms of LH and FSH secretions independently. Here, we generated transgenic medaka lines that express Ca(2+) indicator protein, inverse-pericam, specifically in the LH or FSH cells. We performed cell-type-specific Ca(2+) imaging of LH and FSH cells, respectively, using the whole brain-pituitary preparations of these transgenic fish in which all neural circuits and GnRH neuronal projection to the pituitary are kept intact. LH and FSH cells showed different Ca(2+) responses to GnRH. The results suggest differential regulation mechanisms for LH and FSH release by GnRH. Moreover, we also succeeded in detecting the effect on LH cells of endogenous GnRH peptide, which was released by electrical stimulation of the axons of GnRH1 neurons. Thus, our newly developed experimental model system using the whole brain-pituitary in vitro preparation of the transgenic medaka is a powerful tool for analyzing the differential regulatory mechanisms of the release of LH and FSH by multisynaptic neural inputs to the pituitary.

Seasonal Relationship between Gonadotropin, Growth Hormone, and Estrogen Receptor mRNA Expression in the Pituitary Gland of Largemouth Bass

PubMed Central

Martyniuk, Christopher J; Kroll, Kevin J.; Porak, Wesley F.; Steward, Cheree; Grier, Harry J.; Denslow, Nancy D.

2011-01-01

The objectives of this study were to investigate the seasonal changes in pituitary gonadotropins, growth hormone (GH), and estrogen receptor (ER) isoform mRNA in wild female and male largemouth bass (LMB) (Micropterus salmoides) from an unpolluted habitat to better understand reproductive physiology in this ecologically important species. Female pituitary luteinizing hormone (LH) β subunit and follicle-stimulating hormone (FSH) β subunit mRNA showed significant seasonal variation with levels peaking from January to April and were lowest from May through August. Male LMB showed more variation in gonadotropin subunit expression from month to month. Females had approximately 2–3 times higher gonadotropin mRNA levels in the pituitary when compared to males. All three gonadotropin mRNAs in females were positively correlated to gonadosomatic index (GSI), but only LHβ mRNA was correlated to GSI in males. Gonadotropin mRNA expression also increased with increasing oocyte and sperm maturation. Gonadotropin β subunit mRNA expression was positively correlated to GH mRNA in both sexes. The expression of all three ER isoforms was significantly correlated to each other in both sexes. The concurrent increase in all three ER mRNA isoforms with increasing gonadotropin mRNA in females and males suggests a prominent role for E2 feedback on pituitary gonadotropin synthesis in both sexes and that each of the three ER isoforms are likely to play a role in the pituitary during teleost reproduction. PMID:19416730

Seasonal relationship between gonadotropin, growth hormone, and estrogen receptor mRNA expression in the pituitary gland of largemouth bass.

PubMed

Martyniuk, Christopher J; Kroll, Kevin J; Porak, Wesley F; Steward, Cheree; Grier, Harry J; Denslow, Nancy D

2009-09-15

The objectives of this study were to investigate the seasonal changes in pituitary gonadotropins, growth hormone (GH), and estrogen receptor (ER) isoform mRNA in wild female and male largemouth bass (LMB) (Micropterus salmoides) from an unpolluted habitat to better understand reproductive physiology in this ecologically important species. Female pituitary luteinizing hormone (LH) beta subunit and follicle stimulating hormone (FSH) beta subunit mRNA showed significant seasonal variation with levels peaking from January to April and were lowest from May to August. Male LMB showed more variation in gonadotropin subunit expression from month to month. Females had approximately 2-3 times higher gonadotropin mRNA levels in the pituitary when compared to males. All three gonadotropin mRNAs in females were positively correlated to gonadosomatic index (GSI), but only LHbeta mRNA was correlated to GSI in males. Gonadotropin mRNA expression also increased with increasing oocyte and sperm maturation. Gonadotropin beta subunit mRNA expression was positively correlated to GH mRNA in both sexes. The expression of all three ER isoforms was significantly correlated to each other in both sexes. The concurrent increase in all three ER mRNA isoforms with increasing gonadotropin mRNA in females and males suggests a prominent role for E2 feedback on pituitary gonadotropin synthesis in both sexes and that each of the three ER isoforms are likely to play a role in the pituitary during teleost reproduction.

Genetic Overlap in Kallmann Syndrome, Combined Pituitary Hormone Deficiency, and Septo-Optic Dysplasia

PubMed Central

Raivio, Taneli; Avbelj, Magdalena; McCabe, Mark J.; Romero, Christopher J.; Dwyer, Andrew A.; Tommiska, Johanna; Sykiotis, Gerasimos P.; Gregory, Louise C.; Diaczok, Daniel; Tziaferi, Vaitsa; Elting, Mariet W.; Padidela, Raja; Plummer, Lacey; Martin, Cecilia; Feng, Bihua; Zhang, Chengkang; Zhou, Qun-Yong; Chen, Huaibin; Mohammadi, Moosa; Quinton, Richard; Sidis, Yisrael; Radovick, Sally; Dattani, Mehul T.

2012-01-01

Context: Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in the human forebrain. Objective: The objective of the study was to investigate whether KS, CPHD, and SOD have shared genetic origins. Design and Participants: A total of 103 patients with either CPHD (n = 35) or SOD (n = 68) were investigated for mutations in genes implicated in the etiology of KS (FGFR1, FGF8, PROKR2, PROK2, and KAL1). Consequences of identified FGFR1, FGF8, and PROKR2 mutations were investigated in vitro. Results: Three patients with SOD had heterozygous mutations in FGFR1; these were either shown to alter receptor signaling (p.S450F, p.P483S) or predicted to affect splicing (c.336C>T, p.T112T). One patient had a synonymous change in FGF8 (c.216G>A, p.T72T) that was shown to affect splicing and ligand signaling activity. Four patients with CPHD/SOD were found to harbor heterozygous rare loss-of-function variants in PROKR2 (p.R85G, p.R85H, p.R268C). Conclusions: Mutations in FGFR1/FGF8/PROKR2 contributed to 7.8% of our patients with CPHD/SOD. These data suggest a significant genetic overlap between conditions affecting the development of anterior midline in the human forebrain. PMID:22319038

A novel mutation of LHX3 is associated with combined pituitary hormone deficiency including ACTH deficiency, sensorineural hearing loss, and short neck-a case report and review of the literature.

PubMed

Bonfig, Walter; Krude, Heiko; Schmidt, Heinrich

2011-08-01

The LHX3 LIM-homeodomain transcription factor gene is required for normal pituitary and motoneuron development. LHX3 mutations are associated with growth hormone, prolactin, gonadotropin, and TSH deficiency; abnormal pituitary morphology; and may be accompanied with limited neck rotation and sensorineural hearing loss. We report on a boy, who presented with hypoglycemia in the newborn period. He is the second child of healthy unrelated parents. Short neck, growth hormone deficiency, and central hypothyroidism were diagnosed at a general pediatric hospital. Growth hormone and levothyroxine treatment were started, and blood sugar normalized with this treatment. On cerebral MRI, the anterior pituitary gland was hypoplastic. Sensorineural hearing loss was diagnosed by auditory testing. During follow-up, six repeatedly low morning cortisol levels (<1 μg/dl) and low ACTH levels (<10 pg/ml) were documented, so ACTH deficiency had developed over time and therefore hydrocortisone replacement was started at 1.5 years of age. Mutation analysis of the LHX3 gene revealed a homozygous stop mutation in exon 2: c.229C>T (CGA > TGA), Arg77stop (R77X). A complete loss of function is assumed with this homozygous stop mutation. We report a novel LHX3 mutation, which is associated with combined pituitary hormone deficiency including ACTH deficiency, short neck, and sensorineural hearing loss. All patients with LHX3 defects should undergo longitudinal screening for ACTH deficiency, since corticotrope function may decline over time. All patients should have auditory testing to allow for regular speech development.

Negative Feedback Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Metamorphosis in Xenopus laevis

EPA Science Inventory

A basic understanding of the endocrinology of the hypothalamic-pituitary-thyroid (HPT) axis of anuran larvae is necessary for predicting the consequences of HPT perturbation by thyroid-disrupting chemicals (TDCs) on the whole organism. This project examined negative feedback con...

Identification of Novel PROP1 and POU1F1 Mutations in Patients with Combined Pituitary Hormone Deficiency.

PubMed

Birla, S; Khadgawat, R; Jyotsna, V P; Jain, V; Garg, M K; Bhalla, A S; Sharma, A

2016-12-01

Growth hormone deficiency (GHD) results from variations affecting the production and release of growth hormone (GH) and is of 2 types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). IGHD results from mutations in GH1 and GHRHR while CPHD is associated with defects in transcription factor genes PROP1 , POU1F1 , and HESX1. The present study reports on screening of POU1F1 , PROP1 , and HESX1 in CPHD patients and the novel variations identified. Fifty-one CPHD patients from 49 unrelated families clinically diagnosed on the basis of biochemical and imaging investigations along with 100 controls were enrolled. Detailed family history was noted from all participants and 5 ml blood samples drawn were processed for DNA isolation followed by direct sequencing of POU1F1 , PROP1 , and HESX1 genes. Of the 51 patients, 8 were females and 43 were males. Mean height standard deviation score (SDS) and weight SDS were -5.50 and -2.76, respectively. Thirty-six of the 51 patients underwent MRI of which 9 (25%) had normal pituitary structure and morphology while 27 (75%) showed abnormalities. Molecular analysis revealed 10 (20%) patients to have POU1F1 and PROP1 mutations/variations of which 5 were novel and 2 previously reported. No mutations were identified in HESX1. The novel variations identified were absent in the 100 healthy individuals screened and the control database Exome Aggregation Consortium (ExAC). Reported POU1F1 and PROP1 mutation hotspots were absent in our patients. Instead, novel POU1F1 changes were identified suggesting existence of a distinct mutation spectrum in our population. © Georg Thieme Verlag KG Stuttgart · New York.

Self-stimulating rats combine subjective reward magnitude and subjective reward rate multiplicatively.

PubMed

Leon, M I; Gallistel, C R

1998-07-01

For rats that bar pressed for intracranial electrical stimulation in a 2-lever matching paradigm with concurrent variable interval schedules of reward, the authors found that the time allocation ratio is based on a multiplicative combination of the ratio of subjective reward magnitudes and the ratio of the rates of reward. Multiplicative combining was observed in a range covering approximately 2 orders of magnitude in the ratio of the rates of reward from about 1:10 to 10:1) and an order of magnitude change in the size of rewards. After determining the relation between the pulse frequency of stimulation and subjective reward magnitude, the authors were able to predict from knowledge of the subjective magnitudes of the rewards and the obtained relative rates of reward the subject's time allocation ratio over a range in which it varied by more than 3 orders of magnitude.

In vivo oestrogenic modulation of Egr1 and Pitx1 gene expression in female rat pituitary gland.

PubMed

Gajewska, Alina; Herman, Andrzej P; Wolińska-Witort, Ewa; Kochman, Kazimierz; Zwierzchowski, Lech

2014-12-01

EGR1 and PITX1 are transcription factors required for gonadotroph cell Lhb promoter activation. To determine changes in Egr1 and Pitx1 mRNA levels in central and peripheral pituitary stimulations, an in vivo model based on i.c.v. pulsatile (1 pulse/0.5 h over 2 h) GnRH agonist (1.5 nM buserelin) or antagonist (2 nM antide) microinjections was used. The microinjections were given to ovariectomised and 17β-oestradiol (E2) (3×20 μg), ERA (ESR1) agonist propyl pyrazole triol (PPT) (3×0.5 mg), ERB (ESR2) agonist diarylpropionitrile (DPN) (3×0.5 mg) s.c. pre-treated rats 30 min after last pulse anterior pituitaries were excised. Relative mRNA expression was determined by quantitative RT-PCR (qRT-PCR). Results revealed a gene-specific response for GnRH and/or oestrogenic stimulations in vivo. Buserelin pulses enhanced Egr1 expression by 66% in ovariectomised rats, whereas the oestradiol-supplemented+i.c.v. NaCl-microinjected group showed a 50% increase in Egr1 mRNA expression. The oestrogenic signal was transmitted via ERA (ESR1) and ERB (ESR2) activation as administration of PPT and DPN resulted in 97 and 62%, respectively, elevation in Egr1 mRNA expression. A synergistic action of GnRH agonist and 17β-oestradiol (E2) stimulation of the Egr1 gene transcription in vivo were found. GnRHR activity did not affect Pitx1 mRNA expression; regardless of NaCl, buserelin or antide i.c.v. pulses, s.c. oestrogenic supplementation (with E2, PPT or DPN) consistently decreased (by -46, -48 and -41% respectively) the Pitx1 mRNA in the anterior pituitary gland. Orchestrated Egr1 and Pitx1 activities depending on specific central and peripheral regulatory inputs could be responsible for physiologically variable Lhb gene promoter activation in vivo. © 2014 Society for Endocrinology.

Anterior pituitary failure (panhypopituitarism) with balanced chromosome translocation 46,XY,t(11;22)(q24;q13).

PubMed

Yang, C Y; Chou, C W; Chen, S Y; Cheng, H M

2001-04-01

Hypopituitarism is the clinical syndrome that results from failure of the anterior pituitary gland to produce its hormones. Hypopituitarism can result from: (1) intrinsic or primary pituitary disease; (2) intrinsic hypothalamic or secondary pituitary disease; or (3) extrinsic extrasellar or parasellar disease. The etiologies of primary hypopituitarism are miscellaneous. The dominant clinical picture of hypopituitarism in the adult is that of hypogonadism. Reports have associated hypopituitarism with anti-pituitary-antibodies, hereditary syndrome and chromosome defects, but hypopituitarism has rarely been associated with balanced chromosome translocation (11;22)(q24;q13). Here, we describe a case of anterior pituitary failure with balanced chromosome translocation. A 19-year-old Chinese teenager presented with failure of pubertal development and sexual infantilism. On examination, the patient had the classic appearance of hypogonadism. Endocrine studies and three combined pituitary function tests revealed panhypopituitarism. A chromosomal study revealed 46,XY,t(11;22)(q24;q13), a balanced translocation between 11q24 and 22q13. Chest films showed delayed fusion of bilateral humeral head epiphyses and bilateral acromions. Scrotal sonography revealed testes were small bilaterally. Magnetic resonance imaging (MRI) of the sella revealed pituitary dwarfism. The patient received 19 months replacement therapy, including steroids (prednisolone 5 mg each day), L-thyroxine (Eltroxin 100 ug each day), and testosterone enanthate 250 mg every two weeks. His height increased 4 cm with secondary sexual characteristics developed, and muscle power increased.

BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas

PubMed Central

Ibáñez-Costa, Alejandro; López-Sánchez, Laura M.; Gahete, Manuel D.; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C.; Gálvez, María A.; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J.; Maraver-Selfa, Silvia; Japón, Miguel A.; García-Arnés, Juan A.; Soto-Moreno, Alfonso; Webb, Susan M.; Kineman, Rhonda D.; Culler, Michael D.; Castaño, Justo P.; Luque, Raúl M.

2017-01-01

Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3–5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760. PMID:28181484

BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

PubMed

Ibáñez-Costa, Alejandro; López-Sánchez, Laura M; Gahete, Manuel D; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gálvez, María A; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J; Maraver-Selfa, Silvia; Japón, Miguel A; García-Arnés, Juan A; Soto-Moreno, Alfonso; Webb, Susan M; Kineman, Rhonda D; Culler, Michael D; Castaño, Justo P; Luque, Raúl M

2017-02-09

Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D 2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca 2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3-5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca 2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca 2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca 2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D 2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D 2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.

Gigantism caused by growth hormone secreting pituitary adenoma.

PubMed

Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong

2014-06-01

Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.

Gigantism caused by growth hormone secreting pituitary adenoma

PubMed Central

Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi

2014-01-01

Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings. PMID:25077093

Contributions to muscle force and EMG by combined neural excitation and electrical stimulation

NASA Astrophysics Data System (ADS)

Crago, Patrick E.; Makowski, Nathaniel S.; Cole, Natalie M.

2014-10-01

Objective. Stimulation of muscle for research or clinical interventions is often superimposed on ongoing physiological activity without a quantitative understanding of the impact of the stimulation on the net muscle activity and the physiological response. Experimental studies show that total force during stimulation is less than the sum of the isolated voluntary and stimulated forces, but the occlusion mechanism is not understood. Approach. We develop a model of efferent motor activity elicited by superimposing stimulation during a physiologically activated contraction. The model combines action potential interactions due to collision block, source resetting, and refractory periods with previously published models of physiological motor unit recruitment, rate modulation, force production, and EMG generation in human first dorsal interosseous muscle to investigate the mechanisms and effectiveness of stimulation on the net muscle force and EMG. Main results. Stimulation during a physiological contraction demonstrates partial occlusion of force and the neural component of the EMG, due to action potential interactions in motor units activated by both sources. Depending on neural and stimulation firing rates as well as on force-frequency properties, individual motor unit forces can be greater, smaller, or unchanged by the stimulation. In contrast, voluntary motor unit EMG potentials in simultaneously stimulated motor units show progressive occlusion with increasing stimulus rate. The simulations predict that occlusion would be decreased by a reverse stimulation recruitment order. Significance. The results are consistent with and provide a mechanistic interpretation of previously published experimental evidence of force occlusion. The models also predict two effects that have not been reported previously—voluntary EMG occlusion and the advantages of a proximal stimulation site. This study provides a basis for the rational design of both future experiments and clinical

Contributions to muscle force and EMG by combined neural excitation and electrical stimulation

PubMed Central

Crago, Patrick E; Makowski, Nathaniel S; Cole, Natalie M

2014-01-01

Objective Stimulation of muscle for research or clinical interventions is often superimposed on ongoing physiological activity, without a quantitative understanding of the impact of the stimulation on the net muscle activity and the physiological response. Experimental studies show that total force during stimulation is less than the sum of the isolated voluntary and stimulated forces, but the occlusion mechanism is not understood. Approach We develop a model of efferent motor activity elicited by superimposing stimulation during a physiologically activated contraction. The model combines action potential interactions due to collision block, source resetting, and refractory periods with previously published models of physiological motor unit recruitment, rate modulation, force production, and EMG generation in human first dorsal interosseous muscle to investigate the mechanisms and effectiveness of stimulation on the net muscle force and EMG. Main Results Stimulation during a physiological contraction demonstrates partial occlusion of force and the neural component of the EMG, due to action potential interactions in motor units activated by both sources. Depending on neural and stimulation firing rates as well as on force-frequency properties, individual motor unit forces can be greater, smaller, or unchanged by the stimulation. In contrast, voluntary motor unit EMG potentials in simultaneously stimulated motor units show progressive occlusion with increasing stimulus rate. The simulations predict that occlusion would be decreased by a reverse stimulation recruitment order. Significance The results are consistent with and provide a mechanistic interpretation of previously published experimental evidence of force occlusion. The models also predict two effects that have not been reported previously - voluntary EMG occlusion and the advantages of a proximal stimulation site. This study provides a basis for the rational design of both future experiments and clinical

[Effects on structure and secretion of pituitary gland in rats after electromagnetic pulse exposure].

PubMed

Fang, Heng-hu; Zeng, Gui-ying; Nie, Qing; Kang, Jing-bo; Ren, Dong-qing; Zhou, Jia-xing; Li, Yun-ming

2010-12-07

To investigate the exposure effect of electromagnetic pulse (EMP) on the structure and secretion of pituitary gland in rats. Forty-eight male SD rats were randomly divided into eight groups. Four groups were subject to the EMP exposure of 200 kV/m and the others received a sham exposure. At different time points (12, 24, 48 & 96 h) post-exposure, the pathological changes of pituitary gland were observed by light and transmission electron microscope. And the serum levels of prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH) and luteinizing hormone (LH) were measured dynamically by radioimmunoassay. At 12 h post-exposure, swollen mitochondria with cristae loss, dilatation of Golgi complex and diffusive lysosomes were found in endocrine cells of pituitary gland. The above changes became gradually worse. Mitochondrial vacuolization, the formation of myelin figures, distinct dilatation of endoplasmic reticulum, the occurrence of numerous secondary lysosomes and the clustering of heterochromatin under the nuclear membranes could be observed at 48 h. These lesions were alleviated to some degree at 96 h. The serum levels of PRL and ACTH both increased significantly at 12 h (P < 0.01, P < 0.05) and returned to normal at 24 h. The level of GH decreased significantly at 12 h and then returned gradually to normal at 48 h. The level of TSH decreased at 12 h and reached the lowest point at 24 h, then returned to normal at 96 h. LH increased significantly from 24 h to 96 h. The EMP exposure of 200 kV/m may induce the changes of the structure and secretion of pituitary gland in rats.

Reducing treatments in cattle superovulation protocols by combining a pituitary extract with a 5% hyaluronan solution: Is it able to diminish activation of the hypothalamic pituitary adrenal axis compared to the traditional protocol?

PubMed

Biancucci, Andrea; Sbaragli, Tatiana; Comin, Antonella; Sylla, Lakamy; Monaci, Maurizio; Peric, Tanja; Stradaioli, Giuseppe

2016-03-15

Traditional superovulation protocols that include multiple gonadotropin treatments are time-consuming and labor intensive. These protocols require multiple handling and restraining of embryo donors. This will likely increase the risks of injuries in both animals and humans and induce stress that may lead to a reduced superovulatory response. These are more evident when working with cattle that are rarely handled or raised on extensive grazing. The objectives of this experiment were to compare the efficacy of a split-injection protocol of porcine pituitary-derived porcine FSH (pFSH) preparation (slow release [SR] group) to the traditional 4-day treatment with pFSH administered twice daily (C group) and to determine the concentrations of cortisol in the hair as a marker of activation of the hypothalamic-pituitary-adrenal (HPA) axis during the two superovulatory treatments. Thirty-two heifers were stimulated twice in a 2 × 2 crossover design and compared for ovarian response and numbers and characteristics of recovered ova-embryo among treatments. No differences between SR and C groups were found in terms of percentage of responsive animals (100% vs. 93.8%) and ovulation rate (83.7 ± 1.1 vs. 79.5 ± 1.0%). A positive correlation was found between the number of follicles responsive to pFSH (2-8 mm) at the beginning of treatments and the superovulatory response, and no differences were found in these follicular populations between the two treatment groups. The numbers of CLs, ova-embryos, fertilized ova, transferable and freezable embryos recovered per cow were found to be significantly higher in SR compared with C group (14.0 ± 1.6 vs. 10.6 ± 1.0, 12.1 ± 1.6 vs. 7.6 ± 1.0, 11.1 ± 1.1 vs. 7.3 ± 1.0, 9.6 ± 1.4 vs. 6.6 ± 1.0, and 9.4 ± 1.4 vs. 6.0 ± 1.0 for SR and C group, respectively). The SR group produced also a significantly greater number of excellent- and/or good-quality embryos compared with the C group. The concentrations of cortisol in the hair at

In vivo xenoestrogenic actions of cadmium and arsenic in anterior pituitary and uterus.

PubMed

Ronchetti, Sonia A; Novack, Gisela V; Bianchi, María S; Crocco, Melisa C; Duvilanski, Beatriz H; Cabilla, Jimena P

2016-07-01

Cadmium (Cd) and arsenic (iAs) are toxic metals ubiquitously present in the environment. Both pollutants exert nonmonotonic dose responses, being mostly cytotoxic at high concentrations but mimicking estrogen (E2) effects at low doses. Xenoestrogenic activity of Cd and iAs has been demonstrated in different hormone-dependent tumor cell lines; however, their actions in vivo remain largely unknown. Here, we investigated whether in vivo administration of low doses of Cd and iAs through drinking water would display xenoestrogenic effects in the anterior pituitary gland and uterus of ovariectomized rats. Cd (1ppm) and iAs (0.1ppm) exposure increased the wet weight of anterior pituitary gland and uterus and induced proestrus- and estrus-like vaginal smears. Both metals stimulate cell proliferation of these tissues as they increased the expression of proliferation markers. More importantly, they augmented soluble guanylyl cyclase α1 subunit expression, which has been linked to hormone-dependent tumor progression. Also, Cd and iAs modified protein levels of full-length estrogen receptor α and its truncated variants in an E2-like manner. Anterior pituitary hormone secretion was differentially affected by both metals. Luteinizing hormone synthesis and release were strongly diminished after Cd exposure and only mildly reduced by iAs. Both metals were able to increase prolactin synthesis, although only iAs augmented serum prolactin levels. This study shows for the first time that Cd and iAs exert strong xenoestrogenic effects on anterior pituitary gland at low doses. The differences between Cd and iAs E2-like behavior indicate that other Cd- and iAs-specific mechanisms could be involved. Altogether, these results contribute to the knowledge of reproductive disorders associated with Cd and iAs environmental contamination. © 2016 Society for Reproduction and Fertility.

The leukemia inhibitory factor receptor gene is not involved in the etiology of pituitary dwarfism in German shepherd dogs.

PubMed

Hanson, J M; Mol, J A; Leegwater, P A J; Kooistra, H S; Meij, B P

2006-12-01

Pituitary dwarfism in German shepherd dogs is characterized by combined pituitary hormone deficiency (CPHD) and intrapituitary cyst formation. Activation of the leukemia inhibitory factor (LIF)-LIF receptor (LIFR) signal transduction pathway results in a similar phenotype in (transgenic) mice. We therefore assessed the role of the LIFR in the etiology of pituitary dwarfism in German shepherd dogs. A polymorphic microsatellite marker (UULIFR) was used to analyze the segregation of the LIFR gene in 22 German shepherd dogs from 4 pedigrees, each including one dwarf. There was no allelic association between UULIFR and the dwarfism phenotype. Based on our findings LIFR was excluded as a candidate gene for CPHD.

Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma.

PubMed

Maheshwari, H G; Prezant, T R; Herman-Bonert, V; Shahinian, H; Kovacs, K; Melmed, S

2000-09-01

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.

Breast cancer metastasis to the pituitary gland.

PubMed

Magalhães, Julia Fragoso; Bacchin, Renata Prota; Costa, Priscila Scatena; Alves, Gisele Malavazi; Fraige Filho, Fadlo; Stella, Lenira Cristina

2014-11-01

Metastatic tumors to the pituitary gland are an unusual complication typically seen in elderly patients with diffuse malignant disease. Breast and lung are the commonest sites of the primary tumor. Prognosis of patients with breast cancer metastasis is poor and depends on the primary neoplastic extension. We report a 54 year-old woman with breast cancer metastasis to the pituitary stalk first diagnosed because of visual disturbance with no other symptoms. Pituitary gland stalk metastasis is a very uncommon find and this case report includes a literature review.

Multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells causing acromegaly associated with subclinical Cushing's disease: a case report.

PubMed

Takiguchi, Tomoko; Koide, Hisashi; Nagano, Hidekazu; Nakayama, Akitoshi; Fujimoto, Masanori; Tamura, Ai; Komai, Eri; Shiga, Akina; Kono, Takashi; Higuchi, Seiichiro; Sakuma, Ikki; Hashimoto, Naoko; Suzuki, Sawako; Miyabayashi, Yui; Ishiwatari, Norio; Horiguchi, Kentaro; Nakatani, Yukio; Yokote, Koutaro; Tanaka, Tomoaki

2017-09-02

A functional pituitary adenoma can produce multiple anterior-pituitary hormones, such as growth hormone (GH) -producing adenomas (GHoma) with prolactin or thyrotropin stimulating hormone production in the same lineage. However, it is very rare that acromegaly shows subclinical Cushing's disease (SCD) beyond the lineage. Here we describe the involvement of intratumoral coexistence with 2 types of hormone-producing cells associated with different lineage in acromegaly concomitant with SCD. In our study, we performed clinical evaluation of the patient showing acromegaly with SCD. To elucidate the mechanisms of this pathology, we analyzed immunohistochemistry and gene expression of anterior-pituitary hormones and transcriptional factors in the resected pituitary tumor. On immunohistochemical staining, most of the tumor cells were strongly stained for GH antibody, while some cells were strongly positive for adrenocorticotropic hormone (ACTH). Gene expression analysis of a transsphenoidal surgery sample of the pituitary gland revealed that ACTH-related genes, such as POMC, Tpit, and NeuroD1 mRNA, had higher expression in the tumor tissue than the nonfunctional adenoma but lower expression compared to an adenoma of typical Cushing's disease. Further, double-labeling detection methods with a fluorescent stain for ACTH and GH demonstrated the coexistence of ACTH-positive cells (GH-negative) among the GH-positive cells in the tumor. Additionally, Pit-1 expression was reduced in the ACTH-positive cells from tumor tissue primary culture. Here we described a case of a pituitary tumor diagnosed with acromegaly associated with SCD. We performed quantitative-expression analyses of transcriptional factors of the tumor tissue and immunohistochemistry analysis of tumor-derived primary culture cells, which suggested that the multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells caused acromegaly associated with SCD.

Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

PubMed

Warren, W B; Gurewitsch, E D; Goland, R S

1995-02-01

We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

The combined effects of transcutaneous electrical nerve stimulation (TENS) and stretching on muscle hardness and pressure pain threshold.

PubMed

Karasuno, Hiroshi; Ogihara, Hisayoshi; Morishita, Katsuyuki; Yokoi, Yuka; Fujiwara, Takayuki; Ogoma, Yoshiro; Abe, Koji

2016-04-01

[Purpose] This study aimed to clarify the immediate effects of a combined transcutaneous electrical nerve stimulation and stretching protocol. [Subjects] Fifteen healthy young males volunteered to participate in this study. The inclusion criterion was a straight leg raising range of motion of less than 70 degrees. [Methods] Subjects performed two protocols: 1) stretching (S group) of the medial hamstrings, and 2) tanscutaneous electrical nerve stimulation (100 Hz) with stretching (TS group). The TS group included a 20-minute electrical stimulation period followed by 10 minutes of stretching. The S group performed 10 minutes of stretching. Muscle hardness, pressure pain threshold, and straight leg raising range of motion were analyzed to evaluate the effects. The data were collected before transcutaneous electrical nerve stimulation (T1), before stretching (T2), immediately after stretching (T3), and 10 minutes after stretching (T4). [Results] Combined transcutaneous electrical nerve stimulation and stretching had significantly beneficial effects on muscle hardness, pressure pain threshold, and straight leg raising range of motion at T2, T3, and T4 compared with T1. [Conclusion] These results support the belief that transcutaneous electrical nerve stimulation combined with stretching is effective in reducing pain and decreasing muscle hardness, thus increasing range of motion.

Simultaneous above and below approach to giant pituitary adenomas: surgical strategies and long-term follow-up

PubMed Central

D’Ambrosio, Anthony L.; Grobelny, Bartosz T.; Freda, Pamela U.; Wardlaw, Sharon; Bruce, Jeffrey N.

2012-01-01

Introduction Giant pituitary adenomas of excessive size, fibrous consistency or unfavorable geometric configuration may be unresectable through conventional operative approaches. We present our select case series for operative resection and long-term follow-up for these unusual tumors, employing both a staged procedure and a combined transsphenoidal-transcranial above and below approach. Method A retrospective chart review was performed on patients operated via the staged, and combined approaches by the senior author (J.N·B.). Pre-operative characteristics and postoperative outcomes were reviewed. A detailed description of the operative technique and perioperative management is provided. Results Between 1993 and 1996, two patients harboring giant pituitary adenomas underwent an intentionally staged resection, and between 1997 and 2006, nine patients harboring giant pituitary adenomas underwent surgery via a single-stage above and below approach. Nine patients (82%) presented with non-secreting adenomas and two patients (18%) presented with prolactinomas refractory to medical management. Gross total resection was achieved in six patients (55%), near total resection in 1 (9%), and subtotal removal in 4 (36%). Seven patients (64%) experienced visual improvement postoperatively and no major complications occurred. Long-term follow-up averaged 51.6 months. Panhypopituitarism was observed in four patients, partial hypopituitarism in four, persistent DI in two, and persistent SIADH in one. Conclusions The addition of a transcranial component to the transsphenoidal approach offers additional visualization of critical neurovascular structures during giant pituitary adenoma resection. Complications rates are similar to other series in which complex pituitary adenomas are resected by other means. The above and below approach is both safe and effective and the immediate and long-term advantages of a single-stage approach justify its utility in this select group of patients

Lineage-Specific Restraint of Pituitary Gonadotroph Cell Adenoma Growth

PubMed Central

Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Ben-Shlomo, Anat; Wawrowsky, Kolja; Toledano, Yoel; Tong, Yunguang; Kovacs, Kalman; Scheithauer, Bernd; Melmed, Shlomo

2011-01-01

Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth. PMID:21464964

21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of 0.9...

21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of 0.9...

[Pituitary apoplexy. Report of 25 patients].

PubMed

Khaldi, M; Ben Hamouda, K; Jemel, H; Kallel, J; Zemmel, I

2006-09-01

A series of 25 patients with a clinical diagnosis of pituitary apoplexy (PA) is reviewed. It included 14 men and 11 women aged between 20 to 79 years (mean age: 54 years). Twenty-two patients did not know that they had a pituitary tumor when the apoplexy occurred. A precipitating event was found in 3 cases. Symptoms and signs ranged from isolated ocular paresis to a deep coma. Seventeen patients experienced a decrease in their visual acuity. CTscan and MRI showed a pituitary adenoma in all cases, a hemorrhage was also present in 10 out of the 24 CTscans, and in all the 8 MRI performed. Twenty patients underwent surgery; 18 of them by a transsphenoidal approach. A complete recovery of visual acuity was observed in 75% of patients operated within the week following the onset of symptoms, and in 56% of patients operated later on. There was no case of complete visual recovery among the blind patients. Pituitary apoplexy is a clinical concept. It applies only to symptomatic cases. It is generally a complication of a pituitary adenoma which is in most cases unknown. There are different degrees of severity; PA can even be life-threatening. The principal aim of surgery in the acute phase is the improvement of visual prognosis. In our series, blind patients or those with a history of visual loss for more than a week or with a blindness had a poorer prognosis.

Management of nonfunctioning pituitary incidentaloma.

PubMed

Galland, Françoise; Vantyghem, Marie-Christine; Cazabat, Laure; Boulin, Anne; Cotton, François; Bonneville, Jean-François; Jouanneau, Emmanuel; Vidal-Trécan, Gwénaelle; Chanson, Philippe

2015-07-01

Prevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously discovered adenoma <1cm in diameter) may increase in size, but only 5% exceed 10mm. Pituitary macroincidentalomas (serendipitously discovered adenoma>1cm in diameter) show increased size in 20-24% and 34-40% of cases at respectively 4 and 8years' follow-up. Radiologic differential diagnosis requires MRI centered on the pituitary gland. Initial assessment of nonfunctioning (NF) microincidentaloma is firstly clinical, the endocrinologist looking for signs of hypersecretion (signs of hyperprolactinemia, acromegaly or Cushing's syndrome), followed up by systematic prolactin and IGF-1 assay. Initial assessment of NF macroincidentaloma is clinical, the endocrinologist looking for signs of hormonal hypersecretion or hypopituitarism, followed up by hormonal assay to screen for hypersecretion or hormonal deficiency and by ophthalmologic assessment (visual acuity and visual field) if and only if the lesion is near the optic chiasm (OC). NF microincidentaloma of less than 5mm requires no surveillance; those of≥5mm are not operated on but rather monitored on MRI at 6months and then 2years. Macroincidentaloma remote from the OC is monitored on MRI at 1year, with hormonal exploration (for anterior pituitary deficiency), then every 2years. When macroincidentaloma located near the OC is managed by surveillance rather than surgery, MRI is recommended at 6months, with hormonal and visual exploration, then annual MRI and hormonal and visual assessment every 6months. Surgery is indicated in the following cases: evolutive NF microincidentaloma, NF macroincidentaloma associated with hypopituitarism or showing progression, incidentaloma compressing the OC, possible malignancy, non-compliant patient, pregnancy desired in the short-term, or context at risk of apoplexy. Copyright © 2015 Elsevier Masson SAS. All rights

Effect of hypothalamic neuropeptides on corticotrophin release from quarters of rat anterior pituitary gland in vitro.

PubMed

Nicholson, S A; Adrian, T E; Gillham, B; Jones, M T; Bloom, S R

1984-02-01

The effect of six hypothalamic peptides on the basal release of ACTH and that induced by arginine vasopressin (AVP) or by ovine corticotrophin releasing factor (oCRF) from fragments of the rat anterior pituitary gland incubated in vitro was investigated. Dose-response curves to AVP and to oCRF were obtained, and the response to a low dose of oCRF was potentiated by a low dose of AVP. Basal release of ACTH was not affected by any of the peptides in concentrations in the range 10(-12) to 10(-6) mol/l, and only substance P (SP) and somatostatin (SRIF) inhibited significantly the response to oCRF in a dose-related manner. The responses to a range of doses of oCRF or AVP were reduced by 10(-8) and 10(-6) mol SP or SRIF/l, and to a greater extent by the higher dose. Except in the case of 10(-6) mol SRIF/l on the response to AVP, the response was not further diminished by preincubation of the tissue with the peptide before the stimulating agent was added. The inhibition of the responses to AVP or oCRF by 10(-9) mol SP/l was not potentiated by its combination with either 5 X 10(-10) or 10(-8) mol SRIF/l; the inhibitory effects were merely additive. The results suggest that although SRIF and SP are able to modulate the release of ACTH from the anterior pituitary gland, they do so only at a high concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

PubMed

Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

2016-01-01

To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

Pituitary Volumes Are Reduced in Patients with Somatization Disorder

PubMed Central

Yildirim, Hanefi; Sirlier, Burcu; Kayali, Alperen

2012-01-01

Objective Despite of the suggested physiological relationship between somatoform disorder and disturbances in HPA axis function no volumetric study of pituitary volumes in somatization disorder has been carried out. Therefore, we aimed to use structural MRI to evaluate the pituitary volumes of the patients with somatization disorder. Methods Eighteen female patients with somatization disorder according to DSM-IV and same number of healthy controls were included into the study. All subjects were scanned using a 1.5-T General Electric (GE; Milwaukee, USA) scanner. Pituitary volume measurements were determined by using manuallly tracings according to standard antomical atlases. Results It was found significantly smaller pituitary volumes of the whole group of somatization patients compared to healthy (t=-3.604, p=0.001). ANCOVA predicting pituitary volumes demonstrated a significant main effect of diagnostic group (F=13.530, p<0.001) but TBV (F=1.924, p>0.05) or age (F=1.159, p>0.05). It was determined that there was no significant correlation between smaller pituitary volumes and the duration of illness (r=0.16, p>0.05) in the patient group. Conclusion In conclusion, we suggest that the patients with somatization disorder might have significantly smaller pituitary volumes compared to healthy control subjects. PMID:22993528

Normal dimensions of the posterior pituitary bright spot on magnetic resonance imaging.

PubMed

Côté, Martin; Salzman, Karen L; Sorour, Mohammad; Couldwell, William T

2014-02-01

The normal pituitary bright spot seen on unenhanced T1-weighted MRI is thought to result from the T1-shortening effect of the vasopressin stored in the posterior pituitary. Individual variations in its size may be difficult to differentiate from pathological conditions resulting in either absence of the pituitary bright spot or in T1-hyperintense lesions of the sella. The objective of this paper was to define a range of normal dimensions of the pituitary bright spot and to illustrate some of the most commonly encountered pathologies that result in absence or enlargement of the pituitary bright spot. The authors selected normal pituitary MRI studies from 106 patients with no pituitary abnormality. The size of each pituitary bright spot was measured in the longest axis and in the dimension perpendicular to this axis to describe the typical dimensions. The authors also present cases of patients with pituitary abnormalities to highlight the differences and potential overlap between normal and pathological pituitary imaging. All of the studies evaluated were found to have pituitary bright spots, and the mean dimensions were 4.8 mm in the long axis and 2.4 mm in the short axis. The dimension of the pituitary bright spot in the long axis decreased with patient age. The distribution of dimensions of the pituitary bright spot was normal, indicating that 99.7% of patients should have a pituitary bright spot measuring between 1.2 and 8.5 mm in its long axis and between 0.4 and 4.4 mm in its short axis, an interval corresponding to 3 standard deviations below and above the mean. In cases where the dimension of the pituitary bright spot is outside this range, pathological conditions should be considered. The pituitary bright spot should always be demonstrated on T1-weighted MRI, and its dimensions should be within the identified normal range in most patients. Outside of this range, pathological conditions affecting the pituitary bright spot should be considered.

Rare case of Cushing's disease due to double ACTH-producing adenomas, one located in the pituitary gland and one into the stalk.

PubMed

Mendola, Marco; Dolci, Alessia; Piscopello, Lanfranco; Tomei, Giustino; Bauer, Dario; Corbetta, Sabrina; Ambrosi, Bruno

2014-01-01

We describe a patient affected by Cushing's disease due to the presence of double pituitary adenomas, one located within the anterior pituitary and the other in the infundibulum associated with a remnant of Rakthe's pouch. Cure was achieved only after the infundibulum lesion was surgically removed. A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. Hormonal studies indicated Cushing's disease and MRI showed an enlarged pituitary gland with a marked and homogeneous enhancement after injection of gadolinium and an enlarged infundibulum with a maximum diameter of 8 mm. As a venous sampling of the inferior petrosal sinus after 10 μg iv desmopressin stimulation revealed a central to peripheral ACTH ratio consistent with a pituitary ACTH-secreting tumor, transphenoidal explorative surgery was performed and a 4-mm pituitary adenoma immunopositive for ACTH was disclosed and removed. Since postoperative hormonal evaluation showed persistent hypercortisolism, confirmed by dynamic tests, the patient again underwent surgery by transcranial access and the infundibulum mass was removed. Histology and immunochemistry were consistent with an ACTH-secreting adenoma. A few months after the second operation, cushingoid features were significantly reverted and symptoms improved. Although Cushing's patients bearing multiple adenomas have already been documented, the presence of two adenomas both immunohistochemically positive for ACTH is a very rare cause of Cushing's disease and this is the first report of a case of double ACTH-producing adenomas, one located in the pituitary gland and one attached to the stalk.

The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation.

PubMed

Kurtulmus, Neslihan; Mert, Meral; Tanakol, Refik; Yarman, Sema

2015-04-01

Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11%) exhibited single organ involvement, while eight patients (89%) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44%) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78%), a thalamic mass in one patient (11%), and the absence of the bright spot in all patients. A single patient (11%) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT+CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1%) developed anterior pituitary hormone deficiency, three (43%) were diagnosed with GH deficiency, and one (14%) exhibited gonadotropin deficiency

Frequency of genetic defects in combined pituitary hormone deficiency: a systematic review and analysis of a multicentre Italian cohort.

PubMed

De Rienzo, Francesca; Mellone, Simona; Bellone, Simonetta; Babu, Deepak; Fusco, Ileana; Prodam, Flavia; Petri, Antonella; Muniswamy, Ranjith; De Luca, Filippo; Salerno, Mariacarolina; Momigliano-Richardi, Patricia; Bona, Gianni; Giordano, Mara

2015-12-01

Combined pituitary hormonal deficiency (CPHD) can result from mutations within genes that encode transcription factors. This study evaluated the frequency of mutations in these genes in a cohort of 144 unrelated Italian patients with CPHD and estimated the overall prevalence of mutations across different populations using a systematic literature review. A multicentre study of adult and paediatric patients with CPHD was performed. The PROP1, POU1F1, HESX1, LHX3 and LHX4 genes were analysed for the presence of mutations using direct sequencing. We systematically searched PubMed with no date restrictions for studies that reported genetic screening of CPHD cohorts. We only considered genetic screenings with at least 10 individuals. Data extraction was conducted in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Global mutation frequency in Italian patients with CPHD was 2·9% (4/136) in sporadic cases and 12·5% (1/8) in familial cases. The worldwide mutation frequency for the five genes calculated from 21 studies was 12·4%, which ranged from 11·2% in sporadic to 63% in familial cases. PROP1 was the most frequently mutated gene in sporadic (6·7%) and familial cases (48·5%). The frequency of defects in genes encoding pituitary transcription factors is quite low in Italian patients with CPHD and other western European countries, especially in sporadic patients. The decision of which genes should be tested and in which order should be guided by hormonal and imaging phenotype, the presence of extrapituitary abnormalities and the frequency of mutation for each gene in the patient-referring population. © 2015 John Wiley & Sons Ltd.

Transcranial magnetic stimulation with acepromazine or dexmedetomidine in combination with levomethadone/fenpipramide in healthy Beagle dogs.

PubMed

Amendt, H-L; Siedenburg, J S; Steffensen, N; Söbbeler, F J; Schütter, A; Tünsmeyer, J; Rohn, K; Kästner, S B R; Tipold, A; Stein, V M

2016-11-01

The aim of this study was to evaluate the influence of two sedation protocols on transcranial magnetic motor evoked potentials (TMMEPs) after transcranial magnetic stimulation in medium sized dogs. Onset latencies and peak-to-peak amplitudes, elicited in the extensor carpi radialis and cranial tibial muscles, were analysed in 10 healthy Beagles that received either acepromazine or dexmedetomidine in combination with levomethadone/fenpipramide, in a crossover design. Similar TMMEP recordings could be made using both sedation protocols at 80-90% stimulation intensity; however, there were significantly shorter onset latencies with the acepromazine-levomethadone/fenpipramide protocol at 100% stimulation intensity. Reference values were established and it was concluded that both drug combinations are feasible for measuring TMMEPs in medium sized dogs. Copyright © 2016 Elsevier Ltd. All rights reserved.

The increase of anterior pituitary dopamine in aging C57BL/6J female mice is caused by ovarian steroids, not intrinsic pituitary aging.

PubMed

Telford, N; Mobbs, C V; Sinha, Y N; Finch, C E

1986-01-01

We describe how the increase of anterior pituitary dopamine (DA) during aging in female mice is related to altered secretion of ovarian steroids during reproductive senescence. A number of age-correlated neuroendocrine changes in female rodents result from cumulative exposure to ovarian steroids over a lifetime of estrous cycles, or from the altered pattern of ovarian steroid secretion concomitant with reproductive senescence. Pituitary DA has been shown to increase with age in female rats. To examine how the age-correlated increase of pituitary DA may depend on estradiol (E2), we measured pituitary DA and serum prolactin (PRL) in the following groups of female mice: young (7 months) cycling, middle-aged (14 months) cycling and non-cycling, old (17 months) non-cycling, old (17 months) ovariectomized (OVX) at 4 months, and young mice given 0.2 mg E2 valerate or E2 implants. Mice from some of these groups were OVX 1, 4 or 8 weeks before sacrifice. Compared with young controls, 14-month-old cycling or non-cycling mice had 3-fold higher pituitary DA, and 17-month-old non-cycling mice had 5-fold higher pituitary DA. OVX for 2 or 13 months before sacrifice abolished the effect of age; OVX of young mice had no effect on pituitary DA. Three weeks after implantation of E2 into OVX young mice or 7 weeks after injection of E2 valerate in intact young mice, pituitary DA was elevated. The E2-sensitive fraction of pituitary DA does not appear to decrease PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas.

PubMed

Ntali, Georgia; Wass, John A

2018-04-01

Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms that do not cause a hormonal hypersecretory syndrome. An improved understanding of their epidemiology, clinical presentation and diagnosis is needed. A literature review was performed using Pubmed to identify research reports and clinical case series on NFPAs. They account for 14-54% of pituitary adenomas and have a prevalence of 7-41.3/100,000 population. Their standardized incidence rate is 0.65-2.34/100,000 and the peak occurence is from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from being completely asymptomatic to causing significant hypothalamic/pituitary dysfunction and visual field compromise due to their large size. Most patients present with symptoms of mass effect, such as headaches, visual field defects, ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning pituitary incidentalomas are found on brain imaging performed for an unrelated reason. Diagnostic approach includes magnetic resonance imaging of the sellar region, laboratory evaluations, screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. This article reviews the epidemiology, clinical behaviour and diagnostic approach of non-functioning pituitary adenomas.

The somatostatin analogue octreotide confers sensitivity to rapamycin treatment on pituitary tumor cells.

PubMed

Cerovac, Vesna; Monteserin-Garcia, Jose; Rubinfeld, Hadara; Buchfelder, Michael; Losa, Marco; Florio, Tullio; Paez-Pereda, Marcelo; Stalla, Günter K; Theodoropoulou, Marily

2010-01-15

Rapamycin and its analogues have significant antiproliferative action against a variety of tumors. However, sensitivity to rapamycin is reduced by Akt activation that results from the ablative effects of rapamycin on a p70 S6K-induced negative feedback loop that blunts phosphoinositide 3-kinase (PI3K)-mediated support for Akt activity. Thus, sensitivity to rapamycin might be increased by imposing an upstream blockade to the PI3K/Akt pathway. Here, we investigated this model using the somatostatin analogue octreotide as a tool to decrease levels of activated Ser(473)-phosphorylated Akt (pAkt-Ser(473)) in pituitary tumor cells that express somatostatin receptors. Octreotide increased levels of phosphorylated insulin receptor substrate-1 that were suppressed by rapamycin, subsequently decreasing levels of pAkt-Ser(473) through effects on phosphotyrosine phosphatase SHP-1. Octreotide potentiated the antiproliferative effects of rapamycin in immortalized pituitary tumor cells or human nonfunctioning pituitary adenoma cells in primary cell culture, sensitizing tumor cells even to low rapamycin concentrations. Combined treatment of octreotide and rapamycin triggered G(1) cell cycle arrest, decreasing E2F transcriptional activity and cyclin E levels by increasing levels of p27/Kip1. These findings show that adjuvant treatment with a somatostatin analogue can sensitize pituitary tumor cells to the antiproliferative effects of rapamycin.

Stem cell therapy and its potential role in pituitary disorders.

PubMed

Lara-Velazquez, Montserrat; Akinduro, Oluwaseun O; Reimer, Ronald; Woodmansee, Whitney W; Quinones-Hinojosa, Alfredo

2017-08-01

The pituitary gland is one of the key components of the endocrine system. Congenital or acquired alterations can mediate destruction of cells in the gland leading to hormonal dysfunction. Even though pharmacological treatment for pituitary disorders is available, exogenous hormone replacement is neither curative nor sustainable. Thus, alternative therapies to optimize management and improve quality of life are desired. An alternative modality to re-establish pituitary function is to promote endocrine cell regeneration through stem cells that can be obtained from the pituitary parenchyma or pluripotent cells. Stem cell therapy has been successfully applied to a plethora of other disorders, and is a promising alternative to hormonal supplementation for resumption of normal hormone homeostasis. In this review, we describe the common causes for pituitary deficiencies and the advances in cellular therapy to restore the physiological pituitary function.

Relationship between release of LH and incorporation of tritiated thymidine in the anterior pituitary gland of the castrated male rat: effect of LHRH and its highly active analogue buserelin.

PubMed

Romano, M I; Machiavelli, G A; Alonso, G E; Burdman, J A

1986-01-01

Castration of the adult male rat significantly (P less than 0.01) increased the concentration of LH in serum and the incorporation of (3H) thymidine into the pituitary DNA. The administration of a single dose of LHRH or its analogue buserelin stimulated the release of LH but it did not modify (3H) thymidine incorporation. When multiple doses of LHRH or buserelin were injected, there was a significant (P less than 0.01) inhibition of LH release and also the incorporation of (3H) thymidine into the DNA of the anterior pituitary gland was significantly (P less than 0.01) diminished. These observations are compatible with the idea of the close relationship between hormonal release and DNA synthesis in the anterior pituitary gland of the rat.

A Novel Mutation in OTX2 Causes Combined Pituitary Hormone Deficiency, Bilateral Microphthalmia, and Agenesis of the Left Internal Carotid Artery.

PubMed

Shimada, Aya; Takagi, Masaki; Nagashima, Yuka; Miyai, Kentaro; Hasegawa, Yukihiro

2016-01-01

Mutations in OTX2 cause hypopituitarism, ranging from isolated growth hormone deficiency to combined pituitary hormone deficiency (CPHD), which are commonly detected in association with severe eye abnormalities, including anophthalmia or microphthalmia. Pituitary phenotypes of OTX2 mutation carriers are highly variable; however, ACTH deficiency during the neonatal period is not common in previous reports. We report a novel missense OTX2 (R89P) mutation in a CPHD patient with severe hypoglycemia in the neonatal period due to ACTH deficiency, bilateral microphthalmia, and agenesis of the left internal carotid artery (ICA). We identified a novel heterozygous mutation in OTX2 (c.266G>C, p.R89P). R89P OTX2 showed markedly reduced transcriptional activity of HESX1 and POU1F1 reporters compared with wild-type OTX2. A dominant negative effect was noted only in the transcription analysis with POU1F1 promoter. Electrophoretic mobility shift assay experiments showed that R89P OTX2 abrogated DNA-binding ability. OTX2 mutations can cause ACTH deficiency in the neonatal period. Our study also shows that OTX2 mutations are associated with agenesis of the ICA. To the best of our knowledge, this is the first report of a transcription factor gene mutation, which was identified due to agenesis of the ICA of a patient with CPHD. This study extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in OTX2. © 2016 S. Karger AG, Basel.

Dynamic enhancement MRI of anterior lobe in pituitary dwarfism.

PubMed

Liu, H M; Li, Y W; Tsai, W Y; Su, C T

1995-08-01

We examined 23 patients with pituitary dwarfism by dynamic MRI; with a repetition time of 150 or 50 ms. The time-enhancement difference curves of selected regions in the anterior lobes were plotted. Another 48 patients with no definite clinical pituitary disfunction were examined with the same technique. We found that the intensity of maximum enhancement in both groups was similar, but the time to achieve maximum enhancement was delayed in pituitary dwarfism with or without stalk transection; the time seemed longest with stalk transection. There was little difference in enhancement between patients with multiple hormone deficiency or isolated growth hormone deficiency. Dynamic MRI of the anterior lobes may be an important functional imaging study, and our results imply that poor perfusion is a useful finding in pituitary dwarfism, especially in patients without stalk transection and normal pituitary height.

Air pollution alters brain and pituitary endothelin-1 and inducible nitric oxide synthase gene expression.

PubMed

Thomson, Errol M; Kumarathasan, Prem; Calderón-Garcidueñas, Lilian; Vincent, Renaud

2007-10-01

Recent work suggests that air pollution is a risk factor for cerebrovascular and neurodegenerative disease. Effects of inhaled pollutants on the production of vasoactive factors such as endothelin (ET) and nitric oxide (NO) in the brain may be relevant to disease pathogenesis. Inhaled pollutants increase circulating levels of ET-1 and ET-3, and the pituitary is a potential source of plasma ET, but the effects of pollutants on the expression of ET and NO synthase genes in the brain and pituitary are not known. In the present study, Fischer-344 rats were exposed by nose-only inhalation to particles (0, 5, 50mg/m3 EHC-93), ozone (0, 0.4, 0.8 ppm), or combinations of particles and ozone for 4 h. Real-time reverse transcription polymerase chain reaction was used to measure mRNA levels in the cerebral hemisphere and pituitary 0 and 24 h post-exposure. Ozone inhalation significantly increased preproET-1 but decreased preproET-3 mRNAs in the cerebral hemisphere, while increasing mRNA levels of preproET-1, preproET-3, and the ET-converting enzyme (ECE)-1 in the pituitary. Inducible NO synthase (iNOS) was initially decreased in the cerebral hemisphere after ozone inhalation, but increased 24 h post-exposure. Particles decreased tumour necrosis factor (TNF)-alpha mRNA in the cerebral hemisphere, and both particles and ozone decreased TNF-alpha mRNA in the pituitary. Our results show that ozone and particulate matter rapidly modulate the expression of genes involved in key vasoregulatory pathways in the brain and pituitary, substantiating the notion that inhaled pollutants induce cerebrovascular effects.

Association of craniopharyngioma and pituitary adenoma.

PubMed

Guaraldi, Federica; Prencipe, Nunzia; di Giacomo, Valentina; Scanarini, Massimo; Gasco, Valentina; Gardiman, Marina Paola; Berton, Alessandro M; Ghigo, Ezio; Grottoli, Silvia

2013-08-01

Intracranial tumors of different histologic types infrequently affect patients with pituitary adenomas and no history of head irradiation. The association with craniopharyngioma is extremely rare. Aims of this paper are: (1) to provide a critical literature review of typical features of pituitary adenoma presenting in association with craniopharyngioma; (2) to describe the first documented (clinically, biochemically, histologically, and radiologically) case of aggressive, suprasellar papillary craniopharyngioma presenting with amenorrhea, progressive reduction of visual field, and severe headache in a 38-year-old woman, a decade after surgical cure for microprolactinoma associated with empty sella, during which she had carried two pregnancies; and (3) to discuss common etiopathogenetic mechanisms, in relation to the management of these lesions. Systematic literature search for English literature focusing on the association of craniopharyngioma and pituitary adenoma was performed using PubMed database. Additional relevant articles from references lists were also included. Clinical, laboratory, and radiological examinations performed in our patient for the two brain lesions at diagnosis and follow up were collected. Literature search retrieved nine articles. Typically, craniopharyngioma were of adamantinomatous type, occurred simultaneously to pituitary adenoma, presented with headache and visual loss, and affected men. No case of clearly documented metachronous lesion affecting a woman after pregnancy had been described before. Although very rare and with uncertain etiopathogenesis, second tumors (i.e., craniopharyngioma) should be considered in patients with a history of pituitary adenoma, presenting with suggestive signs and symptoms, even after a long disease-free period, in order to provide proper and prompt treatment.

Regulation of hormone release by cultured cells from a thyrotropin-growth hormone-secreting pituitary tumor. Direct inhibiting effects of 3,5,3'-triiodothyronine and dexamethasone on thyrotropin secretion.

PubMed

Lamberts, S W; Oosterom, R; Verleun, T; Krenning, E P; Assies, H

1984-08-01

The regulation of TSH and GH secretion was investigated in cultured tumor cells prepared from a mixed TSH/GH secreting pituitary tumor. The tumor tissue had been removed transsphenoidally from a patient with hyperthyroidism and inappropriately high serum TSH levels and acromegaly. TSH and GH secretion by cultured cells were stimulated in a parallel way by TRH (300 nM) and LHRH (50 nM), but were unaffected by bromocriptine (10 nM). Exposure of the tumor cells to dexamethasone (0.1 microM) or T3 (50 nM) had differential effects on hormone secretion. GH secretion was greatly stimulated by dexamethasone, but unaffected by T3. TSH secretion was inhibited both by T3 and by dexamethasone. So, T3 and glucocorticoids inhibit TSH release by the human pituitary tumor cells studied at least partly by means of a direct effect.

Promoter CpG methylation of multiple genes in pituitary adenomas: frequent involvement of caspase-8.

PubMed

Bello, M Josefa; De Campos, Jose M; Isla, Alberto; Casartelli, Cacilda; Rey, Juan A

2006-02-01

The epigenetic changes in pituitary adenomas were identified by evaluating the methylation status of nine genes (RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1 and caspase-8) in a series of 35 tumours using methylation-specific PCR analysis plus sequencing. The series included non-functional adenomas (n=23), prolactinomas (n=6), prolactinoma plus thyroid-stimulating hormone adenoma (n=1), growth hormone adenomas (n=4), and adrenocorticotropic adenoma (n=1). All of the tumours had methylation of at least one of these genes and 40% of samples (14 of 35) displayed concurrent methylation of at least three genes. The frequencies of aberrant methylation were: 20% for RB1, 17% for p14(ARF), 34% for p16(INK4a), 29% for p73, 11% for TIMP-3, 23% for MGMT, 6% for DAPK, 43% for THBS1 and 54% for caspase-8. No aberrant methylation was observed in two non-malignant pituitary samples from healthy controls. Although some differences in the frequency of gene methylation between functional and non-functional adenomas were detected, these differences did not reach statistical significance. Our results suggest that promoter methylation is a frequent event in pituitary adenoma tumourigenesis, a process in which inactivation of apoptosis-related genes (DAPK, caspase-8) might play a key role.

Dopamine inhibits reproduction in female zebrafish (Danio rerio) via three pituitary D2 receptor subtypes.

PubMed

Fontaine, Romain; Affaticati, Pierre; Yamamoto, Kei; Jolly, Cécile; Bureau, Charlotte; Baloche, Sylvie; Gonnet, Françoise; Vernier, Philippe; Dufour, Sylvie; Pasqualini, Catherine

2013-02-01

In many teleosts, the stimulatory control of gonadotrope axis by GnRH is opposed by an inhibitory control by dopamine (DA). The functional importance of this inhibitory pathway differs widely from one teleostean species to another. The zebrafish (Danio rerio) is a teleost fish that has become increasingly popular as an experimental vertebrate model. However, the role of DA in the neuroendocrine control of its reproduction has never been studied. Here the authors evaluated in sexually regressed female zebrafish the effects of in vivo treatments with a DA D2 receptor (D2-R) antagonist domperidone, or a GnRH agonist, alone and in combination, on the pituitary level of FSHβ and LHβ transcripts, the gonadosomatic index, and the ovarian histology. Only the double treatment with GnRH agonist and domperidone could induce an increase in the expression of LHβ, in the gonadosomatic index, and a stimulation of ovarian vitellogenesis, indicating that removal of dopaminergic inhibition is required for the stimulatory action of GnRH and reactivation of ovarian function to occur. Using double immunofluorescent staining on pituitary, the authors showed in this species the innervation of LH cells by tyrosine-hydroxylase immunoreactive fibers. Finally, using in situ hybridization and immunofluorescence, the authors showed that the three subtypes of zebrafish DA D2-R (D2a, D2b, and D2c) were expressed in LH-producing cells, suggesting that they all may be involved in mediating this inhibition. These results show for the first time that, in zebrafish, DA has a direct and potent inhibitory action capable of opposing the stimulatory effect of GnRH in the neuroendocrine control of reproduction.

Experiment K-6-20. The effect of spaceflight on pituitary oxytocin and vasopressin content of rats

NASA Technical Reports Server (NTRS)

Keil, L.; Evans, J.; Grindeland, R.; Krasnov, I.

1990-01-01

Pituitary levels of oxytocin (OT) and vasopressin (AVP) were measured in rats exposed to 12.5 days of spaceflight (FLT) as well as ground-based controls, one group synchronously maintained in flight-type cages with similar feeding schedules (SYN), and one group in vivarium cages (VIV). Flight rats had significantly less (p less than 0.05) pituitary OT and AVP(1.10 plus or minus 0.04 and 1.69 plus or minus 0.07 micron g, n=5) than either the SYN(1.60 plus or minus 0.08 and 2.11 plus or minus 0.04 micron g, n=5) or VIV (1.54 plus or minus 0.03 and 2.10 plus or minus 0.09 micron g, n=5) control groups, respectively. Because the FLT group mean body weight was significantly less (p less than 0.05) than either control group, the pituitary hormone content was also calculated on the basis of posterior pituitary protein content. When calculated in this manner, pituitary OT in the FLT rats (5.09 plus or minus 0.15 micron g/mg protein) was significantly less (p less than 0.05) than SYN(7.66 plus or minus 0.39 micron g/mg protein) or VIV controls (8.11 plus or minus 0.64 micron g/mg protein). Pituitary AVP was also less in the FLT animals (7.80 plus or minus 0.13 micron g/mg protein) compared to either SYN(9.84 plus or minus 0.51, p less than 0.05) or VIV controls (11.01 plus or minus 0.76, p less than 0.05). The reduced levels of pituitary OT and AVP may have resulted from increased hormone secretion resulting from the combined effects of water deprivation and the stress of the novel microgravity environment.

G protein abnormalities in pituitary adenomas.

PubMed

Spada, A; Lania, A; Ballarè, E

1998-07-25

It has been demonstrated that the majority of secreting and nonsecreting adenomas is monoclonal in origin suggesting that these neoplasia arise from the replication of a single mutated cell, in which growth advantage results from either activation of protooncogenes or inactivation of antioncogenes. Although a large number of genes has been screened for mutations, only few genetic abnormalities have been found in pituitary tumors such as allelic deletion of chromosome 11q13 where the MEN-1 gene has been localised, and mutations in the gene encoding the alpha subunit of the stimulatory Gs and Gi2 protein. These mutations constitutively activate the alpha subunit of the Gs and Gi2 protein by inhibiting their intrinsic GTPase activity. Both Gs alpha and Gi2alpha can be considered products of protooncogenes (gsp and gip2, respectively) since gain of function mutations that activate mitogenic signals have been recognized in human tumors. Gsp oncogene is found in 30-40% of GH-secreting adenomas, in a low percentage of nonfunctioning and ACTH-secreting pituitary adenomas, in toxic thyroid adenomas and differentiated thyroid carcinomas. The same mutations, occurred early in embriogenesis, have been also identified in tissues from patients affected with the McCune Albright syndrome. These mutations result in an increased cAMP production and in the subsequent overactivation of specific pathways involved in both cell growth and specific programmes of cell differentiation. By consequence, the endocrine tumors expressing gsp oncogene retain differentiated functions. The gip2 oncogene has been identified in about 10% of nonfunctioning pituitary adenomas, in tumors of the ovary and the adrenal cortex. However, it remains to be established whether Gi proteins activate mitogenic signals in pituitary cells. Since Gi proteins are involved in mediating the effect of inhibitory neurohormones on intracellular effectors, it has been proposed that in pituitary tumors the low expression of

Functional morphology of pituitary -thyroid and -adrenocortical axes in middle-aged male rats treated with Vitex agnus castus essential oil.

PubMed

Šošić-Jurjević, Branka; Ajdžanović, Vladimir; Filipović, Branko; Trifunović, Svetlana; Jarić, Ivana; Ristić, Nataša; Milošević, Verica

2016-09-01

We previously reported that Vitex agnus-castus L. essential oil (VACEO), when administered to middle-aged males, exerts a bone-protective effect, induces silencing of locomotor activities and decreases pituitary prolactin immunopositivity. To further assess the putative endocrine effects of VACEO, we examined the pituitary-thyroid and -adrenocortical axes in our model. Sixteen-month-old Wistar rats were subcutaneously administered 60mg/kg of VACEO dissolved in sterile olive oil, while the control group received the same amount of vehicle alone for three weeks. Pituitaries, thyroids and adrenals were analyzed by qualitative and quantitative histological approaches. Concentration of thyroid stimulating hormone (TSH), total thyroxine and triiodothyronine (TH), adrenocorticotrophic hormone (ACTH), corticosterone in serum and in adrenal tissue were measured. In VACEO-treated rats, the relative volume density of pituitary thyrotrophs increased (p<0.001), while intensity of cytoplasmic TSHβ immunostaining decreased (p<0.001), consistent with elevated TSH in serum (p<0.01). The thyroid tissue was characterized by a micro-follicular structure, increased relative volume of follicular epithelium (p<0.05), decreased volume of luminal colloid (p<0.001) and increased basolateral expression of sodium-iodide symporter-immunopositivity (p<0.05). Serum TH also increased (p<0.01). The relative volume density of pituitary corticotrophs decreased (p<0.05), compatible with decline in circulating ACTH (p<0.05). Neither tissue nor serum corticosterone levels were affected by VACEO treatment. In conclusion, the observed changes in TSH and ACTH strongly indicate central endocrine effects of prolonged VACEO treatment. In this respect, production of ACTH decreased without impact on corticosterone production. Increase in serum concentration of both TH and TSH are not compatible with a negative feedback loop and suggest a major change in set-point regulation of the hypothalamic-pituitary

The causes of hypopituitarism in the absence of abnormal pituitary imaging.

PubMed

Wilson, V; Mallipedhi, A; Stephens, J W; Redfern, R M; Price, D E

2014-01-01

Hypopituitarism in the absence of a history of pituitary pathology or abnormal pituitary imaging is rare. To identify the cause of hypopituitarism in individuals in whom pituitary imaging was normal. Retrospective analysis of electronic patient record. A review of the pituitary function in the 506 patients on the Morriston Hospital pituitary database revealed 230 had some degree of hypopituitarism and of these, 21 (9%) had normal pituitary imaging. Of this group, six patients had a past medical history of subarachnoid haemorrhage, head injury or meningitis, and mainly suffered from a deficiency of antidiuretic hormone. One patient had a stroke resulting in multiple anterior hormone deficiencies and six individuals had idiopathic cranial diabetes insipidus (DI). Subsequent investigations of the remaining eight patients with normal pituitary imaging revealed that two had neurosarcoidosis both of whom had panhypopituitarism. Four patients had haemochromatosis which resulted in gonadotropin deficiency in two, DI in one and panhypopituitarism in the other. There were two individuals with confirmed hypopituitarism and multiple hormone deficiencies in which no cause could be identified. These results show that hypopituitarism in the absence of pituitary pathology or an identifiable cause is rare. In patients with multiple anterior pituitary hormone deficiencies haemochromatosis and sarcoidosis should be considered.

Pituitary abscess following transsphenoidal surgery: the experience of 12 cases from a single institution.

PubMed

Wang, Lei; Yao, Yong; Feng, Feng; Deng, Kan; Lian, Wei; Li, Guilin; Wang, Renzhi; Xing, Bing

2014-09-01

To explore possible reasons for the incidence of a pituitary abscess following transsphenoidal surgery and determine the most effective treatment. A series of 12 patients who had undergone transsphenoidal surgery in other hospitals before being treated at Peking Union Medical College Hospital were reviewed. The presence of a pituitary abscess was confirmed when pus was intraoperatively observed within the sella turcica. All patients were treated with debridement of the abscess, nine among whom through a transsphenoidal approach and the other three via a craniotomy, followed by antibiotic treatment and hormone replacement therapy. The mean follow-up time was 27.0 months (range from 3.0 to 79.0 months). Headache (92%), panhypopituitarism (58%) and visual disturbance (50%) were the most common clinical indicators of a pituitary abscess. Imaging tests demonstrated a pituitary mass in all patients, with seven (58%) manifested with typical magnetic resonance features of an abscess. Ten patients (83%) were correctly diagnosed preoperatively. During surgical exploration, six presented with severe inflammation or an abscess within the sphenoidal sinus. Causative organisms were identified in five patients (42%). After surgical and antibiotic therapies, all patients fully recovered except for two presenting with severe visual impairment. Six patients (50%) required hormone replacement therapy. Retrograde infection from the sphenoid sinus may be a vital mechanism underlying the formation of a pituitary abscess following transsphenoidal surgery. Debridement of the abscess through surgical approaches combined with antibiotic treatment has been found to yield positive outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.

Bone morphogenetic protein 4 and bone morphogenetic protein receptor expression in the pituitary gland of adult dogs in healthy condition and with ACTH-secreting pituitary adenoma.

PubMed

Sato, A; Ochi, H; Harada, Y; Yogo, T; Kanno, N; Hara, Y

2017-01-01

The purpose of this study was to investigate the expression of bone morphogenetic protein 4 (BMP4) and its receptors, bone morphogenetic protein receptor I (BMPRI) and BMPRII, in the pituitary gland of healthy adult dogs and in those with ACTH-secreting pituitary adenoma. Quantitative polymerase chain reaction analysis showed that the BMP4 messenger RNA expression level in the ACTH-secreting pituitary adenoma samples was significantly lower than that in the normal pituitary gland samples (P = 0.03). However, there were no statistically significant differences between samples with respect to the messenger RNA expression levels of the receptors BMPRIA, BMPRIB, and BMPRII. Double-immunofluorescence analysis of the normal canine pituitary showed that BMP4 was localized in the thyrotroph (51.3 ± 7.3%) and not the corticotroph cells. By contrast, BMPRII was widely expressed in the thyrotroph (19.9 ± 5.2%) and somatotroph cells (94.7 ± 3.6%) but not in the corticotroph cells (P < 0.001, thyrotroph cells vs somatotroph cells). Similarly, in ACTH-secreting pituitary adenoma, BMP4 and BMPRII were not expressed in the corticotroph cells. Moreover, the percentage of BMP4-positive cells was also significantly reduced in the thyrotroph cells of the surrounding normal pituitary tissue obtained from the resected ACTH-secreting pituitary adenoma (8.3 ± 7.9%) compared with that in normal canine pituitary (P < 0.001). BMP4 has been reported to be expressed in corticotroph cells in the human pituitary gland. Therefore, the results of this study reveal a difference in the cellular pattern of BMP4-positive staining in the pituitary gland between humans and dogs and further revealed the pattern of BMPRII-positive staining in the dog pituitary gland. These species-specific differences regarding BMP4 should be considered when using dogs as an animal model for Cushing's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Reversible suprasellar pituitary mass secondary to hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atchison, J.A.; Lee, P.A.; Albright, A.L.

1989-12-08

Sellar enlargement and suprasellar extension of a pituitary mass, demonstrated by magnetic resonance imaging or computed tomographic scanning in three children with primary hypothyroidism, resolved after treatment with levothyroxine sodium. This condition, a logical consequence of the pathogenesis of primary hypothyroidism, must be considered in patients with pituitary and suprasellar masses.

Endocrine changes in histiocytosis of the hypothalamic-pituitary axis.

PubMed

Toro Galván, Silvia; Planas Vilaseca, Alejandra; Michalopoulou Alevras, Theodora; Torres Díaz, Alberto; Suárez Balaguer, Javier; Villabona Artero, Carles

2015-02-01

Histiocytosis is characterized by proliferation of cells from the mononuclear phagocyte system, and may be divided into Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (including Erdheim-Chester disease [ECD]). While diabetes insipidus (DI) is the most common hypothalamic-pituitary consequence, anterior pituitary deficiencies are less known. This study analyzed the frequency and progression of pituitary hormone deficiencies and the radiographic findings in 9 patients (7 with LCH and 2 with ECD) with hypothalamic-pituitary (HP) axis. Eighty-nine percent of patients had DI (62% at diagnosis), and 78% had one or more anterior pituitary deficiencies (71% at diagnosis). HP involvement is relatively common in patients diagnosed with histiocytosis and hormone deficiencies may be present at diagnosis or appear gradually during the course of disease. Regular monitoring of these patients is recommended. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Transsphenoidal Surgery for Pituitary Tumors and Other Sellar Masses.

PubMed

Owen, Tina J; Martin, Linda G; Chen, Annie V

2018-01-01

Transsphenoidal surgery is an option for dogs and cats with functional and nonfunctional pituitary masses or other sellar and parasellar masses. An adrenocorticotropic hormone-secreting tumor causing Cushing disease is the most common clinically relevant pituitary tumor in dogs, and the most common pituitary tumor seen in cats is a growth hormone-secreting tumor causing acromegaly. Transsphenoidal surgery can lead to rapid resolution of clinical signs and provide a cure for these patients. Because of the risks associated with this surgery, it should only be attempted by a cohesive pituitary surgery group with a sophisticated medical and surgical team. Copyright © 2017 Elsevier Inc. All rights reserved.

Combined effects of cerebellar transcranial direct current stimulation and transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke: A pilot, single blind, randomized controlled trial.

PubMed

Picelli, Alessandro; Chemello, Elena; Castellazzi, Paola; Filippetti, Mirko; Brugnera, Annalisa; Gandolfi, Marialuisa; Waldner, Andreas; Saltuari, Leopold; Smania, Nicola

2018-01-01

Preliminary evidence showed additional effects of anodal transcranial direct current stimulation over the damaged cerebral hemisphere combined with cathodal transcutaneous spinal direct current stimulation during robot-assisted gait training in chronic stroke patients. This is consistent with the neural organization of locomotion involving cortical and spinal control. The cerebellum is crucial for locomotor control, in particular for avoidance of obstacles, and adaptation to novel conditions during walking. Despite its key role in gait control, to date the effects of transcranial direct current stimulation of the cerebellum have not been investigated on brain stroke patients treated with robot-assisted gait training. To evaluate the effects of cerebellar transcranial direct current stimulation combined with transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke. After balanced randomization, 20 chronic stroke patients received ten, 20-minute robot-assisted gait training sessions (five days a week, for two consecutive weeks) combined with central nervous system stimulation. Group 1 underwent on-line cathodal transcranial direct current stimulation over the contralesional cerebellar hemisphere + cathodal transcutaneous spinal direct current stimulation. Group 2 received on-line anodal transcranial direct current stimulation over the damaged cerebral hemisphere + cathodal transcutaneous spinal direct current stimulation. The primary outcome was the 6-minute walk test performed before, after, and at follow-up at 2 and 4 weeks post-treatment. The significant differences in the 6-minute walk test noted between groups at the first post-treatment evaluation (p = 0.041) were not maintained at either the 2-week (P = 0.650) or the 4-week (P = 0.545) follow-up evaluations. Our preliminary findings support the hypothesis that cathodal transcranial direct current stimulation over the contralesional

Case of pituitary stalk transection syndrome ascertained after breech delivery.

PubMed

Fukuta, Kaori; Hidaka, Takao; Ono, Yosuke; Kochi, Keiko; Yasoshima, Kuniaki; Arai, Takashi

2016-02-01

Pituitary stalk transection syndrome (PSTS) is a rare complication that can accompany breech delivery. Early diagnosis of this syndrome is difficult, and it may cause a serious delay in the diagnosis. We present a case of PSTS ascertained after breech delivery. A 20-year-old woman presented with primary amenorrhea. The patient was born by breech delivery and had a history of treatment for pituitary dwarfism. Her laboratory findings showed pituitary hypothyroidism, and hormone replacement therapy was initiated. At 28 years old, she became pregnant and had a normal delivery at 38 weeks' gestation. One year after delivery, her thyroid hormone level changed. Laboratory test showed adrenocortical insufficiency, and magnetic resonance imaging of the pituitary gland showed transection of the pituitary stalk and development of an ectopic posterior lobe. These findings were compatible with PSTS. When a patient who has been born by breech delivery presents with symptoms of pituitary deficiency, PSTS should be considered in the differential diagnosis. © 2015 Japan Society of Obstetrics and Gynecology.

Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors.

PubMed

Japón, Miguel A; Urbano, Angel G; Sáez, Carmen; Segura, Dolores I; Cerro, Alfonso Leal; Diéguez, Carlos; Alvarez, Clara V

2002-04-01

Glial-derived neurotropic factor (GDNF) signaling is mediated through a 2-component system consisting of the so-called GDNF receptor-alpha (GFRalpha1), which binds to GDNF. This complex activates the tyrosine kinase receptor RET. In this paper we demonstrate GDNF, GFRalpha1, and RET mRNA and protein expression in the human anterior pituitary gland. Double immunohistochemistry of anterior pituitary sections showed GDNF immunoreactivity in more than 95% of somatotrophs and to a lesser extent in corticotrophs (20%); it was almost absent in the remaining cell types. Also, although more than 95% of somatotrophs were stained for RET, no positive immunostaining could be detected in other cell types. Furthermore, we have looked for GDNF and RET in human pituitary adenomas of various hormonal phenotypes. Strong positive immunostaining was found for c-RET in all of the GH-secreting adenomas screened as well as in 50% of ACTH-producing adenomas. Positive immunostaining for GDNF was found in all of the GH-secreting adenomas and in 10% of the corticotropinomas. Lastly, we found strong positive immunostaining for GFRalpha1 in 90% of the somatotropinomas and 50% of the corticotropinomas as well as in 1 of 8 prolactinomas and 1 of 13 nonfunctioning adenomas. All of the remaining pituitary tumors screened were negative for RET, GDNF, and GFRalpha1. This study indicates that GDNF may well be acting in the regulation of somatotroph cell growth and/or cell function in the normal human anterior pituitary gland. The expression of RET in all of the somatotropinomas and in 50% of the ACTH-producing tumors implies that GDNF and RET could be involved in the pathogenesis of pituitary tumors.

The Enigma behind Pituitary and Sella Turcica

PubMed Central

Gopalakrishnan, Umarevathi; Mahendra, Lodd; Rangarajan, Sumanth; Madasamy, Ramasamy; Ibrahim, Mohammad

2015-01-01

The pituitary gland's role as a functional matrix for sella turcica has not been suggested in orthodontic literature. This paper is an attempt to correlate the role of pituitary gland in the development of sella turcica. A case report of dwarfism associated with hypopituitarism is presented to highlight the above hypothesis. PMID:26199763

Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report.

PubMed

Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

2015-11-06

Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism.

Surgical Outcomes of Cavernous Sinus Syndrome in Pituitary Adenomas.

PubMed

Fu, Weilun; Duan, Lian; Geng, Sumin

2017-11-01

The type of pituitary adenoma with a manifestation that includes cavernous sinus syndrome is rare. Based on the clinical data of 70 patients, this study investigated the pathogenesis, imaging characteristics, and prognostic factors of pituitary adenoma with cavernous sinus syndrome. We conducted a retrospective analysis of the characteristics of patients with pituitary adenoma with cavernous sinus syndrome who received surgical treatment. The patients were classified into different prognosis groups according to the time required for them to recover from the cavernous sinus syndrome. Univariate analyses were conducted for the correlations between the prognosis and factors. Of the 3598 cases of pituitary adenomas, 70 (1.95%) presented cavernous sinus syndrome. Of the patients, 55.7% recovered within 2 weeks of surgery, 24.3% recovered from 2 weeks to 1 year after surgery, and 20% had not returned to normal after more than 1 year after surgery. Univariate analyses showed that shorter disease duration (P < 0.001), lower Knosp grade (P = 0.045), a transsphenoidal approach (P < 0.001), and associated pituitary apoplexy (P = 0.012) were predictive factors of early postoperative recovery. The prognosis of cavernous sinus syndrome differs depending on the mechanism of the syndrome. There was no significant difference in the prognosis between patients with total pituitary adenoma resection and subtotal resection. Timely surgery within 100 days of symptom occurrence, Knosp grade 0-2, and associated pituitary apoplexy are predictive factors of good prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Pituitary Stem Cell Update and Potential Implications for Treating Hypopituitarism

PubMed Central

Castinetti, Frederic; Davis, Shannon W.; Brue, Thierry

2011-01-01

Stem cells have been identified in organs with both low and high cell turnover rates. They are characterized by the expression of key marker genes for undifferentiated cells, the ability to self-renew, and the ability to regenerate tissue after cell loss. Several recent reports present evidence for the presence of pituitary stem cells. Here we offer a critical review of the field and suggest additional studies that could resolve points of debate. Recent reports have relied on different markers, including SOX2, nestin, GFRa2, and SCA1, to identify pituitary stem cells and progenitors. Future studies will be needed to resolve the relationships between cells expressing these markers. Members of the Sox family of transcription factors are likely involved in the earliest steps of pituitary stem cell proliferation and the earliest transitions to differentiation. The transcription factor PROP1 and the NOTCH signaling pathway may regulate the transition to differentiation. Identification of the stem cell niche is an important step in understanding organ development. The niche may be the marginal zone around the lumen of Rathke's pouch, between the anterior and intermediate lobes of mouse pituitary, because cells in this region apparently give birth to all six pituitary hormone cell lineages. Stem cells have been shown to play a role in recurrent malignancies in some tissues, and their role in pituitary hyperplasia, pituitary adenomas, and tumors is an important area for future investigation. From a therapeutic viewpoint, the ability to cultivate and grow stem cells in a pituitary predifferentiation state might also be helpful for the long-term treatment of pituitary deficiencies. PMID:21493869

Deletion of OTX2 in neural ectoderm delays anterior pituitary development

PubMed Central

Mortensen, Amanda H.; Schade, Vanessa; Lamonerie, Thomas; Camper, Sally A.

2015-01-01

OTX2 is a homeodomain transcription factor that is necessary for normal head development in mouse and man. Heterozygosity for loss-of-function alleles causes an incompletely penetrant, haploinsufficiency disorder. Affected individuals exhibit a spectrum of features that range from developmental defects in eye and/or pituitary development to acephaly. To investigate the mechanism underlying the pituitary defects, we used different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. Mice homozygous for Otx2 deficiency in early head development and pituitary oral ectoderm exhibit craniofacial defects and pituitary gland dysmorphology, but normal pituitary cell specification. The morphological defects mimic those observed in humans and mice with OTX2 heterozygous mutations. Mice homozygous for Otx2 deficiency in the pituitary neural ectoderm exhibited altered patterning of gene expression and ablation of FGF signaling. The posterior pituitary lobe and stalk, which normally arise from neural ectoderm, were extremely hypoplastic. Otx2 expression was intact in Rathke's pouch, the precursor to the anterior lobe, but the anterior lobe was hypoplastic. The lack of FGF signaling from the neural ectoderm was sufficient to impair anterior lobe growth, but not the differentiation of hormone-producing cells. This study demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe and pituitary stalk, and it has significant extrinsic effects on anterior pituitary growth. Otx2 expression early in head development is important for establishing normal craniofacial features including development of the brain, eyes and pituitary gland. PMID:25315894

Maturation of human hypothalamic-pituitary-thyroid function and control.

PubMed

Fisher, D A; Nelson, J C; Carlton, E I; Wilcox, R B

2000-03-01

Measurements of serum thyrotropin (TSH) and free thyroxine (T4) concentrations were conducted in infants, children, and adults to assess maturation of the hypothalamic-pituitary-thyroid (HPT) feedback control axis. Serum free T4 and TSH concentration data were collated for cord blood of the midgestation fetus, for premature and term infants, and for peripheral blood from newborn infants, children, and adults. Mean values were plotted on a nomogram developed to characterize the reference ranges of the normal axis quantitatively based on data from 522 healthy subjects, 2 weeks to 54 years of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Samples for 75 patients with thyroid hormone resistance were also plotted. The characterized pattern of HPT maturation included a progressive decrease in the TSH/free T4 ratio with age, from 15 in the midterm fetus, to 4.7 in term infants, and 0.97 in adults. Maturation plotted on the nomogram was complex, suggesting increasing hypothalamic-pituitary T4 resistance during fetal development, probably secondary to increasing thyrotropin-releasing hormone (TRH) secretion, the marked, cold-stimulated TRH-TSH surge at birth with reequilibration by 2-20 weeks, and a final maturation phase characterized by a decreasing serum TSH with minimal change in free T4 concentration during childhood and adolescence. The postnatal maturative phase during childhood and adolescence correlates with the progressive decrease in thyroxine secretion rate (on a microg/kg per day basis) and metabolic rate and probably reflects decreasing TRH secretion.

Central diabetes insipidus as a very late relapse limited to the pituitary stalk in Langerhans cell histiocytosis.

PubMed

Nakagawa, Shunsuke; Shinkoda, Yuichi; Hazeki, Daisuke; Imamura, Mari; Okamoto, Yasuhiro; Kawakami, Kiyoshi; Kawano, Yoshifumi

2016-07-01

Central diabetes insipidus (CDI) and relapse are frequently seen in multifocal Langerhans cell histiocytosis (LCH). We present two females with multifocal LCH who developed CDI 9 and 5 years after the initial diagnosis, respectively, as a relapse limited to the pituitary stalk. Combination chemotherapy with cytarabine reduced the mass in the pituitary stalk. Although CDI did not improve, there has been no anterior pituitary hormone deficiency (APHD), neurodegenerative disease in the central nervous system (ND-CNS) or additional relapse for 2 years after therapy. It was difficult to predict the development of CDI in these cases. CDI might develop very late in patients with multifocal LCH, and therefore strict follow-up is necessary, especially with regard to symptoms of CDI such as polydipsia and polyuria. For new-onset CDI with LCH, chemotherapy with cytarabine might be useful for preventing APHD and ND-CNS.

Hypopituitarism in the elderly in the presence of elevated thyroid stimulating hormone levels.

PubMed Central

Beringer, T.; McClements, B.; Weir, I.; Gilmore, D.; Kennedy, L.

1988-01-01

Two cases of primary hypothyroidism with hypopituitarism in elderly patients are reported. The elevated levels of thyroid stimulating hormone led to delay in the recognition of accompanying pituitary failure. Elderly patients should not be commenced on thyroxine replacement therapy until the possibility of hypopituitarism and cortisol deficiency has been excluded. PMID:3256811

Pituitary Tumors Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

Cancer.gov

Most pituitary tumors are benign (not cancer), and are called pituitary adenomas. These tumors make extra amounts of certain hormones. Find out about risk factors, signs and symptoms, and tests to diagnose pituitary tumors.

Cellular and molecular specificity of pituitary gland physiology.

PubMed

Perez-Castro, Carolina; Renner, Ulrich; Haedo, Mariana R; Stalla, Gunter K; Arzt, Eduardo

2012-01-01

The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis.

Demographic study of pituitary adenomas undergone trans-sphenoidal surgery in Loghman Hakim Hospital, Tehran, Iran 2001–2013

PubMed Central

Zerehpoosh, Farahnaz Bidari; Sabeti, Shahram; Sharifi, Guive; Shakeri, Hania; Alipour, Setareh; Arman, Farid

2015-01-01

Background: Pituitary adenomas (PAs) are abnormal benign tumors that develop in the pituitary gland. This study aimed to assess the prevalence of different types of PAs with an indication for trans-sphenoidal surgery in a well-defined population referred to Loghman Hakim Hospital during 2001–2013. Subjects and Methods: In this retrospective study, the prevalence rate and symptoms associated with pituitary mass and hormone excess in operated patients were investigated. The diagnosis was verified after retrieval of clinical, hormonal, radiological, and pathological data. Demographic data were collected in all cases. Descriptive analysis, t-test, one-way analysis of variance and Fischer exacts test were used. Results: A total of 278 patients with PAs who underwent surgical interventions were evaluated. Most of the patients were aged 40–50 years with an average of 41 ± 14. The most prominent complaint was pressure effect, which was detected in 153 cases (55.2%). At the second place, hormonal disorders were observed in 125 cases (44.8%). Type of pituitary tumors were: Prolactinomas (29.1%), growth hormone (GH)-producing tumors (25%), nonfunctioning PAs (28.4%), adrenocorticotropic hormone (ACTH)-producing tumors (2.1%), thyroid stimulating hormone (TSH)-producing tumors (0.7%), GH/prolactin (13.6%), GH/ACTH (0.3%), and TSH/ACTH (0.3%). Fifty-seven patients presented with recurrent adenomas. Pituitary apoplexy was found in 11 patients. One case of Sheehan syndrome was recorded among these. The correlations between clinical symptoms and patients, age and sex were not significant. Conclusion: The overview of demographic characteristics in Iranian patients with PAs with surgical indication has been discussed in the present investigation. The prevalence of different types of PAs and the most common clinical symptoms have been demonstrated. PMID:26693430

Nestin-Cre Mice Are Affected by Hypopituitarism, Which Is Not Due to Significant Activity of the Transgene in the Pituitary Gland

PubMed Central

Galichet, Christophe; Lovell-Badge, Robin; Rizzoti, Karine

2010-01-01

Nestin-Cre mice express Cre recombinase under control of the rat nestin promoter and central nervous system (CNS) enhancer. While endogenous Nestin is expressed in some other tissues including the pituitary gland, Nestin-Cre mice induce recombination predominantly in the CNS. For this reason, they have been widely used to explore gene function or cell fate in the latter. Pituitary hormonal deficiencies, or hypopituitarism, are associated with a wide range of symptoms and with a significant morbidity. These can have a neural and/or a pituitary origin as the gland's secretions are controlled by the hypothalamus. We report here that Nestin-Cre mice themselves are affected by mild hypopituitarism. Hence, physiological consequences are expected, especially in combination with defects resulting from Cre mediated deletion of any gene under investigation. To further investigate the origin of this phenotype, we re-examined the activity of the transgene. We compared it with expression of Nestin itself in the context of the hypothalamo-pituitary axis, especially in the light of a recent report showing pituitary Nestin-Cre activity, which contrasts with previous data. Our results disagree with those of this recent study and do not support the claim that Nestin positive cells are present in the pituitary anlagen, the Rathke's pouch (RP). Moreover we did not observe any significant activity in the post-natal pituitary, in agreement with the initial report. PMID:20625432

Impaired Pituitary Axes Following Traumatic Brain Injury

PubMed Central

Scranton, Robert A.; Baskin, David S.

2015-01-01

Pituitary dysfunction following traumatic brain injury (TBI) is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed. PMID:26239686

Utility of bilateral acoustic hearing in combination with electrical stimulation provided by the cochlear implant.

PubMed

Plant, Kerrie; Babic, Leanne

2016-01-01

The aim of the study was to quantify the benefit provided by having access to amplified acoustic hearing in the implanted ear for use in combination with contralateral acoustic hearing and the electrical stimulation provided by the cochlear implant. Measures of spatial and non-spatial hearing abilities were obtained to compare performance obtained with different configurations of acoustic hearing in combination with electrical stimulation. In the combined listening condition participants had access to bilateral acoustic hearing whereas the bimodal condition used acoustic hearing contralateral to the implanted ear only. Experience was provided with each of the listening conditions using a repeated-measures A-B-B-A experimental design. Sixteen post-linguistically hearing-impaired adults participated in the study. Group mean benefit was obtained with use of the combined mode on measures of speech recognition in coincident speech in noise, localization ability, subjective ratings of real-world benefit, and musical sound quality ratings. Access to bilateral acoustic hearing after cochlear implantation provides significant benefit on a range of functional measures.

The pituitary gland: a brief history.

PubMed

Kaplan, Solomon Alexander

2007-01-01

The functions of the pituitary gland as an important constituent of the endocrine system were not understood until the latter part of the nineteenth century and the first half of the 20th century. At one time, the pituitary was deemed to be the "leader of the endocrine orchestra," but more recent studies have shown that its secretions are influenced by external stimuli and that it is largely under the control of the hypothalamus.

AIP mutations impair AhR signaling in pituitary adenoma patients fibroblasts and in GH3 cells.

PubMed

Lecoq, Anne-Lise; Viengchareun, Say; Hage, Mirella; Bouligand, Jérôme; Young, Jacques; Boutron, Audrey; Zizzari, Philippe; Lombès, Marc; Chanson, Philippe; Kamenický, Peter

2016-05-01

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas through unknown molecular mechanisms. The best-known interacting partner of AIP is the aryl hydrocarbon receptor (AhR), a transcription factor that mediates the effects of xenobiotics implicated in carcinogenesis. As 75% of AIP mutations disrupt the physical and/or functional interaction with AhR, we postulated that the tumorigenic potential of AIP mutations might result from altered AhR signaling. We evaluated the impact of AIP mutations on the AhR signaling pathway, first in fibroblasts from AIP-mutated patients with pituitary adenomas, by comparison with fibroblasts from healthy subjects, then in transfected pituitary GH3 cells. The AIP protein level in mutated fibroblasts was about half of that in cells from healthy subjects, but AhR expression was unaffected. Gene expression analyses showed significant modifications in the expression of the AhR target genes CYP1B1 and AHRR in AIP-mutated fibroblasts, both before and after stimulation with the endogenous AhR ligand kynurenine. Kynurenine increased Cyp1b1 expression to a greater extent in GH3 cells overexpressing wild type compared with cells expressing mutant AIP Knockdown of endogenous Aip in these cells attenuated Cyp1b1 induction by the AhR ligand. Both mutant AIP expression and knockdown of endogenous Aip affected the kynurenine-dependent GH secretion of GH3 cells. This study of human fibroblasts bearing endogenous heterozygous AIP mutations and transfected pituitary GH3 cells shows that AIP mutations affect the AIP protein level and alter AhR transcriptional activity in a gene- and tissue-dependent manner. © 2016 Society for Endocrinology.

Spontaneous regression of a pituitary cyst: report of two cases.

PubMed

Nishio, S; Morioka, T; Suzuki, S; Fukui, M

2001-01-01

Two unusual cases of pituitary cysts are described. Both patients presented with sudden onset of severe headache, and magnetic resonance imaging (MRI) demonstrated pituitary cysts, which regressed over months. Although the precise etiology of the cysts was unproven, the cystic lesions in our patients are thought to have shrunken after "pituitary apoplexy."

A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

PubMed

Youssef, M A; van Wely, M; Al-Inany, H; Madani, T; Jahangiri, N; Khodabakhshi, S; Alhalabi, M; Akhondi, M; Ansaripour, S; Tokhmechy, R; Zarandi, L; Rizk, A; El-Mohamedy, M; Shaeer, E; Khattab, M; Mochtar, M H; van der Veen, F

2017-01-01

In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. Ongoing pregnancy rate was 12.8% (25/195) for mild

Intercellular communication within the rat anterior pituitary gland. XV. Properties of spontaneous and LHRH-induced Ca2+ transients in the transitional zone of the rat anterior pituitary in situ.

PubMed

Hattori, Kazuki; Shirasawa, Nobuyuki; Suzuki, Hikaru; Otsuka, Takanobu; Wada, Ikuo; Yashiro, Takashi; Herbert, Damon C; Soji, Tsuyoshi; Hashitani, Hikaru

2013-01-01

In the transitional zone of the rat anterior pituitary, spontaneous and LHRH-induced Ca(2+) dynamics were visualized using fluo-4 fluorescence Ca(2+) imaging. A majority of cells exhibited spontaneous Ca(2+) transients, while small populations of cells remained quiescent. Approximately 70% of spontaneously active cells generated fast, oscillatory Ca(2+) transients that were inhibited by cyclopiazonic acid (10 μm) but not nicardipine (1 μm), suggesting that Ca(2+) handling by endoplasmic reticulum, but not Ca(2+) influx through voltage-dependent L-type Ca(2+) channels, plays a fundamental role in their generation. In the adult rat anterior pituitary, LHRH (100 μg/ml) caused a transient increase in the Ca(2+) level in a majority of preparations taken from the morning group rats killed between 0930 h and 1030 h. However, the second application of LHRH invariably failed to elevate Ca(2+) levels, suggesting that the long-lasting refractoriness to LHRH stimulation was developed upon the first challenge of LHRH. In contrast, LHRH had no effect in most preparations taken from the afternoon group rats euthanized between 1200 h and 1400 h. In the neonatal rat anterior pituitary, LHRH caused a suppression of spontaneous Ca(2+) transients. Strikingly, the second application of LHRH was capable of reproducing the suppression of Ca(2+) signals, indicating that the refractoriness to LHRH had not been established in neonatal rats. These results suggest that responsiveness to LHRH has a long-term refractoriness in adult rats, and that the physiological LHRH surge may be clocked in the morning. Moreover, LHRH-induced excitation and associated refractoriness appear to be incomplete in neonatal rats and may be acquired during development.

Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

PubMed

Jiang, Quan; Lian, Anji; He, Qi

2016-07-01

Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

Pituitary Metastasis from Renal Cell Carcinoma: Description of a Case Report.

PubMed

Wendel, Chloé; Campitiello, Marco; Plastino, Francesca; Eid, Nada; Hennequin, Laurent; Quétin, Philippe; Longo, Raffaele

2017-01-03

BACKGROUND Pituitary metastasis is uncommon, breast and lung cancers being the most frequent primary tumors. Renal cell carcinoma (RCC) is a rare cause of pituitary metastases, with only a few cases described to date. CASE REPORT We report a case of a 61-year-old man who presented with a progressive deterioration of visual acuity and field associated with a bitemporal hemianopsia. Two years ago, he underwent radical right nephrectomy for a clear cell RCC (ccRCC). The biological tests showed pan-hypopituitarism and diabetes insipidus. Brain MRI revealed a large sellar tumor lesion bilaterally infiltrating the cavernous sinuses, which was surgically resected. Histology confirmed a ccRCC pituitary metastasis. The patient received post-surgical radiotherapy. Considering the presence of concomitant extra-pituitary metastases, treatment with sunitinib was started, followed by several lines of therapy with axitinib, everolimus, and sorafenib because of tumor progression. The patient also presented with a pituitary tumor recurrence, which was treated by stereotaxic radiotherapy. He died five years after the initial diagnosis of RCC and 30 months after the diagnosis of the pituitary metastasis.  CONCLUSIONS There are no standardized treatment guidelines for management of pituitary metastases. Pituitary surgery plays a role in symptom palliation, and it does not have any relevant impact on survival. Exclusive radiotherapy or stereotaxic radiotherapy could be an alternative to surgery in patients whose general condition is poor or who have concomitant extra-pituitary metastases.

Combined Effects of Acrobatic Exercise and Magnetic Stimulation on the Functional Recovery after Spinal Cord Lesions

PubMed Central

Wieraszko, Andrzej

2008-01-01

Abstract The objective of the study was to determine whether physical exercise combined with epidural spinal cord magnetic stimulation could improve recovery after injury of the spinal cord. Spinal cord lesioning in mice resulted in reduced locomotor function and negatively affected the muscle strength tested in vitro. Acrobatic exercise attenuated the behavioral effects of spinal cord injury. The exposure to magnetic fields facilitated further this improvement. The progress in behavioral recovery was correlated with reduced muscle degeneration and enhanced muscle contraction. The acrobatic exercise combined with stimulation with magnetic fields significantly facilitates behavioral recovery and muscle physiology in mice following spinal cord injury. PMID:18986227

Kisspeptin stimulates growth hormone release by utilizing Neuropeptide Y pathways and is dependent on the presence of ghrelin

USDA-ARS?s Scientific Manuscript database

Although kisspeptin is the primary stimulator of gonadotropin releasing hormone secretion and therefore the hypothalamic-pituitary gonadal axis, new findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Central delivery of kisspep...

Proteomic Profiling of the Pituitary Gland in Studies of Psychiatric Disorders.

PubMed