Pituitary Gland Tissues Research Articles

Ept7 influences estrogen action in the pituitary gland and body weight of rats

Estrogens control many aspects of pituitary gland biology, including regulation of lactotroph homeostasis and synthesis and secretion of prolactin. In rat models, these actions are strain specific and heritable, and multiple quantitative trait loci (QTL) have been mapped that impact the responsiveness of the lactotroph to estrogens. One such QTL, Ept7, was mapped to RNO7 in female progeny generated in an intercross between BN rats, in which the lactotroph population is insensitive to estrogens, and ACI rats, which develop lactotroph hyperplasia/adenoma and associated hyperprolactinemia in response to estrogen treatment. The primary objective of this study was to confirm the existence of Ept7 and to quantify the impact of this QTL on responsiveness of the pituitary gland of female and male rats to 17β-estradiol (E2) and diethylstilbestrol (DES), respectively. Secondary objectives were to determine if Ept7 influences the responsiveness of the male reproductive tract to DES and to identify other discernible phenotypes influenced by Ept7. To achieve these objectives, a congenic rat strain that harbors BN alleles across the Ept7 interval on the genetic background of the ACI strain was generated and characterized to define the effect of administered estrogens on the anterior pituitary gland and male reproductive tissues. Data presented herein indicate Ept7 exerts a marked effect on development of lactotroph hyperplasia in response to estrogen treatment, but does not affect atrophy of the male reproductive tissues in response to hormone treatment. Ept7 was also observed to exert gender specific effects on body weight in young adult rats.

Acanthomatous ameloblastoma: A clinical rarity

Ameloblastomas are an enigmatic group of tumors affecting different parts of the body, namely, the pituitary gland (craniopharyngioma, Rathke's pouch tumor), long bones, jaws, and soft tissues of the oral cavity. These are slow-growing benign tumors of the jaw, where patients usually present late, after the tumor achieves considerable size and causes facial disfigurement. Ameloblastomas show wide morphological spectra and may pose diagnostic difficulties. Of the different histological variants, acanthomatous type is a rare variant that has distinct features. The challenges in the management of this tumor lie in achieving complete excision, as recurrence is common with incomplete removal, and also to reconstruct the bony defect, to give a reasonable cosmetic and functional outcome to the patient. We report one such rare case of a large acanthomatous ameloblastoma affecting the mandible that has caused gross facial disfigurement.

Factors Determining the Clinical Significance of an “Empty” Sella Turcica

Although often incidental, the "empty" sella turcica can reflect chronically elevated intracranial pressure (ICP). It is particularly common in the setting of idiopathic intracranial hypertension (IIH). This study evaluated which clinical and MRI findings could be used to differentiate patients with chronically elevated ICP from those with incidental empty sella turcica. Forty-five patients with definite IIH and 92 patients with "empty sella" reported on brain MRI were evaluated. Measurements of the sella turcica, diaphragm sella, pituitary gland, infundibulum, and scalp and neck soft tissues were made on MR images. These measurements, age, sex, clinical symptoms, and frequency of previously reported orbital findings of IIH were compared between the IIH and incidental empty sella turcica groups. Measurements on MRI were correlated with patient age in each group. The IIH and incidental empty sella turcica groups had statistically similar sellar, pituitary, and infundibular measurements. The patients with IIH were significantly younger than the patients with incidental empty sella turcica (mean age, 36.1 vs 54.3 years, respectively; p < 0.05); were more likely to report headache (93.3% vs 32.6%; p < 0.05) and visual complaints (66.2% vs 28.3%; p < 0.05); showed greater mean scalp thickness (9.0 vs 6.4 mm; p < 0.05) and neck soft-tissue thickness (19.5 vs 13.8 mm; p < 0.05); and were more likely to have an orbital finding suggestive of IIH (93% vs 14%). Age modestly correlated with the width of the diaphragm sella (r = 0.53) in the IIH group only. The significance of the MRI finding of an empty sella turcica can be determined using a combination of clinical and imaging findings.

Identification of predicted genes expressed differentially in pituitary gland tissue of young growing bulls revealed by cDNA-AFLP technique

Differentially expressed transcript derived fragments (TDFs) of bovine pituitary gland tissue at different developmental ages of Limousine and Hereford bulls were identified by cDNA-AFLP technique. Study revealed comparatively higher differentially expressed transcripts in 6-month Limousine bulls and 12-month Hereford bulls. The BLASTn/p analysis identified 3 and 21 predicted genes which gave significant e-values for Limousine and Hereford respectively, in assembled Bos taurus genome. The identified predicted genes expressed in bovine pituitary gland showed their mapped positions on bovine chromosomes: BTA2, 3, 5, 8, 9, 11, 12, 15&amp;ndash;23, 26, and 28, respectively. Results based on TDF annotation identified 10 sequences that have BLAST hits to known annotated bovine genes and 14 sequences to unannotated contig regions in the latest gene Ensembl database Btau_4.0. Two breed specific predicted target genes were validated by qRT-PCR. Within and between breeds, qRT-PCR results revealed highly significant differences in the expression levels of bovine euchromatic histone-lysine N-methyltransferase 1 (EHMT1) and NCK adaptor protein 2 (NCK2) predicted genes. Obtained results conclude that cDNA-AFLP is a reliable technique for studying within breed age dependent gene expression patterns.

Quantitative Histological Assessment of Xenobiotic-Induced Liver Enzyme Induction and Pituitary-Thyroid Axis Stimulation in Rats Using Whole-Slide Automated Image Analysis

Preclinical evaluation of a new compound, RO2910, identified a hypertrophic response in liver, thyroid gland, and pituitary gland (pars distalis). We aimed to develop and validate automated image analysis methods to quantify and refine the interpretation of semi-quantitative histology. Wistar-Han rats were administered RO2910 for 14 days. Liver, thyroid, and pituitary gland tissues were processed for routine histology and immunolabeled with anti-thyroid stimulating hormone (TSH) antibody (pituitary) and anti-topoisomerase II antibody (thyroid). Glass slides were scanned, image analysis methods were developed and applied to whole-slide images, and numerical results were compared with histopathology, circulating hormone levels, and liver enzyme mRNA expression for validation. Quantitative analysis of slides had strong individual correlation with semi-quantitative histological evaluation of all tissues studied. Hepatocellular hypertrophy quantification also correlated strongly with liver enzyme mRNA expression. In the pars distalis, measurement of TSH weak-staining areas correlated with both hypertrophy scores and circulating TSH levels. Whole-slide image analysis enabled automated quantification of semi-quantitative histopathology findings and a more refined interpretation of these data. The analysis also enabled a direct correlation with non-histological parameters using straightforward statistical analysis to provide a more refined dose- and sex-response relationship and integration among affected parameters. These findings demonstrate the utility of our image analysis to support preclinical safety evaluations.

Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder in which Langerhans's cells accumulate in a variety of organs. LCH affects mostly children and adolescents, involves one or many body systems or tissues such as bone, lung, hypothalamus, posterior pituitary gland, skin, lymph node, liver, and various soft tissues. The clinical features of LCH depend on the extent of involvement. Here in, we report a case of 2-year-old girl presented with fever, swelling in front and behind of right ear and ear discharge. She had anaemia and lytic lesions on skull x-ray and high resolution computed tomography. Biopsy was performed and histopathology and immunohistochemistry findings suggested diagnosis of LCH.

Establishing a protein expression profile database for the normal human pituitary gland using two-dimensional high-performance liquid chromatography combined with LTQ-Orbitrap mass spectrometry.

In this study, we selected adult normal pituitary gland tissues from six patients during operations for pituitary microadenomas via the transsphenoidal approach for extended normal pituitary tissue resection around the tumor, and analyzed the protein expression of human normal pituitary using two-dimensional high-performance liquid chromatography combined with LTQ-Orbitrap mass spectrometry proteomics technology. The ten most highly expressed proteins in normal human pituitary were: alpha 3 type VI collagen isoform 5 precursor (abundance among tall pituitary proteins, 1.30%), fibrinogen beta chain preproprotein (0.99%), vimentin (0.73%), prolactin (0.69%), ATP synthase, H+ transporting and mitochondrial F1 complex beta subunit precursor (0.52%), keratin I (0.49%), growth hormone (0.45%), carbonic anhydrase I (0.40%), heat shock protein 90 kDa I (0.31%), and annexin V (0.30%). Based on the biological function classifications of these proteins, the top three categories by content were neuroendocrine proteins (abundance among all pituitary proteins, 40.1%), catalytic and metabolic proteins (28.3%), and cell signal transduction proteins (9.8%). Based on cell positioning classification, the top three categories were cell organelle (24.5%), membrane (20.8%), and cytoplasm (13.0%). Based on biological process classification, the top three categories of proteins are involved in physiological processes (42.9%), cellular processes (40.4%), and regulation of biological processes (9.1%). Our experimental findings indicate that a protein expression profile database of normal human pituitary can be precisely and efficiently established by proteomics technology.

An essential role for Rax in retina and neuroendocrine system development

In vertebrates, the central nervous system (CNS) develops as a highly hierarchical, patterned organ with a vast diversity of neuronal and glial cell types. The vertebrate retina is developmentally a part of the CNS. Establishment of the vertebrate retina requires a series of developmental steps including specification of the anterior neural plate, evagination of the optic vesicles from the ventral forebrain, and differentiation of cells. The transcription factor RAX is a paired-type homeoprotein that plays a critical role in the eye and forebrain development of vertebrate species. Rax is initially expressed in the anterior neural region of developing mouse embryos, and later in the retina, pituitary gland, hypothalamus, and pineal gland. The targeted deletion of Rax in the mouse results in no eye formation and abnormal forebrain formation. In humans, mutations in the RAX gene lead to anophthalmia and microphthalmia. These observations indicate that RAX plays a pivotal role in the establishment of the retina. In addition, recent studies have reported that retina and pituitary gland tissues can be induced in a culture system from embryonic stem cells, using RAX expression as an indicator of neuronal progenitor cells in the induced tissue, and suggesting that the Rax gene is a key factor in neuronal regeneration. This review highlights the biological functions and molecular mechanisms of RAX in retina, pituitary, hypothalamus, and pineal gland development.

Necrotizing Granulomatous Hypophysitis Presenting as a Sellar Mass

We report the case of a 45-year-old Colombian female with a 3-month history of headache, anorexia, fatigue, and diplopia in addition to left facial nerve palsy 2weeks prior to presentation. On examination, visual fields and fundi were normal, but left abducens and facial nerve palsies were noted. An MRI scan disclosed a sellar mass with suprasellar but neither parasellar nor retrosellar extension. The mass was interpreted as a pituitary tumor and resected via the transsphenoidal approach. Histologic examination revealed necrotizing granulomas in a background of normal pituitary gland tissue. The differential diagnosis includes tuberculosis, sarcoidosis, fungal infection, syphilis, granulomatous autoimmune hypophysitis, Langerhans cell histiocytosis, and Erdheim-Chester disease. Staining for tubercle bacilli (acid fast and fite) as well as for fungi (GMS) was negative and PCR for mycobacteria showed the same result. Postoperative empiric treatment with antituberculous medication resulted in resolution of the cranial nerve palsies within a 1month. The diagnosis of inflammatory/infectious granulomatous hypophysitis can be difficult to diagnose preoperatively and occasionally even postoperatively. A high index of suspicion should be maintained especially in those patients with a history of a systemic granulomatous disease or in regions endemic in granulomatous infectious diseases.

Plasma cell tumors with neurologic symptoms: Cytological findings

Plasma cell neoplasms (plasma cell dyscrasias) are a group of entities characterized by the neoplastic proliferation of a single clone of plasma cells, typically producing a monoclonal immunoglobulin. These tumors can manifest as multiple myeloma, monoclonal gammopathy of undetermined significance, plasma cell myeloma, or plasmacytoma. We report two plasma cell tumors, one of them presented with headache and diplopia, and the second one complained from low back pain. The aspirate exhibited numerous plasma cells in various stage of maturation and was initially diagnosed as extra-skeletal solitary plasmacytoma on fine-needle aspiration cytology (FNAC). Immunohistochemistry demonstrated monoclonal expression of light immunoglobulin chains together with demonstration of CD 38 positivity. Systematic approach such as bone marrow examination, serum protein electrophoresis, skeletal imaging, and urine examination for Bence-Jones proteins were performed for patients. With these investigations, one case was labeled as multiple myeloma with secondary solitary plasmacytoma in pituitary gland and soft tissue and another one as primary extra-skeletal solitary plasmacytoma. Although fine-needle aspiration is a reliable and rapid technique for initial diagnosis, further work-up and clinical follow-up of these patients is necessary to rule out multiple myeloma. Because of cytomorphological similarity between plasma cells and endocrine cells, EMP of sellar region may be confused with pituitary adenoma especially at the time of intraoperative consultation.

Molecular cloning, expression and variation analyses of the dopamine D2 receptor gene in pig breeds in China

The dopamine D2 receptor (DRD2) is a crucial mediator for normal physiological processes. We cloned the pig DRD2 gene, investigated its distribution in tissues and identified polymorphisms by RT-PCR, quantitative real-time PCR and direct sequencing. Two Yorkshire pigs from Guangdong Academy of Agricultural Sciences (Guangzhou, China) were selected to clone the gene and investigate its expression; 16 individuals from four pig breeds (Yorkshire, Landrace, small-ear spotted, and Xinchang) were used to scan the variations. The two transcripts (DRD2L and DRD2S), obtained through insertion or deletion of exon 5 and part of 3'UTR, were found to encode 444- and 415-amino acid proteins, respectively. The 574-bp indel in 3'UTR comprises five miRNA targeting sites, based on bioinformatics predictions. The pig DRD2 gene expresses predominantly in the pituitary gland, and then in oviducts and the hypothalamus. Both DRD2L and DRD2S mRNA were detected in cerebrum, cerebellum, hypothalamus, pituitary gland, back muscle, oviduct, uterus, and testis tissues; DRD2L was more abundant than DRD2S. The DRD2 gene is located on chromosome 9 and contains seven exons. Sixty-one different sequences were identified in this gene; among seven in the coding region, only one altered the encoded amino acid. These findings will help us understand the functions of the DRD2 gene in pigs.

Differential gene expression in anterior pituitary glands from anestrous and cycling postpartum beef cows1

Oligonucleotide microarrays (GeneChip Bovine Genome Arrays, Affymetrix Inc., Santa Clara, CA) were used to evaluate gene expression profiles in anterior pituitary glands collected from 4 anestrous and 4 cycling postpartum primiparous beef cows to provide insight into genes associated with transition from an anestrous to a cycling status. Tissues were collected 40 to 61 d after calving from anestrous cows and from cyclic cows between d 7 and 13 of the estrous cycle (luteal phase) from d 54 to 77 after calving. Hybridization signals were normalized across arrays, and genes with mean differences in expression that were at least 1.5-fold apart and with a minimum difference in mean signal intensity of 10 were compared. Based on these criteria, 47 transcripts were increased (P < 0.025) and 31 transcripts were decreased (P < 0.025) in pituitary gland tissue from cycling compared with anestrous cows. Few transcripts identified in this analysis were associated previously with reproductive function. To provide greater detail on the influence that stage of the estrous cycle (i.e., collection during the luteal phase) might have on the differences detected in gene expression, quantitative real-time PCR was used to compare gene expression in anterior pituitaries of anestrous cows with an additional independent set of anterior pituitary glands collected at 4 different stages of the estrous cycle: 0.5 to 2 d (n = 9), 5 to 6.5 d (n = 5), 11.4 to 13.7 d (n = 5), and 17.9 to 19 d (n = 6) after the onset of estrus. Gastrin-releasing peptide, the gene that exhibited the largest fold increase in expression in the microarray experiment, and IGFBP3 mRNA were expressed at greater (P < 0.004) amounts in samples from the different stages of the estrous cycle than in samples from anestrous cows. In addition, expression of IGFBP3 mRNA was proportional to serum progesterone concentrations throughout the estrous cycle (P < 0.05). Expression of versican mRNA was decreased (P = 0.03) in samples from the different stages of the estrous cycle compared with anestrous cow samples. Results identified numerous genes that may be involved in the transition from anestrous to cycling status, providing novel insight into mechanisms regulating reproductive function.

Analysis of IMP3 Expression in Normal and Neoplastic Human Pituitary Tissues

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant tumors but rarely found in adult benign tissues. In various tumors, IMP3 expression is correlated with increased tumor aggressiveness and reduced overall survival. To our knowledge, IMP3 expression has not been investigated in pituitary tumors. We analyzed the immunohistochemical expression of IMP3 in five normal pituitary tissues and 75 pituitary tumors (64 adenomas and 11 carcinomas) to determine if specific tumor types expressed IMP3 and if there were differences in IMP3 expression between adenomas and carcinomas. Immunohistochemical analysis showed that IMP3 was positive in four (80%) normal pituitaries with focal stain in a subset of normal anterior pituitary cells. IMP3 was expressed in 31% (20/64) of adenomas and in 36% (4/11) of carcinomas. A slightly higher level of IMP3 expression was observed in PRL-GH-TSH adenomas compared to the other types of pituitary adenomas. Expression of IMP3 was not significantly higher in carcinomas than in adenomas (p = 0.737). RT-PCR and Western Blotting supported the heterogeneous expression of IMP3. These results indicate that IMP3 is expressed both in normal and in neoplastic pituitary gland tissues without significant differences in expression levels in pituitary carcinomas.

Neuroendocrine inhibition of glucose production and resistance to cancer in dwarf mice

Pit1 null (Snell dwarf) and Proph1 null (Ames dwarf) mutant mice lack GH, PRL and TSH. Snell and Ames dwarf mice also exhibit reduced IGF-I, resistance to cancer and a longer lifespan than control mice. Endogenous glucose production during fasting is reduced in Snell dwarf mice compared to fasting control mice. In view of cancer cell dependence on glucose for energy, low endogenous glucose production may provide Snell dwarf mice with resistance to cancer. We investigated whether endogenous glucose production is lower in Snell dwarf mice during feeding. Inhibition of endogenous glucose production by glucose injection was enhanced in 12 to 14 month-old female Snell dwarf mice. Thus, we hypothesize that lower endogenous glucose production during feeding and fasting reduces cancer cell glucose utilization providing Snell dwarf mice with resistance to cancer. The elevation of circulating adiponectin, a hormone produced by adipose tissue, may contribute to the suppression of endogenous glucose production in 12 to 14 month-old Snell dwarf mice. We compared the incidence of cancer at time of death between old Snell dwarf and control mice. Only 18% of old Snell dwarf mice had malignant lesions at the time of death compared to 82% of control mice. The median ages at death for old Snell dwarf and control mice were 33 and 26 months, respectively. By contrast, previous studies showed a high incidence of cancer in old Ames dwarf mice at the time of death. Hence, resistance to cancer in old Snell dwarf mice may be mediated by neuroendocrine factors that reduce glucose utilization besides elevated adiponectin, reduced IGF-I and a lack of GH, PRL and TSH, seen in both Snell and Ames dwarf mice. Proteomics analysis of pituitary secretions from Snell dwarf mice confirmed the absence of GH and PRL, the secretion of ACTH and elevated secretion of Chromogranin B and Secretogranin II. Radioimmune assays confirmed that circulating Chromogranin B and Secretogranin II were elevated in 12 to 14 month-old Snell dwarf mice. In summary, our results in Snell dwarf mice suggest that the pituitary gland and adipose tissue are part of a neuroendocrine loop that lowers the risk of cancer during aging by reducing the availability of glucose.

Testicular and Pituitary Inclusion Formation in Fragile X Associated Tremor/Ataxia Syndrome

We describe the medical course, neuropathology and testicular pathology in 2 men who died with fragile X associated tremor/ataxia syndrome. Fragile X associated tremor/ataxia syndrome, which is a recently described, late onset neurodegenerative disorder, affects up to a third of males and occasionally females older than age 50 years who are carriers of premutation alleles (55 to 200 CGG repeats) of the fragile X mental retardation 1 gene FMR1. Clinical manifestations of premutation status are distinct from those of the full mutation, which is the cause of the fragile X syndrome. Standard pathological techniques were used to examine the brain, pituitary gland and testicular tissues of 2 males who had fragile X associated tremor/ataxia syndrome. The clinical course of the 2 cases included impotence before the onset of neurological symptoms of tremor and ataxia. Neuropathological findings included eosinophilic intranuclear inclusions in neurons and astrocytes throughout the central nervous system, and in the anterior and posterior pituitary gland of 1 of the 2 men. Inclusions were also seen in the Leydig and myoid cells in the testicles of these 2 men with fragile X associated tremor/ataxia syndrome. Fragile X associated tremor/ataxia syndrome inclusions are formed in tissues outside of the central nervous system. Involvement of the testicles and the pituitary gland may lead to neuroendocrine dysfunction, including testosterone deficiency. These noncentral nervous system components of fragile X associated tremor/ataxia syndrome require further study.

Molecular cloning and tissue expression of chicken AdipoR1 and AdipoR2 complementary deoxyribonucleic acids

AdipoR1 and AdipoR2 belong to a novel class of transmembrane receptors that mediate the effects of adiponectin. We have cloned the chicken AdipoR1 and AdipoR2 complementary deoxyribonucleic acids (cDNA) and determined their expression in various tissues. We also investigated the effect of feed deprivation on the expression of AdipoR1 or AdipoR2 mRNA in the chicken diencephalon, liver, anterior pituitary gland, and adipose tissue. The chicken AdipoR1 and AdipoR2 cDNA sequences were 76–83% identical to the respective mammalian sequences. A hydrophobicity analysis of the deduced amino acid sequences of chicken AdipoR1/AdipoR2 revealed seven distinct hydrophobic regions representing seven transmembrane domains. By RT-PCR, we detected AdipoR1 and AdipoR2 mRNA in adipose tissue, liver, anterior pituitary gland, diencephalon, skeletal muscle, kidney, spleen, ovary, and blood. AdipoR1 or AdipoR2 mRNA expression in various tissues was quantified by real-time quantitative PCR, and AdipoR1 mRNA expression was the highest in skeletal muscle, adipose tissue and diencephalon, followed by kidney, ovary, liver, anterior pituitary gland, and spleen. AdipoR2 mRNA expression was the highest in adipose tissue followed by skeletal muscle, liver, ovary, diencephalon, anterior pituitary gland, kidney, and spleen. We also found that a 48 h feed deprivation significantly decreased AdipoR1 mRNA quantity in the chicken pituitary gland, while AdipoR2 mRNA quantity was significantly increased in adipose tissue ( P < 0.05). We conclude that the AdipoR1 and AdipoR2 genes are ubiquitously expressed in chicken tissues and that their expression is altered by feed deprivation in the anterior pituitary gland and adipose tissue.

Systemic and pituitary pars intermedia antioxidant capacity associated with pars intermedia oxidative stress and dysfunction in horses

To determine whether a deficiency in systemic or local (pars intermedia) antioxidant capacity is associated with pituitary pars intermedia oxidative stress and pituitary pars intermedia dysfunction (PPID) in horses. Blood samples from 20 horses with PPID and 20 healthy client-owned horses, archived paraffin-embedded adrenal gland and substantia nigra tissues from 20 horses, and pituitary gland tissue from 16 horses. Total glutathione, superoxide dismutase, and glutathione peroxidase activities were determined in RBCs. Accumulation of a systemic marker of oxidative stress (3-nitrotyrosine) was assessed in plasma and formalin-fixed, paraffin-embedded adrenal gland and substantia nigra tissues. Local antioxidants (total and manganese superoxide dismutase, glutathione peroxidase, and total glutathione) were measured in pars intermedia tissues. No significant differences existed in systemic antioxidant enzyme activity or accumulation of 3-nitrotyrosine between horses with PPID and control horses. In pituitary gland tissues, glutathione peroxidase activity was increased in horses with oxidative stress, whereas total glutathione concentration and superoxide dismutase activity remained unchanged. There was an age-associated decrease in manganese superoxide dismutase activity in the pars intermedia. There was no evidence of systemic accumulation of oxidative stress markers or deficiencies in antioxidant capacity in horses with PPID, suggesting that these are unlikely to be major predisposing factors in the development of PPID. Manganese superoxide dismutase activity in the pars intermedia decreased significantly with increasing age. Role of an age-associated decrease in antioxidant capacity for the pars intermedia in the development of PPID in horses warrants further investigation.

Ghrelin, Energy Balance, and Weight in Infants: The Chicken or the Egg?

Ghrelin, a novel peptide consisting of 28 amino acids was first characterized in 1999 (1), is produced predominantly in the stomach, and is now also known to be present in the hypothalamus, the anterior pituitary gland, testis and ovarian tissue and in a variety of tumors (2–4). Ghrelin has been shown to stimulate appetite, gastric motility and acidity in adults and via these mechanisms may also act to regulate energy balance. The effects of ghrelin on appetite appear to be due to its modulation of hypothalamic neuropeptide Y (5). However, ghrelin also likely plays a major role in the modulation of somatic growth via the secretion of pituitary growth hormone (GH). It is now well understood that ghrelin functions in this latter respect by attaching to the growth hormone secretagogue receptor (GHS-R) (1,6), thereby stimulating GH secretion. Further studies (7) have now also shown that in addition to acting upon secretion of stored hormone, ghrelin also stimulates GH gene expression directly, also via the GHS-R. The literature on the effects and biochemistry of ghrelin has grown steadily since its discovery and, to date, a literature search using PubMed (8) produced a total of 1,315 references in which the term ‘‘ghrelin’’ appeared. Because of the link between ghrelin and growth modulating factors, such as GH, Insulin-Like Growth Factor-I (IGF-I) and leptin, a number of investigators have concentrated on the potential for ghrelin to serve as a modulator during the period of rapid growth associated with early infancy (9–12). In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Savino et al. (13) have presented data from their work in a cross sectional study at the University of Turin, Italy, that when data from the study population were pooled, serum concentrations of ghrelin from babies in their first year of life rise with advancing age, with no gender differences noted. Thus, in this cross sectional study, the larger the infant at the time of sampling, the higher the ghrelin concentration. It is not clear whether this finding is based predominantly on the effects of advancing age in general on ghrelin concentration, as this correlation has been documented previously by others (11,12), or whether maturation of the ghrelin-GH axis is an additional independent variable. In term babies, birth weight seems generally not to correlate with ghrelin concentration unless there has been significant growth restriction in utero, in which case cord blood levels have been found to be markedly above those of babies normally grown (9,14). By one year of age, however, these differences are no longer apparent, (15) perhaps due to catch up growth. However, Savino, et al have also shown that although ghrelin concentrations can be directly correlated with postnatal weight and length at time of collection in both breast fed (BF) and formula fed (FF) babies, weight gain from birth correlates negatively with serum ghrelin levels in the BF group but not at all in the FF group. This constitutes an extension of a previous study from birth through 4months of age, in which these authors (16) also found that FF babies had higher serum ghrelin levels during this period, but that these differences did not persist. The negative correlation between total weight gain in the first year of life and ghrelin level in only the BF group is intriguing, particularly since ghrelin is thought This editorial accompanies an article. Please see Savino F, Liguori SA, Fissore MF, et al. Serum ghrelin concentration and weight gain in healthy term infants in the first year of life. J Pediatr Gastroenterol Nutr 2005;41:653–659.

Proopiomelanocortin gene expression and β-endorphin localization in the pituitary, testis, and epididymis of stallion

Proopiomelanocortin (POMC) is a precursor protein that contains the sequences of several bioactive peptides including adrenocorticotropin (ACTH), beta-endorphin (beta-EP), and melanocyte-stimulating-hormone (MSH). POMC is synthesized in the pituitary gland, brain, and many peripheral tissues. Immunoreactive POMC-derived peptides as well as POMC-like mRNA have been evidenced in several nonpituitary tissues, thus suggesting that POMC is actively synthesized by these tissues. The present study was aimed at evaluating if also in the case of stallion POMC-derived peptide, beta-EP, is produced locally in the testis, thus playing effects in a paracrine/autocrine fashion. To investigate this hypothesis the POMC gene expression was analyzed using 3' RACE-PCR and Northern Blot approaches in the testis and epididimys of stallion; moreover, immunocytochemical localization for beta-EP was also performed through confocal laser microscopy. The immunofluorescence results showed a positive beta-EP reaction not only in cellular nest of pituitary but also in the testis and genital tract of stallion, which function could be related with sperm mobility. Such role seem not to be no dependent on the peptide synthesized locally, because the molecular biology approach demonstrated the presence of POMC transcript in the pituitary only. In fact the Northern Blot analysis showed the presence of a single POMC transcript in the pituitary while no signal was detected in the testis and epididimys. The same results were obtained by applied 3' RACE-PCR analysis. In conclusion, opioid-derived peptide beta-EP is present in the genital tract of stallion, but is not locally produced as in other mammalian, and nonmammalian models; its possible biological function at testicular level could be linked to a long-loop feed-back mechanisms.

Langerhans' cell histiocytosis - Case report

angerhans’ cell histiocytosis is a disease of unknown cause and diverse manifestations. In 1953, Lichtenstein [1] proposed that the disease entities known as eosinophilic granuloma, Hand-Schuller-Christian disease and Letterer-Siwe disease all share a common pathologic appearance. This view was challenged by Lieberman et al [2]. They suggested that Letterer-Siwe disease is not a specific entity but may involve several pathologic processes. Evidence however, suggests that at least some examples of disseminated disease with features of Letterer-Siwe syndrome are examples of Langerhans' cell histiocytosis [3]. It was once thought that Langerhans' cell histiocytosis most likely represented a reactive disorder rather than a neoplastic process. More recent studies, however, have demonstrated clonality in Langerhans' cell histiocytosis, supporting a neoplastic origin [4]. Langerhans' cell histiocytosis affects mostly children and adolescents, involves one or many body systems or tissues such as bone, lung, hypothalamus, posterior pituitary gland, skin, lymph node, liver and various soft tissues. The clinical features of Langerhans' cell histiocytosis depend on the extent of involvement. Ordinarily, patients with solitary disease have localized pain. Patients with disseminated disease may have lymphadenopathy, skin lesions, or diabetes insipidus. We report a case of Langerhans' histiocytosis in a 16-year-old adolescent male.