Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

PubMed Central

Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

2016-01-01

Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox9+ adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

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.

Hormone modeling in preterm neonates: establishment of pituitary and steroid hormone reference intervals.

PubMed

Greaves, Ronda F; Pitkin, Janne; Ho, Chung Shun; Baglin, James; Hunt, Rodney W; Zacharin, Margaret R

2015-03-01

Reports suggest significant differences in serum levels of hormones in extremely preterm compared with late preterm and full-term infants. The purpose of this study was to develop reference intervals (RIs) for 3 pituitary hormones and 5 steroid hormones in serum of preterm infants. Blood samples were collected from 248 (128 male and 120 female) preterm neonates born between 24 and 32 weeks' gestation. PARTICIPANTS were recruited from 3 neonatal intensive care wards in Melbourne, Australia. No infant in this cohort had ambiguous genitalia or other endocrine abnormalities. All infants included in the RI determination survived beyond the equivalent of term. Serum was analyzed for prolactin, FSH, and LH by automated electrochemiluminescence immunoassay (Roche Cobas 8000-e601). Liquid chromatography coupled with tandem mass spectrometry was used for analysis of 17-hydroxyprogesterone, androstenedione, cortisol, cortisone, and testosterone. The robust method was applied to define the central 95% RI, after each hormone measure was transformed using a Box-Cox transformation to correct for asymmetry. RIs were established for 8 hormones. Gender-specific intervals were developed for FSH, LH, and testosterone. Cortisone and 17- hydroxyprogesterone required division based on gestational age, with neonates born at <30 weeks' gestation demonstrating higher levels than their older counterparts. Androstenedione, cortisol, and prolactin did not require any division within this cohort for RI assignment. This report provides the first characterization of serum steroids measured by mass spectrometry in preterm neonates, with the additional characterization of 3 pituitary hormones in infants born at ≤32 weeks' gestation. Use of these data allows for correct interpretation of results for very preterm neonates and reduces the risk of incorrect diagnosis due to misinterpretation of data.

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.

Sensitivity of T-Lymphocytes to Hormones of the Anterior Pituitary Gland.

PubMed

Tishevskaya, N V; Gevorkyan, N M; Kozlova, N I

2017-01-01

The review provides information about the features of the sensitivity of thymocytes, lymphoid organs' cells and T-lymphocytes of peripheral blood to the hormones secreted by anterior pituitary gland's cells: growth hormone, thyrotropin, adrenocorticotropic hormone, prolactin and β-endorphin. Some aspects of the T-lymphocytes's response to humoral signals from the hypophysis are shown in the article. Also the pituitary hormones' role in the regulation of proliferation, differentiation, and cytokine production of T-lymphocytes in normal and pathological conditions of the organism being discussed.

Comparison of post-surgical MRI presentation of the pituitary gland and its hormonal function.

PubMed

Bladowska, Joanna; Sokolska, Violetta; Sozański, Tomasz; Bednarek-Tupikowska, Grażyna; Sąsiadek, Marek

2010-01-01

Post-surgical evaluation of the pituitary gland in MRI is difficult because of a change of anatomical conditions. It depends also on numerous other factors, including: size and expansion of a tumour before surgery, type of surgical access, quality and volume of filling material used and time of its resorption.The aim of the study was to compare MR image of the pituitary gland after surgery with clinical findings and to establish a correlation between MRI presentation of spared pituitary and its hormonal function. 124 patients after resection of pituitary adenomas - 409 MRI results in total - were studied. With a 1.5-T unit, T1-weighted sagittal and coronal, enhanced and unenhanced images were obtained. The pituitary gland seemed to be normal in MRI in 11 patients, 8 of them had completely regular pituitary function but in 3 of them we noticed a partial hypopituitarism. In 99 patients only a part of the pituitary gland was recognised, 53 of them had hypopituitarism but 46 of them were endocrinologically healthy. 14 patients seemed to have no persistent pituitary gland in MRI, in comparison to hormonal studies: there was panhypopituitarism in 6 and hypopituitarism in 8 cases. MRI presentation of post - surgical pituitary gland doesn't necessarily correlate with its hormonal function - there was a significant statistical difference. Some patients with partial pituitary seems normal hormonal function. In some cases the pituitary seem normal in MRI but these patients have hormonal disorders and need substitution therapy.

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.

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

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.

Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst.

PubMed

Uppal, Surabhi; Jee, Youn Hee; Lightbourne, Marissa; Han, Joan C; Stratakis, Constantine A

2017-01-01

Tetrasomy X is a rare chromosomal aneuploidy seen in girls, associated with facial dysmorphism, premature ovarian insufficiency and intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's pouch which may cause multiple pituitary hormone deficiencies by exerting pressure on the pituitary gland in the sella. The patient was diagnosed with tetrasomy X by karyotyping during infancy. Brain MRI and multiple endocrine stimulation tests revealed RCC and combined pituitary hormone deficiency (growth hormone deficiency, secondary adrenal insufficiency and central hypothyroidism) likely due to RCC. We report the first case in the literature of a girl with 48, XXXX and combined pituitary hormone deficiency due to Rathke's cyst.

Rare Frequency of Mutations in Pituitary Transcription Factor Genes in Combined Pituitary Hormone or Isolated Growth Hormone Deficiencies in Korea.

PubMed

Choi, Jin Ho; Jung, Chang Woo; Kang, Eungu; Kim, Yoon Myung; Heo, Sun Hee; Lee, Beom Hee; Kim, Gu Hwan; Yoo, Han Wook

2017-05-01

Congenital hypopituitarism is caused by mutations in pituitary transcription factors involved in the development of the hypothalamic-pituitary axis. Mutation frequencies of genes involved in congenital hypopituitarism are extremely low and vary substantially between ethnicities. This study was undertaken to compare the clinical, endocrinological, and radiological features of patients with an isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD). This study included 27 patients with sporadic IGHD and CPHD. A mutation analysis of the POU1F1, PROP1, LHX3, LHX4, and HESX1 genes was performed using genomic DNA from peripheral blood leukocytes. IGHD and CPHD were observed in 4 and 23 patients, respectively. Mean age at diagnosis was 8.28±7.25 years for IGHD and 13.48±10.46 years for CPHD (p=0.37). Serum insulin-like growth factor-1 and peak growth hormone (GH) levels following GH stimulation tests were significantly lower in patients with CPHD than in those with IGHD (p<0.05). Sellar MRI findings revealed structural abnormalities in 3 patients with IGHD (75%) and 21 patients with CPHD (91.3%) (p=0.62). A mutation analysis identified homozygous p.R109Q mutations in HESX1 in a patient with CPHD. Patients with CPHD had more severe GHD than those with IGHD. The frequency of defects in the genes encoding pituitary transcription factors was extremely low in Korean patients with congenital hypopituitarism. Environmental factors and the impact of other causative genes may contribute to this clinical phenotype. © Copyright: Yonsei University College of Medicine 2017

Rare Frequency of Mutations in Pituitary Transcription Factor Genes in Combined Pituitary Hormone or Isolated Growth Hormone Deficiencies in Korea

PubMed Central

Choi, Jin-Ho; Jung, Chang-Woo; Kang, Eungu; Kim, Yoon-Myung; Heo, Sun Hee; Lee, Beom Hee; Kim, Gu-Hwan

2017-01-01

Purpose Congenital hypopituitarism is caused by mutations in pituitary transcription factors involved in the development of the hypothalamic-pituitary axis. Mutation frequencies of genes involved in congenital hypopituitarism are extremely low and vary substantially between ethnicities. This study was undertaken to compare the clinical, endocrinological, and radiological features of patients with an isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD). Materials and Methods This study included 27 patients with sporadic IGHD and CPHD. A mutation analysis of the POU1F1, PROP1, LHX3, LHX4, and HESX1 genes was performed using genomic DNA from peripheral blood leukocytes. Results IGHD and CPHD were observed in 4 and 23 patients, respectively. Mean age at diagnosis was 8.28±7.25 years for IGHD and 13.48±10.46 years for CPHD (p=0.37). Serum insulin-like growth factor-1 and peak growth hormone (GH) levels following GH stimulation tests were significantly lower in patients with CPHD than in those with IGHD (p<0.05). Sellar MRI findings revealed structural abnormalities in 3 patients with IGHD (75%) and 21 patients with CPHD (91.3%) (p=0.62). A mutation analysis identified homozygous p.R109Q mutations in HESX1 in a patient with CPHD. Patients with CPHD had more severe GHD than those with IGHD. Conclusion The frequency of defects in the genes encoding pituitary transcription factors was extremely low in Korean patients with congenital hypopituitarism. Environmental factors and the impact of other causative genes may contribute to this clinical phenotype. PMID:28332357

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.

Lack of normal MR enhancement of the pituitary gland: findings in three siblings with combined pituitary hormone deficiency.

PubMed

Falcone, S; Sanchez, J; Quencer, R M

1998-02-01

We present the MR appearance of the sella turcica in three sibling dwarfs with combined pituitary hormone deficiency in which MR images revealed a peripheral curvilinear band of enhancement about the pituitary gland in all three patients, a normal-size pituitary gland in two siblings, a mildly enlarged pituitary gland in one sibling, and a thin infundibulum and a normal posterior pituitary bright spot in all three siblings. Possible antecedents include an abnormal vascular supply, pituitary gland replacement by a nonfunctioning adenoma, a proteinaceous cyst, or a hamartoma.

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.

Combined pituitary hormone deficiency: current and future status.

PubMed

Castinetti, F; Reynaud, R; Quentien, M-H; Jullien, N; Marquant, E; Rochette, C; Herman, J-P; Saveanu, A; Barlier, A; Enjalbert, A; Brue, T

2015-01-01

Over the last two decades, the understanding of the mechanisms involved in pituitary ontogenesis has largely increased. Since the first description of POU1F1 human mutations responsible for a well-defined phenotype without extra-pituitary malformation, several other genetic defects of transcription factors have been reported with variable degrees of phenotype-genotype correlations. However, to date, despite the identification of an increased number of genetic causes of isolated or multiple pituitary deficiencies, the etiology of most (80-90 %) congenital cases of hypopituitarism remains unsolved. Identifying new etiologies is of importance as a post-natal diagnosis to better diagnose and treat the patients (delayed pituitary deficiencies, differential diagnosis of a pituitary mass on MRI, etc.), and as a prenatal diagnosis to decrease the risk of early death (undiagnosed corticotroph deficiency for instance). The aim of this review is to summarize the main etiologies and phenotypes of combined pituitary hormone deficiencies, associated or not with extra-pituitary anomalies, and to suggest how the identification of such etiologies could be improved in the near future.

Ets-1 is a target of MAPK signaling in the embryonic anterior pituitary gland during glucocorticoid initiation of pituitary growth hormone expression

USDA-ARS?s Scientific Manuscript database

Glucocorticoids play a critical role in functional differentiation of somatotrophs, the growth hormone (GH)-producing cells within the anterior pituitary gland. In chicken embryonic day 11 (e11) pituitary cells, premature induction of growth hormone (GH) resulting from corticosterone (CORT) treatmen...

Purification and cultivation of human pituitary growth hormone secreting cells

NASA Technical Reports Server (NTRS)

Hymer, W. C.

1979-01-01

Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

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.

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....

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.

Pituitary tumour causing gigantism. Morphology and in vitro hormone secretion.

PubMed

Anniko, M; Ritzén, E M

1986-01-01

True gigantism with overproduction of growth hormone (GH) and prolactin (PRL) was diagnosed in a 13-year-old boy. The clinical history indicated that the tumour had caused an oversecretion of GH since the age of 4-5 years. At diagnosis, the sella turcica was markedly enlarged. No infiltrative growth was noted at surgery. Endocrine investigations showed elevated GH and PRL secretion. Light and electron microscopy of tumour tissue revealed densely packed pleomorphic cells of both GH and PRL type. In addition, oncocyte-like cells were observed. Organ culture of pieces of tumour tissue demonstrated continued secretion of GH and PRL into the medium for more than 5 days in vitro. Addition of bromocriptine to the medium caused a rapid decline in PRL secretion while GH secretion remained the same. X-ray irradiation in vitro also caused a decrease in PRL secretion. These effects of bromocriptine and X-ray on hormone secretion in vitro mirrored the corresponding effect of treatment, when the patient showed signs of tumour recurrence after pituitary surgery. It is concluded that also in childhood, the in vitro response of tumour tissue to various treatments may be explored as a possible way to predict the efficacy of pharmacological or irradiation treatment of pituitary tumours.

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

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

Correa, Fernanda A; 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; Carvalho, Luciani R

2017-10-01

Women with hypopituitarism have lower pregnancy rates after ovulation induction. Associated pituitary hormone deficiencies might play a role in this poorer outcome. We evaluated fertility treatment and pregnancy outcomes in five women with childhood-onset combined pituitary hormone deficiencies (CPHD). 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). 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). 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.

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

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.

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.

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.

Thyroid hormone is essential for pituitary somatotropes and lactotropes.

PubMed

Stahl, J H; Kendall, S K; Brinkmeier, M L; Greco, T L; Watkins-Chow, D E; Campos-Barros, A; Lloyd, R V; Camper, S A

1999-04-01

Mice homozygous for a disruption in the alpha-subunit essential for TSH, LH, and FSH activity (alphaGsu-/-) exhibit hypothyroidism and hypogonadism similar to that observed in TSH receptor-deficient hypothyroid mice (hyt) and GnRH-deficient hypogonadal mutants (hpg). Although the five major hormone-producing cells of the anterior pituitary are present in alphaGsu-/- mice, the relative proportions of each cell type are altered dramatically. Thyrotropes exhibit hypertrophy and hyperplasia, and somatotropes and lactotropes are underrepresented. The size and number of gonadotropes in alphaGsu mutants are not remarkable in contrast to the hypertrophy characteristic of gonadectomized animals. The reduction in lactotropes is more severe in alphaGsu mutants (13-fold relative to wild-type) than in hyt or hpg mutants (4.5- and 1.5-fold, respectively). In addition, T4 replacement therapy of alphaGsu mutants restores lactotropes to near-normal levels, illustrating the importance of T4, but not alpha-subunit, for lactotrope proliferation and function. T4 replacement is permissive for gonadotrope hypertrophy in alphaGsu mutants, consistent with the role for T4 in the function of gonadotropes. This study reveals the importance of thyroid hormone in developing the appropriate proportions of anterior pituitary cell types.

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

Hormones and the bone marrow: panhypopituitarism and pancytopenia in a man with a pituitary adenoma.

PubMed

Lang, Dianna; Mead, Jennifer S; Sykes, David B

2015-05-01

In rare cases, pancytopenia results from hormonal deficiencies that arise in the setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old man who presented with progressive fatigue and polyuria, and whose laboratory workup revealed a deficiency of the five hormones associated with the action of the anterior pituitary (thyroid hormone, testosterone, cortisol, prolactin, and insulin-like growth factor-1). Imaging of the pituitary demonstrated a cystic mass consistent with a pituitary adenoma replacing much of the normal pituitary tissue. His symptoms and hematologic abnormalities rapidly resolved with prednisone and levothyroxine supplementation. While the majority of reported cases of panhypopituitarism with bone marrow suppression are the result of peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan's syndrome), it is also important to consider the diagnosis of hypopituitarism in patients with hypothyroidism, low cortisol levels, and pancytopenia. The causal relationship between pancytopenia and panhypopituitarism is not well understood, though it does reinforce the important influence of these endocrine hormones on the health of the bone marrow.

Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones

PubMed Central

Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A.; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

2015-01-01

Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs. PMID:26106585

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.

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

Proteome and radioimmunoassay analyses of pituitary hormones and proteins in response to feed restriction of dairy cows.

PubMed

Kuhla, Björn; Albrecht, Dirk; Bruckmaier, Rupert; Viergutz, Torsten; Nürnberg, Gerd; Metges, Cornelia C

2010-12-01

The hypothalamic-pituitary system controls homeostasis during feed energy reduction. In order to examine which pituitary proteins and hormone variants are potentially associated with metabolic adaptation, pituitary glands from ad libitum and energy restrictively fed dairy cows were characterized using RIA and 2-DE followed by MALDI-TOF-MS. We found 64 different spots of regulatory hormones: growth hormone (44), preprolactin (16), luteinizing hormone (LH) (1), thyrotropin (1), proopiomelanocortin (1) and its cleavage product lipotropin (1), but none of these did significantly differ between feeding groups. Quantification of total pituitary LH and prolactin concentrations by RIA confirmed the results obtained by proteome analysis. Also, feed energy restriction provoked increasing non-esterified fatty acid, decreasing prolactin, but unaltered glucose, LH and growth hormone plasma concentrations. Energy restriction decreased the expression of glial fibrillary acidic protein, triosephosphate isomerase, purine-rich element-binding protein A and elongation factor Tu, whereas it increased expression of proline synthetase co-transcribed homolog, peroxiredoxin III, β-tubulin and annexin A5 which is involved in the hormone secretion process. Our results indicate that in response to feed energy restriction the pituitary reservoir of all posttranslationally modified hormone forms remains constant. Changing plasma hormone concentrations are likely attributed to a regulated releasing process from the gland into the blood. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

PubMed

Zheng, Junjie; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Huang, Bingkun; Liu, Zhaoxiang; Cui, Mingxuan; Xiong, Shuyu; Ma, Wanlu; Min, Le; Kaiser, Ursula B; Nie, Min; Wu, Xueyan

2017-07-01

The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Prospective, self-controlled, 3-month clinical trial. University endocrine clinic. Men with hypogonadotropic hypogonadism caused by CCPHD. Pulsatile GnRH was administered subcutaneously for 3 months. Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice. Copyright © 2017 Endocrine Society

Luteinizing hormone-releasing hormone inactivation by purified pituitary plasma membranes: effects of receptor-binding studies.

PubMed

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

1979-05-01

Inactivation of LHRH by purified bovine pituitary plasma membranes was studied in vitro. After incubation of [125I]iodo-LHRH with plasma membranes, the amount of tracer bound to the pellet was measured, and the integrity of the unbound tracer in the supernatant was assessed. Reduction in ability to bind to anti-LHRH serum and to rebind to plasma membranes together with altered electrophoretic mobility on polyacrylamide gels showed that the unbound [125I]iodo-LHRH was inactivated. LHRH inactivation occurred rapidly and was dependent upon membrane concentration and incubation temperature. These results indicate that hormone inactivation must be taken into account in the interpretation of LHRH-receptor interactions. During 37 C incubations, the apparent absence of specific LHRH binding can be explained by inactivation of tracer hormone. Significant LHRH inactivation also occurred at 0 C, which in part explains the insensitivity of LHRH receptor assays. Assessment of LHRH inactivation by different particulate subcellular fractions of pituitary tissue showed that the inactivating enzyme was associated with the plasma membranes; other organelles did not alter LHRH. The enzyme appeared to be an integral part of the plasma membrane structure, since enzymic activity could not be removed by washing without reducing specific LHRH binding. Additionally, reduction of LHRH inactivation by the inhibitors Bacitracin and Trasylol and by magnesium was also accompanied by reduced LHRH binding. Previous studies have shown that the majority of LHRH binding to pituitary plasma membranes is to the low affinity site (approximately 10(-6) M), but the significance of this binding has been uncertain. Our findings indicate that low affinity binding probably represents binding of LHRH to the inactivating enzyme. The LHRH analog, D-Ser6(TBu), des Gly10, ethylamide, has greater biological activity than LHRH and is not inactivated to a significant extent by pituitary plasma membranes. The

Isolated autosomal dominant growth hormone deficiency: an evolving pituitary deficit? A multicenter follow-up study.

PubMed

Mullis, Primus E; Robinson, Iain C A F; Salemi, Souzan; Eblé, Andrée; Besson, Amélie; Vuissoz, Jean-Marc; Deladoey, Johnny; Simon, Dominique; Czernichow, Paul; Binder, Gerhard

2005-04-01

Four distinct familial types of isolated GH deficiency have been described so far, of which type II is the autosomal dominant inherited form. It is mainly caused by mutations within the first 6 bp of intervening sequence 3. However, other splice site and missense mutations have been reported. Based on in vitro experiments and transgenic animal data, there is strong evidence that there is a wide variability in phenotype in terms of the severity of GH deficiency. Therefore, we studied a total of 57 subjects belonging to 19 families suffering from different splice site as well as missense mutations within the GH-1 gene. The subjects presenting with a splice site mutation within the first 2 bp of intervening sequence 3 (5'IVS +1/+2 bp) leading to a skipping of exon 3 were found to be more likely to present in the follow-up with other pituitary hormone deficiencies. In addition, although the patients with missense mutations have previously been reported to be less affected, a number of patients presenting with the P89L missense GH form, showed some pituitary hormone impairment. The development of multiple hormonal deficiencies is not age dependent, and there is a clear variability in onset, severity, and progression, even within the same families. The message of clinical importance from these studies is that the pituitary endocrine status of all such patients should continue to be monitored closely over the years because further hormonal deficiencies may evolve with time.

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

The gonadotropin-inhibitory hormone (Lpxrfa) system's regulation of reproduction in the brain-pituitary axis of the zebrafish (Danio rerio).

PubMed

Spicer, Olivia Smith; Zmora, Nilli; Wong, Ten-Tsao; Golan, Matan; Levavi-Sivan, Berta; Gothilf, Yoav; Zohar, Yonathan

2017-05-01

Gonadotropin-inhibitory hormone (GNIH) was discovered in quail with the ability to reduce gonadotropin expression/secretion in the pituitary. There have been few studies on GNIH orthologs in teleosts (LPXRFamide (Lpxrfa) peptides), which have provided inconsistent results. Therefore, the goal of this study was to determine the roles and modes of action by which Lpxrfa exerts its functions in the brain-pituitary axis of zebrafish (Danio rerio). We localized Lpxrfa soma to the ventral hypothalamus, with fibers extending throughout the brain and to the pituitary. In the preoptic area, Lpxrfa fibers interact with gonadotropin-releasing hormone 3 (Gnrh3) soma. In pituitary explants, zebrafish peptide Lpxrfa-3 downregulated luteinizing hormone beta subunit and common alpha subunit expression. In addition, Lpxrfa-3 reduced gnrh3 expression in brain slices, offering another pathway for Lpxrfa to exert its effects on reproduction. Receptor activation studies, in a heterologous cell-based system, revealed that all three zebrafish Lpxrfa peptides activate Lpxrf-R2 and Lpxrf-R3 via the PKA/cAMP pathway. Receptor activation studies demonstrated that, in addition to activating Lpxrf receptors, zebrafish Lpxrfa-2 and Lpxrfa-3 antagonize Kisspeptin-2 (Kiss2) activation of Kisspeptin receptor-1a (Kiss1ra). The fact that kiss1ra-expressing neurons in the preoptic area are innervated by Lpxrfa-ir fibers suggests an additional pathway for Lpxrfa action. Therefore, our results suggest that Lpxrfa may act as a reproductive inhibitory neuropeptide in the zebrafish that interacts with Gnrh3 neurons in the brain and with gonadotropes in the pituitary, while also potentially utilizing the Kiss2/Kiss1ra pathway. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Sensitivity of anterior pituitary hormones to graded levels of psychological stress.

PubMed

Armario, A; Lopez-Calderón, A; Jolin, T; Castellanos, J M

1986-08-04

The effect of graded levels of stressor intensity on anterior pituitary hormones was studied in adult male rats. Corticosterone, considered as a reflection of ACTH release, and prolactin responses showed a good correlation with the intensity of the stressors. On the contrary, neither LH, GH nor TSH release showed a parallelism with the intensity of the stressors in spite of the fact that they clearly responded to all the stimuli. It appears that the hormones of the anterior pituitary might be divided into two groups: those whose response is sensitive to the levels of emotional arousal elicited by stress, and those displaying a clear but stereotyped response during stress. However, other alternative explanations might exist to justify the present results. The neural mechanisms underlying the two types of response are at present unknown. These data indicate that only the pituitary-adrenal axis and prolactin have some potential utilities as quantitative indices of emotional arousal elicited by currently applied stressors in the rat.

Hypothalamo-pituitary hormone insufficiency associated with cleft lip and palate.

PubMed Central

Roitman, A; Laron, Z

1978-01-01

Two male patients with congenital cleft lip and palate first seen at ages 10.2 and 21.5 years presented with typical signs of hypothalamic-interior pituitary hormone deficiencies. They were found to lack GH, LH, and FSH and to be partially deficient in TSH and ACTH. Several congenital defects may explain this rare syndrome affecting midline structures in the proximity of the maldeveloped palate, including Rathke's pouch, which migrates distally to develop into the anterior pituitary. PMID:747400

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.

Identification of a novel splicing mutation in the growth hormone (GH)-releasing hormone receptor gene in a Chinese family with pituitary dwarfism.

PubMed

Wang, Qi; Diao, Ying; Xu, Zhenping; Li, Xiaohui; Luo, Xiao Ping; Xu, Haibo; Ouyang, Ping; Liu, Mugen; Hu, Zhongli; Wang, Qing K; Liu, Jing Yu

2009-12-10

A Chinese family with autosomal recessive pituitary dwarfism was identified and the proband was evaluated by MRI and hormonal analysis, which revealed pituitary dwarfism with a complete growth hormone deficiency. MRI showed a pituitary gland with a small anterior pituitary of 2.2mm and evidence of hypoplastic pituitary. Linkage analysis with markers spanning 17 known genes for dwarfism revealed linkage of the family to the growth hormone-releasing hormone receptor (GHRHR) gene. Mutational analysis of all exons and exon-intron boundaries of GHRHR was carried out using direct DNA sequence analysis. A novel homozygosis mutation, a G to A transition located in the splice donor site at the beginning of intron 8 (IVS8+1G>A), was identified in the proband. The two other patients in the family are homozygous, whereas the living mother of the proband is heterozygous for the IVS8+1G>A mutation. The mutation was not found in 100 normal chromosomes from healthy Chinese individuals of Han nationality. An in vitro splicing assay using HeLa cells transfected with expression vectors containing the normal or the mutant GHRHR minigenes consisting of genomic fragments spanning exons 7-9 showed that the IVS8+1G>A mutation caused abnormal splicing, which is predicted to give rise to truncation or frameshift, leading to severely truncated GHRHR proteins. These results provide strong evidence that the splicing mutation IVS8+1G>A of GHRHR is a cause of pituitary dwarfism in the Chinese family.

Purification and Cultivation of Human Pituitary Growth Hormones Secreting Cells

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Todd, P.; Grindeland, R.; Lanham, W.; Morrison, D.

1985-01-01

The rat and human pituitary gland contains a mixture of hormone producing cell types. The separation of cells which make growth hormone (GH) is attempted for the purpose of understanding how the hormone molecule is made within the pituitary cell; what form(s) it takes within the cell; and what form(s) GH assumes as it leaves the cell. Since GH has a number of biological targets (e.g., muscle, liver, bone), the assessment of the activities of the intracellular/extracellular GH by new and sensitive bioassays. GH cells contained in the mixture was separated by free flow electrophoresis. These experiments show that GH cells have different electrophoretic mobilities. This is relevant to NASA since a lack of GH could be a prime causative factor in muscle atrophy. Further, GH has recently been implicated in the etiology of motion sickness in space. Continous flow electrophoresis experiment on STS-8 showed that GH cells could be partially separated in microgravity. However, definitive cell culture studies could not be done due to insufficient cell recoveries.

Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization.

PubMed Central

Lloyd, R. V.; Cano, M.; Chandler, W. F.; Barkan, A. L.; Horvath, E.; Kovacs, K.

1989-01-01

Acidophilic pituitary adenomas commonly produce growth hormone (GH) or prolactin (PRL), according to studies employing immunohistochemical and ultrastructural methods. To examine this question, in situ hybridization with oligonucleotide probes was done on routinely processed tissues received in the pathology laboratory to analyze for the presence of GH and PRL messenger RNA (mRNA) in 4 normal pituitaries, 10 prolactinomas, and 16 GH-secreting adenomas. Most acidophilic cells in normal pituitaries expressed either GH or PRL hormone and the respective mRNAs, but GH mRNA and PRL hormone were also detected in some of the same cells. Patients with a clinical diagnosis of prolactinoma had cells with only PRL mRNA in their tumors, while most (14 of 16) patients with a clinical diagnosis of acromegaly or gigantism had both GH and PRL mRNAs in their tumors. The GH adenomas varied in these studies. In situ hybridization was helpful in characterizing the adenoma from a patient with acromegaly who had immunoreactive PRL, but no immunoreactive GH in the resected tumor; in situ hybridization analysis revealed mRNAs for both GH and PRL in the same tumor cells. Our findings indicate that pituitary adenomas from patients with acromegaly commonly express PRL mRNA. It is concluded that in situ hybridization provides new information about the clinical biology and the histopathologic classification of pituitary adenomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:2466405

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

Curcumin (Diferuloylmethane) Inhibits Cell Proliferation, Induces Apoptosis, and Decreases Hormone Levels and Secretion in Pituitary Tumor Cells

PubMed Central

Miller, Matthew; Chen, Shenglin; Woodliff, Jeffrey; Kansra, Sanjay

2008-01-01

Prolactinomas are the most prevalent functional pituitary adenomas. Dopamine D2 receptor (D2R) agonists, such as bromocriptine are the first line of therapy; however, drug intolerance/resistance to D2R agonists exists. Apart from D2R agonists, there is no established medical therapy for prolactinomas; therefore, identifying novel therapeutics is warranted. Curcumin, a commonly used food additive in South Asian cooking, inhibits proliferation of several tumor cell lines; however, its effect on pituitary tumor cell proliferation has not been determined. Our objectives were to: 1) determine whether curcumin inhibits proliferation of pituitary tumor cell lines; 2) identify the signaling intermediaries that mediate the effect of curcumin; 3) examine whether curcumin inhibited pituitary hormone production and release; and 4) examine whether curcumin could enhance the growth-inhibitory effect of bromocriptine. Using rat lactotroph cell lines, GH3 and MMQ cells, we report that curcumin had a robust dose and time-dependent inhibitory effect on GH3 and MMQ cell proliferation. Inhibitory effects of curcumin persisted, even on removal of curcumin, and curcumin also blocked colony formation ability of pituitary tumor cells. The growth-inhibitory effect of curcumin was accompanied by decreased expression of cyclin D3 and ser 780 phosphorylation of retinoblastoma protein. In addition, curcumin also induced apoptosis in both GH3 and MMQ cells. Furthermore, curcumin suppresses intracellular levels and release of both prolactin and GH. Finally, we show that low concentrations of curcumin enhanced the growth-inhibitory effect of bromocriptine on MMQ cell proliferation. Taken together we demonstrate that curcumin inhibits pituitary tumor cell proliferation, induces apoptosis, and decreases hormone production and release, and thus, we propose developing curcumin as a novel therapeutic tool in the management of prolactinomas. PMID:18450960

Curcumin (diferuloylmethane) inhibits cell proliferation, induces apoptosis, and decreases hormone levels and secretion in pituitary tumor cells.

PubMed

Miller, Matthew; Chen, Shenglin; Woodliff, Jeffrey; Kansra, Sanjay

2008-08-01

Prolactinomas are the most prevalent functional pituitary adenomas. Dopamine D2 receptor (D2R) agonists, such as bromocriptine are the first line of therapy; however, drug intolerance/resistance to D2R agonists exists. Apart from D2R agonists, there is no established medical therapy for prolactinomas; therefore, identifying novel therapeutics is warranted. Curcumin, a commonly used food additive in South Asian cooking, inhibits proliferation of several tumor cell lines; however, its effect on pituitary tumor cell proliferation has not been determined. Our objectives were to: 1) determine whether curcumin inhibits proliferation of pituitary tumor cell lines; 2) identify the signaling intermediaries that mediate the effect of curcumin; 3) examine whether curcumin inhibited pituitary hormone production and release; and 4) examine whether curcumin could enhance the growth-inhibitory effect of bromocriptine. Using rat lactotroph cell lines, GH3 and MMQ cells, we report that curcumin had a robust dose and time-dependent inhibitory effect on GH3 and MMQ cell proliferation. Inhibitory effects of curcumin persisted, even on removal of curcumin, and curcumin also blocked colony formation ability of pituitary tumor cells. The growth-inhibitory effect of curcumin was accompanied by decreased expression of cyclin D3 and ser 780 phosphorylation of retinoblastoma protein. In addition, curcumin also induced apoptosis in both GH3 and MMQ cells. Furthermore, curcumin suppresses intracellular levels and release of both prolactin and GH. Finally, we show that low concentrations of curcumin enhanced the growth-inhibitory effect of bromocriptine on MMQ cell proliferation. Taken together we demonstrate that curcumin inhibits pituitary tumor cell proliferation, induces apoptosis, and decreases hormone production and release, and thus, we propose developing curcumin as a novel therapeutic tool in the management of prolactinomas.

MRI features of growth hormone deficiency in children with short stature caused by pituitary lesions.

PubMed

Xu, Chao; Zhang, Xinxian; Dong, Lina; Zhu, Bin; Xin, Tao

2017-06-01

We verified the advantages of using magnetic resonance imaging (MRI) for improving the diagnostic quality of growth hormone deficiency (GHD) in children with short stature caused by pituitary lesions. Clinical data obtained from 577 GHD patients with short stature caused by pituitary lesions were retrospectively analyzed. There were 354 cases (61.3%) with anterior pituitary dysplasia; 45 cases (7.8%) of pituitary stalk interruption syndrome (PSIS); 15 cases (2.6%) of pituitary hyperplasia due to primary hypothyroidism; 38 cases (6.6%) of Rathke cleft cyst; 68 cases (11.8%) of empty sella syndrome; 16 cases (2.8%) of pituitary invasion from Langerhans cell histiocytosis; 2 cases (0.3%) of sellar regional arachnoid cyst and 39 cases (6.8%) of craniopharyngioma. MRI results showed that the height of anterior pituitary in patients was less than normal. Location, size and signals of posterior pituitary and pituitary stalk were normal in anterior pituitary dysplasia. In all cases pituitary hyperplasia was caused by hypothyroidism. MRI results showed that anterior pituitary was enlarged, and we detected upward apophysis and obvious homogeneous enhancement. There were no pituitary stalk interruption and abnormal signal. We also observed that after hormone replacement therapy the size of pituitary gland was reduced. Anterior pituitary atrophy was observed in Rathke cleft cyst, empty sella syndrome, sellar regional arachnoid cyst and craniopharyngioma. The microstructure of hypophysis and sellar region was studied with MRI. We detected pituitary lesions, and the characteristics of various pituitary diseases of GHD in children with short stature. It was concluded that in children with GHD caused by pituitary lesions, MRI was an excellent method for early diagnosis. This method offers clinical practicability and we believe it can be used for differential diagnosis and to monitor the therapeutic effects.

Binding of Thyrotropin-Releasing Hormone to Plasma Membranes of Bovine Anterior Pituitary Gland

PubMed Central

Labrie, Fernand; Barden, Nicholas; Poirier, Guy; De Lean, Andre

1972-01-01

An assay for the binding of [3H]thyrotropin-releasing hormone ([3H]TRH) is described. Plasma membranes isolated from bovine anterior pituitary gland bind about 600 femtomoles of this hormone per mg of protein, as compared to 15 femtomoles per mg of protein in the total adenohypophyseal homogenate (40-fold purification). The equilibrium constant of membrane receptor-[3H]TRH binding at 0°C is 4.3 × 107 L·M-1, or a half-maximal binding of this hormone at 23 nM. The binding is time-dependent; addition of unlabeled hormone induces dissociation of the receptor-[3H]TRH complex with a half-life of 14 min. The binding of TRH is not altered by 10 μM melanocyte-stimulating hormone-release inhibiting hormone, lysine-vasopressin, adrenocorticotropin, growth hormone, prolactin, luteinizing hormone, insulin, glucagon, L-thyroxine, or L-triiodothyronine. K+ and Mg++ increase formation of the receptor-TRH complex at optimal concentrations of 5-25 mM and 0.5-2.5 mM, respectively, with inhibition at higher concentrations. Ca++ inhibits binding of TRH at all concentrations tested. PMID:4621548

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.

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.

GH and Pituitary Hormone Alterations After Traumatic Brain Injury.

PubMed

Karaca, Züleyha; Tanrıverdi, Fatih; Ünlühızarcı, Kürşad; Kelestimur, Fahrettin

2016-01-01

Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI

Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT).

PubMed

Nose, Osamu; Tatsumi, Keita; Nakano, Yukiko; Amino, Nobuyuki

2006-04-01

Combined pituitary hormone deficiency (CPHD) is an anterior pituitary disorder, commonly resulting in growth retardation. PROP1 gene mutations appear to be frequently responsible for CPHD, particularly in Middle and Eastern Europe and the Americas, but few cases have been reported in Japan. Two sisters (aged 8.4 and 4.3 years at presentation) exhibited proportional short stature from about 2 years of age. Genetic analysis determined the nature and location of mutations. Pituitary size by magnetic resonance imaging (MRI) indicated only slight hypoplasia, while hormone analysis revealed deficiencies in secretion of growth hormone (GH), thyroid stimulating hormone, prolactin and gonadotropins; adrenocortinotropin secretion appeared adequate. Genetic analysis revealed a novel familial inherited PROP1 mutation. A unique insertion mutation was found in codon 156 (467insT) located in the transcription-activating region of the PROP1 gene. The resulting PROP1 protein (191 amino acids) would lack the transcription activation domain and consequently be non-functional. Gene analysis suggested that the siblings had inherited a unique autosomal recessive PROP1 gene mutation resulting in severe GH deficiency and subsequent growth retardation.

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.

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.

The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple pituitary hormone deficiency.

PubMed

Lazea, Cecilia; Grigorescu-Sido, Paula; Popp, Radu; Legendre, Marie; Amselem, Serge; Al-Khzouz, Camelia; Bucerzan, Simona; Creţ, Victoria; Crişan, Mirela; Brad, Cristian

2015-09-01

To establish the frequency of the c.301_302 delAG mutation of the PROP1 gene in Romanian patients with multiple pituitary hormone deficiency (MPHD). Somatic assessment, hormonal test, bone age, magnetic resonance imaging of the pituitary gland, and molecular diagnosis were performed in 26 patients with MPHD (7 patients with familial form of MPHD and 19 patients with sporadic form of MPHD). The c.301_302delAG mutation was detected in the homozygous state in 10 patients belonging to 5 unrelated families (7 patients with familial history of MPHD and 3 patients with sporadic form of MPHD). Those 10 patients presented variable pituitary hormone deficiency and pituitary morphology. The c.301_302delAG homozygous genotype had a high frequency of 38% (10/26), reaching 100% (7/7) in group with familial cases of MPHD and 16% (3/19) in group with sporadic forms of MPHD.

Effects of neonatal hypo- and hyperthyroidism on pituitary growth hormone content in the rat.

PubMed

Coulombe, P; Ruel, J; Dussault, J H

1980-12-01

Thyroid hormones play an important role in growth and development. Therefore, we investigated the effects of neonatal hypo- and hyperthyroidism on pituitary GH content in the rat. In control rats, pituitary GH content increased from 4.16 +/- 0.34 at 2 days to 43.7 +/- 4.2 microgram/gland (mean +/- SE) at 15 days of age, with a t 1/2 of increment of 3.48 +/- 0.40 days. Between 18-60 days of age, pituitary GH content increased from 56.9 +/- 4.0 to 300 +/- 28 microgram/gland, with a t 1/2 of 18.2 +/- 1.5 days. The administration of T3 had no significant effect on the pituitary GH content of these animals. In neonatal hypothyroid rats, pituitary GH content was significantly lower than that of controls at 2 days of age (P < 0.01) and decreased from 8 days on, with a t 1/2 of 3.71 +/- 0.25 days. However, 24 h after the administration of T3 (100 microgram/100 g BW), pituitary GH content was significantly increased in these animals. Similarly, the administration of T3 (0.4 microgram/100 g BW) to 14-day-old hypothyroid rats restored the pituitary GH content to 70-80% of normal after 5 days of therapy. Conversely, hyperthyroidism induced in 14-day-old normal or hypothyroid rats resulted in a significant decrease in their pituitary GH contents after 5 days of treatment. Therefore, the present results indicate that during the neonatal period, thyroid hormones play a primary role in the control of GH accumulation in the pituitary. Furthermore, the lack of increase in pituitary GH content after the administration of T3 during development might suggest that the rate of formation of GH is already maximum during this period of life in the rat, or, alternatively, that the pituitary nuclear T3 receptors are near full saturation during development. Finally, a generally similar effect of T3 on pituitary GH response was observed in the neonatal rat as well as in the adult animal.

The simultaneous isolation of human pituitary hormones. I. Human growth hormone.

PubMed

Simionescu, L; Dimitriu, V; Zamfir-Grigorescu, D; Aman, E; Terbancea, M

1982-01-01

The main purposes of the present work are: a. the preparation of "clinical grade" human growth hormone (hGH), its physico-chemical analysis and the improvement of its solubility for clinical purposes; b. the development of a method for the isolation of high-purity hGH using frozen pituitaries. Nine batches of 20 g acetone powder were processed resulting in 4940 mg of "clinical grade" hGH. Samples of these batches randomly selected were analysed by Sephadex G-100 chromatography and by disc and preparative polyacrylamide gel electrophoresis (PAGE). Lyophilised hGH, soluble in NaCl 0.15 M was prepared and called "Hormcresc" and directions for use were elaborated. One hundred frozen glands were processed and the "crude" hGH was purified by gel filtration on Sephadex G-100 and tested using double diffusion in agar gel, radioimmunoassay (RIA), rechromatography on Sephadex G-100 and disc PAGE. The experiments led to an extraction yield of 550 +/- 165 (means +/- SD) mg "clinical grade" hGH per 20 g of acetone powder. The elution pattern of Sephadex G-100 chromatography and of preparative PAGE as well as the pattern of disc PAGE showed that the "clinical grade" hGH is similar to the already known GH hormones: Raben Somatrotropin, Crescormon (Sweden) and hGH (FRG) but different from Sotropin-H (DDR). The "clinical grade" hGH in lyophilised form is similar to the GH preparations accepted by the European pharmacopoea; it is soluble in NaCl 0.15 M and painless on injection by comparison to hGH in powder form. A method was worked out for the extraction, isolation and purification of "highly pure" hGH using frozen pituitaries, which made it possible to isolate from the same batch of glands not only hGH but also luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin and thyroid stimulating hormone (TSH). During the purification of "crude" hGH on Sephadex G-100 a rather abundant fraction of MW of about 5000-15000 daltons was observed; this fraction, codified

Dynamic changes in the hypothalamic-pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study.

PubMed

Wang, Limin; Wang, Qian; Li, Guimei; Liu, Wendong

2015-09-01

The objective of this study was to investigate changes in the hypothalamic-pituitary-adrenal (HPA) axis after recombinant human growth hormone (rhGH) therapy. Subjects included children with growth hormone deficiency (GHD). We conducted a multicenter, retrospective study that assessed 72 GHD patients treated with rhGH during 6 months. Patients were classified into two groups: isolated GHD (IGHD; n=20) and multiple pituitary hormone deficiencies (MPHD; n=52). The HPA axis and other hormones were evaluated at baseline and every 3 months. In the MPHD group, 32 patients had adrenocorticotrophic hormone deficiency and received hydrocortisone before rhGH therapy. In the other 20/52 MPHD patients, the cortisol (COR) level was significantly reduced after rhGH therapy. Moreover, 10 patients showed low COR levels. In the IGHD group, COR levels also decreased, but remained within the normal range. During rhGH therapy, COR levels were reduced, particularly in patients with MPHD. HPA axis should be monitored during rhGH therapy.

Impaired pituitary hormonal response to exhaustive exercise in overtrained endurance athletes.

PubMed

Urhausen, A; Gabriel, H H; Kindermann, W

1998-03-01

The aim of the present prospective longitudinal study was to investigate the hormonal response in overtrained athletes at rest and during exercise consisting of a short-term exhaustive endurance test on a cycle ergometer at an intensity 10% above the individual anaerobic threshold. Over a period of 19+/-1 months, 17 male endurance athletes (cyclists and triathletes; age 23.4+/-1.6 yr; VO2max. 61.2+/-1.8 mL x min(-1) x kg(-1); means+/-SEM) were examined five times on two separate days under standardized conditions. Short-term overtraining states (OT, N=15) were primarily induced by an increase of frequency of high-intensive bouts of exercise or competitions without increase of the total amount of training. OT was compared with normal training states intraindividually (NS, N=62). During OT, the time to exhaustion of the exercise test was significantly decreased by 27% on average. At rest and during exercise, the concentrations in plasma and the nocturnal excretion in urine of free epinephrine and norepinephrine were not significantly changed during OT. At physical rest, the concentrations of (free) testosterone, cortisol, luteinizing hormone, follicle-stimulating hormone, adrenocorticotropic hormone, growth hormone, and insulin during OT were comparable with those during NS. A significantly (P < 0.025) lower maximal exercise-induced increase of the adrenocorticotropic hormone and growth hormone, as well as a trend for a decrease of cortisol (P=0.060) and insulin (P=0.036), was measured. The response of free catecholamines as well as the ergometric performance of an all-out 30-s test was unchanged. Serum urea, uric acid, ferritin, and activity of creatine kinase showed no differences between conditions. In conclusion, the results confirm the hypothesis of a hypothalamo-pituitary dysregulation during OT expressed by an impaired response of pituitary hormones to exhaustive short-endurance exercise.

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.

Geographic-Related Differences of Pituitary Adenomas Hormone Profile: Analysis of Two Groups Coming from Southeastern and Eastern Europe.

PubMed

Cimpean, Anca Maria; Melnic, Eugen; Bălinişteanu, Bogdan; Corlan, Ana; Coculescu, Mihail; Rusu, Sergiu; Raica, Marius

2015-01-01

We compared the immunoprofile of pituitary adenomas from Romania and Moldova. One hundred and eighty cases coming from Romania (94 cases, group 1) and Moldova (86 cases, group 2) were assessed by immunohistochemistry regarding all six basic hormones expressed in pituitary adenomas. Specific differences and similarities were found and stated for both groups. In group 1, 70% of cases were pituitary adenomas positive for one hormone, 13% were plurihormonal, while 17% were negative. In group 2, 50,3% of the cases expressed only one hormone and 12,5% were negative for all hormones. The highest difference was observed for plurihormonal adenomas, found in about 37,2% of cases for group 2 (2.86 times higher for group 2 compared with group 1). A higher incidence of GH-secreting adenomas characterized group "1," while group "2" had the highest percent of LH-secreting adenomas, 55% of cases being positive. Triple association was noticed in 4.25% of cases of group 1 and in 8,13% out of total cases, from group 2. Four-hormone association was found only in group 2, noticed in 15,56% of the cases. The present paper highlights strong evidences of a particular and different immunoprofile of pituitary adenomas coming from Romania and Moldova.

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

Gonadotropin-releasing hormone regulates expression of the DNA damage repair gene, Fanconi anemia A, in pituitary gonadotroph cells.

PubMed

Larder, Rachel; Chang, Lynda; Clinton, Michael; Brown, Pamela

2004-09-01

Gonadal function is critically dependant on regulated secretion of the gonadotropin hormones from anterior pituitary gonadotroph cells. Gonadotropin biosynthesis and release is triggered by the binding of hypothalamic GnRH to GnRH receptor expressed on the gonadotroph cell surface. The repertoire of regulatory molecules involved in this process are still being defined. We used the mouse L beta T2 gonadotroph cell line, which expresses both gonadotropin hormones, as a model to investigate GnRH regulation of gene expression and differential display reverse transcription-polymerase chain reaction (RT-PCR) to identify and isolate hormonally induced changes. This approach identified Fanconi anemia a (Fanca), a gene implicated in DNA damage repair, as a differentially expressed transcript. Mutations in Fanca account for the majority of cases of Fanconi anemia (FA), a recessively inherited disease identified by congenital defects, bone marrow failure, infertility, and cancer susceptibility. We confirmed expression and hormonal regulation of Fanca mRNA by quantitative RT-PCR, which showed that GnRH induced a rapid, transient increase in Fanca mRNA. Fanca protein was also acutely upregulated after GnRH treatment of L beta T2 cells. In addition, Fanca gene expression was confined to mature pituitary gonadotrophs and adult mouse pituitary and was not expressed in the immature alpha T3-1 gonadotroph cell line. Thus, this study extends the expression profile of Fanca into a highly specialized endocrine cell and demonstrates hormonal regulation of expression of the Fanca locus. We suggest that this regulatory mechanism may have a crucial role in the GnRH-response mechanism of mature gonadotrophs and perhaps the etiology of FA.

Intraoperative Magnetic Resonance Imaging During Endoscopic Transsphenoidal Surgery of Growth Hormone-Secreting Pituitary Adenomas.

PubMed

Netuka, David; Májovský, Martin; Masopust, Václav; Belšán, Tomáš; Marek, Josef; Kršek, Michal; Hána, Václav; Ježková, Jana; Hána, Václav; Beneš, Vladimír

2016-07-01

The effect of intraoperative magnetic resonance imaging (iMRI) on the extent of sellar region tumors treated endonasally has been described in previous research. However, the effects of iMRI on endocrinologic outcome of growth hormone-secreting adenomas have been studied in only a few small cohort studies. Inclusion criteria were primary transsphenoidal surgery for growth hormone-secreting adenoma from January 2009 to December 2014, a minimum follow-up of 1 year, complete endocrinologic data, at least 1 iMRI, and at least 2 postoperative magnetic resonance images. The cohort consisted of 105 patients (54 females, 51 males) with a mean age of 48.3 years (range, 7-77 years). There were 16 microadenomas and 89 macroadenomas. Endocrinologic remission in the whole cohort was achieved in 64 of the patients (60.9%). Resection after iMRI was attempted in 22 of the cases (20.9%). Resection after iMRI led to hormonal remission in 9 cases (8.6%). Endocrinologic postoperative deficit was observed in 10 cases (12.5%). Postoperative cerebrospinal fluid leakage indicated the necessity to reoperate in 3 cases (3.8%). No neurologic deterioration was observed. iMRI influences not only the morphologic extent of pituitary adenomas resection but also the endocrinologic results. We encourage the routine application of iMRI in pituitary adenoma surgery, including hormone-secreting pituitary tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

REGIONAL PATTERNING OF HORMONES IN THE FEMALE RAT ANTERIOR PITUITARY: DISPROPORTIONATE CHANGES OVER THE ESTROUS CYCLE

EPA Science Inventory

The present study addressed the possibility that regional differences exist in the typical patterning of anterlor pituitary hormones seen over the estrous cycle. he results show that LH in the rostral area of the pituitary, significantly higher than in other regions on diestrus, ...

In vivo and in vitro effects of chromium VI on anterior pituitary hormone release and cell viability.

PubMed

Quinteros, Fernanda A; Poliandri, Ariel H B; Machiavelli, Leticia I; Cabilla, Jimena P; Duvilanski, Beatriz H

2007-01-01

Hexavalent chromium (Cr VI) is a highly toxic metal and an environmental pollutant. Different studies indicate that Cr VI exposure adversely affects reproductive functions. This metal has been shown to affect several tissues and organs but Cr VI effects on pituitary gland have not been reported. Anterior pituitary hormones are central for the body homeostasis and have a fundamental role in reproductive physiology. The aim of this study was to evaluate the effect of Cr VI at the pituitary level both in vivo and in vitro. We showed that Cr VI accumulates in the pituitary and hypothalamus, and decreases serum prolactin levels in vivo but observed no effects on LH levels. In anterior pituitary cells in culture, the effect of Cr VI on hormone secretion followed the same differential pattern. Besides, lactotrophs were more sensitive to the toxicity of the metal. As a result of oxidative stress generation, Cr VI induced apoptosis evidenced by nuclear fragmentation and caspase 3 activation. Our results indicate that the anterior pituitary gland can be a target of Cr VI toxicity in vivo and in vitro, thus producing a negative impact on the hypothalamic-pituitary-gonadal axis and affecting the normal endocrine function.

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.

Hyperthyroidism and acromegaly due to a thyrotropin- and growth hormone-secreting pituitary tumor. Lack of hormonal response to bromocriptine.

PubMed

Carlson, H E; Linfoot, J A; Braunstein, G D; Kovacs, K; Young, R T

1983-05-01

A 47-year-old woman with acromegaly and hyperthyroidism was found to have an inappropriately normal serum thyrotropin level (1.5 to 2.5 microU/ml) that responded poorly to thyrotropin-releasing hormone but showed partial responsiveness to changes in circulating thyroid hormones. Serum alpha-subunit levels were high-normal and showed a normal response to thyrotropin-releasing hormone. Growth hormone and thyrotropin hypersecretion persisted despite radiotherapy and bromocriptine treatment. Selective trans-sphenoidal removal of a pituitary adenoma led to normalization of both growth hormone and thyrotropin levels. Both thyrotropes and somatotropes were demonstrated in the adenoma by the immunoperoxidase technique and electron microscopy.

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

Optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone deficiency, and idiopathic short stature.

PubMed

Birkebaek, Niels Holtum; Patel, Leena; Wright, Neville Bryce; Grigg, John Russell; Sinha, Smeeta; Hall, Catherine Margaret; Price, David Anthony; Lloyd, Ian Christopher; Clayton, Peter Ellis

2004-10-01

To objectively define criteria for intracranial optic nerve (ON) size in ON hypoplasia (ONH) on magnetic resonance imaging (MRI) scans. Intracranial ON sizes from MRI were compared between 46 children with ONH diagnosed by ophthalmoscopy (group 1, isolated ONH, 8 children; and group 2, ONH associated with abnormalities of the hypothalamic-pituitary axis and septum pellucidum, 38 children) and children with multiple pituitary hormone deficiency (group 3, multiple pituitary hormone deficiency, 14 children), isolated growth hormone deficiency (group 4, isolated growth hormone deficiency, 15 children), and idiopathic short stature (group 5, idiopathic short stature, 10 children). Intracranial ON size was determined by the cross-sectional area, calculated as [pi x (1/2) height x (1/2) width]. Groups 1 and 2 had lower intracranial ON size than did groups 3, 4, and 5 (P < .001). No patients in groups 3 through 5 who had MRI after 12 months of age (when 95% adult size of ONs is attained) had ONs <2.9 mm 2 . Visual acuity correlated significantly with ON size (P < .01). Magnetic resonance imaging of the ONs with cross-sectional area <2.9 mm 2 in a short child more than 12 months of age, with or without hypothalamic-pituitary axis abnormalities, confirms the clinical diagnosis of ONH.

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.

Gonadotropin-Releasing Hormone Regulates Expression of the DNA Damage Repair Gene, Fanconi anemia A, in Pituitary Gonadotroph Cells1

PubMed Central

Larder, Rachel; Chang, Lynda; Clinton, Michael; Brown, Pamela

2007-01-01

Gonadal function is critically dependant on regulated secretion of the gonadotropin hormones from anterior pituitary gonadotroph cells. Gonadotropin biosynthesis and release is triggered by the binding of hypothalamic GnRH to GnRH receptor expressed on the gonadotroph cell surface. The repertoire of regulatory molecules involved in this process are still being defined. We used the mouse LβT2 gonadotroph cell line, which expresses both gonadotropin hormones, as a model to investigate GnRH regulation of gene expression and differential display reverse transcription-polymerase chain reaction (RT-PCR) to identify and isolate hormonally induced changes. This approach identified Fanconi anemia a (Fanca), a gene implicated in DNA damage repair, as a differentially expressed transcript. Mutations in Fanca account for the majority of cases of Fanconi anemia (FA), a recessively inherited disease identified by congenital defects, bone marrow failure, infertility, and cancer susceptibility. We confirmed expression and hormonal regulation of Fanca mRNA by quantitative RT-PCR, which showed that GnRH induced a rapid, transient increase in Fanca mRNA. Fanca protein was also acutely upregulated after GnRH treatment of LβT2 cells. In addition, Fanca gene expression was confined to mature pituitary gonadotrophs and adult mouse pituitary and was not expressed in the immature αT3-1 gonadotroph cell line. Thus, this study extends the expression profile of Fanca into a highly specialized endocrine cell and demonstrates hormonal regulation of expression of the Fanca locus. We suggest that this regulatory mechanism may have a crucial role in the GnRH-response mechanism of mature gonadotrophs and perhaps the etiology of FA. PMID:15128600

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

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.

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

Growth hormone deficiency and pituitary malformation in a recurrent Cat-Eye syndrome: a family report.

PubMed

Jedraszak, Guillaume; Braun, Karine; Receveur, Aline; Decamp, Matthieu; Andrieux, Joris; Rabbind Singh, Amrathlal; Copin, Henri; Bremond-Gignac, Dominique; Mathieu, Michèle; Rochette, Jacques; Morin, Gilles

2015-10-01

Growth hormone deficiency affects roughly between one in 3000 and one in 4000 children with most instances of growth hormone deficiency being idiopathic. Growth hormone deficiency can also be associated with genetic diseases or chromosome abnormalities. Association of growth hormone deficiency together with hypothalamic-pituitary axis malformation and Cat-Eye syndrome is a very rare condition. We report a family with two brothers presenting with growth delay due to a growth hormone deficiency associated with a polymalformation syndrome. They both displayed pre-auricular pits and tags, imperforate anus and Duane retraction syndrome. Both parents and a third unaffected son displayed normal growth pattern. Cerebral MRI showed a hypothalamic-pituitary axis malformation in the two affected brothers. Cytogenetic studies revealed a type I small supernumerary marker chromosome derived from chromosome 22 resulting in a tetrasomy 22pter-22q11.21 characteristic of the Cat-Eye syndrome. The small supernumerary marker chromosome was present in the two affected sons and the mother in a mosaic state. Patients with short stature due to growth hormone deficiency should be evaluated for chromosomal abnormality. Family study should not be underestimated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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.

Neurotrophins and their receptors in the rat pituitary gland: regulation of BDNF and trkB mRNA levels by adrenal hormones.

PubMed

Kononen, J; Soinila, S; Persson, H; Honkaniemi, J; Hökfelt, T; Pelto-Huikko, M

1994-12-01

We studied the expression of messenger ribonucleic acids (mRNAs) for neurotrophins and neurotrophin receptors in the rat pituitary gland and examined the influence of adrenal hormones on their mRNA levels, using in situ hybridization and Northern blot analysis. The only neurotrophin present at detectable levels in the pituitary was brain-derived neurotrophic factor (BDNF), which was observed in the anterior and intermediate lobes. Several transcripts of the putative receptor for BDNF, trkB, were present in the anterior and posterior lobes of the pituitary. A low amount of trkC mRNA was found in both the anterior and the intermediate lobe. Dexamethasone treatment decreased both BDNF and trkB mRNA levels in the anterior lobe of the pituitary. Adrenalectomy had no effect on trkB expression, but it decreased BDNF mRNA levels in comparison to the control animals. This effect could not be reversed by dexamethasone substitution, suggesting that BDNF, mRNA levels may be regulated not only by glucocorticoids but also by other adrenal hormones. These results demonstrate that BDNF, trkB and trkC are expressed in the pituitary gland and that glucocorticoids and possibly other adrenal hormones may modulate pituitary functions by regulating the expression of neurotrophic factors and their receptors. Whether BDNF acts as a secreted hormone, a trophic factor, or has autocrine/paracrine functions within the pituitary through its receptor, trkB, remains to be studied.

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.

Microgravity associated changes in pituitary growth hormone (GH) cells prepared from rats flown on Space Lab 3

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Farrington, M.; Hayes, C.; Grindeland, R.; Fast, T.

1985-01-01

The effect of microgravity on the release of pituitary growth hormone (GH) in rats is studied. The pituitary glands from six adult rats exposed to microgravity are analyzed for in vitro and in vivo changes in pituitary growth hormone cells. The GH cell functions in the somatotrophs of flight rats are compared to a control group. The two assay procedures employed in the experiment are described. It is observed that intracellular levels of GH are two to three times greater in the flight rats than in the control group; however, the amount of GH released from the somatotrophs is 1.11 + or - 0.4 micrograms for the flight rats and 1.85 + or - 1.3 micrograms for the control rats.

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.

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.

Growth hormone-secreting pituitary adenomas in childhood and adolescence: features and results of transnasal surgery.

PubMed

Abe, T; Tara, L A; Lüdecke, D K

1999-07-01

Pituitary tumors causing gigantism are rare in childhood and adolescence. In a review of 2367 patients with pituitary adenomas who were treated between 1970 and 1997, we found 15 cases (0.63%, 9 male and 6 female patients) of growth hormone-secreting pituitary adenomas in patients who were less than 20 years of age at the time of surgery, and we compared their characteristics with those of adenomas in an adult group. Patients were grouped according to their ages at the first operation, with five patients (33.3%) in the prepubescent group (0-11 yr), eight (53.3%) in the pubescent group (12-17 yr), and two (13.3%) in the postpubescent group (18-19 yr). All 15 patients exhibited the typical symptoms of growth hormone oversecretion. The incidence of hyperprolactinemia among patients with prepubescent onset was 66.7%. Radiological examinations demonstrated microadenomas in 4 patients (26.7%) and macroadenomas in 11 patients (73.3%). The mean follow-up period was 73.5 months. Direct transnasal explorations were performed for all patients. Tumor invasion into the cavernous sinus was observed in six patients (40%). Radical tumor resection was performed for four patients (80%) in the prepubescent group, for five patients (62.5%) in the pubescent group, and for neither patient in the postpubescent group. Surgical morbidity was caused by permanent diabetes insipidus in three patients (20%). Rapid growth was postoperatively improved in 80% of the prepubescent age group. The recurrence rate was 13.3% (2 of 15 patients). Transnasal pituitary surgery was found to be as safe in pediatric patients with gigantism as in adults. Growth hormone-secreting pituitary adenomas in childhood and adolescence were more likely to be invasive or aggressive than were those in adulthood. The clinical biological characteristics for children were different from those for adults.

Cat eye syndrome and growth hormone deficiency with pituitary anomalies: a case report and review of the literature.

PubMed

Melo, Cláudia; Gama-de-Sousa, Susana; Almeida, Filipa; Rendeiro, Paula; Tavares, Purificação; Cardoso, Helena; Carvalho, Sónia

2013-10-15

Cat eye syndrome is a rare congenital disease characterized by the existence of a supernumerary chromosome derived from chromosome 22, with a variable phenotype comprising anal atresia, coloboma of the iris and preauricular tags or pits. We report a girl with cat eye syndrome, presenting short stature, with growth hormone deficiency due to posterior pituitary ectopia. Short stature is a common feature of this syndrome, and the association with a structural pituitary anomaly has been described, however growth hormone deficiency and the underlying mechanisms are rarely reported. A review on short stature and growth hormone deficiency in cat eye syndrome is conducted. © 2013 Elsevier B.V. All rights reserved.

Model of pediatric pituitary hormone deficiency separates the endocrine and neural functions of the LHX3 transcription factor in vivo.

PubMed

Colvin, Stephanie C; Malik, Raleigh E; Showalter, Aaron D; Sloop, Kyle W; Rhodes, Simon J

2011-01-04

The etiology of most pediatric hormone deficiency diseases is poorly understood. Children with combined pituitary hormone deficiency (CPHD) have insufficient levels of multiple anterior pituitary hormones causing short stature, metabolic disease, pubertal failure, and often have associated nervous system symptoms. Mutations in developmental regulatory genes required for the specification of the hormone-secreting cell types of the pituitary gland underlie severe forms of CPHD. To better understand these diseases, we have created a unique mouse model of CPHD with a targeted knockin mutation (Lhx3 W227ter), which is a model for the human LHX3 W224ter disease. The LHX3 gene encodes a LIM-homeodomain transcription factor, which has essential roles in pituitary and nervous system development in mammals. The introduced premature termination codon results in deletion of the carboxyl terminal region of the LHX3 protein, which is critical for pituitary gene activation. Mice that lack all LHX3 function do not survive beyond birth. By contrast, the homozygous Lhx3 W227ter mice survive, but display marked dwarfism, thyroid disease, and female infertility. Importantly, the Lhx3 W227ter mice have no apparent nervous system deficits. The Lhx3 W227ter mouse model provides a unique array of hormone deficits and facilitates experimental approaches that are not feasible with human patients. These experiments demonstrate that the carboxyl terminus of the LHX3 transcription factor is not required for viability. More broadly, this study reveals that the in vivo actions of a transcription factor in different tissues are molecularly separable.

Model of pediatric pituitary hormone deficiency separates the endocrine and neural functions of the LHX3 transcription factor in vivo

PubMed Central

Colvin, Stephanie C.; Malik, Raleigh E.; Showalter, Aaron D.; Sloop, Kyle W.; Rhodes, Simon J.

2011-01-01

The etiology of most pediatric hormone deficiency diseases is poorly understood. Children with combined pituitary hormone deficiency (CPHD) have insufficient levels of multiple anterior pituitary hormones causing short stature, metabolic disease, pubertal failure, and often have associated nervous system symptoms. Mutations in developmental regulatory genes required for the specification of the hormone-secreting cell types of the pituitary gland underlie severe forms of CPHD. To better understand these diseases, we have created a unique mouse model of CPHD with a targeted knockin mutation (Lhx3 W227ter), which is a model for the human LHX3 W224ter disease. The LHX3 gene encodes a LIM-homeodomain transcription factor, which has essential roles in pituitary and nervous system development in mammals. The introduced premature termination codon results in deletion of the carboxyl terminal region of the LHX3 protein, which is critical for pituitary gene activation. Mice that lack all LHX3 function do not survive beyond birth. By contrast, the homozygous Lhx3 W227ter mice survive, but display marked dwarfism, thyroid disease, and female infertility. Importantly, the Lhx3 W227ter mice have no apparent nervous system deficits. The Lhx3 W227ter mouse model provides a unique array of hormone deficits and facilitates experimental approaches that are not feasible with human patients. These experiments demonstrate that the carboxyl terminus of the LHX3 transcription factor is not required for viability. More broadly, this study reveals that the in vivo actions of a transcription factor in different tissues are molecularly separable. PMID:21149718

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 ...

High Prevalence of Chronic Pituitary and Target-Organ Hormone Abnormalities after Blast-Related Mild Traumatic Brain Injury

PubMed Central

Wilkinson, Charles W.; Pagulayan, Kathleen F.; Petrie, Eric C.; Mayer, Cynthia L.; Colasurdo, Elizabeth A.; Shofer, Jane B.; Hart, Kim L.; Hoff, David; Tarabochia, Matthew A.; Peskind, Elaine R.

2011-01-01

Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least 1 year after injury, in 25–50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury severity. Growth hormone deficiency (GHD) and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI), an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least 1 year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I) levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and rehabilitation. PMID

High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury.

PubMed

Wilkinson, Charles W; Pagulayan, Kathleen F; Petrie, Eric C; Mayer, Cynthia L; Colasurdo, Elizabeth A; Shofer, Jane B; Hart, Kim L; Hoff, David; Tarabochia, Matthew A; Peskind, Elaine R

2012-01-01

Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least 1 year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury severity. Growth hormone deficiency (GHD) and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI), an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least 1 year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I) levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and rehabilitation.

Connecting proximate mechanisms and evolutionary patterns: pituitary gland size and mammalian life history.

PubMed

Kamilar, J M; Tecot, S R

2015-11-01

At the proximate level, hormones are known to play a critical role in influencing the life history of mammals, including humans. The pituitary gland is directly responsible for producing several hormones, including those related to growth and reproduction. Although we have a basic understanding of how hormones affect life history characteristics, we still have little knowledge of this relationship in an evolutionary context. We used data from 129 mammal species representing 14 orders to investigate the relationship between pituitary gland size and life history variation. Because pituitary gland size should be related to hormone production and action, we predicted that species with relatively large pituitaries should be associated with fast life histories, especially increased foetal and post-natal growth rates. Phylogenetic analyses revealed that total pituitary size and the size of the anterior lobe of the pituitary significantly predicted a life history axis that was correlated with several traits including body mass, and foetal and post-natal growth rates. Additional models directly examining the association between relative pituitary size and growth rates produced concordant results. We also found that relative pituitary size variation across mammals was best explained by an Ornstein-Uhlenbeck model of evolution, suggesting an important role of stabilizing selection. Our results support the idea that the size of the pituitary is linked to life history variation through evolutionary time. This pattern is likely due to mediating hormone levels but additional work is needed. We suggest that future investigations incorporating endocrine gland size may be critical for understanding life history evolution. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Spontaneous remission of acromegaly or gigantism due to subclinical apoplexy of pituitary growth hormone adenoma.

PubMed

Wang, Xian-Ling; Dou, Jing-Tao; Lü, Zhao-Hui; Zhong, Wen-Wen; Ba, Jian-Ming; Jin, Du; Lu, Ju-Ming; Pan, Chang-Yu; Mu, Yi-Ming

2011-11-01

Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone (GH) adenoma is gigantism and/or acromegaly. We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma. Six patients with spontaneous remission of acromegaly or gigantism were enrolled. The clinical characteristics, endocrinological evaluation and imageological characteristics were retrospectively analyzed. In these cases, the initial clinical presences were diabetes mellitus or hypogonadism. No abrupt headache, vomiting, visual function impairment, or conscious disturbance had ever been complained of. The base levels of GH and insulin growth factor-1 (IGF-1) were normal or higher, but nadir GH levels were all still > 1 µg/L in 75 g oral glucose tolerance test. Magnetic resonance imaging detected enlarged sella, partial empty sella and compressed pituitary. The transsphenoidal surgery was performed in 2 cases, and the other patients were conservatively managed. All the patients were in clinical remission. When the clinical presences, endocrine evaluation, biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly, the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed. To these patients, conservative therapy may be appropriate.

Growth hormone is a cellular senescence target in pituitary and nonpituitary cells

PubMed Central

Chesnokova, Vera; Zhou, Cuiqi; Ben-Shlomo, Anat; Zonis, Svetlana; Tani, Yuji; Ren, Song-Guang; Melmed, Shlomo

2013-01-01

Premature proliferative arrest in benign or early-stage tumors induced by oncoproteins, chromosomal instability, or DNA damage is associated with p53/p21 activation, culminating in either senescence or apoptosis, depending on cell context. Growth hormone (GH) elicits direct peripheral metabolic actions as well as growth effects mediated by insulin-like growth factor 1 (IGF1). Locally produced peripheral tissue GH, in contrast to circulating pituitary-derived endocrine GH, has been proposed to be both proapoptotic and prooncogenic. Pituitary adenomas expressing and secreting GH are invariably benign and exhibit DNA damage and a senescent phenotype. We therefore tested effects of nutlin-induced p53-mediated senescence in rat and human pituitary cells. We show that DNA damage senescence induced by nutlin triggers the p53/p21 senescent pathway, with subsequent marked induction of intracellular pituitary GH in vitro. In contrast, GH is not induced in cells devoid of p53. Furthermore we show that p53 binds specific GH promoter motifs and enhances GH transcription and secretion in senescent pituitary adenoma cells and also in nonpituitary (human breast and colon) cells. In vivo, treatment with nutlin results in up-regulation of both p53 and GH in the pituitary gland, as well as increased GH expression in nonpituitary tissues (lung and liver). Intracrine GH acts in pituitary cells as an apoptosis switch for p53-mediated senescence, likely protecting the pituitary adenoma from progression to malignancy. Unlike in the pituitary, in nonpituitary cells GH exerts antiapoptotic properties. Thus, the results show that GH is a direct p53 transcriptional target and fulfills criteria as a p53 target gene. Induced GH is a readily measurable cell marker for p53-mediated cellular senescence. PMID:23940366

Longitudinal changes in pituitary-adrenal hormones in South African women with burnout.

PubMed

Moch, Shirra L; Panz, Vanessa R; Joffe, Barry I; Havlik, Ivan; Moch, Jonathan D

2003-08-01

The authors' goal was to document baseline pituitary-adrenal hormonal and related metabolic variables in 16 female patients with burnout. Then, following stress management intervention, to compare the changes with an equal number of untreated control subjects. At monthly intervals for 4 mo, 24-h urine samples were obtained for determination of free cortisol excretion. In addition, fasting blood samples were analyzed for levels of cortisol, dehydroepiandrosterone sulfate (DHEAS), ACTH, aldosterone, and catecholamines. Other biochemical measurements included growth hormone, prolactin, insulin, glucose, and lipid components. The Maslach Burnout Inventory, General Health Questionnaire- 28, and Zung depression rating scale were completed on each consecutive visit. The most striking finding was the reduction of urine free-cortisol excretion in the patients compared with controls. Initial urinary free cortisol was significantly lower in the patients (mean +/- SEM = 47.2 +/- 11.0 vs 79.0 +/- 6.8 nmol/L, p = 0.02) and remained significantly reduced at 4 mo (mean +/- SEM = 44.0 +/- 6.1 vs 91.1 +/- 8.8 nmol/L, p = 0.0001). There were no significant changes in the other hormonal and biochemical data. We conclude that there is functional hypocortisolism in burnout, which is not immediately restored on stress management intervention despite clinical and psychological improvement.

The Relationship of Appetitive, Reproductive and Posterior Pituitary Hormones to Alcoholism and Craving in Humans

PubMed Central

Kenna, George A.; Swift, Robert M.; Hillemacher, Thomas; Leggio, Lorenzo

2012-01-01

A significant challenge for understanding alcoholism lies in discovering why some, but not other individuals, become dependent on alcohol. Genetic, environmental, cultural, developmental, and neurobiological influences are recognized as essential factors underlying a person's risk for becoming alcohol dependent (AD); however, the neurobiological processes that trigger this vulnerability are still poorly understood. Hormones are important in the regulation of many functions and several hormones are strongly associated with alcohol use. While medical consequences are important, the primary focus of this review is on the underlying confluence of appetitive/feeding, reproductive and posterior pituitary hormones associated with distinct phases of alcoholism or assessed by alcohol craving in humans. While these hormones are of diverse origin, the involvement with alcoholism by these hormone systems is unmistakable, and demonstrates the complexity of interactions with alcohol and the difficulty of successfully pursuing effective treatments. Whether alcohol associated changes in the activity of certain hormones are the result of alcohol use or are the result of an underlying predisposition for alcoholism, or a combination of both, is currently of great scientific interest. The evidence we present in this review suggests that appetitive hormones may be markers as they appear involved in alcohol dependence and craving, that reproductive hormones provide an example of the consequences of drinking and are affected by alcohol, and that posterior pituitary hormones have potential for being targets for treatment. A better understanding of the nature of these associations may contribute to diagnosing and more comprehensively treating alcoholism. Pharmacotherapies that take advantage of our new understanding of hormones, their receptors, or their potential relationship to craving may shed light on the treatment of this disorder. PMID:22772772

The relationship of appetitive, reproductive and posterior pituitary hormones to alcoholism and craving in humans.

PubMed

Kenna, George A; Swift, Robert M; Hillemacher, Thomas; Leggio, Lorenzo

2012-09-01

A significant challenge for understanding alcoholism lies in discovering why some, but not other individuals, become dependent on alcohol. Genetic, environmental, cultural, developmental, and neurobiological influences are recognized as essential factors underlying a person's risk for becoming alcohol dependent (AD); however, the neurobiological processes that trigger this vulnerability are still poorly understood. Hormones are important in the regulation of many functions and several hormones are strongly associated with alcohol use. While medical consequences are important, the primary focus of this review is on the underlying confluence of appetitive/feeding, reproductive and posterior pituitary hormones associated with distinct phases of alcoholism or assessed by alcohol craving in humans. While these hormones are of diverse origin, the involvement with alcoholism by these hormone systems is unmistakable, and demonstrates the complexity of interactions with alcohol and the difficulty of successfully pursuing effective treatments. Whether alcohol associated changes in the activity of certain hormones are the result of alcohol use or are the result of an underlying predisposition for alcoholism, or a combination of both, is currently of great scientific interest. The evidence we present in this review suggests that appetitive hormones may be markers as they appear involved in alcohol dependence and craving, that reproductive hormones provide an example of the consequences of drinking and are affected by alcohol, and that posterior pituitary hormones have potential for being targets for treatment. A better understanding of the nature of these associations may contribute to diagnosing and more comprehensively treating alcoholism. Pharmacotherapies that take advantage of our new understanding of hormones, their receptors, or their potential relationship to craving may shed light on the treatment of this disorder.

Pituitary volume in children with growth hormone deficiency, idiopathic short stature and controls.

PubMed

Kessler, Marion; Tenner, Michael; Frey, Michael; Noto, Richard

2016-10-01

The objective of the study was to describe the pituitary volume (PV) in pediatric patients with isolated growth hormone deficiency (IGHD), idiopathic short stature (ISS) and normal controls. Sixty-nine patients (57 male, 12 female), with a mean age of 11.9 (±2.0), were determined to have IGHD. ISS was identified in 29 patients (20 male, 9 female), with a mean age of 12.7 (±3.7). Sixty-six controls (28 female, 38 male), mean age 9.8 (±4.7) were also included. Three-dimensional (3D) magnetic resonance images with contrast were obtained to accurately measure PV. There was a significant difference in the mean PV among the three groups. The IGHD patients had a mean PV 230.8 (±89.6), for ISS patients it was 286.8 (±108.2) and for controls it was 343.7 (±145.9) (p<0.001). There was a normal increase in PV with age in the ISS patients and controls, but a minimal increase in the IGHD patients. Those patients with isolated GHD have the greatest reduction in PV compared to controls and the patients with ISS fall in between. We speculate that a possible cause for the slowed growth in some ISS patients might be related to diminished chronic secretion of growth hormone over time, albeit having adequate pituitary reserves to respond acutely to GH stimulation. Thus, what was called neurosecretory GHD in the past, might, in some patients, be relative pituitary hypoplasia and resultant diminished growth hormone secretion. Thus, PV determinations by magnetic resonance imaging (MRI) could assist in the diagnostic evaluation of the slowly growing child.

Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS.

PubMed

Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R; Changelian, Armen; Laws, Edward R; Santagata, Sandro; Agar, Nathalie Y R; Van Berkel, Gary J

2015-08-01

Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC-ESI-MS-MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making. Graphical Abstract Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections.

Gonadotropin Inhibitory Hormone Down-Regulates the Brain-Pituitary Reproductive Axis of Male European Sea Bass (Dicentrarchus labrax).

PubMed

Paullada-Salmerón, José A; Cowan, Mairi; Aliaga-Guerrero, María; Morano, Francesca; Zanuy, Silvia; Muñoz-Cueto, José A

2016-06-01

Gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin synthesis and release from the pituitary of birds and mammals. However, the physiological role of orthologous GnIH peptides on the reproductive axis of fish is still uncertain, and their actions on the main neuroendocrine systems controlling reproduction (i.e., GnRHs, kisspeptins) have received little attention. In a recent study performed in the European sea bass, we cloned a cDNA encoding a precursor polypeptide that contained C-terminal MPMRFamide (sbGnIH-1) and MPQRFamide (sbGnIH-2) peptide sequences, developed a specific antiserum against sbGnIH-2, and characterized its central and pituitary GnIH projections in this species. In this study, we analyzed the effects of intracerebroventricular injection of sbGnIH-1 and sbGnIH-2 on brain and pituitary expression of reproductive hormone genes (gnrh1, gnrh2, gnrh3, kiss1, kiss2, gnih, lhbeta, fshbeta), and their receptors (gnrhr II-1a, gnrhr II-2b, kiss1r, kiss2r, and gnihr) as well as on plasma Fsh and Lh levels. In addition, we determined the effects of GnIH on pituitary somatotropin (Gh) expression. The results obtained revealed the inhibitory role of sbGnIH-2 on brain gnrh2, kiss1, kiss2, kiss1r, gnih, and gnihr transcripts and on pituitary fshbeta, lhbeta, gh, and gnrhr-II-1a expression, whereas sbGnIH-1 only down-regulated brain gnrh1 expression. However, at different doses, central administration of both sbGnIH-1 and sbGnIH-2 decreased Lh plasma levels. Our work represents the first study reporting the effects of centrally administered GnIH in fish and provides evidence of the differential actions of sbGnIH-1 and sbGnIH-2 on the reproductive axis of sea bass, the main inhibitory role being exerted by the sbGnIH-2 peptide. © 2016 by the Society for the Study of Reproduction, Inc.

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

Down-regulation of pituitary receptors for luteinizing hormone-releasing hormone (LH-RH) in rats by LH-RH antagonist Cetrorelix.

PubMed Central

Halmos, G; Schally, A V; Pinski, J; Vadillo-Buenfil, M; Groot, K

1996-01-01

Antagonists of luteinizing hormone-releasing hormone (LH-RH), unlike the LH-RH agonists, suppress gonadotropins and sex steroid secretion immediately after administration, without initial stimulatory effects. [Ac-D-Nal(2)1,D-Ph(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-R H (SB-75; Cetrorelix) is a modern, potent antagonistic analog of LH-RH. In this study, the binding characteristics of receptors for LH-RH in membrane fractions from rat anterior pituitaries were investigated after a single injection of Cetrorelix at a dose of 100 microg per rat. To determine whether the treatment with Cetrorelix can affect the concentration of measurable LH-RH binding sites, we applied an in vitro method to desaturate LH-RH receptors by chaotropic agents such as manganous chloride (MnCl2) and ammonium thiocyanate (NH4SCN). Our results show that the percentages of occupied LH-RH receptors at 1, 3, and 6 h after administration of Cetrorelix were approximately 28%, 14%, and 10%, respectively, of total receptors. At later time intervals, we could not detect occupied LH-RH binding sites. Ligand competition assays, following in vitro desaturation, demonstrated that rat pituitary LH-RH receptors were significantly (P < 0.01) down-regulated for at least 72 h after administration of Cetrorelix. The lowest receptor concentration was found 3-6 h after Cetrorelix treatment and a recovery in receptor number began within approximately 24 h. The down-regulation of LH-RH binding sites induced by Cetrorelix was accompanied by serum LH and testosterone suppression. Higher LH-RH receptor concentrations coincided with elevated serum hormone levels at later time intervals. Our results indicate that administration of LH-RH antagonist Cetrorelix produces a marked down-regulation of pituitary receptors for LH-RH and not merely an occupancy of binding sites. PMID:8637885

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.

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.

Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

PubMed

Takahashi, L K; Kalin, N H

1991-08-30

Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

TAC1 Gene Products Regulate Pituitary Hormone Secretion and Gene Expression in Prepubertal Grass Carp Pituitary Cells.

PubMed

Hu, Guangfu; He, Mulan; Ko, Wendy K W; Wong, Anderson O L

2017-06-01

Tachykinin-1 (TAC1) is known to have diverse functions in mammals, but similar information is scarce in fish species. Using grass carp as a model, the pituitary actions, receptor specificity and postreceptor signaling of TAC1 gene products, namely substance P (SP) and neurokinin A (NKA), were examined. TAC1 encoding SP and NKA as well as tachykinin receptors NK1R and NK2R were cloned in the carp pituitary. The newly cloned receptors were shown to be functional with properties similar to mammalian counterparts. In carp pituitary cells, SP and NKA could trigger luteinizing hormone (LH), prolactin (PRL), and somatolactin α (SLα) secretion, with parallel rises in PRL and SLα transcripts. Short-term SP treatment (3 hours) induced LH release, whereas prolonged induction (24 hours) could attenuate LHβ messenger RNA (mRNA) expression. At pituitary cell level, LH, PRL, and SLα regulation by TAC1 gene products were mediated by NK1R, NK2R, and NK3R, respectively. Apparently, SP- and NKA-induced LH and SLα secretion and transcript expression were mediated by adenylyl cyclase/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), phospholiphase C (PLC)/inositol 1,4,5-triphosphate/protein kinase C (PKC), and Ca2+/calmodulin (CaM)/CaM-dependent protein kinase-II pathways. The signal transduction for PRL responses was similar, except for the absence of a PKC component. Regarding SP inhibition of LHβ mRNA expression, the cAMP/PKA- and PLC/PKC-dependent (but not Ca2+/CaM-dependent) cascades were involved. These results, as a whole, suggest that TAC1 gene products play a role in LH, PRL, and SLα regulation via overlapping postreceptor signaling coupled to different subtypes of tachykinin receptor expressed in the carp pituitary. Copyright © 2017 Endocrine Society.

Impact of selective pituitary gland incision or resection on hormonal function after adenoma or cyst resection.

PubMed

Barkhoudarian, Garni; Cutler, Aaron R; Yost, Sam; Lobo, Bjorn; Eisenberg, Amalia; Kelly, Daniel F

2015-12-01

With the resection of pituitary lesions, the anterior pituitary gland often obstructs transsphenoidal access to the lesion. In such cases, a gland incision and/or partial gland resection may be required to obtain adequate exposure. We investigate this technique and determine the associated risk of post-operative hypopituitarism. All patients who underwent surgical resection of a pituitary adenoma or Rathke cleft cyst (RCC) between July 2007 and January 2013 were analyzed for pre- and post-operative hormone function. The cohort of patients with gland incision/resection were compared to a case-matched control cohort of pituitary surgery patients. Total hypophysectomy patients were excluded from outcome analysis. Of 372 operations over this period, an anterior pituitary gland incision or partial gland resection was performed in 79 cases (21.2 %). These include 53 gland incisions, 12 partial hemi-hypophysectomies and 14 resections of thinned/attenuated anterior gland. Diagnoses included 64 adenomas and 15 RCCs. New permanent hypopituitarism occurred in three patients (3.8 %), including permanent DI (3) and growth hormone deficiency (1). There was no significant difference in the rate of worsening gland dysfunction nor gain of function. Compared to a control cohort, there was a significantly lower incidence of transient DI (1.25 vs. 11.1 %, p = 0.009) but no significant difference in permanent DI (3.8 vs. 4.0 %) in the gland incision group. Selective gland incisions and gland resections were performed in over 20 % of our cases. This technique appears to minimize traction on compressed normal pituitary gland during removal of large lesions and facilitates better visualization and removal of cysts, microadenomas and macroadenomas.

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.

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.

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.

Greater inhibition of the pituitary--ovarian axis in oral contraceptive regimens with a shortened hormone-free interval.

PubMed

Willis, Sherilyn A; Kuehl, Thomas J; Spiekerman, A Michael; Sulak, Patricia J

2006-08-01

Our objective was to test the hypothesis that shortening the hormone-free interval (HFI) between cycles of 21 days of oral contraceptives (OCs) reduces pituitary secretion of gonadotropins and ovarian production of estradiol and inhibin-B. We used a prospective trial design comparing the standard 7-day HFI and shortened HFI during cycles, with an OC containing 0.03 mg of ethinyl estradiol and 3 mg of drospirenone. Twelve current OC users initially utilized an OC in the standard fashion, with 21 days of active pills and a 7-day HFI, followed by 21 days of active pills with randomization to either a 3-day or a 4-day HFI. Nine daily blood samples were obtained for the measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and inhibin-B, beginning with active pill 21 days before each HFI of the two cycles. Analysis of variance was used to compare hormones for 9 days bracketing the standard 7-day HFI and to compare, within individuals, the 7-day HFI and the subsequent shortened HFI. During the 7-day HFI, all four hormones significantly (p>.001) increased from baseline. FSH increased beginning on HFI Day 4, inhibin-B increased beginning on HFI Day 5, and LH and estradiol increased beginning on HFI Day 6. Subjects randomized to the 3-day or the 4-day HFI did not differ with regard to age and body size (p=.88) or initial hormone level (p=.67). Greater pituitary and ovarian suppression was seen with the shortened HFI for all four hormones (p<.001). Hormone levels in the 7 days after the last active pill of the second cycle did not differ (p>.4) between the 3-day and the 4-day HFI groups. Shortening the HFI from 7 days to 3 or 4 days blunts increases in the pituitary-ovarian axis during cycles of OC use.

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.

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.

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 ...

Thyrotropin-secreting pituitary adenomas: biological and molecular features, diagnosis and therapy.

PubMed

Losa, M; Fortunato, M; Molteni, L; Peretti, E; Mortini, P

2008-12-01

Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Patients with TSH-secreting adenoma usually present with signs and symptoms of hyperthyroidism milder than those in patients with hyperthyroidism of thyroid origin, in addition to symptoms secondary to mass effects of the pituitary tumour. Mixed pituitary tumours co-secrete growth hormone and prolactin. The characteristic biochemical abnormalities are normal or high serum TSH concentrations in the presence of elevated total and/or free thyroid hormones concentrations. Measurement of markers of peripheral thyroid hormone action and dynamic tests may aid in the differential diagnosis with the syndrome of resistance to thyroid hormone. Neuroimaging is fundamental to visualize the pituitary tumor. Therapy of TSH-secreting adenomas can be accomplished by surgery, radiation therapies, and medical treatment with somatostatin analogs or dopamine agonists. Nowadays, and in contrast with the first reports on this rare disease, most patients are well controlled by current therapies.

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.

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

Effects of corticotropin-releasing hormone and its antagonist on the gene expression of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in the hypothalamus and anterior pituitary gland of follicular phase ewes.

PubMed

Ciechanowska, Magdalena; Łapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek

2011-01-01

There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo-pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo-anterior pituitary unit. © CSIRO 2011 Open Access

[Clinical study on the postburn change in the hypothalamus-pituitary-adrenal hormones in severely burned patients].

PubMed

Li, Hong-mian; Liang, Zi-qian; Luo, Zuo-jie

2003-06-01

To investigate the postburn dynamic changes in the hypothalamus-pituitary-adrenal hormones in severely burned patients. Fifty burn patients were enrolled in the study. The plasma contents of total GC (cortisol), ACTH and aldosterone (ALDO) and urinary contents of 17-OHO and 17-KS were determined with radio-immunological assay (RIA) method after burn injury to compare with the normal values which were well established clinically. The postburn plasma and urinary contents of the above indices were increased evidently with two peak values in shock and infectious stages, whilst the majority of he indices were lower than the normal values after 6 postburn weeks (PBWs). The values of these hormones were the lowest in dying patients. On the other hand, the values approached normal levels in those patients whose burn wounds were healing. Increases of the plasma and urinary levels of hypothalamus-pituitary -adrenal hormones in severely burned patients were constantly seen. Burn shock and infection seemed to be the two major factors in inducing postburn stress reaction in burn victims. Abrupt decrease of the hormone levels in plasma and or urine indicated adrenal failure predicting a poor prognosis of the burn patients.

In situ hybridization analysis of anterior pituitary hormone gene expression during fetal mouse development.

PubMed

Japón, M A; Rubinstein, M; Low, M J

1994-08-01

We used 35S-labeled oligonucleotides and cRNAs (riboprobes) to detect the temporal order and spatial pattern of anterior pituitary hormone gene expression in (B6CBF1 x B6CBF1)F2 fetal mice from embryonic Day 9.5 (E9.5) to postnatal Day 1 (P1). Pro-opiomelanocortin (POMC) mRNA was expressed in the basal diencephalon on Day E10.5, in the ventromedial zone of the pars distalis on Day E12.5, and in the pars intermedia on Day E14.5. The common alpha-glycoprotein subunit (alpha-GSU) mRNA first appeared in the anterior wall of Rathke's pouch on Day E11.5 and extended to the pars tuberalis and ventromedial zone of the pars distalis on Day E12.5. Thyroid-stimulating hormone-beta (TSH beta) subunit mRNA was expressed initially in both the pas tuberalis and ventromedial pars distalis on Day E14.5, with an identical spatial distribution to alpha-GSU at the time. In contrast, luteinizing hormone-beta (LH beta) subunit and follicle-stimulating hormone beta (FSH beta) subunit mRNAs were detected initially only in the ventromedial pars distalis on Days E16.5 and E17.5, respectively, in an identical distribution to each other. POMC-, alpha-GSU-, TSH beta, LH beta-, and FSH beta-positive cells within the pars distalis all increased in number and autoradiographic signal with differing degrees of spatial expansion posteriorly, laterally, and dorsally up to Day P1. POMC expression was typically the most intense and extended circumferentially to include the entire lateral and dorsal surfaces of the pars distalis. The expression of both growth hormone (GH) and prolactin (PRL) started coincidentally on Day E15.5. However PRL cells localized in the ventromedial area similarly to POMC and the glycoprotein hormone subunits, whereas GH cells were found initially in a more lateral and central distribution within the lobes of the pars distalis. Somatotrophs increased dramatically in number and autoradiographic signal, extending throughout the pars distalis except for the most peripheral layer

The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats

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

Bowyer, J.F.; Latendresse, J.R.; Delongchamp, R.R.

Acrylamide (AA) is an important industrial chemical that is neurotoxic in rodents and humans and carcinogenic in rodents. The observation of cancer in endocrine-responsive tissues in Fischer 344 rats has prompted hypotheses of hormonal dysregulation, as opposed to DNA damage, as the mechanism for tumor induction by AA. The current investigation examines possible evidence for disruption of the hypothalamic-pituitary-thyroid axis from 14 days of repeated exposure of male Fischer 344 rats to doses of AA that range from one that is carcinogenic after lifetime exposure (2.5 mg/kg/d), an intermediate dose (10 mg/kg/d), and a high dose (50 mg/kg/d) that ismore » neurotoxic for this exposure time. The endpoints selected include: serum levels of thyroid and pituitary hormones; target tissue expression of genes involved in hormone synthesis, release, and receptors; neurotransmitters in the CNS that affect hormone homeostasis; and histopathological evaluation of target tissues. These studies showed virtually no evidence for systematic alteration of the hypothalamic-pituitary-thyroid axis and do not support hormone dysregulation as a plausible mechanism for AA-induced thyroid cancer in the Fischer 344 rat. Specifically, there were no significant changes in: 1) mRNA levels in hypothalamus or pituitary for TRH, TSH, thyroid hormone receptor {alpha} and {beta}, as well 10 other hormones or releasing factors; 2) mRNA levels in thyroid for thyroglobulin, thyroid peroxidase, sodium iodide symporter, or type I deiodinases; 3) serum TSH or T3 levels (T4 was decreased at high dose only); 4) dopaminergic tone in the hypothalamus and pituitary or importantly 5) increased cell proliferation (Mki67 mRNA and Ki-67 protein levels were not increased) in thyroid or pituitary. These negative findings are consistent with a genotoxic mechanism of AA carcinogenicity based on metabolism to glycidamide and DNA adduct formation. Clarification of this mechanistic dichotomy may be useful in human

Experimental Modification of Rat Pituitary Growth Hormone Cell Function During and After Spaceflight

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Salada, T.; Nye, P.; Grossman, E. J.; Lane, P. K.; Grindeland, R. E.

1996-01-01

Space-flown rats show a number of flight-induced changes in the structure and function of pituitary Growth Hormone (GH) cells after in vitro postflight testing. To evaluate the possible effects of microgravity on GH cells themselves, freshly dispersed rat anterior pituitary gland cells were seeded into vials containing serum +/- 1 micron HydroCortisone (HC) before flight. Five different cell preparations were used: the entire mixed-cell population of various hormone-producing cell types, cells of density less than 1.071 g/sq cm (band 1), cells of density greater than 1.071 g/sq cm (band 2), and cells prepared from either the dorsal or ventral part of the gland. Relative to ground control samples, bioactive GH released from dense cells during flight was reduced in HC-free medium but was increased in HC-containing medium. Band I and mixed cells usually showed opposite HC-dependent responses. Release of bioactive GH from ventral flight cells was lower; postflight responses to GH-releasing hormone challenge were reduced, and the cytoplasmic area occupied by GH in the dense cells was greater. Collectively, the data show that the chemistry and cellular makeup of the culture system modifies the response of GH cells to microgravity. As such, these cells offer a system to identify gravisensing mechanisms in secretory cells in future microgravity research.

Pegvisomant treatment in gigantism caused by a growth hormone-secreting giant pituitary adenoma.

PubMed

Müssig, K; Gallwitz, B; Honegger, J; Strasburger, C J; Bidlingmaier, M; Machicao, F; Bornemann, A; Ranke, M B; Häring, H-U; Petersenn, S

2007-03-01

Gigantism is rare with the majority of cases caused by a growth hormone (GH)-secreting pituitary adenoma. Treatment options for GH-secreting pituitary adenomas have been widened with the availability of long-acting dopamine agonists, depot preparations of somatostatin analogues, and recently the GH receptor antagonist pegvisomant. A 23-year-old male patient presented with continuous increase in height during the past 6 years due to a GH-secreting giant pituitary adenoma. Because of major intracranial extension and failure of octreotide treatment to shrink the tumour, the tumour was partially resected by a trans-frontal surgical approach. At immunohistochemistry, the tumour showed a marked expression of GH and a sparsely focal expression of prolactin. Somatostatin receptors (sst) 1-5 were not detected. Tumour tissue weakly expressed dopamine receptor type 2. The Gs alpha subunit was intact. Conversion from somatostatin analogue to pegvisomant normalized insulin-like-growth-factor-I (IGF-I) levels and markedly improved glucose tolerance. Pegvisomant is a potent treatment option in patients with pituitary gigantism. In patients who do not respond to somatostatin analogues, knowledge of the SST receptor status may shorten the time to initiation of pegvisomant treatment.

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 ...

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

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

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

Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary

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

Moran, Tyler B.; Brannick, Katherine E.; Raetzman, Lori T., E-mail: raetzman@life.illinois.edu

2012-11-15

Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotrope and lactotrope adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that are persistent in the environment, may predispose to pituitary dysfunction through activation of AhR. In the present study, we examined the effect of AhR activation on proliferationmore » and endogenous pituitary hormone expression in the GH3 rat somatolactotrope tumor cell line and the effect of loss of AhR action in knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist β-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon β-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with β-naphthoflavone suppresses Ahr expression and impairs expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In mice, loss of Ahr similarly leads to a reduction in Prl mRNA at P3, while Gh is unaffected. Additionally, there is a significant reduction in pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggest that environmental dioxins can exert endocrine disrupting effects at the pituitary. -- Highlights: ► AhR signaling suppresses Prl mRNA expression. ► AhR signaling does not influence pituitary proliferation in culture. ► AhR is necessary for Prl, Lhb and Fshb expression at postnatal day 3.« less

Reassembly of Anterior Pituitary Organization by Hanging Drop Three-Dimensional Cell Culture

PubMed Central

Tsukada, Takehiro; Kouki, Tom; Fujiwara, Ken; Ramadhani, Dini; Horiguchi, Kotaro; Kikuchi, Motoshi; Yashiro, Takashi

2013-01-01

The anterior pituitary gland comprises 5 types of hormone-producing cells and non-endocrine cells, such as folliculostellate (FS) cells. The cells form a lobular structure surrounded by extracellular matrix (ECM) but are not randomly distributed in each lobule; hormone-producing cells have affinities for specific cell types (topographic affinity), and FS cells form a homotypic meshwork. To determine whether this cell and ECM organization can be reproduced in vitro, we developed a 3-dimensional (3D) model that utilizes hanging drop cell culture. We found that the topographic affinities of hormone-producing cells were indeed maintained (ie, GH to ACTH cells, GH to TSH cells, PRL to LH/FSH cells). Fine structures in hormone-producing cells retained their normal appearance. In addition, FS cells displayed well-developed cytoplasmic protrusions, which interconnected with adjacent FS cells to form a 3D meshwork. In addition, reassembly of gap junctions and pseudofollicles among FS cells was observed in cell aggregates. Major ECM components—collagens and laminin—were deposited and distributed around the cells. In sum, the dissociated anterior pituitary cells largely maintained their in vivo anterior pituitary architectures. This culture system appears to be a powerful experimental tool for detailed analysis of anterior pituitary cell organization. PMID:24023396

Reassembly of anterior pituitary organization by hanging drop three-dimensional cell culture.

PubMed

Tsukada, Takehiro; Kouki, Tom; Fujiwara, Ken; Ramadhani, Dini; Horiguchi, Kotaro; Kikuchi, Motoshi; Yashiro, Takashi

2013-08-29

The anterior pituitary gland comprises 5 types of hormone-producing cells and non-endocrine cells, such as folliculostellate (FS) cells. The cells form a lobular structure surrounded by extracellular matrix (ECM) but are not randomly distributed in each lobule; hormone-producing cells have affinities for specific cell types (topographic affinity), and FS cells form a homotypic meshwork. To determine whether this cell and ECM organization can be reproduced in vitro, we developed a 3-dimensional (3D) model that utilizes hanging drop cell culture. We found that the topographic affinities of hormone-producing cells were indeed maintained (ie, GH to ACTH cells, GH to TSH cells, PRL to LH/FSH cells). Fine structures in hormone-producing cells retained their normal appearance. In addition, FS cells displayed well-developed cytoplasmic protrusions, which interconnected with adjacent FS cells to form a 3D meshwork. In addition, reassembly of gap junctions and pseudofollicles among FS cells was observed in cell aggregates. Major ECM components-collagens and laminin-were deposited and distributed around the cells. In sum, the dissociated anterior pituitary cells largely maintained their in vivo anterior pituitary architectures. This culture system appears to be a powerful experimental tool for detailed analysis of anterior pituitary cell organization.

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

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.

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

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.

Regional differences in the pituitary distribution of luteinizing hormone in the gonadectomized and proestrous female rat

EPA Science Inventory

Previous data have shown regional differences in the presence of anterior pituitary luteinizing hormone (LH) that generally correlate with comparable disparities in the distribution of gonadotropes throughout the gland. In female rats, the differences are apparent over the estro...

Ultradian rhythms in pituitary and adrenal hormones: their relations to sleep.

PubMed

Gronfier, C; Brandenberger, G

1998-02-01

Sleep and circadian rhythmicity both influence the 24-h profiles of the main pituitary and adrenal hormones. From studies using experimental strategies including complete and partial sleep deprivation, acute and chronic shifts in the sleep period, or complete sleep-wake reversal as occurs with transmeridian travel or shift-work, it appears that prolactin (PRL) and growth hormone (GH) profiles are mainly sleep related, while cortisol profile is mainly controlled by the circadian clock with a weak influence of sleep processes. Thyrotropin (TSH) profile is under the dual influence of sleep and circadian rhythmicity. Recent studies, in which we used spectral analysis of sleep electroencephalogram (EEG) rather than visual scoring of sleep stages, have evaluated the temporal associations between pulsatile hormonal release and the variations in sleep EEG activity. Pulses in PRL and in GH are positively linked to increases in delta wave activity, whereas TSH and cortisol pulses are related to decreases in delta wave activity. It is yet not clear whether sleep influences endocrine secretion, or conversely, whether hormone secretion affects sleep structure. These well-defined relationships raise the question of their physiological significance and of their clinical implications.

Surface plasmon resonance immunoassay analysis of pituitary hormones in urine and serum samples.

PubMed

Treviño, Juan; Calle, Ana; Rodríguez-Frade, José Miguel; Mellado, Mario; Lechuga, Laura M

2009-05-01

Direct determination of four pituitary peptide hormones: human thyroid stimulating hormone (hTSH), growth hormone (hGH), follicle stimulating hormone (hFSH), and luteinizing hormone (hLH) has been carried out using a portable surface plasmon resonance (SPR) immunosensor. A commercial SPR biosensor was employed. The immobilization of the hormones was optimized and monoclonal antibodies were selected in order to obtain the best sensor performance. Assay parameters as running buffer and regeneration solution composition or antibody concentration were adjusted to achieve a sensitive analyte detection. The performance of the assays was assessed in buffer solution, serum and urine, showing sensitivity in the range from 1 to 6 ng/mL. The covalent attachment of the hormones ensured the stability of the SPR signal through repeated use in up to 100 consecutive assay cycles. Mean intra- and inter-day coefficients of variation were all <7%, while batch-assay variability using different sensor surfaces was <5%. Taking account both the excellent reutilization performance and the outstanding reproducibility, this SPR immunoassay method turns on a highly reliable tool for endocrine monitoring in laboratory and point-of-care (POC) settings.

Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis.

PubMed

Goldsammler, Michelle; Merhi, Zaher; Buyuk, Erkan

2018-05-09

Besides being a risk factor for multiple metabolic disorders, obesity could affect female reproduction. While increased adiposity is associated with hormonal changes that could disrupt the function of the hypothalamus and the pituitary, compelling data suggest that obesity-related hormonal and inflammatory changes could directly impact ovarian function. To review the available data related to the mechanisms by which obesity, and its associated hormonal and inflammatory changes, could affect the female reproductive function with a focus on the hypothalamic-pituitary-ovarian (HPO) axis. PubMed database search for publications in English language until October 2017 pertaining to obesity and female reproductive function was performed. The obesity-related changes in hormone levels, in particular leptin, adiponectin, ghrelin, neuropeptide Y and agouti-related protein, are associated with reproductive dysfunction at both the hypothalamic-pituitary and the ovarian levels. The pro-inflammatory molecules advanced glycation end products (AGEs) and monocyte chemotactic protein-1 (MCP-1) are emerging as relatively new players in the pathophysiology of obesity-related ovarian dysfunction. There is an intricate crosstalk between the adipose tissue and the inflammatory system with the HPO axis function. Understanding the mechanisms behind this crosstalk could lead to potential therapies for the common obesity-related reproductive dysfunction.

Congenital gigantism due to growth hormone-releasing hormone excess and pituitary hyperplasia with adenomatous transformation.

PubMed

Zimmerman, D; Young, W F; Ebersold, M J; Scheithauer, B W; Kovacs, K; Horvath, E; Whitaker, M D; Eberhardt, N L; Downs, T R; Frohman, L A

1993-01-01

The cause of gigantism in most patients is a GH-secreting pituitary tumor. In this report, a case of congenital gigantism due to probable central hypersection of GH-releasing hormone (GHRH) is described. Normal at birth (4.4 kg; 53 cm), our 7-yr-old male patient grew progressively thereafter to attain a height of 182 cm and a weight of 99.4 kg at the time of our evaluation. The markedly increased baseline plasma levels of GH (730 micrograms/L) did not suppress during a standard 3-h oral glucose tolerance test, but did increase 54% after iv infusion of GHRH. Baseline plasma levels of insulin-like growth factor-I, PRL, and immunoreactive GHRH were also markedly increased. Computed imaging of the head showed a large, partially cystic sellar and suprasellar mass. Extensive imaging studies did not localize a potential source of GHRH. Preoperative treatment with octreotide and bromocriptine for 4 months resulted in a 25% reduction of suprasellar tissue mass. The pituitary tissue removed at transsphenoidal and transfrontal operations showed massive somatotroph, lactotroph, and mammosomatotroph hyperplasia. Areas of GH- and PRL-secreting cell adenomatous transformation were also evident. No histological or immunohistochemical evidence of a pituitary source of GHRH was found. The peripheral plasma immunoreactive GHRH concentration remained unaffected by pharmacological and surgical interventions. We suspect that a congenital hypothalamic regulatory defect may be responsible for the GHRH excess in this case.

Ultrastructural modifications and changes in the expression of hormonal genes produced by indomethacin in the anterior pituitary gland of the rat.

PubMed

Romano, L A; Rivolta, C; Machiavelli, G A; Burdman, J A

1995-10-01

Indomethacin decreases the level of prolactin (50%) and growth hormone (70%) mRNA in the anterior pituitary gland of the rat. Actin mRNA increases (59%). Ultrastructurally there is a decrease in the number of secretory granules. Indomethacin also prevents the increase in prolactin secretory granules produced by the administration of estradiol. The results indicate that indomethacin inhibits hormonal synthesis in the APG at a transcriptional level. This effect appears selective because mRNA level for actin synthesis in the pituitary gland was higher than in nontreated rats.

Radioiodinated nondegradable gonadotropin-releasing hormone analogs: new probes for the investigation of pituitary gonadotropin-releasing hormone receptors.

PubMed

Clayton, R N; Shakespear, R A; Duncan, J A; Marshall, J C; Munson, P J; Rodbard, D

1979-12-01

Studies of pituitary plasma membrane gonadotropin-releasing hormone (GnRH) receptors using [125I]-iodo-GnRH suffer major disadvantages. Only a small (less than 25%) proportion of specific tracer binding is to high affinity sites, with more than 70% bound to low affinity sites (Ka = 1 x 10(6) M-1). [125I]Iodo-GnRH is also inactivated during incubation with pituitary plasma membrane preparations. Two superactive analongs of GnRH, substituted in positions 6 and 10, were used as the labeled ligand to overcome these problems. Both analogs bound to the same high affinity sites as GnRH on bovine pituitary plasma membranes, though the affinity of the analogs was higher than that of the natural decapeptide (Ka = 2.0 x 10(9), 6.0 x 10(9), and 3.0 x 10(8) M-1 for [D-Ser(TBu)6]des-Gly10-GnRH ethylamide, [D-Ala6]des-Gly10-GnRH ethylamide, and GnRH, respectively. The labeled analogs bound to a single class of high affinity sites with less than 15% of the specific binding being to low affinity sites (Ka approximately equal to 1 x 10(6) M-1). The labeled analogs were not inactivated during incubation with the pituitary membrane preparations. Using the analogs as tracer, a single class of high affinity sites (K1 = 4.0 x 10(9) M-1) was also demonstrated on crude 10,800 x g rat pituitary membrane preparations. Use of these analogs as both the labeled and unlabeled ligand offers substantial advantages over GnRH for investigation of GnRH receptors, allowing accurate determination of changes in their numbers and affinities under various physiological conditions.

Concentrations of the adrenocorticotropic hormone, corticosterone and sex steroid hormones and the expression of the androgen receptor in the pituitary and adrenal glands of male turkeys (Meleagris gallopavo) during growth and development.

PubMed

Kiezun, J; Kaminska, B; Jankowski, J; Dusza, L

2015-01-01

Androgens take part in the regulation of puberty and promote growth and development. They play their biological role by binding to a specific androgen receptor (AR). The aim of this study was to evaluate the expression of AR mRNA and protein in the pituitary and adrenal glands, to localize AR protein in luteinizing hormone (LH)-producing pituitary and adrenocortical cells, to determine plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone and the concentrations of corticosterone, testosterone (T), androstenedione (A4) and oestradiol (E2) in the adrenal glands of male turkeys at the age of 4, 8, 12, 16, 20, 24 and 28weeks. The concentrations of hormones and the expression of AR varied during development. The expression of AR mRNA and protein in pituitary increased during the growth. The increase of AR mRNA levels in pituitary occurred earlier than increase of AR protein. The percentage of pituitary cells expressing ARs in the population of LH-secreting cells increased in week 20. It suggests that AR expression in LH-producing pituitary cells is determined by the phase of development. The drop in adrenal AR mRNA and protein expression was accompanied by an increase in the concentrations of adrenal androgens. Those results could point to the presence of a compensatory mechanism that enables turkeys to avoid the potentially detrimental effects of high androgen concentrations. Our results will expand our knowledge of the role of steroids in the development of the reproductive system of turkeys from the first month of age until maturity. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: distributions of sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

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

Green, E.D.; Baenziger, J.U.

1988-01-05

The asparagine-linked oligosaccharides on the pituitary glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) consist of a heterogeneous array of neutral, sulfated, sialylated, and sulfated/sialylated structures. In this study, the authors determined the relative quantities of the various asparagine-linked oligosaccharides on LH, FSH, and TSH from these three animal species. The proportions of sulfated versus sialylated oligosaccharides varied markedly among the different hormones. Both hormone- and animal species-specific differences in the types and distributions of sulfated, sialylated, and sulfated/sialylated structures were evident. In particular, LH and FSH, which are synthesized in the same pituitary cell and bear ..cap alpha..-subunitsmore » with the identical amino acid sequence, contained significantly different distributions of sulfated and sialylated oligosaccharides. For all three animal species, the ratio of sialylated to sulfated oligosaccharides differed by >10-fold for LH and FSH, with sulfated structures dominating on LH and sialylated structures on FSH. Sialylated oligosaccharides were also heterogeneous with respect to sialic acid linkage (..cap alpha..2,3 versus ..cap alpha..2,6). The differences in oligosaccharide structures among the various pituitary glycoprotein hormones as well as among the various glycosylation sites within a single hormone support the hypothesis that glycosylation may serve important functional roles in the expression and/or regulation of hormone bioactivity.« less

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 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.

Regulation of fish growth hormone transcription.

PubMed

Farchi-Pisanty, O; Hackett, P B; Moav, B

1995-09-01

Regulation of endogenous fish growth hormone transcription was studied using carp pituitaries in vitro. It was demonstrated that thyroid hormone (T3) and 9-cis retinoic acid have increased the steady state levels of growth hormone messenger RNA in pituitary cells, as compared with beta-actin messenger RNA levels. In contrast, estrogen failed to increase growth hormone mRNA levels. The possible involvement of thyroid hormone receptor in pituitary gene expression was demonstrated by in situ localization of both growth hormone mRNA and thyroid hormone receptor mRNA in the pituitaries as early as 4 days after fertilization.

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.

The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

PubMed

Root, A W; Shulman, D; Root, J; Diamond, F

1986-01-01

Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

All Hormone-Producing Cell Types of the Pituitary Intermediate and Anterior Lobes Derive From Prop1-Expressing Progenitors

PubMed Central

Keisler, Jessica L.; Pérez-Millán, María I.; Schade, Vanessa; Camper, Sally A.

2016-01-01

Mutations in PROP1, the most common known cause of combined pituitary hormone deficiency in humans, can result in the progressive loss of all hormones of the pituitary anterior lobe. In mice, Prop1 mutations result in the failure to initiate transcription of Pou1f1 (also known as Pit1) and lack somatotropins, lactotropins, and thyrotropins. The basis for this species difference is unknown. We hypothesized that Prop1 is expressed in a progenitor cell that can develop into all anterior lobe cell types, and not just the somatotropes, thyrotropes, and lactotropes, which are collectively known as the PIT1 lineage. To test this idea, we produced a transgenic Prop1-cre mouse line and conducted lineage-tracing experiments of Prop1-expressing cells. The results reveal that all hormone-secreting cell types of both the anterior and intermediate lobes are descended from Prop1-expressing progenitors. The Prop1-cre mice also provide a valuable genetic reagent with a unique spatial and temporal expression for generating tissue-specific gene rearrangements early in pituitary gland development. We also determined that the minimal essential sequences for reliable Prop1 expression lie within 10 kilobases of the mouse gene and demonstrated that human PROP1 can substitute functionally for mouse Prop1. These studies enhance our understanding of the pathophysiology of disease in patients with PROP1 mutations. PMID:26812162

All Hormone-Producing Cell Types of the Pituitary Intermediate and Anterior Lobes Derive From Prop1-Expressing Progenitors.

PubMed

Davis, Shannon W; Keisler, Jessica L; Pérez-Millán, María I; Schade, Vanessa; Camper, Sally A

2016-04-01

Mutations in PROP1, the most common known cause of combined pituitary hormone deficiency in humans, can result in the progressive loss of all hormones of the pituitary anterior lobe. In mice, Prop1 mutations result in the failure to initiate transcription of Pou1f1 (also known as Pit1) and lack somatotropins, lactotropins, and thyrotropins. The basis for this species difference is unknown. We hypothesized that Prop1 is expressed in a progenitor cell that can develop into all anterior lobe cell types, and not just the somatotropes, thyrotropes, and lactotropes, which are collectively known as the PIT1 lineage. To test this idea, we produced a transgenic Prop1-cre mouse line and conducted lineage-tracing experiments of Prop1-expressing cells. The results reveal that all hormone-secreting cell types of both the anterior and intermediate lobes are descended from Prop1-expressing progenitors. The Prop1-cre mice also provide a valuable genetic reagent with a unique spatial and temporal expression for generating tissue-specific gene rearrangements early in pituitary gland development. We also determined that the minimal essential sequences for reliable Prop1 expression lie within 10 kilobases of the mouse gene and demonstrated that human PROP1 can substitute functionally for mouse Prop1. These studies enhance our understanding of the pathophysiology of disease in patients with PROP1 mutations.

[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

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.

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.

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.

Regulation of Pituitary Stem Cells by Epithelial to Mesenchymal Transition Events and Signaling Pathways

PubMed Central

Cheung, Leonard Y. M.; Davis, Shannon W.; Brinkmeier, Michelle L.; Camper, Sally A.; Pérez-Millán, María Inés

2017-01-01

The anterior pituitary gland is comprised of specialized cell-types that produce and secrete polypeptide hormones in response to hypothalamic input and feedback from target organs. These specialized cells arise from stem cells that express SOX2 and the pituitary transcription factor PROP1, which is necessary to establish the stem cell pool and promote an epithelial to mesenchymal-like transition, releasing progenitors from the niche. The adult anterior pituitary responds to physiological challenge by mobilizing the SOX2-expressing progenitor pool and producing additional hormone-producing cells. Knowledge of the role of signaling pathways and extracellular matrix components in these processes may lead to improvements in the efficiency of differentiation of embryonic stem cells or induced pluripotent stem cells into hormone producing cells in vitro. Advances in our basic understanding of pituitary stem cell regulation and differentiation may lead to improved diagnosis and treatment for patients with hypopituitarism. PMID:27650955

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.

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.

Clinical guidelines for management of diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion after pituitary surgery.

PubMed

Lamas, Cristina; del Pozo, Carlos; Villabona, Carles

2014-04-01

Changes in water metabolism and regulation of vasopressin (AVP) or antidiuretic hormone (ADH) are common complications of pituitary surgery. The scarcity of studies comparing different treatment and monitoring strategies for these disorders and the lack of prior clinical guidelines makes it difficult to provide recommendations following a methodology based on grades of evidence. This study reviews the pathophysiology of diabetes insipidus and inappropriate ADH secretion after pituitary surgery, and is intended to serve as a guide for their diagnosis, differential diagnosis, treatment, and monitoring. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Hypergravity and estrogen effects on avian anterior pituitary growth hormone and prolactin levels

NASA Technical Reports Server (NTRS)

Fiorindo, R. P.; Negulesco, J. A.

1980-01-01

Developing female chicks with fractured right radii were maintained for 14 d at either earth gravity (1 g) or a hypergravity state (2 g). The birds at 1 g were divided into groups which received daily injections of (1) saline, (2) 200 micrograms estrone, and (3) 400 micrograms estrone for 14 d. The 2-g birds were divided into three similarly treated groups. All 2-g birds showed significantly lower body weights than did 1-g birds. Anterior pituitary (AP) glands were excised and analyzed for growth hormone and prolactin content by analytical electrophoresis. The 1-g chicks receiving either dose of daily estrogen showed increased AP growth hormone levels, whereas hypergravity alone did not affect growth hormone content. Chicks exposed to daily estrogen and hypergravity displayed reduced growth hormone levels. AP prolactin levels were slightly increased by the lower daily estrogen dose in 1-g birds, but markedly reduced in birds exposed only to hypergravity. Doubly-treated chicks displayed normal prolactin levels. Reduced growth in 2-g birds might be due, in part, to reduced AP levels of prolactin and/or growth hormone.

Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: structural elucidation of the sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

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

Green, E.D.; Baenziger, J.U.

1988-01-05

The authors have elucidated the structures of the anionic asparagine-linked oligosaccharides present on the glycoprotein hormones lutropin (luteinizing hormone), follitropin (follicle-stimulating hormone), and thyrotropin (thyroid-stimulating hormone). Purified hormones, isolated from bovine, ovine, and human pituitaries, were digested with N-glycanase, and the released oligosaccharides were reduced with NaB(/sup 3/H)/sub 4/. The /sup 3/H-labeled oligosaccharides from each hormone were then fractionated by anion-exchange high performance liquid chromatography (HPLC) into populations differing in the number of sulfate and/or sialic acid moieties. The sulfated, sialylated, and sulfated/sialylated structures, which together comprised 67-90% of the asparagine-linked oligosaccharides on the pituitary glycoprotein hormones, were highly heterogeneousmore » and displayed hormone- as well as animal species-specific features. A previously uncharacterized dibranched oligosaccharide, bearing one residue each of sulfate and sialic acid, was found on all of the hormones except bovine lutropin. In this study, they describe the purification and detailed structural characterizations of the sulfated, sialylated, and sulfated/sialylated oligosaccharides found on lutropin, follitropin, and thyrotropin from several animal species.« less

Irisin inhibition of growth hormone secretion in cultured tilapia pituitary cells.

PubMed

Lian, Anji; Li, Xin; Jiang, Quan

2017-01-05

Irisin, the product of fibronectin type III domain-containing protein 5 (FNDC5) gene, is well-documented to be a regulator of energy metabolism. At present, not much is known about its biological function in non-mammalian species. In this study, a full-length tilapia FDNC5 was cloned and its tissue expression pattern has been confirmed. Based on the sequence obtained, we produced and purified recombinant irisin which could induce uncoupling protein 1 (UCP1) gene expression in tilapia hepatocytes. Further, the rabbit polyclonal irisin antiserum was produced and its specificity was confirmed by antiserum preabsorption. In tilapia pituitary cells, irisin inhibited growth hormone (GH) gene expression and secretion and triggered rapid phosphorylation of Akt, Erk1/2, and p38 MAPK. Furthermore, irisin-inhibited GH mRNA expression could be prevented by inhibiting PI3K/Akt, MEK1/2, and p38 MAPK, respectively. Apparently, fish irisin can act directly at the pituitary level to inhibit GH transcript expression via multiple signaling pathways. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effect of growth hormone replacement in patients with hypopituitarism on pituitary tumor recurrence, secondary cancer, and stroke.

PubMed

Jasim, Sina; Alahdab, Fares; Ahmed, Ahmed T; Tamhane, Shrikant U; Sharma, Anu; Donegan, Diane; Nippoldt, Todd B; Murad, M Hassan

2017-05-01

Growth hormone replacement therapy has benefits for patients with hypopituitarism. The safety profile in regard to tumor recurrence or progression, development of secondary malignancies, or cerebrovascular stroke is still an area of debate. A comprehensive search of multiple databases-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August 2015. Eligible studies that evaluated long-term adverse events in adult patients with hypopituitarism treated with growth hormone replacement therapy and reported development of pituitary tumor recurrence or progression, secondary malignancies, or cerebrovascular stroke were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. Random-effects meta-analysis was used to pool relative risks and 95 % confidence intervals. We included 15 studies (published 1995-2015) that reported on 46,148 patients. Compared to non-replacement, growth hormone replacement therapy in adults with hypopituitarism was not associated with statistically significant change in pituitary tumor progression or recurrence (relative risk, 0.77; 95 % confidence interval, 0.53-1.13) or development of secondary malignancy (relative risk, 0.99; 95 % confidence interval, 0.70-1.39). In two retrospective studies, there was higher risk of stroke in patients who did not receive replacement (relative risk, 2.07; 95 % confidence interval, 1.51-2.83). The quality of evidence is low due to study limitations and imprecision. This systematic review and meta-analysis supports the overall safety of growth hormone therapeutic use in adults with hypopituitarism with no clear evidence of increased risk of pituitary tumor recurrence, malignancy, or stroke.

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

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.

Hormone levels

MedlinePlus

Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

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.

Vincent du Vigneaud: following the sulfur trail to the discovery of the hormones of the posterior pituitary gland at Cornell Medical College.

PubMed

Ottenhausen, Malte; Bodhinayake, Imithri; Banu, Matei A; Stieg, Philip E; Schwartz, Theodore H

2016-05-01

In 1955, Vincent du Vigneaud (1901-1978), the chairman of the Department of Biochemistry at Cornell University Medical College, was awarded the Nobel Prize for Chemistry for his research on insulin and for the first synthesis of the posterior pituitary hormones-oxytocin and vasopressin. His tremendous contribution to organic chemistry, which began as an interest in sulfur-containing compounds, paved the way for a better understanding of the pituitary gland and for the development of diagnostic and therapeutic tools for diseases of the pituitary. His seminal research continues to impact neurologists, endocrinologists, and neurosurgeons, and enables them to treat patients who had no alternatives prior to du Vigneaud's breakthroughs in peptide structure and synthesis. The ability of neurosurgeons to aggressively operate on parasellar pathology was directly impacted and related to the ability to replace these hormones after surgery. The authors review the life and career of Vincent du Vigneaud, his groundbreaking discoveries, and his legacy of the understanding and treatment of the pituitary gland in health and disease.

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

PubMed Central

Peroni, Cibele N.; Hayashida, Cesar Y.; Nascimento, Nancy; Longuini, Viviane C.; Toledo, Rodrigo A.; Bartolini, Paolo; Bowers, Cyril Y.; Toledo, Sergio P.A.

2012-01-01

OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a model of GH deficiency arising from mutated growth hormone-releasing hormone-receptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a. PMID:22473409

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.

Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS

DOE PAGES

Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R.; ...

2015-06-18

Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections using a fully automated droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system for spatially resolved sampling, HPLC separation, and mass spectral detection. Excellent correlation was found between the protein distribution data obtained with this droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system and those data obtained with matrix assisted laser desorption ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland.more » AVP was most abundant in the posterior pituitary gland region (neurohypophysis) and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH secreting adenomas and in normal anterior adenohypophysis compared to non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis as anticipated. This work demonstrates that a fully automated droplet-based liquid microjunction surface sampling system coupled to HPLC-ESI-MS/MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, such as AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity and specificity of the current methodology support the potential of this basic technology with further advancement for assisting surgical decision-making.« less

Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS

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

Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R.

Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections using a fully automated droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system for spatially resolved sampling, HPLC separation, and mass spectral detection. Excellent correlation was found between the protein distribution data obtained with this droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system and those data obtained with matrix assisted laser desorption ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland.more » AVP was most abundant in the posterior pituitary gland region (neurohypophysis) and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH secreting adenomas and in normal anterior adenohypophysis compared to non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis as anticipated. This work demonstrates that a fully automated droplet-based liquid microjunction surface sampling system coupled to HPLC-ESI-MS/MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, such as AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity and specificity of the current methodology support the potential of this basic technology with further advancement for assisting surgical decision-making.« less

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.

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

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.

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.

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.

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.

Spontaneous endocrine cure of gigantism due to pituitary apoplexy.

PubMed

Arisaka, O; Hall, R; Hughes, I A

1983-10-08

An 11 year old, tall boy presented with symptoms typical of pituitary apoplexy. A large necrotic and haemorrhagic tumour was removed, which was shown to be an adenoma secreting growth hormone and prolactin. Subsequent treatment comprised cranial irradiation and hormone replacement. Eighteen months after operation growth was static and plasma growth hormone and prolactin concentrations were undetectable. Treatment of pituitary apoplexy should comprise excision of the tumour and postoperative irradiation; such treatment after early recognition of the condition offers the best chance of preserving normal pituitary function in children with gigantism.

Spontaneous endocrine cure of gigantism due to pituitary apoplexy.

PubMed Central

Arisaka, O; Hall, R; Hughes, I A

1983-01-01

An 11 year old, tall boy presented with symptoms typical of pituitary apoplexy. A large necrotic and haemorrhagic tumour was removed, which was shown to be an adenoma secreting growth hormone and prolactin. Subsequent treatment comprised cranial irradiation and hormone replacement. Eighteen months after operation growth was static and plasma growth hormone and prolactin concentrations were undetectable. Treatment of pituitary apoplexy should comprise excision of the tumour and postoperative irradiation; such treatment after early recognition of the condition offers the best chance of preserving normal pituitary function in children with gigantism. PMID:6311318

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.

Creutzfeldt-Jakob disease in United Kingdom patients treated with human pituitary growth hormone.

PubMed

Swerdlow, A J; Higgins, C D; Adlard, P; Jones, M E; Preece, M A

2003-09-23

To investigate risk factors for Creutzfeldt-Jakob disease (CJD) in patients in the United Kingdom treated with human pituitary growth hormone (hGH). Incidence rates of CJD, based on person-year denominators, were assessed in a cohort of 1,848 patients treated with hGH in the United Kingdom from 1959 through 1985 and followed to the end of 2000. CJD developed in 38 patients. Risk of CJD was significantly increased by treatment with hGH prepared by the Wilhelmi method of extraction from human pituitaries. Risk was further raised if this treatment was administered at ages 8 to 10 years. The peak risk of CJD was estimated to occur 20 years after first exposure, and the estimated lifetime cumulative risk of CJD in Wilhelmi-treated patients was 4.5%. Size-exclusion chromatography, used in non-Wilhelmi preparation methods, may prevent CJD infection. Susceptibility to CJD may vary with age, and susceptibility may be present in only a few percent of the population.

Changes in pituitary growth hormone cells prepared from rats flown on Spacelab 3

NASA Technical Reports Server (NTRS)

Grindeland, R.; Hymer, W. C.; Farrington, M.; Fast, T.; Hayes, C.; Motter, K.; Patil, L.; Vasques, M.

1987-01-01

The effect of exposure to microgravity on pituitary gland was investigated by examining cells isolated from anterior pituitaries of rats flown on the 7-day Spacelab 3 mission and, subsequently, cultured for 6 days. Compared with ground controls, flight cells contained more intracellular growth hormone (GH); however, the flight cells released less GH over the 6-day culture period and after implantation into hypophysectomized rats than did the control cells. Compared with control rats, glands from large rats (400 g) contained more somatotrophs (44 percent compared with 37 percent in control rats); small rats (200 g) showed no difference. No major differences were found in the somatotroph ultrastructure (by TEM) or in the pattern of the immunoactive GH variants. However, high-performance liquid chromatography fractionation of culture media indicated that flight cells released much less of a biologically active high-molecular weight GH variant, suggesting that space flight may lead to secretory dysfunction.

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

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

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.

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

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.

Comparison of mechanisms of action of luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix and LHRH agonist triptorelin on the gene expression of pituitary LHRH receptors in rats

PubMed Central

Kovacs, Magdolna; Schally, Andrew V.

2001-01-01

The mechanisms through which luteinizing hormone (LH)-releasing hormone (LHRH) antagonists suppress pituitary gonadotroph functions and LHRH-receptor (LHRH-R) expression are incompletely understood. Consequently, we investigated the direct effect of LHRH antagonist cetrorelix in vitro on the expression of the pituitary LHRH-R gene and its ability to counteract the exogenous LHRH and the agonist triptorelin in the regulation of this gene. We also compared the effects of chronic administration of cetrorelix and triptorelin on the LHRH-R mRNA level and gonadotropin secretion in ovariectomized (OVX) and normal female rats. The exposure of pituitary cells in vitro to 3-min pulses of 1 nM LHRH or 0.1 nM triptorelin for 5 h increased the LHRH-R mRNA level by 77–88%. Continuous perfusion of the cells with 50 nM cetrorelix did not cause any significant changes, but prevented the stimulatory effect of LHRH pulses on the receptor mRNA expression. In OVX rats, 10 days after administration of a depot formulation of cetrorelix, releasing 100 μg of peptide daily, the elevated LHRH-R mRNA level was decreased by 73%, whereas daily injection of 100 μg of triptorelin caused a 41% suppression. In normal female rats, cetrorelix treatment suppressed the LHRH-R mRNA level by 33%, but triptorelin increased it by 150%. The highly elevated serum LH levels in OVX rats and the normal LH concentration of cycling rats were rapidly and completely suppressed by cetrorelix. Triptorelin decreased the serum LH in OVX rats to the precastration level, but had no effect on basal LH in normal rats. Our results confirm that LHRH antagonists, such as cetrorelix, inhibit the gene expression of pituitary LHRH-R indirectly, by counteracting the stimulatory effect of LHRH. A rapid suppression of serum LH by LHRH antagonists would be advantageous in the treatment of sex hormone-dependent tumors and other conditions. PMID:11593037

[The ultradian rhythm of sleep: diverse relations with pituitary and adrenal hormones].

PubMed

Brandenberger, G

2003-11-01

We evaluated the relationship between the ultradian rhythm of sleep and the secretory episodes of pituitary-adrenal hormones. Prolactin (PRL) and TSH exhibited opposite phase relationships with delta waves, PRL increasing and TSH decreasing when delta waves developed. Delta waves never increased together with an increase in cortisol secretion. They oscillated independently from each other throughout the 24 hour period, but when they were present at the same time, they oscillated in opposing phases. Concerning growth hormone (GH), its major peak which occurred shortly after sleep onset in association with the first slow wave sleep episode was blunted during sleep deprivation. However, this blunting was compensated during the day, so that the amount of GH secreted during a 24-hr period was similar whether or not a person had slept during the night. The physiological significance and the clinical implications of the various relationships of the endocrine systems with sleep are poorly known.

Pituitary cell differentiation from stem cells and other cells: toward restorative therapy for hypopituitarism?

PubMed

Willems, Christophe; Vankelecom, Hugo

2014-01-01

The pituitary gland, key regulator of our endocrine system, produces multiple hormones that steer essential physiological processes. Hence, deficient pituitary function (hypopituitarism) leads to severe disorders. Hypopituitarism can be caused by defective embryonic development, or by damage through tumor growth/resection and traumatic brain injury. Lifelong hormone replacement is needed but associated with significant side effects. It would be more desirable to restore pituitary tissue and function. Recently, we showed that the adult (mouse) pituitary holds regenerative capacity in which local stem cells are involved. Repair of deficient pituitary may therefore be achieved by activating these resident stem cells. Alternatively, pituitary dysfunction may be mended by cell (replacement) therapy. The hormonal cells to be transplanted could be obtained by (trans-)differentiating various kinds of stem cells or other cells. Here, we summarize the studies on pituitary cell regeneration and on (trans-)differentiation toward hormonal cells, and speculate on restorative therapies for pituitary deficiency.

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

Auxologic parameters and response to 2-year therapy with recombinant human growth hormone in growth hormone deficient children with an ectopic posterior pituitary.

PubMed

Kalina, Maria; Kalina-Faska, Barbara; Gruszczyńska, Katarzyna; Baron, Jan; Cisowska, Anita; Morawiec, Karolina; Biel-Lewandowska, Paulina; Małecka-Tendera, Ewa

2015-01-01

Structural defects of the hypothalamic-pituitary area in MRI are suggested as being a more accurate marker of growth hormone deficiency (GHD) than laboratory assays. To compare auxological characteristics in GHD children with normal pituitary (NP) function and with ectopic posterior pituitary (EPP), prior to therapy with recombinant human growth hormone (rhGH), extending the follow-up to two years following treatment. Eighty-six (86) GHD patients were divided into two groups depending on the pituitary MRI: the EPP (23 children, 3.2-16.8 years old) and the NP group (63 children, 3.3-14.8 years old). Height deficits in the population (hSD) and parents (hSD-mpSD) and the change of hSD and bone/chronological age ratio were assessed before and after 12 and 24 months of rhGH therapy. Height deficits before treatment were significantly greater in EPP compared to NP [median -4.07 (-7.06, -2.75) vs -3.15 (-4.9, -2.35) for hSD, and -3.65 (-7.06, -1.21) vs -1.83 (-4.31, -0.28) for hSD-mpSD; p<0.05]. Bone age was significantly delayed in the EPP group [0.62 (0.27, 0.92) vs 0.75 (0.21, 0.71); p<0.05]; differences remained significant during follow-up. After 12 months of rhGH therapy, EPP showed significantly greater catch-up growth compared to NP [ΔhSD=1.2 (0.42, 2.69) vs 0.74 (0.05, 1.48); p<0.05]. In the 2nd year, height velocity slowed down and was comparable in the two groups. At the conclusion of the study, hSD was similar in both groups, but hSD-mpSD was more deviated in EPP [-1.79 (-3.71, -1.21) vs -1.1 (0.98, -0.07); p<0.05]. The study showed relevant auxologic differences between EPP and NP children, as well as beneficial effects of rhGH therapy in both groups.

Growth, development, puberty and adult height of patients with congenital multiple pituitary hormone deficiencies.

PubMed

Haim-Pinhas, Hadar; Kauli, Rivka; Lilos, Pearl; Laron, Zvi

2016-04-01

Congenital MPHD is a rare condition caused by mutations in pituitary transcription factors genes: PROP1, POU1F1 (PIT1), HESX1, LHX3, LHX4. We evaluated in a retrospective study the effects on growth and development in 29 patients with congenital MPHD (cMPHD), during hGH replacement therapy alone and combined with sex hormones. Twenty nine patients with cMPHD were included and diagnosed, treated and followed in our clinic from diagnosis to adult age. Measurements on growth and development were taken by the same medical team. Mean birth weight of 21/29 neonates was 3126 ± 536 g. Mean birth length of 7/29 neonates was 48.7 ± 2 cm. Neuromotor development was normal or slightly delayed. Mean age at referral was 9.5 ± 7 years (m), 6.7 ± 3.5 years (f) (p=0.17). Height (SDS) before treatment was -2.8 ± 1.0 (m), -2.8 ± 1.0 (f) (p=0.99). Mean age at initiation of hGH treatment was 9.9 ± 6.7 years (m), 10.3 ± 4.2 years (f) (p=0.85). Mean age at initiation of sex hormone treatment was 17.0 ± 3.5 years (m), 17.1 ± 2.3 years (f) (p=0.88). Penile and testicular sizes were below normal before and after treatment. Head circumference (SD) was -1.9 ± 0.9 before and -0.6 ± 1.8 at end of treatment (p<0.001). Adult height (SDS) reached -1.1 ± 0.6 (p<0.001) for both males and females. Despite the multiple pituitary hormone deficiencies including hGH, children with congenital MPHD present with a better auxological development than children with congenital IGHD or congenital IGF-1 deficiency. These findings may be due to irregular and incomplete hormone deficiencies increasing with progressive age and late initiation of puberty. Copyright © 2016. Published by Elsevier Ltd.

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

Pituitary resistance to thyroid hormone associated with a base mutation in the hormone-binding domain of the human 3,5,3'-triiodothyronine receptor-beta.

PubMed

Sasaki, S; Nakamura, H; Tagami, T; Miyoshi, Y; Nogimori, T; Mitsuma, T; Imura, H

1993-05-01

Point mutations in the human T3 receptor-beta (TR beta) gene causing single amino acid substitutions have been identified in several different kindreds with generalized resistance to thyroid hormone. Until now, no study has been reported on the TR gene in cases of pituitary resistance (PRTH). In the present study, we analyzed the TR beta gene in a 30-yr-old Japanese female with PRTH. She exhibited clinical features of hyperthyroidism, elevated serum thyroid hormone levels accompanied by inappropriately increased secretion of TSH, mildly elevated basal metabolic rate, and increased urinary excretion of hydroxyproline. No pituitary tumor was detected. DNA fragments of exons 3-8 of the genomic TR beta gene were generated by the polymerase chain reaction and analyzed by a single stranded conformation polymorphism method. Exon 7 of the patient's TR beta gene showed an abnormal band, suggesting the existence of mutation(s). By subcloning and sequencing the DNA, a point mutation was identified in one allele at nucleotide 1297 (C to T), which altered the 333rd amino acid, arginine, to tryptophan. Neither of her apparently normal parents had any mutations of the TR beta gene. In vitro translation products of the mutant TR beta gene showed remarkably decreased T3-binding activity (Ka, 2.1 x 10(8) M-1; normal TR beta Ka, 1.1 x 10(10) M-1). Since the molecular defect detected in a patient with PRTH is similar to that seen in subjects with generalized resistance to thyroid hormone, both types of the syndrome may represent a continuous spectrum of the same etiological defect with variable tissue resistance to thyroid hormone.

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.

Serum concentrations of pituitary and adrenal hormones in female pigs exposed to two photoperiods.

PubMed

Kraeling, R R; Rampacek, G B; Mabry, J W; Cunningham, F L; Pinkert, C A

1983-11-01

Serum concentrations of pituitary and adrenal hormones were determined in lactating sows and ovariectomized (OVX) gilts exposed to 8 h (8L:16D) or 16 h of light (16L:8D). In addition serum prolactin (PRL) concentrations were determined after a thyrotropin releasing hormone (TRH) challenge. At 103 +/- 2 d of gestation or 3 wk after ovariectomy of nulliparous gilts on d 7 to 9 of the estrous cycle (d - 10), blood samples were collected from jugular vein cannulae at 30-min intervals for 8 h beginning at 0800 h. Immediately after the last sample, 13 sows and five OVX gilts were assigned to 8L:16D and 14 sows and five OVX gilts were assigned to 16L:8D/d and placed in two identical chambers in the farrowing house. Blood sampling was repeated on d 7, 14 and 21 of lactation in the sows and on d 7, 14, 21 and 28 in the OVX gilts. In Exp. 1, serum cortisol (C) concentrations were similar for sows exposed to 8L:16D (n = 7) and 16L:8D (n = 6) treatments, whereas in Exp. 2, serum C concentrations for sows exposed to 8L:16D (n = 6) were lower than those exposed to 16L:8D (n = 6) on d 7, 14 and 21. Photoperiod failed to influence serum concentrations of PRL, luteinizing hormone (LH) and growth hormone in the lactating sows or PRL in the OVX gilts. Photoperiod also failed to affect mean basal serum concentrations, peak height and peak frequency for PRL and LH in the lactating sows or for PRL in the OVX gilts.(ABSTRACT TRUNCATED AT 250 WORDS)

Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes

PubMed Central

Cheung, Leonard Y. M.; Okano, Hideyuki

2016-01-01

The hypothalamic-pituitary axes are the coordinating centers for multiple endocrine gland functions and physiological processes. Defects in the hypothalamus or pituitary gland can cause reduced growth and severe short stature, affecting approximately 1 in 4000 children, and a large percentage of cases of pituitary hormone deficiencies do not have an identified genetic cause. SOX21 is a protein that regulates hair, neural, and trophoblast stem cell differentiation. Mice lacking Sox21 have reduced growth, but the etiology of this growth defect has not been described. We studied the expression of Sox21 in hypothalamic-pituitary development and examined multiple endocrine axes in these mice. We find no evidence of reduced intrauterine growth, food intake, or physical activity, but there is evidence for increased energy expenditure in mutants. In addition, despite changes in pituitary hormone expression, hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants may be a cause of non-endocrine short stature in humans. PMID:27616671

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.

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

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.

The pituitary - Aging and spaceflown rats

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Grindeland, R. E.

1991-01-01

Decrements in growth hormone (GH) release we observed in two spaceflight experiments and four tail-suspended rat studies mimic age-associated changes in the mammalian pituitary GH system seen by Meites and others. The spaceflight data suggest that formation of high molecular weight bioactive disulfide-linked aggregates of the 20 and 22K monomeric GH forms may be reduced in microgravity, thereby, reducing target tissue activity. Correlative studies to confirm spaceflight as a model for pituitary GH system aging should include: (1) investigation of mechanisms of intracellular hormone packaging, (2) consequences to biological activity of the hormone molecule, and (3) study of intracellular microtubule dynamics.

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.

Hormones

MedlinePlus

Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

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

T3 receptors in human pituitary tumors.

PubMed

Machiavelli, Gloria A; Pauni, Micaela; Heredia Sereno, Gastón M; Szijan, Irene; Basso, Armando; Burdman, José A

2009-11-01

The purpose of this work was to investigate the synthesis of T3 receptors in human tumors of the anterior pituitary gland, its relationship with the hormone synthesized and/or secreted by the tumor and the post-surgical evolution of the patient. Patients were evaluated clinically and by magnetic nuclear resonance to classify the adenoma according to their size. Hormonal concentrations in sera were determined by radioimmunoassay. Immunohistochemistry of the pituitary hormones was performed in the tumors. Tumors were obtained at surgery and immediately frozen in ice, transported to the laboratory and stored at -70 degrees C. Reverse transcription was performed with purified RNA from the tumors. Out of 33 pituitary tumors, 29 had RNA for T3 receptors synthesis (88%). They were present in different histological specimens, the tumors were grades 1-4 according to their size, and there was no relationship between the size of the tumor and the presence of T3 receptor RNAs. The post-surgical evolution of the patient was mostly dependent on the size and not on the presence of T3 receptors. The presence of thyroid hormone receptors in pituitary tumors is in line with two important characteristics of these tumors: they are histologically benign and well differentiated.

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.

Fractures in pituitary adenoma patients from the Dutch National Registry of Growth Hormone Treatment in Adults.

PubMed

van Varsseveld, N C; van Bunderen, C C; Franken, A A M; Koppeschaar, H P F; van der Lely, A J; Drent, M L

2016-08-01

The effects of growth hormone (GH) replacement therapy on fracture risk in adult GH deficient (GHD) patients with different etiologies of pituitary GHD are not well known, due to limited data. The aim of this study was to investigate characteristics and fracture occurrence at start of (baseline) and during long-term GH replacement therapy in GHD adults previously treated for Cushing's disease (CD) or acromegaly, compared to patients with previous nonfunctioning pituitary adenoma (NFPA). From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severe GHD adults, all patients using ≥30 days of GH replacement therapy with previous NFPA (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient characteristics, fractures and potential influencing factors were investigated. At baseline, patients with previous CD were younger, more often female and had more often a history of osteopenia or osteoporosis, whereas patients with previous acromegaly had more often received cranial radiotherapy and a longer duration between treatment of their pituitary tumor and start of adult GH replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of all patients. Compared to patients with previous NFPA, only patients with previous acromegaly had an increased fracture risk after 6 years of GH replacement therapy. During GH replacement therapy, an increased fracture risk was observed in severe GHD adult patients previously treated for acromegaly, but not in those previously treated for CD, compared to severe GHD adult patients using GH replacement therapy because of previous NFPA. Further studies are needed to confirm these findings and to elucidate potential underlying mechanisms.

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

Expression of the putative gonadotropin-inhibitory hormone receptor, NPFFR1, in the anterior pituitary gland of the gilt is affected by age and sexual maturation

USDA-ARS?s Scientific Manuscript database

Gonadotropin-inhibitory hormone (GnIH) purportedly suppresses secretion of luteinizing hormone (LH) by acting through a G-protein coupled receptor (NPFFR1) in the anterior pituitary gland and hypothalamus. The objective of these studies was to determine if expression of mRNA for NPFFR1 in the reprod...

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).

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.

Pituitary Tumors in Childhood: an update in their diagnosis, treatment and molecular genetics

PubMed Central

Keil, Margaret F.; Stratakis, Constantine A.

2009-01-01

Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2 - 6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are of two types mainly, craniopharyngiomas and adenomas; craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex, familial isolated pituitary adenoma (FIPA), and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. PMID:18416659

Pituitary oxytocin and vasopressin content of rats flown on Cosmos 2044

NASA Technical Reports Server (NTRS)

Keil, L.; Evans, J.; Grindeland, R.; Krasnov, I.

1992-01-01

Preliminary studies in rats (COSMOS 1887) suggested that levels of posterior pituitary hormones were reduced by exposure to spaceflight. To confirm these preliminary findings, pituitary tissue from rats flown for 14 days on Cosmos 2044 is obtained. Posterior pituitary content of oxytocin (OT) and vasopressin (VP) were measured in these tissues as well as those from ground-based controls. The synchronous control group had feeding and lighting schedules synchronized to those in the spacecraft and were maintained in flight-type cages. Another group was housed in vivarium cages; a third group was tail suspended (T), a method used to simulate microgravity. Flight rats showed an average reduction of 27 in pituitary OT and VP compared with the three control groups. When hormone content was expressed in terms of pituitary protein (microg hormone/mg protein), the average decrease in OT and VP for the flight animals ranged from 20 to 33 percent compared with the various control groups. Reduced levels of pituitary OT and VP were similar to preliminary measurements from the Cosmos 1887 mission and appear to result from exposure to spaceflight. These data suggest that changes in the rate of hormone secretion or synthesis may have occurred during exposure to microgravity.

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.

Correlation of serum androgens and pituitary hormone levels with serum PSA less than 2.5 ng/ml.

PubMed

Sofikerim, Mustafa; Oruç, Ozgür; Eskicorapci, Sadettin; Guliyev, Fuat; Ozen, Haluk

2007-07-27

The aim of this clinical study was to determine whether there is a relationship between total serum testosterone, free testosterone, FSH (Follicle-Stimulating Hormone), LH (Luteinizing Hormone) and serum prostate specific antigen (PSA) levels. We postulated that such a correlation existed then the use of hormone specific reference ranges might enhance the usefullness of PSA concentrations <2.5 ng/mL as a marker for prostate cancer. Prior to digital rectal examination, serum was obtained from all patients between 8.30-10:00 AM for hormone and PSA concentrations. The study was performed on 210 male patients >40 years of age visiting our urology outpatient clinics. PSA was correlated to age (r = 0.23, p = 0.019), but there none between serum testosterone and age. No significant correlation was noted between testosterone or free testosterone and serum PSA levels, and none between serum FSH or LH and PSA. In age specific reference groups (41-49; 50-59; 60-69 years), we found no significant correlation between PSA and hormone concentrations. In this population of eugonadal men with serum PSA values less than 2.5 ng/ml, serum androgens and pituitary hormones do not appear to correlate with serum PSA.

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.

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.

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

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

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

Matrix metalloproteinase-9, a potential biological marker in invasive pituitary adenomas.

PubMed

Gong, Jian; Zhao, Yunge; Abdel-Fattah, Rana; Amos, Samson; Xiao, Aizhen; Lopes, M Beatriz S; Hussaini, Isa M; Laws, Edward R

2008-01-01

We analyzed MMP-9 expression using mRNA and protein level determinations and explored the possibility that matrix metalloproteinase-9 (MMP-9) is a potential biological marker of pituitary adenoma invasiveness and whether MMP-9 could be used to discriminate the extent of invasiveness among different hormonal subtypes, tumor sizes, growth characteristics, and primary versus recurrent tumors. 73 pituitary tumor specimens were snap frozen in liquid nitrogen immediately after surgical resection. RNA and protein were extracted. MMP-9 mRNA transcripts were analyzed by quantitative RT-PCR. MMP-9 protein activity was analyzed by gelatin zymography and validated by western blot analysis. Immunohistochemistry was performed to identify the presence and localization of MMP-9 in pituitary adenomas. Statistical differences between results were determined using Student's t-test or one way ANOVA. Comparing different hormonal subtypes of noninvasive and invasive pituitary tumors, MMP-9 mRNA expression was significantly increased in the majority of invasive adenomas. Considering the protein levels, our data also showed a significant increase in MMP-9 activity in the majority of invasive adenomas and these differences were confirmed by western blot analysis and immunohistochemistry. In addition, consistent differences in MMP-9 expression levels were found according to tumor subtype, tumor size, tumor extension and primary versus redo-surgery. MMP-9 expression can consistently distinguish invasive pituitary tumors from noninvasive pituitary tumors and would reflect the extent of invasiveness in pituitary tumors according to tumor subtype, size, tumor extension, primary and redo surgery, even at early stages of invasiveness. MMP-9 may be considered a potential biomarker to determine and predict the invasive nature of pituitary tumors.

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.

A GRFa2/Prop1/stem (GPS) cell niche in the pituitary.

PubMed

Garcia-Lavandeira, Montse; Quereda, Víctor; Flores, Ignacio; Saez, Carmen; Diaz-Rodriguez, Esther; Japon, Miguel A; Ryan, Aymee K; Blasco, Maria A; Dieguez, Carlos; Malumbres, Marcos; Alvarez, Clara V

2009-01-01

The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as

A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary

PubMed Central

Garcia-Lavandeira, Montse; Quereda, Víctor; Flores, Ignacio; Saez, Carmen; Diaz-Rodriguez, Esther; Japon, Miguel A.; Ryan, Aymee K.; Blasco, Maria A.; Dieguez, Carlos; Malumbres, Marcos; Alvarez, Clara V.

2009-01-01

Background The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. Principal Findings We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. Significance Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the

A FEEDBACK MODEL FOR TESTICULAR-PITUITARY AXIS HORMONE KINETICS AND THEIR EFFECTS ON THE REGULATION OF THE PROSTATE IN ADULT MALE RATS

EPA Science Inventory

The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. A model describing the kinetics and dynamics of testosterone (T), dihydrotestosterone (DHT) and luteinizing hormone (LH) was developed based on a model by Barton and Anderson (1997). The mode...

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.

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.

Leucine-enkephalin-like immunoreactivity is localized in luteinizing hormone-producing cells in the axolotl (Ambystoma mexicanum) pituitary.

PubMed

Suzuki, Hirohumi; Yamamoto, Toshiharu

2014-02-01

In this study, we used immunohistochemical techniques to determine the cell type of leucine-enkephalin (Leu-ENK)-immunoreactive cells in the axolotl (Ambystoma mexicanum) pituitary. Immunoreactive cells were scattered throughout the pars distalis except for the dorso-caudal portion. These cells were immuno-positive for luteinizing hormone (LH), but they were immuno-negative for adrenocorticotrophic, growth, and thyroid-stimulating hormones, as well as prolactin. Immunoelectron microscopy demonstrated that Leu-ENK-like substance and LH co-localized within the same secretory granules. Leu-ENK secreted from gonadotrophs may participate in LH secretion in an autocrine fashion, and/or may participate in the release of sex steroids together with LH. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Effects of prenatal lipopolysaccharide exposure on reproductive activities and serum concentrations of pituitary-gonadal hormones in mice offspring.

PubMed

Solati, Jalal; Hajikhani, Ramin; Rashidieh, Behnam; Jalilian, Mahshid Fatipour

2012-04-01

Maternal infection during pregnancy is a risk factor for some behavioral problems with neurodevelopmental origin. This study aimed to evaluate the effects of exposure of pregnant mice to the bacterial lipopolysaccharide (LPS) on sexual behaviour and serum level of pituitary-gonadal hormones of offspring in adulthood. In this Expremental study, pregnant NMRI mice (n=7/group) were treated with intra-peritoneal administration of LPS (1, 5 and 10 µg/kg) at day 10 of gestation. Induction of the pro-inflammatory cytokines, Tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were measured in maternal serum 2 hours following the maternal LPS challenge. Behavior in the adult male offspring reproductive activity was investigated using receptive female mice. Concentrations of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in adult offspring serum were measured using the enzyme-linked immunosorbent assay (ELISA) method (at postnatal day 60, n=10/group). One-way ANOVA showed that LPS administration induces a significant increase in TNF-α, IL-1β and IL-6 levels of maternal serum. Prenatal LPS exposure reduces sexual behavior and serum concentration of LH and testosterone in adult male offspring. The overall results suggest that prenatal exposure to LPS increases pro- inflammatory cytokine levels, affects development of neuroendocrine systems and results in the inhibition of reproductive behaviors and reactivity of hypothalamic-pituitary-gonadal (HPG) axis in adult male offspring.

Relationships between the pituitary-adrenal hormones, insulin, and glucose in middle-aged men: moderating influence of psychosocial stress.

PubMed

Keltikangas-Järvinen, L; Ravaja, N; Räikkönen, K; Hautanen, A; Adlercreutz, H

1998-12-01

We examined whether the relationships between the pituitary-adrenal hormones (corticotropin [ACTH) and cortisol), insulin, and glucose differ as a function of psychosocial stress defined in terms of vital exhaustion (VE) and depressive behavior (DB). The participants were 69 normotensive and 21 unmedicated borderline hypertensive (BH) middle-aged men whose work is stressful. Hormonal and metabolic variables were measured during an oral glucose tolerance test (OGTT), and the cortisol response to dexamethasone (DXM) suppression and intravenous ACTH stimulation was also measured. We found that the basal ACTH level during the OGTT was positively associated with the cortisol response to ACTH at 60 minutes, the fasting insulin level, and the insulin to glucose ratio among exhausted and high DB men, while the reverse was true for nonexhausted and low DB men. Also, a high cortisol response to ACTH, a low cortisol level during the OGTT, and a high ratio of these cortisol determinations (cortisol ratio) were associated with high fasting insulin and glucose levels, the summed insulin values, and the insulin to glucose ratio only among nonexhausted and low DB men; among exhausted and high DB men, these associations were less pronounced, absent, or in the opposite direction. The findings suggest that VE and DB have a moderating influence on the relationships among the hormonal and metabolic parameters studied. Psychosocial stress may affect the pituitary-adrenocortical system in complex ways, contributing thereby to insulin resistance, hyperinsulinemia, and coronary heart disease (CHD) risk.

Expression and regulation of glucocorticoid-induced leucine zipper in the developing anterior pituitary gland.

PubMed

Ellestad, Laura E; Malkiewicz, Stefanie A; Guthrie, H David; Welch, Glenn R; Porter, Tom E

2009-02-01

The expression profile of glucocorticoid-induced leucine zipper (GILZ) in the anterior pituitary during the second half of embryonic development in the chick is consistent with in vivo regulation by circulating corticosteroids. However, nothing else has been reported about the presence of GILZ in the neuroendocrine system. We sought to characterize expression and regulation of GILZ in the chicken embryonic pituitary gland and determine the effect of GILZ overexpression on anterior pituitary hormone levels. Pituitary GILZ mRNA levels increased during embryogenesis to a maximum on the day of hatch, and decreased through the first week after hatch. GILZ expression was rapidly upregulated by corticosterone in embryonic pituitary cells. To determine whether GILZ regulates hormone gene expression in the developing anterior pituitary, we overexpressed GILZ in embryonic pituitary cells and measured mRNA for the major pituitary hormones. Exogenous GILZ increased prolactin mRNA above basal levels, but not as high as that in corticosterone-treated cells, indicating that GILZ may play a small role in lactotroph differentiation. The largest effect we observed was a twofold increase in FSH beta subunit in cells transfected with GILZ but not treated with corticosterone, suggesting that GILZ may positively regulate gonadotroph development in a manner not involving glucocorticoids. In conclusion, this is the first report to characterize avian GILZ and examine its regulation in the developing neuroendocrine system. We have shown that GILZ is upregulated by glucocorticoids in the embryonic pituitary gland and may regulate expression of several pituitary hormones.

Gonadotrophin-releasing activity of neurohypophysial hormones: II. The pituitary oxytocin receptor mediating gonadotrophin release differs from that of corticotrophs.

PubMed

Evans, J J; Catt, K J

1989-07-01

Neurohypophysial hormones stimulate gonadotrophin release from dispersed rat anterior pituitary cells in vitro, acting through receptors distinct from those which mediate the secretory response to gonadotrophin-releasing hormone (GnRH). The LH response to oxytocin was not affected by the presence of the phosphodiesterase inhibitor, methyl isobutylxanthine, but was diminished in the absence of extracellular calcium and was progressively increased as the calcium concentration in the medium was raised to normal. In addition, the calcium channel antagonist, nifedipine, suppressed oxytocin-stimulated secretion of LH. It is likely that the mechanisms of LH release induced by GnRH and neurohypophysial hormones are similar, although stimulation of gonadotrophin secretion is mediated by separate receptor systems. Oxytocin was more active than vasopressin in releasing LH, but less active in releasing ACTH. The highly selective oxytocin agonist, [Thr4,Gly7]oxytocin, elicited concentration-dependent secretion of LH but had little effect on corticotrophin secretion. The neurohypophysial hormone antagonist analogues, [d(CH2)5Tyr(Me)2]vasopressin, [d(CH2)5Tyr(Me)2,Orn8]vasotocin and [d(CH2)5D-Tyr(Et)2Val4,Cit8]vasopressin, inhibited the LH response to both oxytocin and vasopressin. However, [d(CH2)5Tyr(Me)2]vasopressin was much less effective in inhibiting the ACTH response to the neurohypophysial hormones, and [d(CH2)5Tyr-(Me)2,Orn8]vasotocin and [d(CH2)5D-Tyr(Et)2,Val4,Cit8]vasopressin exhibited no inhibitory activity against ACTH release. Thus, agonist and antagonist analogues of neurohypophysial hormones display divergent activities with regard to LH and ACTH responses, and the neuropeptide receptor mediating gonadotroph activation is clearly different from that on the corticotroph. Whereas the corticotroph receptor is a vasopressin-type receptor an oxytocin-type receptor is responsible for gonadotrophin release by neurohypophysial hormones.

Mutation analysis of inhibitory guanine nucleotide binding protein alpha (GNAI) loci in young and familial pituitary adenomas.

PubMed

Demir, Hande; Donner, Iikki; Kivipelto, Leena; Kuismin, Outi; Schalin-Jäntti, Camilla; De Menis, Ernesto; Karhu, Auli

2014-01-01

Pituitary adenomas are neoplasms of the anterior pituitary lobe and account for 15-20% of all intracranial tumors. Although most pituitary tumors are benign they can cause severe symptoms related to tumor size as well as hypopituitarism and/or hypersecretion of one or more pituitary hormones. Most pituitary adenomas are sporadic, but it has been estimated that 5% of patients have a familial background. Germline mutations of the tumor suppressor gene aryl hydrocarbon receptor-interacting protein (AIP) predispose to hereditary pituitary neoplasia. Recently, it has been demonstrated that AIP mutations predispose to pituitary tumorigenesis through defective inhibitory GTP binding protein (Gαi) signaling. This finding prompted us to examine whether germline loss-of-function mutations in inhibitory guanine nucleotide (GTP) binding protein alpha (GNAI) loci are involved in genetic predisposition of pituitary tumors. To our knowledge, this is the first time GNAI genes are sequenced in order to examine the occurrence of inactivating germline mutations. Thus far, only somatic gain-of-function hot-spot mutations have been studied in these loci. Here, we have analyzed the coding regions of GNAI1, GNAI2, and GNAI3 in a set of young sporadic somatotropinoma patients (n = 32; mean age of diagnosis 32 years) and familial index cases (n = 14), thus in patients with a disease phenotype similar to that observed in AIP mutation carriers. In addition, expression of Gαi proteins was studied in human growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH)-secreting and non-functional pituitary tumors. No pathogenic germline mutations affecting the Gαi proteins were detected. The result suggests that loss-of-function mutations of GNAI loci are rare or nonexistent in familial pituitary adenomas.

Mutation Analysis of Inhibitory Guanine Nucleotide Binding Protein Alpha (GNAI) Loci in Young and Familial Pituitary Adenomas

PubMed Central

Demir, Hande; Donner, Iikki; Kivipelto, Leena; Kuismin, Outi; Schalin-Jäntti, Camilla; De Menis, Ernesto; Karhu, Auli

2014-01-01

Pituitary adenomas are neoplasms of the anterior pituitary lobe and account for 15–20% of all intracranial tumors. Although most pituitary tumors are benign they can cause severe symptoms related to tumor size as well as hypopituitarism and/or hypersecretion of one or more pituitary hormones. Most pituitary adenomas are sporadic, but it has been estimated that 5% of patients have a familial background. Germline mutations of the tumor suppressor gene aryl hydrocarbon receptor-interacting protein (AIP) predispose to hereditary pituitary neoplasia. Recently, it has been demonstrated that AIP mutations predispose to pituitary tumorigenesis through defective inhibitory GTP binding protein (Gαi) signaling. This finding prompted us to examine whether germline loss-of-function mutations in inhibitory guanine nucleotide (GTP) binding protein alpha (GNAI) loci are involved in genetic predisposition of pituitary tumors. To our knowledge, this is the first time GNAI genes are sequenced in order to examine the occurrence of inactivating germline mutations. Thus far, only somatic gain-of-function hot-spot mutations have been studied in these loci. Here, we have analyzed the coding regions of GNAI1 , GNAI2, and GNAI3 in a set of young sporadic somatotropinoma patients (n = 32; mean age of diagnosis 32 years) and familial index cases (n = 14), thus in patients with a disease phenotype similar to that observed in AIP mutation carriers. In addition, expression of Gαi proteins was studied in human growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH)-secreting and non-functional pituitary tumors. No pathogenic germline mutations affecting the Gαi proteins were detected. The result suggests that loss-of-function mutations of GNAI loci are rare or nonexistent in familial pituitary adenomas. PMID:25291362

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.

[Influence of replacement growth hormone therapy (hGH) on pituitary-thyroid and pituitary-adrenal systems in prepubertal children with GH deficiency].

PubMed

Vyshnevs'ka, O A; Bol'shova, O V

2013-06-01

Today, the most pathogenic therapy of GH deficiency is hGH replacement therapy. Replacement hGH therapy a highly effective method of growth correction in children with GH deficiency, but further investigations are necessary for timely detection of disturbances of other organs and systems. The authors reported that hGH therapy supressed thyroid and adrenal functions. Besides, most patients with GH deficiency have multiple defficiency of pituitary hormones (both TSH and ACTH), so hGH therapy can enhances hypothyroidism and hypoadrenalism. In the Department of Pediatric Endocrinology of the Institute of Endocrinology and Metabolism a great experience was accumulated in the treatment of GH deficiency children and in the study of the efficacy and safety of this treatment.

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.

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.

Metabolic regulation of ghrelin O-acyl transferase (GOAT) expression in the mouse hypothalamus, pituitary, and stomach.

PubMed

Gahete, Manuel D; Córdoba-Chacón, Jose; Salvatori, Roberto; Castaño, Justo P; Kineman, Rhonda D; Luque, Raul M

2010-04-12

Ghrelin acts as an endocrine link connecting physiological processes regulating food intake, body composition, growth, and energy balance. Ghrelin is the only peptide known to undergo octanoylation. The enzyme mediating this process, ghrelin O-acyltransferase (GOAT), is expressed in the gastrointestinal tract (GI; primary source of circulating ghrelin) as well as other tissues. The present study demonstrates that stomach GOAT mRNA levels correlate with circulating acylated-ghrelin levels in fasted and diet-induced obese mice. In addition, GOAT was found to be expressed in both the pituitary and hypothalamus (two target tissues of ghrelin's actions), and regulated in response to metabolic status. Using primary pituitary cell cultures as a model system to study the regulation of GOAT expression, we found that acylated-ghrelin, but not desacyl-ghrelin, increased GOAT expression. In addition, growth-hormone-releasing hormone (GHRH) and leptin increased, while somatostatin (SST) decreased GOAT expression. The physiologic relevance of these later results is supported by the observation that pituitary GOAT expression in mice lacking GHRH, SST and leptin showed opposite changes to those observed after in vitro treatment with the corresponding peptides. Therefore, it seems plausible that these hormones directly contribute to the regulation of pituitary GOAT. Interestingly, in all the models studied, pituitary GOAT expression paralleled changes in the expression of a dominant spliced-variant of ghrelin (In2-ghrelin) and therefore this transcript may be a primary substrate for pituitary GOAT. Collectively, these observations support the notion that the GI tract is not the only source of acylated-ghrelin, but in fact locally produced des-acylated-ghrelin could be converted to acylated-ghrelin within target tissues by locally active GOAT, to mediate its tissue-specific effects.

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.

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.

ZBTB20 is required for anterior pituitary development and lactotrope specification.

PubMed

Cao, Dongmei; Ma, Xianhua; Cai, Jiao; Luan, Jing; Liu, An-Jun; Yang, Rui; Cao, Yi; Zhu, Xiaotong; Zhang, Hai; Chen, Yu-Xia; Shi, Yuguang; Shi, Guang-Xia; Zou, Dajin; Cao, Xuetao; Grusby, Michael J; Xie, Zhifang; Zhang, Weiping J

2016-04-15

The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

ZBTB20 is required for anterior pituitary development and lactotrope specification

PubMed Central

Cao, Dongmei; Ma, Xianhua; Cai, Jiao; Luan, Jing; Liu, An-Jun; Yang, Rui; Cao, Yi; Zhu, Xiaotong; Zhang, Hai; Chen, Yu-Xia; Shi, Yuguang; Shi, Guang-Xia; Zou, Dajin; Cao, Xuetao; Grusby, Michael J.; Xie, Zhifang; Zhang, Weiping J.

2016-01-01

The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification. PMID:27079169

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 ...

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.

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.

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.

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.

Control of leptin by metabolic state and its regulatory interactions with pituitary growth hormone and hepatic growth hormone receptors and insulin like growth factors in the tilapia (Oreochromis mossambicus).

PubMed

Douros, Jonathan D; Baltzegar, David A; Mankiewicz, Jamie; Taylor, Jordan; Yamaguchi, Yoko; Lerner, Darren T; Seale, Andre P; Grau, E Gordon; Breves, Jason P; Borski, Russell J

2017-01-01

Leptin is an important cytokine for regulating energy homeostasis, however, relatively little is known about its function and control in teleost fishes or other ectotherms, particularly with regard to interactions with the growth hormone (GH)/insulin-like growth factors (IGFs) growth regulatory axis. Here we assessed the regulation of LepA, the dominant paralog in tilapia (Oreochromis mossambicus) and other teleosts under altered nutritional state, and evaluated how LepA might alter pituitary growth hormone (GH) and hepatic insulin-like growth factors (IGFs) that are known to be disparately regulated by metabolic state. Circulating LepA, and lepa and lepr gene expression increased after 3-weeks fasting and declined to control levels 10days following refeeding. This pattern of leptin regulation by metabolic state is similar to that previously observed for pituitary GH and opposite that of hepatic GHR and/or IGF dynamics in tilapia and other fishes. We therefore evaluated if LepA might differentially regulate pituitary GH, and hepatic GH receptors (GHRs) and IGFs. Recombinant tilapia LepA (rtLepA) increased hepatic gene expression of igf-1, igf-2, ghr-1, and ghr-2 from isolated hepatocytes following 24h incubation. Intraperitoneal rtLepA injection, on the other hand, stimulated hepatic igf-1, but had little effect on hepatic igf-2, ghr1, or ghr2 mRNA abundance. LepA suppressed GH accumulation and gh mRNA in pituitaries in vitro, but had no effect on GH release. We next sought to test if abolition of pituitary GH via hypophysectomy (Hx) affects the expression of hepatic lepa and lepr. Hypophysectomy significantly increases hepatic lepa mRNA abundance, while GH replacement in Hx fish restores lepa mRNA levels to that of sham controls. Leptin receptor (lepr) mRNA was unchanged by Hx. In in vitro hepatocyte incubations, GH inhibits lepa and lepr mRNA expression at low concentrations, while higher concentration stimulates lepa expression. Taken together, these findings

Role of Growth Hormone in Breast Cancer.

PubMed

Subramani, Ramadevi; Nandy, Sushmita B; Pedroza, Diego A; Lakshmanaswamy, Rajkumar

2017-06-01

Breast cancer is one of the most common cancers diagnosed in women. Approximately two-thirds of all breast cancers diagnosed are classified as hormone dependent, which indicates that hormones are the key factors that drive the growth of these breast cancers. Ovarian and pituitary hormones play a major role in the growth and development of normal mammary glands and breast cancer. In particular, the effect of the ovarian hormone estrogen has received much attention in regard to breast cancer. Pituitary hormones prolactin and growth hormone have also been associated with breast cancer. Although the role of these pituitary hormones in breast cancers has been studied, it has not been investigated extensively. In this review, we attempt to compile basic information from most of the currently available literature to understand and demonstrate the significance of growth hormone in breast cancer. Based on the available literature, it is clear that growth hormone plays a significant role in the development, progression, and metastasis of breast cancer by influencing tumor angiogenesis, stemness, and chemoresistance. Copyright © 2017 Endocrine Society.

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.

Patient reported outcome in posttraumatic pituitary deficiency: results from The Danish National Study on posttraumatic hypopituitarism.

PubMed

Klose, Marianne; Stochholm, Kirstine; Janukonyté, Jurgita; Christensen, Louise Lehman; Cohen, Arieh S; Wagner, Aase; Laurberg, Peter; Christiansen, Jens Sandahl; Andersen, Marianne; Feldt-Rasmussen, Ulla

2015-06-01

Posttraumatic pituitary hormone deficiency is often suggested. The impact of these predominantly mild and often irreproducible deficiencies on outcome is less clear. The aim of the present study was to describe patient reported outcome in a national a priori unselected cohort of patients with traumatic brain injury (TBI) in relation to deficiencies identified upon pituitary assessment. We conducted a nationwide population-based cohort study. Participants were Danish patients with a head trauma diagnosis recorded in the Danish Board of Health diagnostic code registry; 439 patients (and 124 healthy controls) underwent assessment of anterior pituitary function 2.5 years (median) after TBI. Questionnaires on health-related quality of life (QoL) (SF36, EuroQoL-5D, QoL assessment of GH deficiency in adults) and fatigue (MFI-20) were completed in parallel to pituitary assessment. Patients with TBI had significant detriments in QoL. Impairment (mainly physical scales) related to pituitary deficiency, although only partially confirmed after adjustment for demographic differences. Hypogonadotropic hypogonadism related to several QoL scores. Increasing impairments were observed with declining total testosterone concentrations (men), but not free testosterone concentrations or any other hormone concentrations. Total testosterone was not independently related to impaired QoL and fatigue, after adjustment for demographics, and treatment with antidiabetics, opioids, antidepressants, and anticonvulsants. Only a very limited relationship between pituitary hormone deficiencies and QoL/fatigue was demonstrated. Due to the dominating influence of concurrent comorbidities, pituitary deficiencies were not independently related to QoL/fatigue. Causality is still to be shown, and whether substitution therapy could be of additional relevance in selected patients needs to be proven. © 2015 European Society of Endocrinology.

Chronic food restriction and the circadian rhythms of pituitary-adrenal hormones, growth hormone and thyroid-stimulating hormone.

PubMed

Armario, A; Montero, J L; Jolin, T

1987-01-01

Adult male Sprague-Dawley rats were subjected to food restriction so that they ate 65% of food ingested by control rats. While control rats had free access to food over the 24-hour period, food-restricted rats were provided with food daily at 10 a.m. The experimental period lasted for 34 days. On day 35, rats from both experimental groups were killed at 08.00, 11.00, 14.00, 24.00 and 02.00 h. Food restriction modified the circadian rhythms of ACTH and corticosterone. In addition, total circulating corticosterone throughout the day was higher in food-restricted than in control rats. In contrast, food restriction resulted in depressed secretion of thyroid-stimulating hormone and growth hormone. The results indicate that time of food availability entrained circadian corticosterone rhythm but not thyroid-stimulating hormone and growth hormone rhythms.

Relative contributions of pituitary-adrenal hormones to the ontogeny of behavioral inhibition in the rat.

PubMed

Takahashi, L K; Kim, H

1995-04-01

Recent investigations revealed that adrenalectomized (ADX) rat pups exhibit deficits in behavioral inhibition. Furthermore, administration of exogenous corticosterone (CORT) restores behavioral inhibition in ADX pups. Although these studies suggest that CORT has an important role in the development of behavioral inhibition, the relative behavioral effects of elevated pituitary hormone secretion induced by ADX are not known. Therefore, experiments were conducted to assess the potential behavioral effects of elevated adrenocorticotropin (ACTH) secretion induced by ADX and to further evaluate the contribution of endogenous CORT to the development of behavioral inhibition. In Experiment 1., we verified that 10-day-old ADX rats exhibit high levels of plasma ACTH throughout the preweaning period associated with the development of behavioral inhibition. In Experiment 2, 10-day-old pups were hypophysectomized (HYPOX) and ADX and were compared behaviorally to sham-operated controls on day 14. When tested in the presence of an anesthetized unfamiliar adult male rat, HYPOX + ADX pups exhibited low levels of freezing accompanied by ultrasonic vocalizations. These pups also had reduced concentrations of plasma ACTH and CORT. In Experiment 3, 10-day-old pups were HYPOX and tested for behavioral inhibition on day 14. In comparison to sham-operated controls, HYPOX rats exhibited significantly lower levels of freezing and had reduced plasma concentrations of ACTH and CORT. Results demonstrate clearly that deficits in freezing occur even in the presence of low plasma ACTH concentrations. Therefore, elevated secretion of pituitary hormones is not a major factor that contributes to the ADX-induced deficits in behavioral inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes of rats with mammary gland cancer induced by N-methyl nitrosourea.

PubMed

Carrera, M P; Ramírez-Expósito, M J; Valenzuela, M T; García, M J; Mayas, M D; Arias de Saavedra, J M; Sánchez, R; Pérez, M C; Martínez-Martos, J M

2005-02-01

Pyrrolidon carboxypeptidase is an omega-peptidase that hydrolyses N-terminal pyroglutamyl residues from biologically active peptides such as gonadotropin-releasing and thyrotrophin-releasing hormones. We previously described a decrease in both rat and human pyrrolidon carboxypeptidase activity with breast cancer, suggesting that gonadotropin-releasing hormone may be an important local intracrine, autocrine and/or paracrine hormonal factor in the pathogenesis of breast cancer while playing a role in the tumoral process. However, the other susceptible substrate of pyrrolidon carboxypeptidase, thyrotrophin-releasing hormone, may also be modified with breast cancer, supporting an association between breast cancer and thyroid disorders. The present work analyses soluble and membrane-bound pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes in N-methyl nitrosourea-induced breast cancer in rats. Our aim was to determine the possible relationship between gonadotropin-releasing hormone and thyrotrophin-releasing hormone regulation through pyrrolidon carboxypeptidase activity. We propose that pyrrolidon carboxypeptidase activity dysregulation at various local and systemic levels may participate in the initiation, promotion and progression of breast cancer induced in rat by N-methyl nitrosourea through the increase in gonadotropin-releasing hormone. Since pyrrolidon carboxypeptidase activity also acts on thyrotrophin-releasing hormone, the dysregulation of this enzyme's activity could indirectly affect hypothalamus-pituitary-thyroid axis function, and thus potentially represent a link between the diseases of thyroid and breast cancer.

Prospective investigation of pituitary functions in patients with acute infectious meningitis: is acute meningitis induced pituitary dysfunction associated with autoimmunity?

PubMed

Tanriverdi, F; De Bellis, A; Teksahin, H; Alp, E; Bizzarro, A; Sinisi, A A; Bellastella, G; Paglionico, V A; Bellastella, A; Unluhizarci, K; Doganay, M; Kelestimur, F

2012-12-01

Previous case reports and retrospective studies suggest that pituitary dysfunction may occur after acute bacterial or viral meningitis. In this prospective study we assessed the pituitary functions, lipid profile and anthropometric measures in adults with acute bacterial or viral meningitis. Moreover, in order to investigate whether autoimmune mechanisms could play a role in the pathogenesis of acute meningitis-induced hypopituitarism we also investigated the anti-pituitary antibodies (APA) and anti-hypothalamus antibodies (AHA) prospectively. Sixteen patients (10 males, 6 females; mean ± SD age 40.9 ± 15.9) with acute infectious meningitis were included and the patients were evaluated in the acute phase, and at 6 and 12 months after the acute meningitis. In the acute phase 18.7% of the patients had GH deficiency, 12.5% had ACTH and FSH/LH deficiencies. At 12 months after acute meningitis 6 of 14 patients (42.8%) had GH deficiency, 1 of 14 patients (7.1%) had ACTH and FSH/LH deficiencies. Two of 14 patients (14.3%) had combined hormone deficiencies and four patients (28.6%) had isolated hormone deficiencies at 12 months. Four of 9 (44.4%) hormone deficiencies at 6 months were recovered at 12 months, and 3 of 8 (37.5%) hormone deficiencies at 12 months were new-onset hormone deficiencies. At 12 months there were significant negative correlations between IGF-I level vs. LDL-C, and IGF-I level vs. total cholesterol. The frequency of AHA and APA positivity was substantially high, ranging from 35 to 50% of the patients throughout the 12 months period. However there were no significant correlations between AHA or APA positivity and hypopituitarism. The risk of hypopituitarism, GH deficiency in particular, is substantially high in the acute phase, after 6 and 12 months of the acute infectious meningitis. Moreover we found that 6th month after meningitis is too early to make a decision for pituitary dysfunction and these patients should be screened for at least 12 months

Prospective investigation of anterior pituitary function in the acute phase and 12 months after pediatric traumatic brain injury.

PubMed

Ulutabanca, Halil; Hatipoglu, Nihal; Tanriverdi, Fatih; Gökoglu, Abdülkerim; Keskin, Mehmet; Selcuklu, Ahmet; Kurtoglu, Selim; Kelestimur, Fahrettin

2014-06-01

Although head trauma is common in childhood, there is no enough prospective study investigating both acute phase and 12 months after injury. Therefore, a prospective clinical trial was planned to evaluate the pituitary function in childhood in the acute and chronic phase after traumatic brain injury (TBI). Forty-one children (27 boys and 14 girls, mean age 7 ± 4.3), who were admitted to neurosurgery intensive care unit due to head trauma, were included. Twenty-one (51.2 %) patients had mild, 10 (24.4 %) had moderate, and 10 (24.4 %) had severe TBI. Twenty-two of them were reevaluated 12 months after TBI. Basal pituitary hormone levels were measured during acute (first 24 h) and chronic phase of TBI. Additionally, in the chronic phase, GHRH-arginine test was used for the diagnosis of growth hormone (GH) deficiency. In the acute phase, 10 patients (24.4 %) had ACTH deficiency, and the overall 44.3 % of patients had at least one pituitary hormone dysfunction. All the pituitary hormone deficiencies during the acute phase were recovered after 12 months. Two patients (9.1 %) had new-onset GH deficiency in the chronic phase, and in one of them, ACTH deficiency was also present. Present prospective data clearly demonstrated that most of the hormonal changes in the early acute phase were transient, suggesting an adaptive response, and these changes did not predict the hormone deficiencies after 1 year. In the chronic phase, although GH deficiency was present, the frequency of TBI-induced hypopituitarism was clearly lower than the adult patients.

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.

Body composition and metabolic health of young male adults with childhood-onset multiple pituitary hormone deficiency after cessation of growth hormone treatment.

PubMed

Yang, Hongbo; Wang, Linjie; Qiu, Xiaonan; Yan, Kemin; Gong, Fengying; Zhu, Huijuan; Pan, Hui

2018-04-25

Recombinant human growth hormone (rhGH) replacement therapy is usually stopped after linear growth completion in patients with growth hormone deficiency. In patients with multiple pituitary hormone deficiency (MPHD), the long-term effects of discontinuation of rhGH replacement are unknown. In this study, the anthropometric and metabolic parameters of 24 male patients with adult growth hormone deficiency (AGHD) due to MPHD in childhood after cessation of rhGH therapy for a mean of 7.1 years were measured and compared with 35 age-matched controls. Body composition was evaluated by bioelectrical impedance analysis (BIA). In the AGHD group, body mass index (BMI) was significantly increased and 29.2% had obesity. The AGHD group had a 17.7 cm increase in waist circumference (WC). The fat free mass (FFM) was significantly lower in the AGHD group. Both the fat mass (FM) and percentage of fat mass (FM%) were significantly increased in the AGHD group. Both the systolic blood pressure (BP) and diastolic pressure were significantly lower in AGHD group. The lipid profile was generally similar in both groups, except for a decrease of high density lipoprotein-cholesterol (HDL-C) in the AGHD group. There was significant hyperuricemia in the AGHD group. Cessation of rhGH leads to a significant increase of FM in early adulthood in male patients with childhood-onset MPHD (CO-MPHD).

TSH-induced hyperthyroidism caused by a pituitary tumor.

PubMed

Beck-Peccoz, Paolo; Persani, Luca

2006-09-01

A 45-year-old man presented with frontal headache and visual disturbances to our clinic. For the previous 5 years, he had been receiving treatment for long-lasting mild hyperthyroidism with antithyroid therapy, but therapy had not been carefully followed. During the last 2 years he had also complained of erectile dysfunction and loss of libido. On physical examination, he had a small goiter, normal skin, no Graves' ophthalmopathy, normal BMI, and reduced testis volume and pubic hair. Serum levels of free T3 and T4, serum prolactin, testosterone, serum gonadotropins, insulin-like growth factor 1, adrenocorticotropic hormone, and cortisol were measured. MRI scan, TSH-releasing hormone test, and T3 suppression test were carried out. Levels of pituitary glycoprotein hormone alpha-subunit and sex-hormone-binding protein were also measured. Hyperthyroidism caused by a mixed pituitary adenoma that secretes prolactin and TSH. Trans-sphenoidal resection of the pituitary tumor. After surgery, T3 suppression test failed to completely suppress TSH secretion, which suggested a persistence of residual adenomatous cells. Hyperthyroidism and hypogonadism recurred after 5 years, therefore, treatment with lanreotide was initiated, and resulted in complete resolution of signs and symptoms of the disease.

Pituitary-ovarian hormone levels and symptoms in oral contraceptive users: comparison of a 21/7-day and extended regimen.

PubMed

Kuehl, Thomas J; Speikermann, A Michael; Willis, Sherilyn A; Coffee, Andrea; Sulak, Patricia J

2008-04-01

To compare hormone levels and symptoms during transition from standard to extended oral contraceptive (OC) regimens. A prospective analysis of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and inhibin-B levels with symptoms during 21/7-day vs. 168/7-day extended OCs containing 3 mg of drosperinone and 30 mcg of ethinyl estradiol. Blood samples were obtained from 10 subjects in each of 4 weeks in the 21/7 regimen, in the first 6 weeks of the extended regimen, and again the week before, the week of and the week after the 7-day hormone-free interval (HFI) at the end of the extended regimen. All 4 hormones followed a cyclic pattern with decreasing levels during the 3 active pill weeks of the 21/7 cycle, followed by an increase during the 7-day HFI, which continued into the extended regimen. Levels then decreased during the extended regimen and remained low at week 24. During the 7-day HFI after the extended regimen FSH and LH again increased above baseline (p > 0.07). Hormone withdrawal symptoms increased at the end of 21 active pills with increasing severity during the 7-day HFI. Absence of pituitary and ovarian suppression associated with HFI leads to fluctuations in hormones and associated hormone withdrawal symptoms.

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.

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

[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.

Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas

PubMed Central

Wang, Ji-wen; Li, Ying; Mao, Zhi-gang; Hu, Bin; Jiang, Xiao-bing; Song, Bing-bing; Wang, Xin; Zhu, Yong-hong; Wang, Hai-jun

2014-01-01

Excessive growth hormone (GH) is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF) 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4–6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits. PMID:24421637

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.

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.

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

Prolactin-Producing Pituitary Carcinoma, Hypopituitarism, and Graves' Disease-Report of a Challenging Case and Literature Review.

PubMed

Bettencourt-Silva, Rita; Pereira, Josué; Belo, Sandra; Magalhães, Daniela; Queirós, Joana; Carvalho, Davide

2018-01-01

The diagnosis of pituitary carcinoma is very rare, requires the evidence of metastatic disease, and has a poor overall survival. Malignant prolactinoma frequently requires dopamine agonist therapy, pituitary surgery, radiotherapy, and even chemotherapy. A 19-year-old female presented with galactorrhea, primary amenorrhea, and left hemianopsia. Complementary study detected hyperprolactinemia and a pituitary macroadenoma with cavernous sinus invasion and suprasellar growth. She was treated with cabergoline and bromocriptine without clinical or analytical improvement. Resection of the pituitary lesion was programmed and a non-contiguous lesion of the nasal mucosa was detected during the approach. This metastasis led to the diagnosis of prolactin-producing pituitary carcinoma. After partial resection, the patient was submitted to radiotherapy for residual disease with persistent symptoms. She developed growth hormone deficiency, central hypothyroidism, hypogonadism, and permanent diabetes insipidus. Six years later she was admitted for the suspicion of secondary adrenal insufficiency and thyrotoxicosis. Physical findings, laboratory data, thyroid ultrasound, and scintigraphy achieved the diagnosis of Graves' disease and hypocortisolism. She was treated with hydrocortisone and methimazole, but central hypothyroidism recurred after antithyroid drug withdrawal. Nine years after the diagnosis of a pituitary carcinoma, she maintains treatment with bromocriptine, has a locally stable disease, with no metastases. This report highlights an unusual presentation of a prolactin-producing pituitary carcinoma in a young female. The patient had multiple hormone deficiencies due to a pituitary lesion and treatments. The posterior development of hyperthyroidism and adrenal insufficiency brought an additional difficulty to the approach.

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.

Cre-mediated recombination in pituitary somatotropes

PubMed Central

Nasonkin, Igor O.; Potok, Mary Anne; Camper, Sally A.

2009-01-01

We report a transgenic line with highly penetrant cre recombinase activity in the somatotrope cells of the anterior pituitary gland. Expression of the cre transgene is under the control of the locus control region of the human growth hormone gene cluster and the rat growth hormone promoter. Cre recombinase activity was assessed with two different lacZ reporter genes that require excision of a floxed stop sequence for expression: a chick β-actin promoter with the CMV enhancer transgene and a ROSA26 knock-in. Cre activity is detectable in the developing pituitary after initiation of Gh transcription and persists through adulthood with high penetrance in Gh expressing cells and lower penetrance in lactotropes, a cell type that shares a common origin with somatotropes. This Gh-cre transgenic line is suitable for efficient, cell-specific deletion of floxed regions of genomic DNA in differentiated somatotropes and a subset of lactotrope cells of the anterior pituitary gland. PMID:19039787

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

Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.

PubMed

Ding, Yu; Li, Juan; Yu, Yongguo; Yang, Peirong; Li, Huaiyuan; Shen, Yongnian; Huang, Xiaodong; Liu, Shijian

2018-03-28

This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.

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

Electrophoretic separation of kidney and pituitary cells on STS-8

NASA Technical Reports Server (NTRS)

Morrison, D. R.; Nachtwey, D. S.; Barlow, G. H.; Cleveland, C.; Lanham, J. W.; Farrington, M. A.; Hatfield, J. M.; Hymer, W. C.; Grindeland, R.; Lewis, M. L.

1984-01-01

Specific secretory cells were separated from suspensions of cultured primary human embryonic cells and rat pituitary cells in microgravity conditions, with an objective of isolating the subfractions of kidney cells that produce the largest amount of urakinase, and the subfractions of rat pituitary cells that secrete growth hormones (GH), prolactin (PRL), and other hormones. It is inferred from the experimental observations that the surface charge distributions of the GH-containing cells differ from those of the PRL-containing cells, which is explained by the presence of secretory products on the surface of pituitary cells. For kidney cells, the electrophoretic mobility distributions in flight experiments were spread more than the ground controls.

Analysis of differential gene expression by bead-based fiber-optic array in growth-hormone-secreting pituitary adenomas.

PubMed

Jiang, Zhiquan; Gui, Songbo; Zhang, Yazhuo

2010-09-01

Growth-hormone-secreting pituitary adenomas (GHomas) account for approximately 20% of all pituitary neoplasms. However, the pathogenesis of GHomas remains to be elucidated. To explore the possible pathogenesis of GHomas, we used bead-based fiber-optic arrays to examine the gene expression in five GHomas and compared them to three healthy pituitaries. Four differentially expressed genes were chosen randomly for validation by quantitative real-time reverse transcription-polymerase chain reaction. We then performed pathway analysis on the identified differentially expressed genes using the Kyoto Encyclopedia of Genes and Genomes. Array analysis showed significant increases in the expression of 353 genes and 206 expressed sequence tags (ESTs) and decreases in 565 genes and 29 ESTs. Bioinformatic analysis showed that the genes HIGD1B, HOXB2, ANGPT2, HPGD and BTG2 may play an important role in the tumorigenesis and progression of GHomas. Pathway analysis showed that the wingless-type signaling pathway and extracellular-matrix receptor interactions may play a key role in the tumorigenesis and progression of GHomas. Our data suggested that there are numerous aberrantly expressed genes and pathways involved in the pathogenesis of GHomas. Bead-based fiber-optic arrays combined with pathway analysis of differentially expressed genes appear to be a valid method for investigating the pathogenesis of tumors.

Analysis of differential gene expression by bead-based fiber-optic array in growth-hormone-secreting pituitary adenomas

PubMed Central

JIANG, ZHIQUAN; GUI, SONGBO; ZHANG, YAZHUO

2010-01-01

Growth-hormone-secreting pituitary adenomas (GHomas) account for approximately 20% of all pituitary neoplasms. However, the pathogenesis of GHomas remains to be elucidated. To explore the possible pathogenesis of GHomas, we used bead-based fiber-optic arrays to examine the gene expression in five GHomas and compared them to three healthy pituitaries. Four differentially expressed genes were chosen randomly for validation by quantitative real-time reverse transcription-polymerase chain reaction. We then performed pathway analysis on the identified differentially expressed genes using the Kyoto Encyclopedia of Genes and Genomes. Array analysis showed significant increases in the expression of 353 genes and 206 expressed sequence tags (ESTs) and decreases in 565 genes and 29 ESTs. Bioinformatic analysis showed that the genes HIGD1B, HOXB2, ANGPT2, HPGD and BTG2 may play an important role in the tumorigenesis and progression of GHomas. Pathway analysis showed that the wingless-type signaling pathway and extracellular-matrix receptor interactions may play a key role in the tumorigenesis and progression of GHomas. Our data suggested that there are numerous aberrantly expressed genes and pathways involved in the pathogenesis of GHomas. Bead-based fiber-optic arrays combined with pathway analysis of differentially expressed genes appear to be a valid method for investigating the pathogenesis of tumors. PMID:22993617

Forkhead Box O1 Is Present in Quiescent Pituitary Cells during Development and Is Increased in the Absence of p27Kip1

PubMed Central

Majumdar, Sreeparna; Farris, Corrie L.; Kabat, Brock E.; Jung, Deborah O.; Ellsworth, Buffy S.

2012-01-01

Congenital pituitary hormone deficiencies have been reported in approximately one in 4,000 live births, however studies reporting mutations in some widely studied transcription factors account for only a fraction of congenital hormone deficiencies in humans. Anterior pituitary hormones are required for development and function of several glands including gonads, adrenals, and thyroid. In order to identify additional factors that contribute to human congenital hormone deficiencies, we are investigating the forkhead transcription factor, FOXO1, which has been implicated in development of several organs including ovary, testis, and brain. We find that FOXO1 is present in the nuclei of non-dividing pituitary cells during embryonic development, consistent with a role in limiting proliferation and/or promoting differentiation. FOXO1 is present in a subset of differentiated cells at e18.5 and in adult with highest level of expression in somatotrope cells. We detected FOXO1 in p27Kip1-positive cells at e14.5. In the absence of p27Kip1 the number of pituitary cells containing FOXO1 is significantly increased at e14.5 suggesting that a feedback loop regulates the interplay between FOXO1 and p27Kip1. PMID:23251696

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.

Electrophoretic separation of cells and particles from rat pituitary and rat spleen

NASA Technical Reports Server (NTRS)

Hymer, Wesley C.

1993-01-01

There are 3 parts to the IML-2 TX-101 experiment. Part 1 is a pituitary cell culture experiment. Part 2 is a pituitary cell separation experiment using the Japanese free flow electrophoresis unit (FFEU). Part 3 is a pituitary secretory granule separation experiment using the FFEU. The objectives of this three part experiment are: (1) to determine the kinetics of production of biologically active growth hormone (GH) and prolactin (PRL) in rat pituitary GH and PRL cells in microgravity (micro-g); (2) to investigate three mechanisms by which a micro-g-induced lesion in hormone production may occur; and (3) to determine the quality of separations of pituitary cells and organelles by continuous flow electrophoresis (CFE) in micro-g under conditions where buoyancy-induced convection is eliminated.

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.

The Characteristics of Incidental Pituitary Microadenomas in 120 Korean Forensic Autopsy Cases

PubMed Central

Kim, Jang-Hee; Seo, Jung-Seok; Lee, Bong-Woo; Lee, Sang-Young; Jeon, Seok-Hoon

2007-01-01

To investigate the characteristics of incidental pituitary microadenomas, we examined 120 pituitary glands from Korean forensic autopsy cases, from which eight tumors were identified (incidence 6.7%). The average age of the affected subjects was 50 yr (range: 33-96 yr) with a female predominance. The maximum diameters of the tumors ranged from 0.4 to 5.4 mm (mean: 2.8 mm). Immunohistochemical analysis of pituitary hormones revealed three growth hormone-secreting adenomas, one prolactin-producing adenoma, one gonadotropin-producing adenoma, one plurihormonal adenoma, and two null cell adenomas. MIB-1 staining for Ki-67 antigen showed no positive expression. The microvessel density (MVD) of the pituitary microadenomas ranged from 2.3 to 11.6% (mean: 5.3%) and was significantly lower than that of nonneoplastic pituitary glands (11.9-20.1%, mean: 14.8%). Our study provides reference data on incidental pituitary microadenomas in the Korean population. PMID:17923757

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.

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

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.

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 ...

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.

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.

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.

Outcomes of Pituitary Radiation for Cushing's Disease.

PubMed

Ironside, Natasha; Chen, Ching-Jen; Lee, Cheng-Chia; Trifiletti, Daniel M; Vance, Mary Lee; Sheehan, Jason P

2018-06-01

Achievement of biochemical remission with preservation of normal pituitary function is the goal of treatment for Cushing's disease. For patients with persistent or recurrent Cushing's disease after transsphenoidal resection, radiation therapy may be a safe and effective treatment. Stereotactic radiosurgery is favored over conventional fractionated external beam radiation. Hormonal recurrence rates range from 0% to 36% at 8 years after treatment. Tumor control rates are high. New pituitary hormone deficiency is the most common adverse effect after stereotactic radiosurgery and external beam radiation. The effects of radiation planning optimization and use of adjuvant medication on endocrine remission rates warrant investigation. Copyright © 2018 Elsevier Inc. All rights reserved.

Extracellular accumulations in the avian pituitary gland: histochemical analysis in two species of Indian wild birds.

PubMed

Mohanty, Banalata

2006-01-01

Extracellular accumulations of two distinct types, colloid-filled follicles and fibrous-material-containing cysts, were observed in the pituitary gland of two species of Indian wild birds, Halcyon smyrnensis perpulchra and Lonchura striata striata. Colloid follicles were regular structures and distributed throughout the pars distalis (PD). The fibrous cysts were irregular structures, bigger than the colloid follicles and mostly observed towards the ventral margin of the PD. Sometimes disruption of the outer margin with depletion of fibrous material from the cavity was observed. Hormone-secreting cells of various types, anti-adrenocorticotropic-hormone-, anti-prolactin-, anti-growth-hormone- and anti-luteinizing-hormone-immunoreactive cells were encountered bordering both the colloid follicles and fibrous cysts. Neither the colloid nor the fibrous material showed any immunoreaction to any of the pituitary hormone antisera. On histochemical staining colloid was positive to periodic acid-Schiff (PAS) and fibrous materials stained with Alcian blue-PAS-orange G staining. Colloid depositions in the pituitary gland of these two wild birds were correlated to age, more in numbers in the adult birds than in the young ones. Fibrous-material-containing cysts were elucidated in the pituitary gland of adult birds only. These were more prevalent in the pituitary of reproductively active birds. Regular morphology of the colloid follicles, overall distribution in the adenohypophysis and dense nature of deposition of the colloid suggest the accumulation of this type may be the secretory products of both granulated and agranulated pituitary cell types. Absence of immunoreactivity of the colloid against pituitary hormone antisera points out that the storage form may differ chemically from the bioactive hormones. The spatial distribution of fibrous-material-containing cysts mostly towards the ventral PD, observations of immunoreactive cell fragmentations inside the cysts, and their

Pathology of excessive production of growth hormone.

PubMed

Scheithauer, B W; Kovacs, K; Randall, R V; Horvath, E; Laws, E R

1986-08-01

Since its clinical description in the last century, much progress has been made in our understanding of acromegaly. From an initial description of pituitary enlargement as just another manifestation of generalized visceromegaly, the pituitary abnormality has come to be recognized, in most instances, as the underlying aetiological factor. Gigantism and acromegaly are manifestations of disordered pituitary physiology, but the lesion responsible may be hypothalamic, adenohypophyseal or ectopic in location. The best known pathological hypothalamic basis for acromegaly is represented by a neuronal malformation or 'gangliocytoma'. It usually takes the form of an intrasellar gangliocytoma or, more rarely, a hypothalamic hamartoma. The neuronal elaboration of GHRH may play a role in the development of a growth hormone adenoma; the pituitary process may pass through an intermediate stage of somatotropic hyperplasia. When acromegaly has its basis in a pituitary abnormality, the lesion is almost exclusively an adenoma; the non-tumorous adenohypophysis shows no evidence of coexistent hyperplasia. Surprisingly, such tumours are more often engaged in the formation of multiple hormones rather than GH alone. They frequently produce not only GH and prolactin, the products characteristics of cells of the acidophil line, but also glycoprotein hormones, usually TSH. The spectrum of adenomas also varies in its degree of differentiation from a histogenetically primitive lesion, the acidophil stem cell adenoma, to well-differentiated tumours of varying cellular composition and hormone content. Each adenoma type has its clinicopathological, histochemical, immunocytological and ultrastructural characteristics. The isolation and characterization of GHRH has permitted the identification of neuroendocrine tumours, most of foregut origin, elaborating this releasing hormone. Such functional tumours induce hyperplasia of pituitary somatotrophs and may, on occasion, result in the formation of

Transcription elongation factors are involved in programming hormone production in pituitary neuroendocrine GH4C1 cells.

PubMed

Fujita, Toshitsugu; Piuz, Isabelle; Schlegel, Werner

2010-05-05

Transcription elongation of many eukaryotic genes is regulated. Two negative transcription elongation factors, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF) and negative elongation factor (NELF) are known to stall collaboratively RNA polymerase II promoter proximally. We discovered that DSIF and NELF are linked to hormone expression in rat pituitary GH4C1 cells. When NELF-E, a subunit of NELF or Spt5, a subunit of DSIF was stably knocked-down, prolactin (PRL) expression was increased both at the mRNA and protein levels. In contrast, stable knock-down of only Spt5 abolished growth hormone (GH) expression. Transient NELF-E knock-down increased coincidentally PRL expression and enhanced transcription of a PRL-promoter reporter gene. However, no direct interaction of NELF with the PRL gene could be demonstrated by chromatin immuno-precipitation. Thus, NELF suppressed PRL promoter activity indirectly. In conclusion, transcription regulation by NELF and DSIF is continuously involved in the control of hormone production and may contribute to neuroendocrine cell differentiation. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

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

Prevalence and Predictors of Overweight and Obesity in Patients with Pituitary Dysfunctions.

PubMed

Harbeck, Birgit; Danneberg, Sven; Rahvar, Amir-Hossein; Monig, Heiner; Haas, Christian S

2016-01-01

Patients with hypothalamic-pituitary disorders (HPD) may be of increased risk to develop overweight and obesity, thereby fostering cardiovascular events. However, it remains unclear if patients with pituitary dysfunctions per se have an increased risk of becoming obese. The objective of this study was to evaluate prevalence and to identify possible predictors of overweight and obesity in patients with pituitary dysfunctions. A total of 121 out-patients having various causes for HPD were assessed for height and body weight; body mass index (BMI) was calculated and correlated with clinical features. Patients were divided into various subgroups depending on underlying conditions and therapeutic modalities. Most of the HPD patients were overweight or obese with males being significantly more affected. Of interest, patients with macroadenomas suffered significantly more often from overweight and obesity than individuals with microadenomas (73.4% vs. 43.5%, p= 0.006). Increased BMI (≥25 kg/m2) tended to be more common in patients with prolactinomas (70.0%), hormone deficiencies (76.1%) and hormone replacement therapies (76.6%) than in a healthy population. In conclusion, we showed that patients with HPD: (i) frequently suffer from overweight and obesity; (ii) prevalence of overweight and obesity however is comparable to that in the general population; (iii) only patients with macroadenomas seem to have a significantly higher risk; (iv) hormone deficiencies and hormonal replacement therapy may foster weight gain and (v) radiation and surgical tumour therapy per se do not seem to be additional risk factors for weight gain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Outcomes of Aggressive Surgical Resection in Growth Hormone-Secreting Pituitary Adenomas with Cavernous Sinus Invasion.

PubMed

Park, Hun Ho; Kim, Eui Hyun; Ku, Cheol Ryong; Lee, Eun Jig; Kim, Sun Ho

2018-06-12

Cavernous sinus (CS) invasion is an unfavorable factor hindering remission of growth hormone (GH)-secreting pituitary adenomas. However, few data exist on aggressive surgical resection. The authors investigate the role of CS exploration for GH-secreting pituitary adenomas with CS invasion. We classified 132 patients with GH-secreting pituitary adenomas invading CS into 4 groups. The patients underwent surgery using a microsurgical transsphenoidal approach (TSA) with assistance of an endoscope. For adenomas with CS invasion confined to the medial compartment of ICA (internal carotid artery), they were divided into type A (without radiological evidence) and B (with radiological evidence). For adenomas with ICA encasement, tumors were divided according to the surgical approach: type C (standard TSA) and D (far-lateral TSA). Surgical and endocrinologic outcomes were compared between each group. Gross total resection rates were 100%, 73.6%, 14.7%, 0% and endocrinologic remission rates by surgery alone were 100% , 62.3%, 26.5%, 0% for type A, B, C, and D tumors, respectively. There was no endocrinologic remission by surgery alone for type D tumors. Nevertheless, it showed marked reduction of postoperative nadir GH at 1 week, 6 months, 1 year, and IGF-I at 1 year compared to type C tumors. For tumors with CS invasion confined to the medial compartment of ICA, total resection should be attempted by direct visualization of the entire medial wall of CS. Even for tumors with ICA encasement, aggressive tumor resection by far-lateral TSA can increase the chance of remission with the help of adjuvant treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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

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...

Calcitonin: regional distribution of the hormone and its binding sites in the human brain and pituitary.

PubMed

Fischer, J A; Tobler, P H; Kaufmann, M; Born, W; Henke, H; Cooper, P E; Sagar, S M; Martin, J B

1981-12-01

Immunoreactive calcitonin (CT), indistinguishable from human CT-(1-32) and its sulfoxide, has been identified in extracts of the hypothalamus, the pituitary, and the thyroid obtained from human subjects at autopsy. DCT concentrations were highest in a region encompassing the posterior hypothalamus, the median eminence, and the pituitary; intermediate in the substantia nigra, the anterior hypothalamus, the globus pallidus, and the inferior colliculus; and low in the caudate nucleus, the hippocampus, the amygdala, and the cerebral and cerebellar cortices. Specific CT binding measured with 125I-labeled salmon CT was highest in homogenates of the posterior hypothalamus and the median eminence, shown to contain the highest concentrations of endogenous CT in the brain; CT binding was less than 12% of hypothalamic binding in all of the other regions of the brain examined and was negligible in the pituitary. Half-maximal binding was achieved with 0.1 nM nonradioactive salmon CT-(1-32), and the binding was directed to structural or conformational sites, or both, in the COOH-terminal half of salmon CT. The rank order of the inhibition of the binding by CT from different species and analogues of the human hormone was the same as in receptors on a human lymphoid cell line (Moran, J., Hunziker, W. & Fischer, J. A. (1978) Proc. Natl. Acad. Sci. USA 75, 3984-3988). The functional role of CT and of its binding sites in the brain remains to be elucidated.

Effects of gonadoliberin analogue triptorelin on the pituitary-testicular complex in neonatal rats.

PubMed

Dygalo, N N; Shemenkova, T V; Kalinina, T S; Shishkina, G T

2014-02-01

Triptorelin, a synthetic analogue of neurohormone gonadoliberin (gonadotropin-releasing hormone, GnRH) administered daily to rats on postnatal days 5-7 suppressed the expression of GnRH receptor in the pituitary gland, but did not change functioning of the pituitary-testicular complex. Administration of triptorelin on postnatal days 12-14 (i.e. during the formation of pulsatile pattern of GnRH secretion and increasing levels of its mRNA receptor in the pituitary gland) had no effect on receptor expression, but increased the levels of luteinizing hormone mRNA in the pituitary gland and the weight of testes. At that time, blood levels of testosterone were lowered, which indicated disturbed pulsatile pattern of GnRH secretion.

Melanin concentrating hormone (MCH) is involved in the regulation of growth hormone in Cichlasoma dimerus (Cichlidae, Teleostei).

PubMed

Pérez Sirkin, D I; Cánepa, M M; Fossati, M; Fernandino, J I; Delgadin, T; Canosa, L F; Somoza, G M; Vissio, P G

2012-03-01

Growth hormone (GH) is the main pituitary hormone involved in somatic growth. In fish, the neuroendocrine control of GH is multifactorial due to the interaction of multiple inhibitors and stimulators. Melanin-concentrating hormone (MCH) is a cyclic peptide involved in skin color regulation of fish. In addition, MCH has been related to the regulation of food intake in both mammals and fish. There is only one report presenting evidences on the GH release stimulation by MCH in mammals in experiments in vitro, but there are no data on non-mammals. In the present work, we report for the first time the sequence of MCH and GH cDNA in Cichlasoma dimerus, a freshwater South American cichlid fish. We detected contacts between MCH fibers and GH cells in the proximal pars distalis region of the pituitary gland by double label confocal immunofluorescence indicating a possible functional relationship. Besides, we found that MCH increased GH transcript levels and stimulated GH release in pituitary cultures. Additionally, C. dimerus exposed to a white background had a greater number of MCH neurons with a larger nuclear area and higher levels of MCH transcript than those fish exposed to a black background. Furthermore, fish reared for 3 months in a white background showed a greater body weight and total length compared to those from black background suggesting that MCH might be related to somatic growth in C. dimerus. Our results report for the first time, that MCH is involved in the regulation of the synthesis and release of GH in vitro in C. dimerus, and probably in the fish growth rate. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

Growth Hormone Deficiency in the Transition Age.

PubMed

Loche, Sandro; Di Iorgi, Natascia; Patti, Giuseppa; Noli, Serena; Giaccardi, Marta; Olivieri, Irene; Ibba, Anastasia; Maghnie, Mohamad

2018-01-01

Growth hormone (GH) is essential not only for normal growth during childhood, but also for the acquisition of bone mass and muscle strength in both sexes. This process is completed after the achievement of adult height in the phase of transition from adolescence to adulthood. Adolescents with childhood onset GH deficiency (GHD) show reduction of bone mineral density, decrease in lean body mass, increase in fat mass, and deterioration of the lipid profile. For this reason, continuation of GH replacement therapy in the transition age is recommended in all patients with a confirmed diagnosis of GHD. To confirm the diagnosis of GHD, GH treatment should be discontinued for at least 1 month after the attainment of adult height, and the patient should be re-evaluated for GH secretion. Current guidelines indicate that retesting is not required for those with a transcription factor mutation, more than 3 pituitary hormone deficits, or isolated GHD associated with an identified mutation. The key predictors of persistent GHD are its severity, the presence of additional pituitary hormone deficits, low insulin-like growth factor I (IGF-I) concentration, and the presence of structural hypothalamic-pituitary abnormalities Treatment should be initiated with a low dose (0.2-0.5 mg/day s.c.) and then adjusted according to IGF-I concentrations. © 2018 S. Karger AG, Basel.

Pituitary gigantism: update on molecular biology and management.

PubMed

Lodish, Maya B; Trivellin, Giampaolo; Stratakis, Constantine A

2016-02-01

To provide an update on the mechanisms leading to pituitary gigantism, as well as to familiarize the practitioner with the implication of these genetic findings on treatment decisions. Prior studies have identified gigantism as a feature of a number of monogenic disorders, including mutations in the aryl hydrocarbon receptor interacting protein gene, multiple endocrine neoplasia types 1 and 4, McCune Albright syndrome, Carney complex, and the paraganglioma, pheochromocytoma, and pituitary adenoma association because of succinate dehydrogenase defects. We recently described a previously uncharacterized form of early-onset pediatric gigantism caused by microduplications on chromosome Xq26.3 and we termed it X-LAG (X-linked acrogigantism). The age of onset of increased growth in X-LAG is significantly younger than other pituitary gigantism cases, and control of growth hormone excess is particularly challenging. Knowledge of the molecular defects that underlie pituitary tumorigenesis is crucial for patient care as they guide early intervention, screening for associated conditions, genetic counseling, surgical approach, and choice of medical management. Recently described microduplications of Xq26.3 account for more than 80% of the cases of early-onset pediatric gigantism. Early recognition of X-LAG may improve outcomes, as successful control of growth hormone excess requires extensive anterior pituitary resection and are difficult to manage with medical therapy alone.

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.

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

Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.

PubMed

Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gahete, Manuel D; Jiménez-Reina, Luis; Venegas-Moreno, Eva; de la Riva, Andrés; Arráez, Miguel Ángel; González-Molero, Inmaculada; Schmid, Herbert A; Maraver-Selfa, Silvia; Gavilán-Villarejo, Inmaculada; García-Arnés, Juan Antonio; Japón, Miguel A; Soto-Moreno, Alfonso; Gálvez, María A; Luque, Raúl M; Castaño, Justo P

2016-11-01

Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca 2+ signaling ([Ca 2+ ] i ), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca 2+ ] i more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca 2+ ] i in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response. © 2016 Society for Endocrinology.

Successful Pregnancies and Deliveries in a Patient With Evolving Hypopituitarism due to Pituitary Stalk Transection Syndrome: Role of Growth Hormone Replacement

PubMed Central

Yoshizawa, Miyako; Ieki, Yasuhiko; Takazakura, Eisuke; Fukuta, Kaori; Hidaka, Takao; Wakasugi, Takanobu; Shimatsu, Akira

2017-01-01

We herein report a 31-year-old Japanese woman with evolving hypopituitarism due to pituitary stalk transection syndrome. She had a history of short stature treated with growth hormone (GH) in childhood and had hypothyroidism and primary amenorrhea at 20 years old. Levothyroxine replacement and recombinant follicle stimulating hormone-human chorionic gonadotropin (FSH-hCG) therapy for ovulation induction were started. GH replacement therapy (GHRT) was resumed when she was 26 years old. She developed mild adrenocortical insufficiency at 31 years old. She succeeded in becoming pregnant and delivered twice. GHRT was partially continued during pregnancy and stopped at the end of the second trimester without any complications. PMID:28250299

Mammosomatotroph adenoma of the pituitary associated with gigantism and hyperprolactinemia. A morphological study including immunoelectron microscopy.

PubMed

Felix, I A; Horvath, E; Kovacs, K; Smyth, H S; Killinger, D W; Vale, J

1986-01-01

A 29-year old giantess with growth hormone excess and hyperprolactinemia underwent transsphenoidal surgery to remove her pituitary tumor. Electron microscopy revealed a mammosomatotroph adenoma composed of one cell type. Immunoelectron microscopy, using the immunogold technique, demonstrated predominantly growth hormone or prolactin or a varying mixture of both growth hormone and prolactin in the adenoma cells. The presence of growth hormone and prolactin was found not only in the cytoplasm of the same adenoma cells but also in the same secretory granules. In the nontumorous adenohypophysis, somatotrophs and lactotrophs showed ultrastructural signs of hyperactivity. This finding is in contrast with the presence of suppressed somatotrophs and lactotrophs seen in nontumorous portions of adult pituitaries harboring growth hormone or prolactin-secreting adenomas. Our morphological study reinforces the view that growth hormone-producing pituitary tumors, originating in childhood, are different from those of the adult gland.

The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis.

PubMed

Astapova, Inna; Vella, Kristen R; Ramadoss, Preeti; Holtz, Kaila A; Rodwin, Benjamin A; Liao, Xiao-Hui; Weiss, Roy E; Rosenberg, Michael A; Rosenzweig, Anthony; Hollenberg, Anthony N

2011-02-01

The role of nuclear receptor corepressor (NCoR) in thyroid hormone (TH) action has been difficult to discern because global deletion of NCoR is embryonic lethal. To circumvent this, we developed mice that globally express a modified NCoR protein (NCoRΔID) that cannot be recruited to the thyroid hormone receptor (TR). These mice present with low serum T(4) and T(3) concentrations accompanied by normal TSH levels, suggesting central hypothyroidism. However, they grow normally and have increased energy expenditure and normal or elevated TR-target gene expression across multiple tissues, which is not consistent with hypothyroidism. Although these findings imply an increased peripheral sensitivity to TH, the hypothalamic-pituitary-thyroid axis is not more sensitive to acute changes in TH concentrations but appears to be reset to recognize the reduced TH levels as normal. Furthermore, the thyroid gland itself, although normal in size, has reduced levels of nonthyroglobulin-bound T(4) and T(3) and demonstrates decreased responsiveness to TSH. Thus, the TR-NCoR interaction controls systemic TH sensitivity as well as the set point at all levels of the hypothalamic-pituitary-thyroid axis. These findings suggest that NCoR levels could alter cell-specific TH action that would not be reflected by the serum TSH.

Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction.

PubMed

Curtò, L; Trimarchi, F

2016-10-01

Hypopituitarism is an uncommon and under-investigated endocrine disorder in old age since signs and symptoms are unspecific and, at least in part, can be attributed to the physiological effects of aging and related co-morbidities. Clinical presentation is often insidious being characterized by non-specific manifestations, such as weight gain, fatigue, low muscle strength, bradipsychism, hypotension or intolerance to cold. In these circumstances, hypopituitarism is a rarely life-threatening condition, but evolution may be more dramatic as a result of pituitary apoplexy, or when a serious condition of adrenal insufficiency suddenly occurs. Clinical presentation depends on the effects that each pituitary deficit can cause, and on their mutual relationship, but also, inevitably, it depends on the severity and duration of the deficit itself, as well as on the general condition of the patient. Indeed, indications and methods of hormone replacement therapy must include the need to normalize the endocrine profile without contributing to the worsening of intercurrent diseases, such as those of glucose and bone metabolism, and the cardiovascular system, or to the increasing cancer risk. Hormonal requirements of elderly patients are reduced compared to young adults, but a prompt diagnosis and appropriate treatment of pituitary deficiencies are strongly recommended, also in this age range.

Effects of long-term treatment with the luteinizing hormone-releasing hormone (LHRH) agonist Decapeptyl and the LHRH antagonist Cetrorelix on the levels of pituitary LHRH receptors and their mRNA expression in rats

PubMed Central

Horvath, Judit E.; Bajo, Ana M.; Schally, Andrew V.; Kovacs, Magdolna; Herbert, Francine; Groot, Kate

2002-01-01

The effects of depot formulations of the luteinizing hormone-releasing hormone (LHRH) agonist Decapeptyl (25 μg/day) for 30 days or LHRH antagonist Cetrorelix pamoate (100 μg/day) for 30 days and daily injections of 100 μg of Decapeptyl for 10 days on the expression of mRNA for pituitary LHRH receptor (LHRH-R) and the levels of LHRH-R protein were evaluated in rats. Serum sex steroid concentrations and the weights of the reproductive organs were greatly reduced in all groups treated with analogs, demonstrating an efficient blockade of the pituitary–gonadal axis. Decapeptyl microcapsules elevated serum LH in female rats, but decreased it in male rats. LHRH-R mRNA expression in female pituitaries was reduced to 41% and 56–65% on days 10 and 30, respectively, whereas LHRH-R protein was 64% of control on day 10 and returned to pretreatment levels on day 30. Decapeptyl microcapsules reduced LHRH-R mRNA expression in male pituitaries to 58% on day 30 but not LHRH-R protein. Daily injections of Decapeptyl caused a desensitization of LH responses in female rats, while raising LHRH-R mRNA expression in female rats by 23% and LHRH-R protein levels by 119%. Cetrorelix pamoate reduced serum LH in female rats and diminished LHRH-R mRNA to 30% and 26% and LHRH-R protein to 57% and 48% on days 10 and 30, respectively. Elevated LHRH-R protein levels of ovariectomized rats were reduced after 10-day treatment with Cetrorelix or 100 μg/day Decapeptyl. Thus, changes in the mRNA expression after treatment with Cetrorelix, but not always Decapeptyl, paralleled those of LHRH-R protein. The inhibitory effect of Cetrorelix on serum LH, pituitary LHRH-R mRNA, and LHRH-R protein was greater than that of Decapeptyl. PMID:12409615

Thyroid hormone receptor beta2 is strongly up-regulated at all levels of the hypothalamo-pituitary-thyroidal axis during late embryogenesis in chicken.

PubMed

Grommen, Sylvia V H; Arckens, Lutgarde; Theuwissen, Tim; Darras, Veerle M; De Groef, Bert

2008-03-01

In this study, we tried to elucidate the changes in thyroid hormone (TH) receptor beta2 (TRbeta2) expression at the different levels of the hypothalamo-pituitary-thyroidal (HPT) axis during the last week of chicken embryonic development and hatching, a period characterized by an augmented activity of the HPT axis. We quantified TRbeta2 mRNA in retina, pineal gland, and the major control levels of the HPT axis - brain, pituitary, and thyroid gland - at day 18 of incubation, and found the most abundant mRNA content in retina and pituitary. Thyroidal TRbeta2 mRNA content increased dramatically between embryonic day 14 and 1 day post-hatch. In pituitary and hypothalamus, TRbeta2 mRNA expression rose gradually, in parallel with increases in plasma thyroxine concentrations. Using in situ hybridization, we have demonstrated the presence of TRbeta2 mRNA throughout the diencephalon and confirmed the elevation in TRbeta2 mRNA expression in the hypophyseal thyrotropes. In vitro incubation with THs caused a down-regulation of TRbeta2 mRNA levels in embryonic but not in post-hatch pituitaries. The observed expression patterns in pituitary and diencephalon may point to substantial changes in TRbeta2-mediated TH feedback active during the perinatal period. The strong rise in thyroidal TRbeta2 mRNA content could be indicative of an augmented modulation of thyroid development and/or function by THs toward and after hatching. Finally, THs proved to exert an age-dependent effect on pituitary TRbeta2 mRNA expression.

Treatment of pituitary gigantism with the growth hormone receptor antagonist pegvisomant.

PubMed

Goldenberg, Naila; Racine, Michael S; Thomas, Pamela; Degnan, Bernard; Chandler, William; Barkan, Ariel

2008-08-01

Treatment of pituitary gigantism is complex and the results are usually unsatisfactory. The objective of the study was to describe the results of therapy of three children with pituitary gigantism by a GH receptor antagonist, pegvisomant. This was a descriptive case series of up to 3.5 yr duration. The study was conducted at a university hospital. Patients included three children (one female, two males) with pituitary gigantism whose GH hypersecretion was incompletely controlled by surgery, somatostatin analog, and dopamine agonist. The intervention was administration of pegvisomant. Plasma IGF-I and growth velocity were measured. In all three children, pegvisomant rapidly decreased plasma IGF-I concentrations. Growth velocity declined to subnormal or normal values. Statural growth fell into lower growth percentiles and acromegalic features resolved. Pituitary tumor size did not change in two children but increased in one boy despite concomitant therapy with a somatostatin analog. Pegvisomant may be an effective modality for the therapy of pituitary gigantism in children. Titration of the dose is necessary for optimal efficacy, and regular surveillance of tumor size is mandatory.

Flow cytometric immunofluorescence of rat anterior pituitary cells

NASA Technical Reports Server (NTRS)

Hatfield, J. Michael; Hymer, W. C.

1985-01-01

A flow cytometric immunofluorescence technique was developed for the quantification of growth hormone, prolactin, and luteinizing hormone producing cells. The procedure is based on indirect-immunofluorescence of intracellular hormone using an EPICS V cell sorter and can objectively count 50,000 cells in about 3 minutes. It can be used to study the dynamics of pituitary cell populations under various physiological and pharmacological conditions.

Peroxisome proliferator-activated receptor (PPAR)gamma is highly expressed in normal human pituitary gland.

PubMed

Bogazzi, F; Russo, D; Locci, M T; Chifenti, B; Ultimieri, F; Raggi, F; Viacava, P; Cecchetti, D; Cosci, C; Sardella, C; Acerbi, G; Gasperi, M; Martino, E

2005-11-01

Expression of peroxisome proliferator-activated receptor (PPAR)gamma in normal pituitary seems to be restricted to ACTH-secreting cells. The aim of the study was to evaluate the expression of PPARgamma in normal human pituitary tissue and to study its localization in the pituitary secreting cells. Normal pituitary tissue samples were obtained form 11 patients with non-secreting adenoma who underwent surgical excision of the tumor. Expression of PPARgamma was evaluated by immunostaining and western blotting; localization of PPARgamma in each pituitary secreting cell lineage was evaluated by double immunofluorescence using confocal microscopy. Pituitary non-functioning adenomas served as Controls. PPARgamma was highly expressed in all pituitary samples with a (mean +/- SD) 81 +/- 6.5% of stained cells; expression of PPARgamma was confirmed by western blotting. Non-functioning pituitary adenomas had 74 +/- 11% PPARgamma positive cells. Expression of PPARy was either in cytoplasm or nuclei. In addition, treatment of GH3 cells, with a PPARgamma ligand was associated with traslocation of the receptor from cytoplasm into the nucleus. Double immunostaining revealed that every pituitary secreting cell (GH, TSH, LH, FSH, PRL and ACTH) had PPARgamma expressed. The present study demonstrated that PPARgamma is highly expressed in every normal pituitary secreting cell lineage. It can translocate into the nucleus by ligand binding; however, its role in pituitary hormone regulation remains to be elucidated.

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.

Insulin and growth hormone-releasing peptide-6 (GHRP-6) have differential beneficial effects on cell turnover in the pituitary, hypothalamus and cerebellum of streptozotocin (STZ)-induced diabetic rats.

PubMed

Granado, Miriam; García-Cáceres, Cristina; Tuda, María; Frago, Laura M; Chowen, Julie A; Argente, Jesús

2011-04-30

Poorly controlled type1 diabetes is associated with hormonal imbalances and increased cell death in different tissues, including the pituitary, hypothalamus and cerebellum. In the pituitary, lactotrophs are the cell population with the greatest increase in cell death, whereas in the hypothalamus and cerebellum astrocytes are most highly affected. Insulin treatment can delay, but does not prevent, diabetic complications. As ghrelin and growth hormone (GH) secretagogues are reported to prevent apoptosis in different tissues, and to modulate glucose homeostasis, a combined hormonal treatment may be beneficial. Hence, we analyzed the effect of insulin and GH-releasing peptide 6 (GHRP-6) on diabetes-induced apoptosis in the pituitary, hypothalamus and cerebellum of diabetic rats. Adult male Wistar rats were made diabetic by streptozotocin injection (65 mg/kg ip) and divided into four groups from diabetes onset: those receiving a daily sc injection of saline (1 ml/kg/day), GHRP-6 (150 μg/kg/day), insulin (1-8U/day) or insulin plus GHRP-6 for 8 weeks. Control non-diabetic rats received saline (1 ml/kg/day). Diabetes increased cell death in the pituitary, hypothalamus and cerebellum (P<0.05). In the pituitary, insulin treatment prevented diabetes-induced apoptosis (P<0.01), as well as the decline in prolactin and GH mRNA levels (P<0.05). In the hypothalamus, neither insulin nor GHRP-6 decreased diabetes-induced cell death. However, the combined treatment of insulin+GHRP-6 prevented the diabetes induced-decrease in glial fibrillary acidic protein (GFAP) levels (P<0.05). In the cerebellum, although insulin treatment increased GFAP levels (P<0.01), only the combined treatment of insulin+ GHRP-6 decreased diabetes-induced apoptosis (P<0.05). In conclusion, insulin and GHRP-6 exert tissue specific effects in STZ-diabetic rats and act synergistically on some processes. Indeed, insulin treatment does not seem to be effective on preventing some of the diabetes-induced alterations

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

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.

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

Kisspeptin regulates the hypothalamus-pituitary-gonad axis gene expression during sexual maturation in the cinnamon clownfish, Amphiprion melanopus.

PubMed

Kim, Na Na; Shin, Hyun Suk; Choi, Young Jae; Choi, Cheol Young

2014-02-01

Kisspeptins (Kiss) have been recognized as potent regulators of reproduction in teleosts, and Kiss is suggested to be a key regulator of the hypothalamus-pituitary-gonad axis (HPG). However, its regulatory role on reproduction in fish remains unclear. Therefore, to investigate the role of Kiss on fish reproduction, this study aimed to test differences in the hormones of the HPG axis, Kiss as neuropeptides, and sex steroids on the sexual maturation of paired cinnamon clownfish, Amphiprion melanopus, following treatment with Kiss. We investigated the actions of sex maturation hormones, including HPG axis hormones and sex steroid hormones, such as gonadotropin-releasing hormones, gonadotropin hormones (GTHs), GTH receptors, estrogen receptors, and vitellogenin in the pituitary, gonads, and liver following treatment with Kiss. The expression levels of HPG axis genes increased after the Kiss injection. In addition, the levels of plasma 17α-hydroxypregnenolone, estradiol-17β, and 11-ketotestosterone increased. These results support the hypothesis that Kiss play important roles in the regulation of the HPG axis and are most likely involved in gonadal development and sexual maturation in cinnamon clownfish. Copyright © 2013 Elsevier Inc. All rights reserved.

Regulation of LH/FSH expression by secretoglobin 3A2 in the mouse pituitary gland.

PubMed

Miyano, Yuki; Tahara, Shigeyuki; Sakata, Ichiro; Sakai, Takafumi; Abe, Hiroyuki; Kimura, Shioko; Kurotani, Reiko

2014-04-01

Secretoglobin (SCGB) 3A2 was originally identified as a downstream target for the homeodomain transcription factor NKX2-1 in the lung. NKX2-1 plays a role in the genesis and expression of genes in the thyroid, lung and ventral forebrain; Nkx2-1-null mice have no thyroid and pituitary and severely hypoplastic lungs and hypothalamus. To demonstrate whether SCGB3A2 plays any role in pituitary hormone production, NKX2-1 and SCGB3A2 expression in the mouse pituitary gland was examined by immunohistochemical analysis and RT-PCR. NKX2-1 was localized in the posterior pituitary lobe, whereas SCGB3A2 was observed in both anterior and posterior lobes as shown by immunohistochemistry and RT-PCR. Expression of CCAAT-enhancer binding proteins (C/EBPs), which regulate mouse Scgb3a2 transcription, was also examined by RT-PCR. C/EBPβ, γ, δ and ζ were expressed in the adult mouse pituitary gland. SCGB3A2 was expressed in the anterior and posterior lobes from postnatal days 1 and 5, respectively and the areas where SCGB3A2 expression was found coincided with the area where FSH-secreting cells were found. Double-staining for SCGB3A2 and pituitary hormones revealed that SCGB3A2 was mainly localized in gonadotrophs in 49 % of FSH-secreting cells and 47 % of LH-secreting cells. In addition, SCGB3A2 dramatically inhibited LH and FSH mRNA expression in rat pituitary primary cell cultures. These results suggest that SCGB3A2 regulates FSH/LH production in the anterior pituitary lobe and that transcription factors other than NKX2-1 may regulate SCGB3A2 expression.

Macrophage colony-stimulating factor induces prolactin expression in rat pituitary gland.

PubMed

Hoshino, Satoya; Kurotani, Reiko; Miyano, Yuki; Sakahara, Satoshi; Koike, Kanako; Maruyama, Minoru; Ishikawa, Fumio; Sakatai, Ichiro; Abe, Hiroyuki; Sakai, Takafumi

2014-06-01

We investigated the role of macrophage colony-stimulating factor (M-CSF) in the pituitary gland to understand the effect of M-CSF on pituitary hormones and the relationship between the endocrine and immune systems. When we attempted to establish pituitary cell lines from a thyrotropic pituitary tumor (TtT), a macrophage cell line, TtT/M-87, was established. We evaluated M-CSF-like activity in conditioned media (CM) from seven pituitary cell lines using TtT/M-87 cells. TtT/M-87 proliferation significantly increased in the presence of CM from TtT/GF cells, a pituitary folliculostellate (FS) cell line. M-CSF mRNA was detected in TtT/GF and MtT/E cells by reverse transcriptase-polymerase chain reaction (RT-PCR), and its expression in TtT/GF cells was increased in a lipopolysaccharide (LPS) dose-dependent manner. M-CSF mRNA expression was also increased in rat anterior pituitary glands by LPS. M-CSF receptor (M-CSFR) mRNA was only detected in TtT/ M-87 cells and increased in the LPS-stimulated rat pituitary glands. In rat pituitary glands, M-CSF and M-CSFR were found to be localized in FS cells and prolactin (PRL)-secreting cells, respectively, by immunohistochemistry. The PRL concentration in rat sera was significantly increased at 24 h after M-CSF administration, and mRNA levels significantly increased in primary culture cells of rat anterior pituitary glands. In addition, TNF-α mRNA was increased in the primary culture cells by M-CSF. These results revealed that M-CSF was secreted from FS cells and M-CSF regulated PRL expression in rat pituitary glands.

Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

PubMed

Mehta, M K; Garde, S V; Sheth, A R

1995-01-01

To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

Treatment of Pituitary Gigantism with the Growth Hormone Receptor Antagonist Pegvisomant

PubMed Central

Goldenberg, Naila; Racine, Michael S.; Thomas, Pamela; Degnan, Bernard; Chandler, William; Barkan, Ariel

2008-01-01

Context: Treatment of pituitary gigantism is complex and the results are usually unsatisfactory. Objective: The objective of the study was to describe the results of therapy of three children with pituitary gigantism by a GH receptor antagonist, pegvisomant. Design: This was a descriptive case series of up to 3.5 yr duration. Setting: The study was conducted at a university hospital. Patients: Patients included three children (one female, two males) with pituitary gigantism whose GH hypersecretion was incompletely controlled by surgery, somatostatin analog, and dopamine agonist. Intervention: The intervention was administration of pegvisomant. Main Outcome Measures: Plasma IGF-I and growth velocity were measured. Results: In all three children, pegvisomant rapidly decreased plasma IGF-I concentrations. Growth velocity declined to subnormal or normal values. Statural growth fell into lower growth percentiles and acromegalic features resolved. Pituitary tumor size did not change in two children but increased in one boy despite concomitant therapy with a somatostatin analog. Conclusions: Pegvisomant may be an effective modality for the therapy of pituitary gigantism in children. Titration of the dose is necessary for optimal efficacy, and regular surveillance of tumor size is mandatory. PMID:18492755

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

Autosomal Dominant Growth Hormone Deficiency (Type II).

PubMed

Alatzoglou, Kyriaki S; Kular, Dalvir; Dattani, Mehul T

2015-06-01

Isolated growth hormone deficiency (IGHD) is the commonest pituitary hormone deficiency resulting from congenital or acquired causes, although for most patients its etiology remains unknown. Among the known factors, heterozygous mutations in the growth hormone gene (GH1) lead to the autosomal dominant form of GHD, also known as type II GHD. In many cohorts this is the commonest form of congenital isolated GHD and is mainly caused by mutations that affect the correct splicing of GH-1. These mutations cause skipping of the third exon and lead to the production of a 17.5-kDa GH isoform that exerts a dominant negative effect on the secretion of the wild type GH. The identification of these mutations has clinical implications for the management of patients, as there is a well-documented correlation between the severity of the phenotype and the increased expression of the 17.5-kDa isoform. Patients with type II GHD have a variable height deficit and severity of GHD and may develop additional pituitary hormone defiencies over time, including ACTH, TSH and gonadotropin deficiencies. Therefore, their lifelong follow-up is recommended. Detailed studies on the effect of heterozygous GH1 mutations on the trafficking, secretion and action of growth hormone can elucidate their mechanism on a cellular level and may influence future treatment options for GHD type II.

Pituitary, gonadal and adrenal hormones after prolonged residence at extreme altitude in man.

PubMed

Basu, M; Pal, K; Prasad, R; Malhotra, A S; Rao, K S; Sawhney, R C

1997-06-01

High altitude-induced alterations in pituitary, gonadal and adrenal hormones were studied in (i) eugonadal men from the armed forces who were resident at sea level (SL), (ii) SL residents staying at an altitude of 3542 m for periods ranging from 3 to 12 months (acclimatized lowlanders, ALL), (iii) ALL who stayed at 6300 m for 6 months, (iv) ALL who trekked from 3542 to 5080 m and stayed at an altitude of more than 6300 m in the glacier region for 6 months, and (v) high-altitude natives (HAN) resident at an altitude of 3300-3700 m. Circulating levels of LH, FSH, prolactin, cortisol, testosterone, dihydrotestosterone (DHT) and progesterone in ALL at 3542 m and in HAN were not significantly different (p > 0.05) from the SL control values. When the ALL living at 3542 m trekked to an extreme altitude of 5080 m, their testosterone levels showed a significant decrease (p < 0.01) compared to the preceding altitude values but had returned to SL values when measured after 6 months' continuous stay at 6300 m. As with testosterone, the levels of DHT and oestradiol-17 beta (E2) after prolonged stay at extreme altitude were also not significantly different (p > 0.05) from the SL values. The LH levels after trekking to 5080 m were significantly higher (p < 0.01) than at an altitude of 3542 m, but decreased to levels found at 3542 m or SL after prolonged residence at extreme altitude. Plasma levels of ACTH, prolactin, FSH and cortisol on arrival at 5080 m, and after a 6-month stay at extreme altitude, were not significantly different (p > 0.05) from the SL values. Plasma progesterone levels tended to increase on arrival at 5080 m but a significant increase (p < 0.001) was evident only after a 6-month stay at extreme altitude. These observations suggest that prolonged residence at lower as well as at extreme altitude does not appreciably alter blood levels of pituitary, gonadal or adrenal hormones except for plasma levels of progesterone. The exact mechanism and significance of

Pituitary genomic expression profiles of steers are altered by grazing of high vs. low endophyte-infected tall fescue forages.

PubMed

Li, Qing; Hegge, Raquel; Bridges, Phillip J; Matthews, James C

2017-01-01

Consumption of ergot alkaloid-containing tall fescue grass impairs several metabolic, vascular, growth, and reproductive processes in cattle, collectively producing a clinical condition known as "fescue toxicosis." Despite the apparent association between pituitary function and these physiological parameters, including depressed serum prolactin; no reports describe the effect of fescue toxicosis on pituitary genomic expression profiles. To identify candidate regulatory mechanisms, we compared the global and selected targeted mRNA expression patterns of pituitaries collected from beef steers that had been randomly assigned to undergo summer-long grazing (89 to 105 d) of a high-toxic endophyte-infected tall fescue pasture (HE; 0.746 μg/g ergot alkaloids; 5.7 ha; n = 10; BW = 267 ± 14.5 kg) or a low-toxic endophyte tall fescue-mixed pasture (LE; 0.023 μg/g ergot alkaloids; 5.7 ha; n = 9; BW = 266 ± 10.9 kg). As previously reported, in the HE steers, serum prolactin and body weights decreased and a potential for hepatic gluconeogenesis from amino acid-derived carbons increased. In this manuscript, we report that the pituitaries of HE steers had 542 differentially expressed genes (P < 0.001, false discovery rate ≤ 4.8%), and the pattern of altered gene expression was dependent (P < 0.001) on treatment. Integrated Pathway Analysis revealed that canonical pathways central to prolactin production, secretion, or signaling were affected, in addition to those related to corticotropin-releasing hormone signaling, melanocyte development, and pigmentation signaling. Targeted RT-PCR analysis corroborated these findings, including decreased (P < 0.05) expression of DRD2, PRL, POU1F1, GAL, and VIP and that of POMC and PCSK1, respectively. Canonical pathway analysis identified HE-dependent alteration in signaling of additional pituitary-derived hormones, including growth hormone and GnRH. We conclude that consumption of endophyte-infected tall fescue alters the pituitary

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

Management of clinically non-functioning pituitary adenoma.

PubMed

Chanson, Philippe; Raverot, Gerald; Castinetti, Frédéric; Cortet-Rudelli, Christine; Galland, Françoise; Salenave, Sylvie

2015-07-01

Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15-30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Growth hormone-secreting macroadenoma of the pituitary gland successfully treated with the radiolabeled somatostatin analog (90)Y-DOTATATE: case report.

PubMed

Waligórska-Stachura, Joanna; Gut, Paweł; Sawicka-Gutaj, Nadia; Liebert, Włodzimierz; Gryczyńska, Maria; Baszko-Błaszyk, Daria; Blanco-Gangoo, Al Ricardo; Ruchała, Marek

2016-08-01

Pituitary tumors causing acromegaly are usually macroadenomas at the time of diagnosis, and they can grow aggressively, infiltrating surrounding tissues. Difficulty in achieving complete tumor removal at surgery can lead toward a strong tendency for recurrence, making it necessary to consider a means of treatment other than those currently used such as somatostatin analogs (SSAs), growth hormone (GH) receptor antagonist, surgical removal, and radiotherapy. The purpose of this paper is to describe a patient diagnosed with an aggressive, giant GH-secreting tumor refractory to medical therapy but ultimately treated with the radiolabeled somatostatin analog (90)Y-DOTATATE. A 26-year-old male with an invasive macroadenoma of the pituitary gland (5.6 × 2.5 × 3.6 cm) and biochemically confirmed acromegaly underwent 2 partial tumor resections: the first used the transsphenoidal approach and the second used the transcranial method. The patient received SSAs pre- and postoperatively. Because of the progression in pituitary tumor size, he underwent classic irradiation of the tumor (50 Gy). One and a half years later, the patient presented with clinically and biochemically active disease, and the tumor size was still 52 mm in diameter (height). Two neurosurgeons disqualified him from further surgical procedures. After confirming the presence of somatostatin receptors in the pituitary tumor by using (68)Ga-DOTATATE PET/CT, we treated the patient 4 times with an SSA bound with (90)Y-DOTATATE. After this treatment, the patient attained partial biochemical remission and a reduction in the tumor mass for the first time. Treatment with an SSA bound with (90)Y-DOTATATE may be a promising option for some aggressive GH-secreting pituitary adenomas when other methods have failed.

Decreased apparent diffusion coefficient in the pituitary and correlation with hypopituitarism in patients with traumatic brain injury.

PubMed

Zheng, Ping; He, Bin; Guo, Yijun; Zeng, Jingsong; Tong, Wusong

2015-07-01

The relationship between microstructural abnormality in patients with traumatic brain injury (TBI) and hormone-secreting status remains unknown. In this study, the authors aimed to identify the role of the apparent diffusion coefficient (ADC) using a diffusion-weighted imaging (DWI) technique and to evaluate the association of such changes with hypopituitarism in patients with TBI. Diffusion-weighted images were obtained in 164 consecutive patients with TBI within 2 weeks after injury to generate the pituitary ADC as a measure of microstructural change. Patients with TBI were further grouped into those with and those without hypopituitarism based on the secretion status of pituitary hormones at 6 months postinjury. Thirty healthy individuals were enrolled in the study and underwent MRI examinations for comparison. Mean ADC values were compared between this control group, the patients with TBI and hypopituitarism, and the patients with TBI without hypopituitarism; correlational studies were also performed. Neurological outcome was assessed with the Glasgow Outcome Scale (GOS) for all TBI patients 6 months postinjury. In the TBI group, 84 patients had hypopituitarism and 80 had normal pituitary function. The pituitary ADC in TBI patients was significantly less than that in controls (1.83 ± 0.16 vs 4.13 ± 0.33, p < 0.01). Furthermore, the mean ADC was much lower in TBI patients with hypopituitarism than in those without pituitary dysfunction (1.32 ± 0.09 vs 2.28 ± 0.17, p < 0.05). There was also a significant difference in ADC values between patients with hyperprolactinemia and those with normal prolactin levels (p < 0.05). Additionally, the receiver operating characteristic curve analysis showed that the pituitary ADC could predict hypopituitarism with a sensitivity of 90.0% and a specificity of 90.1% at the level of 1.720 (ADC value). Finally, the ADC value was positively correlated with neurological outcome at 6 months following TBI (r = 0.602, p < 0.05). Use

Cloning and identification of a novel thyroid hormone receptor β isoform expressed in the pituitary gland.

PubMed

Zhao, Rong-Lan; Sun, Bei; Liu, Ying; Li, Jing-Hua; Xiong, Wei-Li; Liang, Dong-Chun; Guo, Gang; Zuo, Ai-Jun; Zhang, Jing-Yu

2014-04-01

We have previously identified a novel Trβ isoform (TrβΔ) in the rat, in which a novel exon N (108 bps) was found between exon 3 and exon 4 of TrβΔ, which represents the only difference between TrβΔ and Trβ1. In this study, we searched for an elongated Trβ2-like subtype with one additional exon N. We successfully isolated the entire mRNA/cDNA of a novel elongated Trβ2 isoform via PCR in the rat pituitary gland. The mRNA/cDNA was only 108 bps (exon N) longer than that Trβ2, and the extension of the sequence was between exon 3 and 4 of Trβ. The whole sequence of this novel Trβ isoform has been published in NCBI GenBank (HM043807.1); it is named TRbeta2Delta (Trβ2Δ). In adult rat pituitary tissue, quantitative real-time RT-PCR analysis showed that the mRNA levels of Trβ2Δ and Trβ2 were roughly equal (P > 0.05). We cloned, expressed, and purified the His-Trβ2Δ protein [recombinant TRβ2Δ (rTRβ2Δ)]. SDS-PAGE and western blotting revealed that the molecular weight of rTRβ2Δ was 58.2 kDa. Using a radioligand binding assay and an electrophoretic mobility shift assay, rTRβ2Δ-bound T3 with high affinity and recognized thyroid hormone response element (TRE) binding sites. Finally, in vitro transfection experiments further confirmed that rTRβ2Δ binding T3 significantly promotes the transcription of target genes via the TRE. Here, we have provided evidence suggesting that rTRβ2Δ is a novel functional TR isoform.

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

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.

Generation of immortal cell lines from the adult pituitary: role of cAMP on differentiation of SOX2-expressing progenitor cells to mature gonadotropes.

PubMed

Kim, Ginah L; Wang, Xiaomei; Chalmers, Jennifer A; Thompson, David R; Dhillon, Sandeep S; Koletar, Margaret M; Belsham, Denise D

2011-01-01

The pituitary is a complex endocrine tissue composed of a number of unique cell types distinguished by the expression and secretion of specific hormones, which in turn control critical components of overall physiology. The basic function of these cells is understood; however, the molecular events involved in their hormonal regulation are not yet fully defined. While previously established cell lines have provided much insight into these regulatory mechanisms, the availability of representative cell lines from each cell lineage is limited, and currently none are derived from adult pituitary. We have therefore used retroviral transfer of SV40 T-antigen to mass immortalize primary pituitary cell culture from an adult mouse. We have generated 19 mixed cell cultures that contain cells from pituitary cell lineages, as determined by RT-PCR analysis and immunocytochemistry for specific hormones. Some lines expressed markers associated with multipotent adult progenitor cells or transit-amplifying cells, including SOX2, nestin, S100, and SOX9. The progenitor lines were exposed to an adenylate cyclase activator, forskolin, over 7 days and were induced to differentiate to a more mature gonadotrope cell, expressing significant levels of α-subunit, LHβ, and FSHβ mRNAs. Additionally, clonal populations of differentiated gonadotropes were exposed to 30 nM gonadotropin-releasing hormone and responded appropriately with a significant increase in α-subunit and LHβ transcription. Further, exposure of the lines to a pulse paradigm of GnRH, in combination with 17β-estradiol and dexamethasone, significantly increased GnRH receptor mRNA levels. This array of adult-derived pituitary cell models will be valuable for both studies of progenitor cell characteristics and modulation, and the molecular analysis of individual pituitary cell lineages.

Feeding Frequency Affects Cultured Rat Pituitary Cells in Low Gravity

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Grindeland, R. E.; Salada, T.; Cenci, R.; Krishnan, K.; Mukai, C.; Nagaoka, S.

1996-01-01

In this report, we describe the results of a rat pituitary cell culture experiment done on STS-65 in which the effect of cell feeding on the release of the six anterior pituitary hormones was studied. We found complex microgravity related interactions between the frequency of cell feeding and the quantity and quality (i.e. biological activity) of some of the six hormones released in flight. Analyses of growth hormone (GH) released from cells into culture media on different mission days using gel filtration and ion exchange chromatography yielded qualitatively similar results between ground and flight samples. Lack of cell feeding resulted in extensive cell clumping in flight (but not ground) cultures. Vigorous fibroblast growth occurred in both ground and flight cultures fed 4 times. These results are interpreted within the context of autocrine and or paracrine feedback interactions. Finally the payload specialist successfully prepared a fresh trypsin solution in microgravity, detached the cells from their surface and reinserted them back into the culture chamber. These cells reattached and continued to release hormone in microgravity. In summary, this experiment shows that pituitary cells are microgravity sensitive and that coupled operations routinely associated with laboratory cel1 culture can also be accomplished in low gravity.