Search NASA⌕ Search

SEARCH · Search NASA

Results for “PITUITARY HORMONES”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Dioxin-induced retardation of development through a reduction in the expression of pituitary hormones and possible involvement of an aryl hydrocarbon receptor in this defect: A comparative study using two strains of mice with different sensitivities to dioxin

We have previously revealed that treating pregnant rats with 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) reduces the expression of gonadotropins and growth hormone (GH) in the fetal and neonatal pituitary. A change in gonadotropin expression impairs the testicular expression of steroidogenic proteins in perinatal pups, and imprint defects in sexual behavior after reaching maturity. In this study, we examined whether TCDD also affects the expression of gonadotropin and GH in mice using C57BL/6J and DBA/2J strains which express the aryl hydrocarbon receptor (Ahr) exhibiting a different affinity for TCDD. When pregnant C57BL/6J mice at gestational day (GD) 12 were given oral TCDD (0.2–20 μg/kg), all doses significantly attenuated the pituitary expression of gonadotropin mRNAs in fetuses at GD18. On the other hand, in DBA/2J mice, a much higher dose of TCDD (20 μg/kg) was needed to produce a significant attenuation. Such reduction in the C57BL/6J strain continued until at least postnatal day (PND) 4. In agreement with this, TCDD reduced the testicular expression of steroidogenic proteins in C57BL/6J neonates at PND2 and 4, although the same did not occur in the fetal testis and ovary. Furthermore, TCDD reduced the perinatal expression of GH, litter size and the body weight of newborn pups only in the C57BL/6J strain. These results suggest that 1) also in mice, maternal exposure to TCDD attenuates gonadotropin-regulated steroidogenesis and GH expression leading to the impairment of pup development and sexual immaturity; and 2) Ahr activation during the late fetal and early postnatal stages is required for these defects. - Highlights: • The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse growth was studied. • TCDD reduced the levels of luteinizing hormone and growth hormone in perinatal pups. • Maternal exposure to TCDD also attenuated testicular steroidogenesis in pups. • The above effects of TCDD were more pronounced in C57BL/6J than in DBA/2J strain. • TCDD seems to disturb pup maturation by activating aryl hydrocarbon receptor.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Development of xeno-free epithelial differentiation media for adherent, non-expanded adipose stromal vascular cell cultures

Reconstruction of respiratory epithelium is critical for the fabrication of bioengineered airway implants. Epithelial differentiation is typically achieved using bovine pituitary extract (BPE). Due to the xenogenic nature and undefined composition of BPE, an alternative for human clinical applications, devoid of BPE, must be developed. The goal of this study was to develop two different BPE-free media, with and without select pituitary hormone (PH), which could initiate epithelial differentiation for use in human implantation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Long-Term Outcomes and Complications in Patients With Craniopharyngioma: The British Columbia Cancer Agency Experience

Purpose: We report long-term outcomes and complications of craniopharyngioma patients referred to our institution. Methods and Materials: Between 1971 and 2010, 123 consecutive patients received primary treatment for craniopharyngioma in British Columbia and were referred to our institution. The median age was 30 years (range, 2-80 years). Thirty-nine percent of patients were treated primarily with subtotal resection (STR) and radiation therapy (RT), 28% with STR alone, 15% with gross total resection, 11% with cyst drainage (CD) alone, 5% with CD+RT, and 2% with RT alone. Eight percent of patients received intracystic bleomycin (ICB) therapy. Results: Median follow-up was 8.9 years, and study endpoints were reported at 10 years. Ten-year Kaplan-Meier progression-free survival (PFS) was 46%. Patients treated with STR+RT or CD+RT had the highest PFS (82% and 83%, respectively). There were no significant differences between PFS after adjuvant versus salvage RT (84% vs 74%, respectively; P=.6). Disease-specific survival (DSS) was 88%, and overall survival (OS) was 80%. Primary treatment modality did not affect DSS or OS, while older age was a negative prognostic factor for OS but not DSS. Kaplan-Meier rates for visual deterioration, anterior pituitary hormone deficiency, diabetes insipidus, seizure disorder, and cerebrovascular events (CVE) due to treatment, not tumor progression, were 27%, 76%, 45%, 16%, and 11%, respectively. The CVE rate was 29% in patients who received ICB compared to 10% in those who did not (P=.07). Conclusions: We report favorable PFS in patients with craniopharyngioma, especially in those who received RT after surgery. DSS and OS rates were excellent regardless of primary treatment modality. We observed a high incidence of hypopituitarism, visual deterioration, and seizure disorder. Eleven percent of patients experienced CVEs after treatment. There was a suggestion of increased CVE risk in patients treated with ICB.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

A possible mechanism for 2,2',4,4',5,5'-hexachlorobiphenyl-mediated decrease in serum thyroxine level in mice

Serum total thyroxine (T{sub 4}) level was markedly decreased, without significant increases in the levels of hepatic T{sub 4}-UDP-glucuronosyltransferase (T{sub 4}-UGT) and serum thyroid-stimulating hormone, 3 days after treatment with 2,2',4,4',5,5'-hexachlorobiphenyl (CB153) (100 mg/kg, ip) in both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive C57BL/6 and TCDD-resistant DBA/2 mice. Likewise, in either strain of mice, no CB153-mediated changes in the binding levels of [{sup 125}I]T{sub 4} to serum proteins, such as transthyretin, albumin, and thyroxine binding globulin, were observed, while in CB153-pretreated C57BL/6 mice, but not in CB153-pretreated DBA/2 mice, the levels of biliary [{sup 125}I]T{sub 4} and [{sup 125}I]T{sub 4}-glucuronide at 90-120 min after injection of [{sup 125}I]T{sub 4} slightly increased, as compared with those in the corresponding control mice. Concerning tissue distribution of [{sup 125}I]T{sub 4}, liver-selective increases in the [{sup 125}I]T{sub 4} accumulation by CB153-pretreatment were observed in both C57BL/6 and DBA/2 mice, and the hepatic levels of [{sup 125}I]T{sub 4} in the C57BL/6 and DBA/2 mice became more than 44% and 34% of the [{sup 125}I]T{sub 4} dosed, respectively. The present findings indicated that the CB153-mediated decreases in the level of serum total T{sub 4} in C57BL/6 and DBA/2 mice occur mainly through an increase in the accumulation of T{sub 4} in the liver.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T{sub 4}) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T{sub 3}) and tetraiodothyronine (T{sub 4}) levels accompanied by a dramatic decrease of TSH and application of L-T{sub 4} restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T{sub 4} treatment. L-T{sub 4} treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T{sub 4} relieves chronic Pb exposure-induced impairment of synaptic plasticity. - Highlights: > Lead may interfere with thyroid hormone homeostasis and induce hypothyroidism. > Levothyroxine decreases the hippocampal and blood Pb concentration. > Levothyroxine amends the T{sub 3}, T{sub 4} and TSH levels in blood. > Levothyroxine rescues the impaired LTP in CA1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary

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 proliferation 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.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Arecoline augments cellular proliferation in the prostate gland of male Wistar rats

Areca nut chewing is the fourth most popular habit in the world due to its effects as a mild stimulant, causing a feeling of euphoria and slightly heightened alertness. Areca nuts contain several alkaloids and tannins, of which arecoline is the most abundant and known to have several adverse effects in humans, specially an increased risk of oral cancer. On evaluating the effects of arecoline on the male endocrine physiology in Wistar rats, it was found that arecoline treatment led to an overall enlargement and increase in the wet weight of the prostate gland, and a two-fold increase in serum gonadotropin and testosterone levels. Since the prostate is a major target for testosterone, the consequences of arecoline consumption were studied specifically in the prostate gland. Arecoline treatment led to an increase in the number of rough endoplasmic reticulum and reduction of secretory vesicles, signifying a hyperactive state of the prostate. Increased expression of androgen receptors in response to arecoline allowed for enhanced effect of testosterone in the prostate of treated animals, which augmented cell proliferation, subsequently confirmed by an increase in the expression of Ki-67 protein. Cellular proliferation was also the outcome of concomitant over expression of the G{sub 1}-to-S cell cycle regulatory proteins, cyclin D1 and CDK4, both at the transcriptional and translational levels. Taken together, the findings provide the first evidence that regular use of arecoline may lead to prostatic hyperplasia and hypertrophy, and eventually to disorders associated with prostate enlargement. - Highlights: > Effect of arecoline was investigated on the endocrine physiology of male Wistar rats. > Increase observed in prostate size, wet weight, serum testosterone and gonadotropins. > Arecoline increased RER, expression of androgen receptor and cellular proliferation. > Upregulation of cyclin D1 and CDK4 seen at transcriptional and translational levels. > It may cause disorders associated with prostatic hyperplasia and hyperactivity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Altered cardiovascular reactivity and osmoregulation during hyperosmotic stress in adult rats developmentally exposed to polybrominated diphenyl ethers (PBDEs)

Polybrominated diphenyl ethers (PBDEs) and the structurally similar chemicals polychlorinated biphenyls (PCBs) disrupt the function of multiple endocrine systems. PCBs and PBDEs disrupt the secretion of vasopressin (VP) from the hypothalamus during osmotic activation. Since the peripheral and central vasopressinergic axes are critical for osmotic and cardiovascular regulation, we examined whether perinatal PBDE exposure could impact these functions during physiological activation. Rats were perinatally dosed with a commercial PBDE mixture, DE-71. Dams were given 0 (corn oil control), 1.7 (low dose) or 30.6 mg/kg/day (high dose) in corn oil from gestational day (GD) 6 through postnatal day (PND) 21 by oral gavage. In the male offspring exposed to high dose PBDE plasma thyroxine and triiodothyronine levels were reduced at PND 21 and recovered to control levels by PND 60 when thyroid stimulating hormone levels were elevated. At 14-18 months of age, cardiovascular responses were measured in four groups of rats: Normal (Oil, normosmotic condition), Hyper (Oil, hyperosmotic stress), Hyper PBDE low (1.7 mg/kg/day DE-71 perinatally, hyperosmotic stress), and Hyper PBDE high (30.6 mg/kg/day DE-71 perinatally, hyperosmotic stress). Systolic blood pressure (BP), diastolic BP, and heart rate (HR) were determined using tail cuff sphygmomanometry and normalized to pretreatment values (baseline) measured under basal conditions. Hyperosmotic treatment yielded significant changes in systolic BP in PBDE exposed rats only. Hyper PBDE low and high dose rats showed 36.1 and 64.7% greater systolic BP responses at 3 h post hyperosmotic injection relative to pretreatment baseline, respectively. No treatment effects were measured for diastolic BP and HR. Hyper and Hyper PBDE rats showed increased mean plasma osmolality values by 45 min after injection relative to normosmotic controls. In contrast to Hyper rats, Hyper PBDE (high) rats showed a further increase in mean plasma osmolality at 3 h (358.3 {+-} 12.4 mOsm/L) relative to 45 min post hyperosmotic injection (325.1 {+-} 11.4 mOsm/L). Impaired osmoregulation in PBDE-treated animals could not be attributed to decreased levels of plasma vasopressin. Our findings suggest that developmental exposure to PBDEs may disrupt cardiovascular reactivity and osmoregulatory responses to physiological activation in late adulthood. - Highlights: > We examined whether PBDE exposure could impact osmotic and cardiovascular regulation. > Hyperosmotic treatment yielded significant changes in systolic BP in PBDE exposed rats only. > PBDEs may disrupt cardiovascular and osmoregulatory responses to physiological activation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

2,3,4,7,8-Pentachlorodibenzofuran is far less potent than 2,3,7,8-tetrachlorodibenzo-p-dioxin in disrupting the pituitary–gonad axis of the rat fetus

The effect of 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) on the fetal pituitary–gonad axis was compared with that produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Wistar rats. Maternal treatment at gestational day (GD) 15 with PnCDF and TCDD reduced the fetal expression at GD20 of pituitary luteinizing hormone (LH) and the testicular proteins necessary for steroidogenesis. The relative potencies of PnCDF ranged from 1/42nd to 1/63rd of the TCDD effect. While PnCDF, at a dose sufficient to cause a reduction in fetal LH, provoked defects in sexual behavior at adulthood, a dose less than the ED{sub 50} failed to produce any abnormality. There was a loss of fetal body weight following in utero exposure to PnCDF, and the effect of PnCDF was also much less than that of TCDD. The disturbance in fetal growth was suggested to be due to a reduction in the level of fetal growth hormone (GH) by dioxins. The disorder caused by PnCDF/TCDD in the fetal pituitary–gonad axis occurred at doses less than those needed to cause wasting syndrome in pubertal rats. The harmful effect of PnCDF relative to TCDD was more pronounced in fetal rats than in pubertal rats. These lines of evidence suggest that: 1) PnCDF as well as TCDD imprints defects in sexual behavior by disrupting the fetal pituitary–gonad axis; 2) these dioxins hinder fetal growth by reducing the expression of fetal GH; and 3) the fetal effects of PnCDF/TCDD are more sensitive than sub-acute toxicity during puberty, and the relative effect of PnCDF varies markedly depending on the indices used. - Highlights: • 2,3,4,7,8-Pentachlorodibenzofuran (PnCDF) lowers gonadal steroidogenesis in fetuses. • PnCDF exerts the above effect through an initial attenuation in gonadotropin level. • PnCDF imprints sexual immaturity by transiently disrupting the pituitary–gonad axis. • PnCDF also disturbs pup growth probably due to a reduction in growth hormone level. • The above effects are far lesser in PnCDF than 2,3,7,8-tetrachlorodibenzo-p-dioxin.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Ozone-Induced Dysregulation of Neuroendocrine Axes Requires Adrenal-Derived Stress Hormones

Abstract Acute ozone inhalation increases circulating stress hormones through activation of the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes. Rats with adrenalectomy (AD) have attenuated ozone-induced lung responses. We hypothesized that ozone exposure will induce changes in circulating pituitary-derived hormones and global gene expression in the brainstem and hypothalamus, and that AD will ameliorate these effects. Male Wistar-Kyoto rats (13 weeks) that underwent sham surgery (SHAM) or AD were exposed to ozone (0.8 ppm) or filtered-air for 4 h. In SHAM rats, ozone exposure decreased circulating thyroid-stimulating hormone (TSH), prolactin (PRL), and luteinizing hormone (LH). AD prevented reductions in TSH and PRL, but not LH. AD increased adrenocorticotropic hormone approximately 5-fold in both air- and ozone-exposed rats. AD in air-exposed rats resulted in few significant transcriptional differences in the brainstem and hypothalamus (approximately 20 genes per tissue). In contrast, ozone-exposure in SHAM rats resulted in either increases or decreases in expression of hundreds of genes in the brainstem and hypothalamus relative to air-exposed SHAM rats (303 and 568 genes, respectively). Differentially expressed genes from ozone exposure were enriched for pathways involving hedgehog signaling, responses to alpha-interferon, hypoxia, and mTORC1, among others. Gene changes in both brain areas were analogous to those altered by corticosteroids and L-3,4-dihydroxyphenylalanine, suggesting a role for endogenous glucocorticoids and catecholamines. AD completely prevented this ozone-induced transcriptional response. These findings show that short-term ozone inhalation promotes a shift in brainstem and hypothalamic gene expression that is dependent upon the presence of circulating adrenal-derived stress hormones. This is likely to have profound downstream influence on systemic effects of ozone.

Henriquez, Andres R.↗
DOE OSTI2018

A crossover–crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and serum reproductive hormones in men

Highlights: • Mesalamine medications with coatings that contain dibutyl phthalate (DBP) lead to very high DBP exposure. • New exposure to high DBP from mesalamine medications disrupted pituitary-gonadal hormones in adult men. • Among men with no or short previous high DBP exposure, the hormone disruption was reversed after exposure removal. • Long term high DBP exposure may alter the pituitary-gonadal axis and make it insensitive to removal of exposure. Phthalates, such as dibutyl phthalate (DBP), are endocrine disruptors used in some medication coatings e.g., mesalamine to treat inflammatory bowel disease (IBD).

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

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

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. 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.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Generation and characterization of gsuα:EGFP transgenic zebrafish for evaluating endocrine-disrupting effects

The glycoprotein subunit α (gsuα) gene encodes the shared α subunit of the three pituitary heterodimeric glycoprotein hormones: follicle-stimulating hormone β (Fshβ), luteinizing hormone β (Lhβ) and thyroid stimulating hormone β (Tshβ). In our current study, we identified and characterized the promoter region of zebrafish gsuα and generated a stable gsuα:EGFP transgenic line, which recapitulated the endogenous gsuα expression in the early developing pituitary gland. A relatively conserved regulatory element set is presented in the promoter regions of zebrafish and three other known mammalian gsuα promoters. Our results also demonstrated that the expression patterns of the gsuα:EGFP transgene were all identical to those expression patterns of the endogenous gsuα expression in the pituitary tissue when our transgenic fish were treated with various endocrine chemicals, including forskolin (FSK), SP600125, trichostatin A (TSA), KClO{sub 4}, dexamethasone (Dex), β-estradiol and progesterone. Thus, this gsuα:EGFP transgenic fish reporter line provides another valuable tool for investigating the lineage development of gsuα-expressing gonadotrophins and the coordinated regulation of various glycoprotein hormone subunit genes. These reporter fish can serve as a novel platform to perform screenings of endocrine-disrupting chemicals (EDCs) in vivo as well. - Highlights: • Identification of the promoter of zebrafish glycoprotein subunit α (gsuα) gene • Generation of stable transmission gsuα:EGFP transgenic zebrafish reporter • Demonstration of the recapitulation of the gsuα:EGFP and endogenous gsuα expression • Suggestion of the gsuα:EGFP transgenic zebrafish as a novel platform for EDC study.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with GCT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

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

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. - 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.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Interactive effects of nonylphenol and bisphenol A exposure with oxidative stress on fetal reproductive indices

Highlights: • Maternal NP exposure may induce 8-OHdG and 8-NO{sub 2}Gua. • Prenatal BPA may induce 8-isoPF{sub 2α}. • Concurrent exposure to NP and BPA may enhance 8-OHdG. • In the high 8-isoPF{sub 2α} group, NP/BPA is inversely related with the fetal penis length. • The interactions of NP/BPA, oxidative stress and penis length should be considered. Nonylphenol (NP) and/or bisphenol A (BPA) may have reproductive effects. Although the mechanisms of action remain unclear, steroid hormones biosynthesis, hypothalamus pituitary adrenal axis activity, oxidative stress, and crosstalk interaction of NP and BPA mixture and its pathways may play a contributory role. This cross-sectional study examined whether the interactive effects of NP/BPA and oxidative stress biomarkers played a role in reproductive indices (penis length and anogenital distance (AGD)) in 244 mother-fetus pairs. Four biomarkers of oxidative stress, (8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO{sub 2}Gua), 8-iso-prostaglandin F{sub 2α} (8-isoPF{sub 2α}), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) were simultaneously analyzed using the high-performance liquid chromatography-electrospray ionization tandem mass spectrometry method. No significant associations were found between reproductive indices and NP/BPA or oxidative stress biomarkers. Maternal exposure to a mixture of NP and BPA may enhance 8-OHdG. Interactive effects were found in the high 8-isoPF{sub 2α} group, and prenatal NP exposure was inversely associated with penis length (β = −3.68 mm; p = 0.01). Similar results were noted among boys who were born to mothers in the high 8-isoPF{sub 2α} group, in which BPA was inversely associated with penis length (β = −4.43 mm; p = 0.005). Our findings suggest important implications for prenatal exposure to oxidative stress, as evidenced by the 8-isoPF2α level. Thus, NP and BPA may interact to shape fetal reproductive tract development, particularly in boys. The interactive effects of NP/BPA, oxidative stress, and reproductive indices should be considered.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

Silent Corticotroph Adenomas After Stereotactic Radiosurgery: A Case–Control Study

Purpose: To investigate the safety and effectiveness of stereotactic radiosurgery (SRS) in patients with a silent corticotroph adenoma (SCA) compared with patients with other subtypes of non–adrenocorticotropic hormone staining nonfunctioning pituitary adenoma (NFA). Methods and Materials: The clinical features and outcomes of 104 NFA patients treated with SRS in our center between September 1994 and August 2012 were evaluated. Among them, 34 consecutive patients with a confirmatory SCA were identified. A control group of 70 patients with other subtypes of NFA were selected for review based on comparable baseline features, including sex, age at the time of SRS, tumor size, margin radiation dose to the tumor, and duration of follow-up. Results: The median follow-up after SRS was 56 months (range, 6-200 months). No patients with an SCA developed Cushing disease during the follow-up. Tumor control was achieved in 21 of 34 patients (62%) in the SCA group, compared with 65 of 70 patients (93%) in the NFA group. The median progression-free survival (PFS) was 58 months in the SCA group. The actuarial PFS was 73%, 46%, and 31% in the SCA group and was 94%, 87%, and 87% in the NFA group at 3, 5, and 8 years, respectively. Silent corticotroph adenomas treated with a dose of ≥17 Gy exhibited improved PFS. New-onset loss of pituitary function developed in 10 patients (29%) in the SCA group, whereas it occurred in 18 patients (26%) in the NFA group. Eight patients (24%) in the SCA group experienced worsening of a visual field deficit or visual acuity attributed to the tumor progression, as did 6 patients (9%) in the NFA group. Conclusion: Silent corticotroph adenomas exhibited a more aggressive course with a higher progression rate than other subtypes of NFAs. Stereotactic radiosurgery is an important adjuvant treatment for control of tumor growth. Increased radiation dose may lead to improved tumor control in SCA patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗