bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endocrine and Paracrine Regulation of Birth at Term and Preterm*
Authors: Challis John R.G. , Matthews Stephen G. , Gibb William , Lye Stephen J. 
Published: January 2014

AbstractWe have examined factors concerned with the maintenance of uterine quiescence during pregnancy and the onset of uterine activity at term in an animal model, the sheep, and in primate species. We suggest that in both species the fetus exerts a critical role in the processes leading to birth, and that activation of the fetal hypothalamic-pituitary-adrenal axis is a central mechanism by which the fetal influence on gestation length is exerted. Increased cortisol output from the fetal adrenal gland is a common characteristic across animal species. In primates, there is, in addition, increased output of estrogen precursor from the adrenal in late gestation. The end result, however, in primates and in sheep is similar: an increase in estrogen production from the placenta and intrauterine tissues. We have revised the pathway by which endocrine events associated with parturition in the sheep come about and suggest that fetal cortisol directly affects placental PGHS expression. In human pregnancy we suggest that cortisol increases PGHS expression, activity, and PG output in human fetal membranes in a similar manner. Simultaneously, cortisol contributes to decreases in PG metabolism and to a feed-forward loop involving elevation of CRH production from intrauterine tissues. In human pregnancy, there is no systemic withdrawal of progesterone in late gestation. We have argued that high circulating progesterone concentrations are required to effect regionalization of uterine activity, with predominantly relaxation in the lower uterine segment, allowing contractions in the fundal region to precipitate delivery. This new information, arising from basic and clinical studies, should further the development of new methods of diagnosing the patient at risk of preterm labor, and the use of scientifically based strategies specifically for the management of this condition, which will improve the health of the newborn.
Endocrine Manifestations of Stimulatory G Protein α-Subunit Mutations and the Role of Genomic Imprinting
Authors: Weinstein Lee S. , Yu Shuhua , Warner Dennis R. , Liu Jie 
Published: January 2014

AbstractThe heterotrimeric G protein Gs couples hormone receptors (as well as other receptors) to the effector enzyme adenylyl cyclase and is therefore required for hormone-stimulated intracellular cAMP generation. Receptors activate Gs by promoting exchange of GTP for GDP on the Gs α-subunit (Gsα) while an intrinsic GTPase activity of Gsα that hydrolyzes bound GTP to GDP leads to deactivation. Mutations of specific Gsα residues (Arg201 or Gln227) that are critical for the GTPase reaction lead to constitutive activation of Gs-coupled signaling pathways, and such somatic mutations are found in endocrine tumors, fibrous dysplasia of bone, and the McCune-Albright syndrome. Conversely, heterozygous loss-of-function mutations may lead to Albright hereditary osteodystrophy (AHO), a disease characterized by short stature, obesity, brachydactyly, sc ossifications, and mental deficits. Similar mutations are also associated with progressive osseous heteroplasia. Interestingly, paternal transmission of GNAS1 mutations leads to the AHO phenotype alone (pseudopseudohypoparathyroidism), while maternal transmission leads to AHO plus resistance to several hormones (e.g., PTH, TSH) that activate Gs in their target tissues (pseudohypoparathyroidism type IA). Studies in Gsα knockout mice demonstrate that Gsα is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in some tissues (e.g., renal proximal tubule, the major site of renal PTH action), while being biallelically expressed in most other tissues. Disrupting mutations in the maternal allele lead to loss of Gsα expression in proximal tubules and therefore loss of PTH action in the kidney, while mutations in the paternal allele have little effect on Gsα expression or PTH action. Gsα has recently been shown to be also imprinted in human pituitary glands. The Gsα gene GNAS1 (as well as its murine ortholog Gnas) has at least four alternative promoters and first exons, leading to the production of alternative gene products including Gsα, XLαs (a novel Gsα isoform that is expressed only from the paternal allele), and NESP55 (a chromogranin-like protein that is expressed only from the maternal allele). A fourth alternative promoter and first exon (exon 1A) located approximately 2.5 kb upstream of the Gsα promoter is normally methylated on the maternal allele and transcriptionally active on the paternal allele. In patients with isolated renal resistance to PTH (pseudohypoparathyroidism type IB), the exon 1A promoter region has a paternal-specific imprinting pattern on both alleles (unmethylated, transcriptionally active), suggesting that this region is critical for the tissue-specific imprinting of Gsα. The GNAS1 imprinting defect in pseudohypoparathyroidism type IB is predicted to decrease Gsα expression in renal proximal tubules. Studies in Gsα knockout mice also demonstrate that this gene is critical in the regulation of lipid and glucose metabolism.
Postpartum Thyroiditis and Autoimmune Thyroiditis in Women of Childbearing Age: Recent Insights and Consequences for Antenatal and Postnatal Care
Authors: Muller Alex F. , Drexhage Hemmo A. , Berghout Arie 
Published: January 2014

AbstractPostpartum thyroiditis is a syndrome of transient or permanent thyroid dysfunction occurring in the first year after delivery and based on an autoimmune inflammation of the thyroid. The prevalence ranges from 5–7%. We discuss the role of antibodies (especially thyroid peroxidase antibodies), complement, activated T cells, and apoptosis in the outbreak of postpartum thyroiditis. Postpartum thyroiditis is conceptualized as an acute phase of autoimmune thyroid destruction in the context of an existing and ongoing process of thyroid autosensitization. From pregnancy an enhanced state of immune tolerance ensues. A rebound reaction to this pregnancy-associated immune suppression after delivery explains the aggravation of autoimmune syndromes in the puerperal period, e.g., the occurrence of clinically overt postpartum thyroiditis. Low thyroid reserve due to autoimmune thyroiditis is increasingly recognized as a serious health problem. 1) Thyroid autoimmunity increases the probability of spontaneous fetal loss. 2) Thyroid failure due to autoimmune thyroiditis—often mild and subclinical—can lead to permanent and significant impairment in neuropsychological performance of the offspring. 3) Evidence is emerging that as women age subclinical hypothyroidism—as a sequel of postpartum thyroiditis—predisposes them to cardiovascular disease. Hence, postpartum thyroiditis is no longer considered a mild and transient disorder. Screening is considered.
Hepatic Nuclear Factor 3 and High Mobility Group I/Y Proteins Bind the Insulin Response Element of the Insulin-Like Growth Factor-Binding Protein-1 Promoter*
Authors: Allander Susanne V. , Durham Susan K. , Scheimann Ann O. , Wasserman Richard M. , Suwanichkul Adisak , Powell David R. 
Published: January 2014

AbstractThe insulin response element (IRE) of the human insulin-like growth factor-binding protein-1 (IGFBP-1) promoter contains a palindrome of the T(A/G)TTT sequence crucial to hormonal regulation of many genes. In initial studies of how this IRE participates in hormonal regulation, the electromobility shift assay was used under a variety of conditions to identify IRE-binding proteins. An exhaustive search identified five proteins that specifically bind this IRE; purified proteins were used to show that all five are related to either the high mobility group I/Y (HMGI/Y) or hepatic nuclear factor 3 (HNF3) protein families. Further studies used purified HNF3 and HMGI proteins to show: 1) each protects the IGFBP-1 IRE from deoxyribonuclease I (DNaseI) digestion; and 2) HNF3 but not HMGI/Y binds to the related phosphoenolpyruvate carboxykinase and Apo CIII IREs. A series of IRE mutants with variable responsiveness to insulin were used to show that the presence of a TGTTT sequence in the mutants did parallel, but HMGI/Y and HNF3 binding to the mutants did not parallel, the ability of the mutants to confer the inhibitory effect of insulin. In contrast, HNF3 binding to these IRE mutants roughly correlates with response of the mutants to glucocorticoids. The way by which HNF3 and/or other as yet unidentified IRE-binding proteins confer insulin inhibition to IGFBP-1 transcription and the role of HMGI/Y in IRE function have yet to be established.
Low Density Lipoprotein Binding and Uptake by Human and Rat Isletβ Cells*
Authors: Grupping A. Y. , Cnop M. , Van Schravendijk C. F. H. , Hannaert J. C. , Van Berkel Th. J. C. , Pipeleers D. G. 
Published: January 2014

Abstract
Abnormalities in lipoprotein metabolism are common in diabetes. It is unknown whether variations in form or concentration of lipoproteins influence the function of pancreatic β cells. This study investigates whether low density lipoproteins (LDL) exhibit specific interactions with islet β cells. Radioactively labeled LDL (125I-LDL) and fluorescently labeled LDL (DiI-LDL) were used as tracers. Rat islet cells express high affinity LDL binding sites (Kd = 9 nm), which are also recognized by very low density lipoproteins and which are down-regulated by LDL. Binding of LDL appears restricted to the β cells, as it was not detected on islet endocrine non-β cells. At 37 C, LDL is taken up and lysosomally degraded by islet β cells but not by islet non-β cells. Human islet cells were also found to present LDL binding, uptake, and degradation. Compared with rat islet cells, human islet cells exhibit 10-fold less binding sites (2.107vs. 2.108 per 103 cells) with a 2-fold lower Kd value (5 nm) and an equal sensitivity to LDL-induced down-regulation. In conclusion, human and rat islet β cells express LDL receptors that can internalize the lipoprotein. This pathway should be examined for its potential role in (dys)regulating pancreatic β cell functions.
Characterization of Germ Cell-Specific Expression of the Orphan Nuclear Receptor, Germ Cell Nuclear Factor*
Authors: Katz Deborah , Niederberger Craig , Slaughter Gayle R. , Cooney Austin J. 
Published: January 2014

Abstract
Nuclear receptors, such as those for androgens, estrogens, and progesterones, control many reproductive processes. Proteins with structures similar to these receptors, but for which ligands have not yet been identified, have been termed orphan nuclear receptors. One of these orphans, germ cell nuclear factor (GCNF), has been shown to be germ cell specific in the adult and, therefore, may also participate in the regulation of reproductive functions. In this paper, we examine more closely the expression patterns of GCNF in germ cells to begin to define spatio-temporal domains of its activity. In situ hybridization showed that GCNF messenger RNA (mRNA) is lacking in the testis of hypogonadal mutant mice, which lack developed spermatids, but is present in the wild-type testis. Thus, GCNF is, indeed, germ cell specific in the adult male. Quantitation of the specific in situ hybridization signal in wild-type testis reveals that GCNF mRNA is most abundant in stage VII round spermatids. Similarly, Northern analysis and specific in situ hybridization show that GCNF expression first occurs in testis of 20-day-old mice, when round spermatids first emerge. Therefore, in the male, GCNF expression occurs postmeiotically and may participate in the morphological changes of the maturing spermatids. In contrast, female expression of GCNF is shown in growing oocytes that have not completed the first meiotic division. Thus, GCNF in the female is expressed before the completion of meiosis. Finally, the nature of the two different mRNAs that hybridize to the GCNF complementary DNA was studied. Although both messages contain the DNA binding domain, only the larger message is recognized by a probe from the extreme 3′ untranslated region. In situ hybridization with these differential probes demonstrates that both messages are present in growing oocytes. In addition, the coding region and portions of the 3′ untranslated region of the GCNF complementary DNA are conserved in the rat.
Examination of Guinea Pig Luteinizing Hormone-Releasing Hormone Gene Reveals a Unique Decapeptide and Existence of Two Transcripts in the Brain*
Authors: Jimenez-Liñan Mercedes , Rubin Beverly S. , King Joan C. 
Published: January 2014

AbstractWe sequenced the complementary DNA (cDNA) encoding guinea pig LHRH from an expression library derived from the preoptic area-anterior hypothalamus. Data from in situ hybridization and RNase protection assays verified that the cloned cDNA was complementary to guinea pig LHRH messenger RNA. The architecture of the deduced precursor resembles that of LHRH precursors identified in other species. In contrast, the predicted sequence of the decapeptide differs from mammalian LHRH by two amino acid substitutions in positions 2 and 7. This is a novel finding, because the amino acid sequence that comprises LHRH decapeptide is identical in all mammals studied to date. Moreover, the predicted substitution in amino acid position 2 is unique among vertebrates. A second observation of potential significance is the existence of two subspecies of LHRH messenger RNA differing only in the length of their 3′ untranslated regions. These two transcripts were verified by sequence analysis of positive clones from the cDNA library and by RNase protection analysis of preoptic area-anterior hypothalamus extracts, and their presence is consistent with the two polyadenylation signals identified in the untranslated regions of the LHRH gene. Future studies will examine LHRH gene expression in guinea pigs, which like primates but unlike rats, have a true luteal phase as a component of their reproductive cycle.
Breed Differences in Expression of Inhibin/Activin Subunits in Porcine Anterior Pituitary Glands*
Authors: Li M. D. , MacDonald G. J. , Ford J. J. 
Published: January 2014

AbstractChinese Meishan (MS) boars have greater plasma FSH concentrations than European White Composite boars, but this difference does not occur in females of these breeds. To understand this disparity, we studied expression of the follistatin gene and of genes for the inhibin/activinα -, βA-, and βB-subunits in porcine anterior pituitary glands using quantitative reverse transcription-PCR and ribonuclease protection techniques. We found that 1) the inhibin/activin βA- and βB-subunits and follistatin were expressed in porcine pituitary; 2) the α-subunit was not detected in the porcine pituitary, but was highly expressed in porcine follicles; and 3) the βB-subunit gene is more abundantly expressed (2-fold greater) in MS boar pituitaries than in pituitaries of White Composite boars. We conclude that this is not due to a breed difference, because the expression levels of this gene were similar in pituitaries of females of these breeds. No breed differences were detected for other genes screened in this study. From these observations, we propose that activin B, a dimer ofβ B-subunits and a stimulator of FSH secretion, may be partially responsible for the elevated plasma FSH concentrations in MS boars, and intrapituitary inhibin plays no or a very minimal role.
Only the Substitution of Methionine 918 with a Threonine and Not with Other Residues Activates RET Transforming Potential*
Authors: Cirafici Anna Maria , Salvatore Giuliana , De Vita Gabriella , Carlomagno Francesca , Dathan Nina A. , Visconti Roberta , Melillo Rosa Marina , Fusco Alfredo , Santoro Massimo 
Published: January 2014

AbstractSpecific point-mutations of the RET receptor tyrosine kinase protooncogene are responsible for the inheritance of multiple endocrine neoplasia type 2A (MEN2A) and 2B (MEN2B), and familial medullary thyroid carcinoma (FMTC). MEN2B is caused by the substitution of methionine 918 by a threonine in the tyrosine kinase (TK) domain of RET. This mutation converts RET into a dominant transforming oncogene. We have substituted Met918 with four different residues and found that RET acquired transforming activity only when Met918 was substituted with a threonine. However, also when serine and valine, but not leucine or phenylalanine, were inserted in position 918, the RET TK function was activated and induced, especially in the case of the RET(918Ser), immmediate-early response genes. We conclude that the preservation of Met918 is critical for the control of RET kinase. However, only when a threonine residue is present in position 918, does RET efficiently couple with a transforming pathway.
Nuclear Transport of Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3 in Opossum Kidney Cells
Authors: Li Wenlu , Fawcett Janet , Widmer H. Ramon , Fielder Paul J. , Rabkin Ralph , Keller Gilbert-André 
Published: January 2014

Abstract
When added to cultured opossum kidney cells, IGF-I is internalized and transported to distinct intracellular compartments that depend on the cell location within the monolayer. In resting cells away from the periphery of the monolayer, IGF-I is internalized by a clathrin coated pit pathway and delivered to the endosomal compartment. In contrast, cells growing at the edges of a monolayer or an experimental wound internalize IGF-I by an alternative route which rapidly delivers IGF-I to the nucleus. Similarly to IGF-I, IGFBP-3 is also internalized and accumulates in the endosomal compartment in resting cells whereas it is targeted to the nucleus in proliferating cells. IGFBP-3, which contains a putative nuclear targeting signal, may act as a carrier for IGF-I nuclear transport. The transport of IGF-I and IGFBP-3 to two different compartments may influence their biological activity.
Increased Pancreatic Islet Blood Flow in 48-Hour Glucose-Infused Rats: Involvement of Central and Autonomic Nervous Systems*
Authors: Atef Nadia , Laury Marie-Claude , N’Guyen Jean-Michel , Mokhtar Najad , Ktorza Alain , Penicaud Luc 
Published: January 2014

AbstractThe pancreatic islet blood flow of rats 24 h after a prolonged (48-h) glucose infusion was investigated using a nonradioactive microsphere technique. In the basal state, islet blood flow was significantly increased in previously hyperglycemic rats (HG) compared to that in controls (C). During an iv glucose challenge, both plasma insulin and islet blood flow were increased in the two groups, but these increases were significantly higher in HG than in C rats. Although less pronounced, the results were similar when glucose was injected into the carotid artery toward the brain at a dose that did not modify the peripheral glucose level. The effect of this intracarotid injection was abolished after bilateral subdiaphragmatic vagotomy in both C and HG rats. Furthermore, in the latter group, both plasma insulin concentration and islet blood flow returned to values similar to those observed in the basal state in C rats. After pretreatment with the α2-adrenoceptor agonist clonidine, the insulin response to the intracarotid glucose load was totally blunted in the two groups of rats. By contrast, whereas such a pretreatment lowered the glucose-induced increase in islet blood flow in C rats, it was without effect in HG rats. These data suggest that a period of hyperglycemia and/or hyperinsulinemia is sufficient to induce a perturbation of pancreatic islet blood flow, which appears to be mainly due to an increased parasympathetic activity, whereas the decrease in sympathetic tone does not play a role. These modifications in autonomic nervous system activity could be due to alterations in some brain areas involved in “glucose sensing.”
Potential Role of Protein Kinase B in Glucose Transporter 4 Translocation in Adipocytes*
Authors: Tanti Jean-François , Grillo Sophie , Grémeaux Thierry , Coffer Paul J. , Van Obberghen Emmanuel , Le Marchand-Brustel Yannick 
Published: January 2014

AbstractPhosphatidylinositol 3-kinase (PI 3-kinase) activation promotes glucose transporter 4 (Glut 4) translocation in adipocytes. In this study, we demonstrate that protein kinase B, a serine/threonine kinase stimulated by PI 3-kinase, is activated by both insulin and okadaic acid in isolated adipocytes, in parallel with their effects on Glut 4 translocation. In 3T3-L1 adipocytes, platelet-derived growth factor activated PI 3-kinase as efficiently as insulin but was only half as potent as insulin in promoting protein kinase B (PKB) activation. To look for a potential role of PKB in Glut 4 translocation, adipocytes were transfected with a constitutively active PKB (Gag-PKB) together with an epitope tagged transporter (Glut 4 myc). Gag-PKB was associated with all membrane fractions, whereas the endogenous PKB was mostly cytosolic. Expression of Gag-PKB led to an increase in Glut 4 myc amount at the cell surface. Our results suggest that PKB could play a role in promoting Glut 4 appearance at the cell surface following exposure of adipocytes to insulin and okadaic acid stimulation.
Cloning and Characterization of the Vitamin D Receptor from Xenopus laevis*
Authors: Li Yan Chun , Bergwitz Clemens , Jüppner Harald , Demay Marie B. 
Published: January 2014

AbstractThe Vitamin D receptor (VDR), a member of the nuclear receptor superfamily, mediates the effects of 1,25-dihydroxyvitamin D3 on mineral ion homeostasis. Although the mammalian and avian VDRs have been extensively studied, little is known about the VDR in lower vertebrate species. To address this, we have isolated the Xenopus laevis VDR (xVDR) complementary DNA. Overall, the xVDR shares 79%, 73%, 73%, and 75% identity at the amino acid level with the chicken, mouse, rat, and human VDRs, respectively. The amino acid residues and subdomains important for DNA binding, hormone binding, dimerization, and transactivation are mostly conserved among all VDR species.The xVDR polypeptide can heterodimerize with the mouse retinoid X receptor α, bind to the rat osteocalcin vitamin D response element (VDRE), and induce vitamin D-dependent transactivation in transfected mammalian cells. Northern analysis reveals two xVDR messenger RNA species of 2.2 kb and 1.8 kb in stage 60 Xenopus tissues. In the adult, xVDR expression is detected in many tissues including kidney, intestine, skin, and bone. During Xenopus development, xVDR messenger RNA first appears at developmental stage 13 (preneurulation), increasing to maximum at stages 57–61 (metamorphosis). Our data demonstrate that, in Xenopus, VDR expression is developmentally regulated and that the vitamin D endocrine system is highly conserved during evolution.