Abstract:
:The FOXO1 transcription factor is important for multiple aspects of reproductive function. We previously reported that FOXO1 functions as a repressor of gonadotropin hormone synthesis, but how FOXO1 is regulated in pituitary gonadotropes is unknown. The growth factors, insulin and insulin-like growth factor I (IGF1), function as key regulators of cell proliferation, metabolism and apoptosis in multiple cell types through the PI3K/AKT signaling pathway. In this study, we found that insulin and IGF1 signaling in gonadotropes induced FOXO1 phosphorylation through the PI3K/AKT pathway in immortalized and primary cells, resulting in FOXO1 relocation from the nucleus to the cytoplasm. Furthermore, insulin administration in vivo induced phosphorylation of FOXO1 and AKT in the pituitary. Thus, insulin and IGF1 act as negative regulators of FOXO1 activity and may serve to fine-tune gonadotropin expression.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Skarra DV,Thackray VGdoi
10.1016/j.mce.2015.02.006subject
Has Abstractpub_date
2015-04-15 00:00:00pages
14-24eissn
0303-7207issn
1872-8057pii
S0303-7207(15)00082-9journal_volume
405pub_type
杂志文章abstract::Type 4 phosphodiesterases (PDE4s) of the large PDE enzyme superfamily have unique specificity for cAMP and may, therefore, be relevant for somatotroph tumorigenesis. Somatotroph adenomas typically overexpress PDEs probably as part of a compensatory mechanism to reduce cAMP levels. The rat PDE4A5 isoform (human homolog...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2018.04.014
更新日期:2018-11-15 00:00:00
abstract::The activity of the hypothalamic-pituitary-adrenal (HPA) axis is characterized by an ultradian (pulsatile) pattern of hormone secretion. Pulsatility of glucocorticoids has been found critical for optimal transcriptional, neuroendocrine and behavioral responses. This review will focus on the mechanisms underlying the o...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2015.02.005
更新日期:2015-06-15 00:00:00
abstract::As part of an ongoing study of the cell-specific expression of glandular kallikrein genes in mice, we have investigated cellular sites of expression of the renal/pancreatic kallikrein gene, mGK-6, during fetal life. Expression of alpha I and beta-subunit genes of Na+K+ATPase and bradykinin binding were used as an indi...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(92)90005-q
更新日期:1992-10-01 00:00:00
abstract::Using primary cultures of porcine Sertoli cells as a model, the effects of ovine prolactin (oPRL) on Sertoli cell function were investigated through FSH binding. PRL treatment (0.3-5 ng/ml) induced a dose-dependent increase (ED50 = 5.10(-11) M) of 125I-FSH binding to Sertoli cells to a maximal stimulation (about 2.5-f...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(96)03891-9
更新日期:1996-09-18 00:00:00
abstract::Rat ovarian membrane luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor was reconstituted into proteoliposomes. The ability of sodium cholate to extract and reconstitute hCG binding activity was dependent on the protein/detergent ratio. Trypsinization of the LH/hCG receptor containing proteoliposomes i...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(92)90160-8
更新日期:1992-02-01 00:00:00
abstract::A working model for haematopoietic cytokine signal transduction has been hypothesised as follows. Binding of cytokines to specific receptor molecules leads to phosphorylation and activation of receptor associated members of the Janus kinase family. This is followed by tyrosine phosphorylation of the associated recepto...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(98)00054-9
更新日期:1998-03-16 00:00:00
abstract::Even though the levels of circulating sex steroid hormones are to a large extent heritable, their genetic determinants are largely unknown. With the advent of genome-wide association studies (GWAS), much progress has been made and several genetic loci have been identified to be associated with serum levels of dehydroe...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2013.03.009
更新日期:2014-01-25 00:00:00
abstract::Patients with PS or non-syndromic deafness were submitted to genetic/functional analyzes of SLC26A4, of its binding domain for FOXI1 (FOXI1-DBD), of the transcription activator FOXI1, and of the potassium channel KCNJ10. SLC26A4 was the most frequently mutated gene. An altered intracellular localization with immunocyt...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2012.01.013
更新日期:2012-04-04 00:00:00
abstract::Humans maintain core temperature through a complex neuroendocrine circuitry, coupling environmental thermal and nutritional cues to heat-producing and dissipating mechanisms. Up to 40% of resting energy expenditure contributes to thermal homeostasis maintenance. Recent re-discovery of thermogenic brown adipose tissue ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2015.05.025
更新日期:2015-12-15 00:00:00
abstract::Rat adipocytes in primary culture have been used to study the intracellular processing of growth hormone (GH) receptors. Pretreatment of adipocytes with 20 micrograms/ml cycloheximide resulted in a rapid decline (t1/2 approximately 45 min) of the 125I-human growth hormone (hGH) binding capacity of the cells. This decl...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(88)90037-8
更新日期:1988-05-01 00:00:00
abstract::Relaxin is a peptide hormone which consists of two polypeptide chains that are synthesized as a B-chain/C-peptide/A-chain precursor. We have used the polymerase chain reaction (PCR) to isolate and clone a relaxin-like cDNA from sheep placental RNA. This cDNA and two sheep genomic clones were characterised by nucleotid...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(93)90250-n
更新日期:1993-02-01 00:00:00
abstract::The aim of this study is to further characterize the prolactin receptors (PRL-R) previously reported in the murine Leydig tumor MA-10 cell line, as well as to study their homologous and heterologous regulation. Two forms of PRL-R, a high and a low molecular weight form, were revealed by studies of covalent crosslinkin...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(98)00134-8
更新日期:1998-08-25 00:00:00
abstract::We have previously demonstrated that maternal undernutrition during either the 'periconceptional' (i.e. from 60 days (d) before until 7 d after mating) or 'gestational' periods (i.e. from 8 d after mating until the end of pregnancy) have differential effects on the subsequent development of the hypothalamo-pituitary-a...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(02)00256-3
更新日期:2002-10-31 00:00:00
abstract::We have used a new methodology to generate a monospecific antiserum to the corticotropin (ACTH) receptor on mouse Y-1 adrenal cells. Using immunoaffinity chromatography the ACTH receptor was purified, and the molecular structure and 125I-ACTH binding characteristics were determined. A molecular weight (Mr) of 225 000 ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(86)90099-7
更新日期:1986-01-01 00:00:00
abstract::The inappropriate expressions of insulin-like growth factors (IGF-I and II) and IGF-I receptor (IGF-IR) are implicated in the malignant growth of many cancers. To determine changes, if any, in the levels of expression of IGFs and IGF receptor genes in neoplastic endometrium, relative to normal endometrium, the mRNA le...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(99)00092-1
更新日期:1999-07-20 00:00:00
abstract::Platelet-derived growth factor (PDGF) is a potent mitogen for several cell types. In addition, PDGF has vasoconstrictive action and shares some signal transduction mechanisms with angiotensin II (AII). In the present study, we have examined the effects of PDGF on basal and AII-induced aldosterone synthesis in freshly ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(92)90195-c
更新日期:1992-01-01 00:00:00
abstract::The identification of XY females carrying a duplication of a region of the X chromosome (Xp21) led to the hypothesis that a double dose of a gene in the duplicated region causes sex reversal (DSS; dosage sensitive sex reversal). A gene isolated from this region, named DAX-1 (DSS-AHC critical region on the X), encodes ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(97)00189-5
更新日期:1997-11-30 00:00:00
abstract::The classic renin-angiotensin system (RAS) is a complex system in which angiotensin II (Ang II) has been identified as an important endogenous regulator that influences both smooth muscle contraction and cell growth. Although a local RAS is known to exist in the gastrointestinal tract, it is unclear whether Ang II is ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2016.01.002
更新日期:2016-03-05 00:00:00
abstract::The transcription factors involved in the activation of cardiac gene expression by angiotensin II (Ang II) in vivo are not well understood. Here we studied the contribution of transcriptional elements to the activation of the cardiac B-type natriuretic peptide (BNP) gene promoter by Ang II in conscious rats and in ang...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2007.05.003
更新日期:2007-07-15 00:00:00
abstract::Receptors for calcitriol are described in human decidua. They exhibit a dissociation constant of 35 +/- 6 pM and they are at concentrations similar to those found in other tissues (0.45 +/- 0.04 fmol/micrograms DNA). They are highly specific for calcitriol since neither of the other vitamin D3 derivatives nor the ster...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(90)90023-2
更新日期:1990-07-09 00:00:00
abstract::One of the key messages of recent Salpea and Stratakis work is to underline the clinical similarities shared by these syndromes that could be explained by a defect in the same signaling pathway, i.e. activation of the cAMP pathway. That being said, we would like to emphasize that hepatopancreato-biliary lesions are on...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2013.10.020
更新日期:2014-01-25 00:00:00
abstract::Growth hormone (GH) secretion, evoked by either pituitary adenylate cyclase-activating polypeptide (PACAP) or dopamine (DA), is dependent on both voltage-sensitive calcium channels (VSCC) and cAMP signaling in goldfish. We further characterized the involvement of Ca2+ in evoked release by PACAP and DA, by examining th...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(03)00234-x
更新日期:2003-08-29 00:00:00
abstract::Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are essential factors in mammary-gland (MG) development and are altered during fasting. However, no studies have investigated the alterations in the expression of GH/IGF-I and its regulatory systems (somatostatin/cortistatin and ghrelin) in MG during fasting...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2016.06.014
更新日期:2016-10-15 00:00:00
abstract::The recent growth of interest in developmental programming of physiological systems has generally focused on the cardiovascular system (especially hypertension) and predisposition to metabolic dysfunction (mainly obesity and diabetes). However, it is now clear that the full range of altered offspring phenotypes includ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2013.09.008
更新日期:2014-01-25 00:00:00
abstract::Our previous studies have provided evidence for the existence of an intrinsic renin-angiotensin system (RAS) in the rat pancreas, which may play a role in the regulation of pancreatic microcirculation and ductal secretion. Such a pancreatic RAS has recently shown to be activated by chronic hypoxia. The activation of a...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(00)00275-6
更新日期:2000-08-30 00:00:00
abstract::Since occupational exposure to acrylamide (ACR) may cause nerve damage, sensitive biomarkers to evaluate the early effects of ACR on human health are needed. In the present study, we have compared a group of individuals with occupational exposure to ACR (contact group, n = 65) with a group of individuals with no expos...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2017.02.003
更新日期:2017-03-15 00:00:00
abstract:CONTEXT:Hyperandrogenic states and obesity in women are associated with insulin-resistance. Androgens reduce glucose uptake in adipose cells and increase TNFα production in peripheral monocytes. Inflammatory cytokines have a known detrimental effect on insulin resistance. The aim of the present study was to explore the...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2017.01.051
更新日期:2017-03-15 00:00:00
abstract::The pineal hormone melatonin modulates constitutive protein secretion from melanoma M2R cells. Nanomolar concentrations of melatonin inhibited protein secretion early after plating or at low cell density, but facilitated it late after plating or at high cell density. Inhibition by melatonin of adenylate cyclase is the...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(95)03592-u
更新日期:1995-08-11 00:00:00
abstract::The aim of our study was to investigate the direct effects of atypical antipsychotics on muscle cell functions in order to ascertain the diabetic liability of these drugs. We investigated the effects of olanzapine, clozapine and alpha-methyl-5-hydroxytryptamine on basal glucose uptake and glucose uptake in response to...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2008.04.010
更新日期:2008-09-24 00:00:00
abstract::Regulation of the ovalbumin (Ov) gene is strictly controlled by precise developmental, tissue-specific, and hormonal cues. The Ov gene is transcriptionally activated by four classes of steroid hormones: estrogens, androgens, glucocorticoids, and progestins. Although it has served as a model to study multi-hormone gene...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(02)00088-6
更新日期:2002-06-28 00:00:00