A yeast two-hybrid assay was employed to identify androgen receptor (AR) protein partners in gonadotropin-releasing hormone neuronal cells. By using an AR deletion construct (AR-(⌬371-485)) as a bait, ␤-catenin was identified as an AR-interacting protein from a gonadotropin-releasing hormone neuronal cell library. Immunolocalization of co-transfected AR and FLAG-␤-catenin demonstrated that FLAG-␤-catenin was predominantly cytoplasmic in the absence of androgen. In the presence of 5␣-dihydrotestosterone, FLAG-␤-catenin completely co-localized to the nucleus with AR. This effect was specific to AR because liganded progesterone, glucocorticoid, or estrogen ␣ receptors did not translocate FLAG-␤-catenin to the nucleus. Agonist-bound AR was required because the AR antagonists casodex and hydroxyflutamide failed to translocate ␤-catenin. Time course experiments demonstrated that co-translocation occurred with similar kinetics. Nuclear co-localization was independent of the glycogen synthase kinase-3␤, p42/44 ERK mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways because inhibitors of these pathways had no effect. Transcription assays demonstrated that liganded AR repressed ␤-catenin/T cell factor-responsive reporter gene activity. Conversely, co-expression of ␤-catenin/T cell factor repressed AR stimulation of AR-responsive reporter gene activity. Our data suggest that liganded AR shuttles ␤-catenin to the nucleus and that nuclear interaction of AR with ␤-catenin may modulate transcriptional activity in androgen target tissues.

Pituitary tumors are common intracranial neoplasms that often result in endocrine dysfunction due to hormone overproduction or deficiencies from mass effects. Gonadotrope cell or gonadotropinomas are tumors that produce LH and/or FSH and represent 40% of macroadenomas. Little is known about their underlying pathogenic mechanisms. We compared expression profiles of 10 gonadotropinomas with nine normal pituitaries by cDNA array and identified bone morphogenetic protein- and retinoic acid-inducible neural-specific protein-3 (BRINP3) as overexpressed in tumors, compared with normals. BRINP3 is a novel, normally brain restricted protein of unknown function. BRINP3 mRNA was expressed selectively in gonadotropinomas. Subcellular localization studies showed that BRINP3 was targeted to the mitochondria, but BRINP3 overexpression was unable to protect pituitary cells against programmed cell death induced by growth factor withdrawal. However, BRINP3 overexpression in pituitary gonadotrope cells promoted proliferation, migration, and invasion. A BRINP3 antibody was raised that demonstrated clustered expression of BRINP3 protein in gonadotropinomas and not in normal human pituitary samples. Thus, BRINP3 is a mitochondrially localized protein that is selectively up-regulated in human gonadotropinomas. Its actions to increase proliferation, migration, and invasion suggest it may play an important role in pituitary tumorigenesis.

Remote sensing-based assessments of tree cover and extent provide insight into global and local land use planning. However, there remains considerable uncertainty about the extent of drylands forests and trees in areas with non-forest land use. Here, we present a 10-meter tree extent map for 4.35 billion hectares in the tropics (-23.44° to 23.44° latitude) based on multitemporal composites of Sentinel-1 and Sentinel-2 analyzed with convolutional neural networks. We identify 2,719 million hectares of tropical land with ≥10% tree cover, including 680 million hectares in drylands. We find that 52% of tropical cropland and 46% of tropical urban areas had ≥10% tree cover in 2020. Compared to previous datasets, we demonstrate improved ability to map fragmented and open canopy forests at small spatial scales, especially in drylands, urban areas, and on cropland. As such, this data is expected to enable improved monitoring of tree dynamics at local scales.

No abstract

Gonadotropinomas that make α, LHβ and/or FSHβ glycoprotein hormone subunits are the most prevalent type of pituitary macroadenoma. These tumors present a diagnostic challenge, as they are rarely associated with a characteristic clinical hypersecretory syndrome and thus difficult to recognize until large enough to cause mass effects. Mechanisms underlying the pathogenesis of gonadotropinomas have not been identified. Common oncogene mutations involved in other human cancers, such as Ras and Rb, are not involved in pituitary tumor formation. The aims of the current study were to elucidate molecular events responsible for the development of gonadotropinomas. We compared gene expression profiles between six normal human pituitaries and five glycoprotein-secreting tumors by cDNA microarray analysis. Pairwise comparisons of normal pituitaries and gonadotropinomas demonstrated consistent, greater than two-fold increased expression in 671 genes and decreased expression in 878 genes. Gene Ontology Database analysis was used to categorize differentially expressed genes into classes that may affect tumorigenic or cell proliferative properties. Relative to tumor versus normal, the following data were obtained: transcription factors (184 up/165 down), cell cycle regulation (104 up/62 down), apoptosis regulation (68 up/50 down), cancer genes (72 up/55 down), and signal transduction (158 up/240 down). Candidate genes were then selected based on the magnitude and consistency of change. RT-PCR was performed to confirm array-based results of differential expression in candidate genes. Deleted in Bladder Cancer Chromosome Region 1-Like (DBCCR1-L) is an attractive candidate as it was completely absent in all normal pituitary samples, but expressed in all tumor samples. DBCCR1-L is a novel gene. Its homologue, DBCCR1, is involved in G1 cell cycle transition and colon, breast, esophageal, ovarian, and bladder cancer. Investigation is underway to evaluate the consequences of DBCCR1-L knockdown and overexpression in pituitary cell lines and its effects on cell cycle progression. Our results demonstrate the differential expression of many genes, including DBCCR1-L, which may be involved in pituitary tumorigenesis. Future studies on candidate genes identified in this analysis may lead to the identification of tumor markers to detect, prognostically evaluate, and eventually medically treat gonadotropinomas. Sponsored by VA Merit to MEW and NIH and UCHSC Cancer Center Fellowships to DSM and MML