Faculty Opinions recommendation of Nonclassical androgen and estrogen signaling is essential for normal spermatogenesis.

2021 ◽  
Author(s):  
Gary Klinefelter
Keyword(s):  
Estrogen Signaling ◽  
Normal Spermatogenesis

Membrane estrogen receptor α is essential for estrogen signaling in the male skeleton

2018 ◽  
Vol 239 (3) ◽  
pp. 303-312 ◽  
Author(s):  
H H Farman ◽  
K L Gustafsson ◽  
P Henning ◽  
L Grahnemo ◽  
V Lionikaite ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Areal Bone Mineral Density ◽  
Male Mice ◽  
Mineral Density ◽  
Intact Male ◽  
Trabecular Thickness ◽  
Total Body

The importance of estrogen receptor α (ERα) for the regulation of bone mass in males is well established. ERα mediates estrogenic effects both via nuclear and membrane-initiated ERα (mERα) signaling. The role of mERα signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERα signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ERα to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (µCT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mERα is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.

scholarly journals Regulatory Interplay between miR-181a-5p and Estrogen Receptor Signaling Cascade in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 543
Author(s):  
Rosaria Benedetti ◽  
Chiara Papulino ◽  
Giulia Sgueglia ◽  
Ugo Chianese ◽  
Tommaso De Marchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Mirna Expression ◽  
Estrogen Receptor Alpha ◽  
Estrogen Signaling ◽  
Integrated Analysis ◽  
Tumor Resistance ◽  
Estrogen Receptor Signaling

The efficacy and side effects of endocrine therapy in breast cancer (BC) depend largely on estrogen receptor alpha (ERα) expression, the specific drug administered, and treatment scheduling. Although the benefits of endocrine therapy outweigh any adverse effects in the initial stages of BC, later- or advanced-stage tumors acquire resistance to treatments. The mechanisms underlying tumor resistance to therapy are still not well understood, posing a major challenge for BC patient care. Epigenetic regulation and miRNA expression may be involved in the switch from a treatment-sensitive to a treatment-resistant state and could provide a valid therapeutic strategy for ERα negative BC. Here, a hybrid lysine-specific histone demethylase inhibitor, MC3324, displaying selective estrogen receptor down-regulator-like activities in BC, was used to highlight the interplay between epigenetic and ERα signaling. MC3324 anticancer action is mediated by microRNA (miRNA) expression regulation, indicating an innovative function for this molecule. Integrated analysis suggests a crosstalk between estrogen signaling, ERα interactors, miRNAs, and their putative targets. Specifically, miR-181a-5p expression is regulated by MC3324 and has an impact on cellular levels of ERα. A comparison of breast tumor versus healthy mammary tissues confirmed the important role of miR-181a-5p in ERα regulation and points to its putative predictive function in BC therapy.

scholarly journals Early and late stage MPN patients show distinct gene expression profiles in CD34+ cells

2021 ◽  
Author(s):  
Julian Baumeister ◽  
Tiago Maié ◽  
Nicolas Chatain ◽  
Lin Gan ◽  
Barbora Weinbergerova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Late Stage ◽  
Rna Splicing ◽  
Bone Marrow Cells ◽  
Myeloproliferative Neoplasms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Primary Myelofibrosis ◽  
Estrogen Signaling ◽  
Therapeutic Modalities

AbstractMyeloproliferative neoplasms (MPN), comprising essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are hematological disorders of the myeloid lineage characterized by hyperproliferation of mature blood cells. The prediction of the clinical course and progression remains difficult and new therapeutic modalities are required. We conducted a CD34+ gene expression study to identify signatures and potential biomarkers in the different MPN subtypes with the aim to improve treatment and prevent the transformation from the rather benign chronic state to a more malignant aggressive state. We report here on a systematic gene expression analysis (GEA) of CD34+ peripheral blood or bone marrow cells derived from 30 patients with MPN including all subtypes (ET (n = 6), PV (n = 11), PMF (n = 9), secondary MF (SMF; post-ET-/post-PV-MF; n = 4)) and six healthy donors. GEA revealed a variety of differentially regulated genes in the different MPN subtypes vs. controls, with a higher number in PMF/SMF (200/272 genes) than in ET/PV (132/121). PROGENγ analysis revealed significant induction of TNFα/NF-κB signaling (particularly in SMF) and reduction of estrogen signaling (PMF and SMF). Consistently, inflammatory GO terms were enriched in PMF/SMF, whereas RNA splicing–associated biological processes were downregulated in PMF. Differentially regulated genes that might be utilized as diagnostic/prognostic markers were identified, such as AREG, CYBB, DNTT, TIMD4, VCAM1, and S100 family members (S100A4/8/9/10/12). Additionally, 98 genes (including CLEC1B, CMTM5, CXCL8, DACH1, and RADX) were deregulated solely in SMF and may be used to predict progression from early to late stage MPN. Graphical abstract

scholarly journals Comparison of proteomic profiles from the testicular tissue of males with impaired and normal spermatogenesis

2020 ◽  
pp. 1-10
Author(s):  
Jiaying Liang ◽  
Yichun Zheng ◽  
Weihong Zeng ◽  
Liuqing Chen ◽  
Shaofen Yang ◽  
...  
Keyword(s):  
Testicular Tissue ◽  
Normal Spermatogenesis

Sertoli cell expression of the cystic fibrosis transmembrane conductance regulator

1998 ◽  
Vol 274 (4) ◽  
pp. C922-C930 ◽  
Author(s):  
Fredric R. Boockfor ◽  
Rebecca A. Morris ◽  
Dennis C. DeSimone ◽  
D. Margaret Hunt ◽  
Kenneth B. Walsh
Keyword(s):  
Cystic Fibrosis ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Patch Clamp Technique ◽  
Immunoreactive Material ◽  
Normal Spermatogenesis ◽  
Cell Expression ◽  
Cystic Fibrosis Transmembrane

Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been associated with a number of male reproductive problems, including testis abnormalities and a reduction in germ cell quality and number. To establish at least one site of functional CFTR expression in the testis, we subjected cultured Sertoli cells to analysis of message, protein, and channel activity for CFTR. With reverse transcription-polymerase chain reaction, we obtained evidence for the presence of CFTR RNA when CFTR primers were used with RNA from cultured Sertoli cells. Western analysis performed with both anti-R and anti-C domain CFTR antibodies revealed immunoreactive material in extracts from primary Sertoli cell cultures that seemed consistent with CFTR previously identified in other cells and tissues. This led us to perform more detailed studies using the whole cell arrangement of the patch-clamp technique. Application of the membrane-soluble cAMP analog, 8-chlorophenylthio-cAMP, resulted in the activation of a Cl− current that displayed a permeability sequence of Br− > I− ≥ Cl− and was blocked by diphenylamine-2-carboxylate and glibenclamide. In addition, a 13-pS conductance Cl− channel was measured in excised membrane patches exposed to the catalytic subunit of protein kinase A. When taken together, our findings of evidence of CFTR message, immunoreactive material that appeared consistent with CFTR, and Cl− channels with properties similar to those reported for CFTR provide strong evidence that Sertoli cells express a functional CFTR-like protein. The presence of CFTR in these cells may be needed to maintain the specific nutritional and fluid balance in the seminiferous tubule that is vital for normal spermatogenesis.

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