scholarly journals Coexistence of Intracellular and Membrane-Bound Progesterone Receptors in Human Testis

2005 ◽  
Vol 90 (1) ◽  
pp. 474-483 ◽  
Author(s):  
Chirag Shah ◽  
Deepak Modi ◽  
Geetanjali Sachdeva ◽  
Sushama Gadkar ◽  
Chander Puri
Keyword(s):  
Expression Profiles ◽  
Progesterone Receptors ◽  
Spermatogenic Cell ◽  
Human Testis ◽  
Molecular Characteristics ◽  
Northern Blot Hybridization ◽  
Spermatogenic Cells ◽  
Female Reproduction ◽  
Pr Protein ◽  
Membrane Bound

Abstract Progesterone and progesterone receptors (PR) play a crucial role in female reproduction, but their roles in male reproductive physiology are largely unknown. Our previous studies demonstrated the presence of a specific membrane-bound PR in mature human spermatozoa that is known to regulate important sperm functions. The present study was undertaken to determine whether there exist PR in human testis and to investigate their molecular characteristics and expression profiles. PR mRNA and protein were detected in the spermatogenic cells, Sertoli cells, and occasionally the Leydig cells. PR protein was localized in nucleus and cytoplasm of spermatogonia, primary and secondary spermatocytes, and round spermatids in a stage-specific manner. Intense PR localization was observed in stages IV and V, whereas it was low at stages I, II, and III of spermatogenesis. RT-PCR studies revealed the presence of transcripts for PR in human testis and spermatogenic cells. In accordance with the reported molecular sizes of the known isoforms of PR, two mRNA transcripts of 3.8 and 2.8 kb for PR in adult human testis and spermatogenic cell RNA were detected by Northern blot hybridization. Western blot analysis of testicular and spermatogenic cell lysates revealed two bands of 120 and 90 kDa, corresponding to the conventional PR. In these tissue lysates, an additional band of approximately 55 kDa was detected that was also observed as a single band in sperm lysates, indicating that this smaller protein may correspond to the membrane-bound PR. The membrane-bound PR protein was demonstrated on the spermatogenic cells when probed with progesterone-bound fluorescein conjugate. The results of the present study demonstrate the existence of both intracellular PR-B and PR-A mRNA and protein in the spermatogenic cells of the human testis. A membrane-bound PR was also localized in these cells. The varying levels of intracellular PR during different stages of spermatogenesis and the presence of the membrane-bound PR imply the significance of progesterone in male reproductive events such as regulation of spermatogenesis.

scholarly journals Pan-Cancer Transcriptional Models Predicting Chemosensitivity in Human Tumors

2021 ◽  
Vol 20 ◽  
pp. 117693512110024
Author(s):  
Jason D Wells ◽  
Jacqueline R Griffin ◽  
Todd W Miller
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Human Tumors ◽  
Molecular Characteristics ◽  
Survival Times ◽  
Chemotherapy Drugs ◽  
Testing Dataset ◽  
Cancer Models ◽  
Cancer Types ◽  
Pan Cancer

Motivation: Despite increasing understanding of the molecular characteristics of cancer, chemotherapy success rates remain low for many cancer types. Studies have attempted to identify patient and tumor characteristics that predict sensitivity or resistance to different types of conventional chemotherapies, yet a concise model that predicts chemosensitivity based on gene expression profiles across cancer types remains to be formulated. We attempted to generate pan-cancer models predictive of chemosensitivity and chemoresistance. Such models may increase the likelihood of identifying the type of chemotherapy most likely to be effective for a given patient based on the overall gene expression of their tumor. Results: Gene expression and drug sensitivity data from solid tumor cell lines were used to build predictive models for 11 individual chemotherapy drugs. Models were validated using datasets from solid tumors from patients. For all drug models, accuracy ranged from 0.81 to 0.93 when applied to all relevant cancer types in the testing dataset. When considering how well the models predicted chemosensitivity or chemoresistance within individual cancer types in the testing dataset, accuracy was as high as 0.98. Cell line–derived pan-cancer models were able to statistically significantly predict sensitivity in human tumors in some instances; for example, a pan-cancer model predicting sensitivity in patients with bladder cancer treated with cisplatin was able to significantly segregate sensitive and resistant patients based on recurrence-free survival times ( P = .048) and in patients with pancreatic cancer treated with gemcitabine ( P = .038). These models can predict chemosensitivity and chemoresistance across cancer types with clinically useful levels of accuracy.

Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4210-4218 ◽  
Author(s):  
Guibin Chen ◽  
Weihua Zeng ◽  
Akira Miyazato ◽  
Eric Billings ◽  
Jaroslaw P. Maciejewski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Small Sample ◽  
Hematopoietic Progenitor Cell ◽  
Molecular Characteristics ◽  
Hematopoietic Progenitor ◽  
Trisomy 8 ◽  
Monosomy 7 ◽  
Cd34 Cells

Abstract Aneuploidy, especially monosomy 7 and trisomy 8, is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDSs). Patients with monosomy 7 and trisomy 8 have distinctly different clinical courses, responses to therapy, and survival probabilities. To determine disease-specific molecular characteristics, we analyzed the gene expression pattern in purified CD34 hematopoietic progenitor cells obtained from MDS patients with monosomy 7 and trisomy 8 using Affymetrix GeneChips. Two methods were employed: standard hybridization and a small-sample RNA amplification protocol for the limited amounts of RNA available from individual cases; results were comparable between these 2 techniques. Microarray data were confirmed by gene amplification and flow cytometry using individual patient samples. Genes related to hematopoietic progenitor cell proliferation and blood cell function were dysregulated in CD34 cells of both monosomy 7 and trisomy 8 MDS. In trisomy 8, up-regulated genes were primarily involved in immune and inflammatory responses, and down-regulated genes have been implicated in apoptosis inhibition. CD34 cells in monosomy 7 showed up-regulation of genes inducing leukemia transformation and tumorigenesis and apoptosis and down-regulation of genes controlling cell growth and differentiation. These results imply distinct molecular mechanisms for monosomy 7 and trisomy 8 MDS and implicate specific pathogenic pathways.

Transcription of the rat and mouse proenkephalin genes is initiated at distinct sites in spermatogenic and somatic cells

1990 ◽  
Vol 10 (7) ◽  
pp. 3717-3726
Author(s):  
D L Kilpatrick ◽  
S A Zinn ◽  
M Fitzgerald ◽  
H Higuchi ◽  
S L Sabol ◽  
...  
Keyword(s):  
Germ Cell ◽  
Somatic Cells ◽  
Tata Box ◽  
Spermatogenic Cell ◽  
Spermatogenic Cells ◽  
Consensus Binding Site ◽  
Base Pairs ◽  
Promoter Motif ◽  
Specific Manner ◽  
Rna Protection

During spermatogenesis, several genes are expressed in a germ cell-specific manner. Previous studies have demonstrated that rat and mouse spermatogenic cells produce a 1,700-nucleotide proenkephalin RNA, while somatic cells that express the proenkephalin gene contain a 1,450-nucleotide transcript. Using cDNA cloning, RNA protection, and primer extension analyses, we showed that transcription of the rat and mouse spermatogenic-cell RNAs is initiated downstream from the proenkephalin somatic promoter in the first somatic intron (intron As). In both species, the germ cell cap site region consists of multiple start sites distributed over a length of approximately 30 base pairs. Within rat and mouse intron As, the region upstream of the germ cell cap sites is GC rich and lacks TATA sequences. A consensus binding site for the transcription factor SP1 was identified in intron As downstream of the proenkephalin germ cell cap site region. These features are characteristic of several previously described promoters that lack TATA sequences. Homologies were also identified between the proenkephalin and rat cytochrome c spermatogenic-cell promoters, including the absence of a TATA box, a multiple start site region, and several common sequences. This promoter motif thus may be shared with other genes expressed in male germ cells.

scholarly journals CIB4 is essential for the haploid phase of spermatogenesis in mice†

2020 ◽  
Vol 103 (2) ◽  
pp. 235-243
Author(s):  
Zoulan Xu ◽  
Haruhiko Miyata ◽  
Yuki Kaneda ◽  
Julio M Castaneda ◽  
Yonggang Lu ◽  
...  
Keyword(s):  
Developmental Process ◽  
Human Testis ◽  
Seminiferous Tubules ◽  
Apical Region ◽  
Spermatogenic Cells ◽  
Male Mice ◽  
Essential Function ◽  
Diploid Cells ◽  
Shed Light

Abstract Spermatogenesis is a complex developmental process that involves the proliferation of diploid cells, meiotic division, and haploid differentiation. Many genes are shown to be essential for male fertility using knockout (KO) mice; however, there still remain genes to be analyzed to elucidate their molecular mechanism and their roles in spermatogenesis. Calcium- and integrin-binding protein 1 (CIB1) is a ubiquitously expressed protein that possesses three paralogs: CIB2, CIB3, and CIB4. It is reported that Cib1 KO male mice are sterile due to impaired haploid differentiation. In this study, we discovered that Cib4 is expressed strongly in mouse and human testis and begins expression during the haploid phase of spermatogenesis in mice. To analyze the function of CIB4 in vivo, we generated Cib4 KO mice using the CRISPR/Cas9 system. Cib4 KO male mice are sterile due to impaired haploid differentiation, phenocopying Cib1 KO male mice. Spermatogenic cells isolated from seminiferous tubules demonstrate an essential function of CIB4 in the formation of the apical region of the sperm head. Further analysis of CIB4 function may shed light on the etiology of male infertility caused by spermatogenesis defects, and CIB4 could be a target for male contraceptives because of its dominant expression in the testis.

scholarly journals Transcription of the rat and mouse proenkephalin genes is initiated at distinct sites in spermatogenic and somatic cells.

1990 ◽  
Vol 10 (7) ◽  
pp. 3717-3726 ◽  
Author(s):  
D L Kilpatrick ◽  
S A Zinn ◽  
M Fitzgerald ◽  
H Higuchi ◽  
S L Sabol ◽  
...  
Keyword(s):  
Germ Cell ◽  
Somatic Cells ◽  
Tata Box ◽  
Spermatogenic Cell ◽  
Spermatogenic Cells ◽  
Consensus Binding Site ◽  
Base Pairs ◽  
Promoter Motif ◽  
Specific Manner ◽  
Rna Protection

During spermatogenesis, several genes are expressed in a germ cell-specific manner. Previous studies have demonstrated that rat and mouse spermatogenic cells produce a 1,700-nucleotide proenkephalin RNA, while somatic cells that express the proenkephalin gene contain a 1,450-nucleotide transcript. Using cDNA cloning, RNA protection, and primer extension analyses, we showed that transcription of the rat and mouse spermatogenic-cell RNAs is initiated downstream from the proenkephalin somatic promoter in the first somatic intron (intron As). In both species, the germ cell cap site region consists of multiple start sites distributed over a length of approximately 30 base pairs. Within rat and mouse intron As, the region upstream of the germ cell cap sites is GC rich and lacks TATA sequences. A consensus binding site for the transcription factor SP1 was identified in intron As downstream of the proenkephalin germ cell cap site region. These features are characteristic of several previously described promoters that lack TATA sequences. Homologies were also identified between the proenkephalin and rat cytochrome c spermatogenic-cell promoters, including the absence of a TATA box, a multiple start site region, and several common sequences. This promoter motif thus may be shared with other genes expressed in male germ cells.

scholarly journals Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Christopher A Natale ◽  
Elizabeth K Duperret ◽  
Junqian Zhang ◽  
Rochelle Sadeghi ◽  
Ankit Dahal ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Treatment Options ◽  
Skin Pigmentation ◽  
Progesterone Receptors ◽  
Steroid Hormone Receptors ◽  
Pigment Synthesis ◽  
17Β Estradiol ◽  
Membrane Bound ◽  
Epidermal Melanocyte ◽  
G Protein Coupled

The association between pregnancy and altered cutaneous pigmentation has been documented for over two millennia, suggesting that sex hormones play a role in regulating epidermal melanocyte (MC) homeostasis. Here we show that physiologic estrogen (17β-estradiol) and progesterone reciprocally regulate melanin synthesis. This is intriguing given that we also show that normal primary human MCs lack classical estrogen or progesterone receptors (ER or PR). Utilizing both genetic and pharmacologic approaches, we establish that sex steroid effects on human pigment synthesis are mediated by the membrane-bound, steroid hormone receptors G protein-coupled estrogen receptor (GPER), and progestin and adipoQ receptor 7 (PAQR7). Activity of these receptors was activated or inhibited by synthetic estrogen or progesterone analogs that do not bind to ER or PR. As safe and effective treatment options for skin pigmentation disorders are limited, these specific GPER and PAQR7 ligands may represent a novel class of therapeutics.

scholarly journals Molecular characteristics of papillary thyroid carcinomas without BRAF mutation or RET/PTC rearrangement: relationship with clinico-pathological features

2009 ◽  
Vol 16 (2) ◽  
pp. 467-481 ◽  
Author(s):  
Stéphanie Durand ◽  
Carole Ferraro-Peyret ◽  
Mireille Joufre ◽  
Annie Chave ◽  
Françoise Borson-Chazot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Normal Tissue ◽  
Expression Profiles ◽  
Strong Association ◽  
The Other ◽  
Marker Genes ◽  
Molecular Characteristics ◽  
Papillary Thyroid ◽  
Thyroid Carcinomas ◽  
Gene Alteration

About 60–70% of papillary thyroid carcinomas (PTC) present a BRAFT1799A gene mutation or a rearrangement of RET gene (RET/PTC). In this study, we examined whether PTC without BRAFT1799A mutation and without RET/PTC rearrangement named PTC-ga(−) were distinguishable from PTC-ga(+) (with one or the other gene alteration) on the basis of gene expression characteristics. We analyzed the mutational state of 116 PTC and we compared gene expression profiles of PTC-ga(+) and PTC-ga(−) from data of a 200 gene macroarray and quantitative PCR. Seventy five PTC were PTC-ga(+) and 41 were PTC-ga(−). Unsupervised analyses of macroarray data by hierarchical clustering led to a complete segregation of PTC-ga(+) and PTC-ga(−). In a series of 42 genes previously recognized as PTC ‘marker’ genes, 22 were found to be expressed at a comparable level in PTC-ga(−) and normal tissue. Thyroid-specific genes, TPO, TG, DIO1, and DIO2 were under-expressed in PTC-ga(+) but expressed at a normal level in PTC-ga(−). A few genes including DUOX1 and DUOX2 were selectively dys-regulated in PTC-ga(−). Tumor grade of PTC-ga(−) was lower than that of PTC-ga(+). There was a strong association between the mutational state and histiotype of PTC; 81% of PTC follicular variants were corresponded to PTC-ga(−), whereas 84% of PTC of classical form were PTC-ga(+). In conclusion, we show that PTC without BRAFT1799A mutation or RET/PTC rearrangement, mainly corresponding to follicular variants, maintain a thyroid differentiation expression level close to that of normal tissue and should be of better prognosis than PTC with one or the other gene alteration.

scholarly journals Gene Expression Profiles in Different Stages of Mouse Spermatogenic Cells During Spermatogenesis1

2003 ◽  
Vol 69 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Zuoren Yu ◽  
Rui Guo ◽  
Yehua Ge ◽  
Jing Ma ◽  
Jikui Guan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Spermatogenic Cells

scholarly journals Expression of a novel reticulon-like gene in human testis

Reproduction ◽  
2002 ◽  
pp. 227-234 ◽  
Author(s):  
ZM Zhou ◽  
JH Sha ◽  
JM Li ◽  
M Lin ◽  
H Zhu ◽  
...  
Keyword(s):  
Short Form ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Human Testis ◽  
Nylon Membrane ◽  
Adult Testis ◽  
Fetal Testis ◽  
Pcr Products ◽  
Testis Cdna ◽  
Membrane Spanning

Identification of genes that are specifically expressed in the adult testis or the fetal testis is important for the study of genes related to the development of the testis. In this study, a human testis cDNA microarray was established. PCR products of 9216 clones from a human testis cDNA library were dotted on a nylon membrane; mRNA from adult and fetal testes were purified and probes were prepared by a reverse transcription reaction with testis mRNA as template. The microarray was hybridized with probes of adult and fetal testes, and 96.8 and 95.4% of clones were positive, respectively. In total, 731 clones were differentially expressed: 592 were highly expressed in adult testis and 139 were highly expressed in fetal testis. Among these genes, a new reticulon (Rtn)-like gene was detected and named Rtn-T. Rtn-T was highly expressed in adult human testis. The cDNA of Rtn-T contains 3491 bp and the putative protein had 968 amino acids. This protein is homologous to the six known members of the Rtn family (KIAA0886, Rtn xL, reticulon 4a, Nogo-A, Nogo-A short form, and brain my043) but was different at the 5' end. All homologues originate from one gene, and result from both different promotor regions and different splicing. Rtn-T lacks the first exon and contains a second exon that is lacking in the other homologues. Rtn-T is shorter than KIAA0886, Rtn xL, reticulon 4a and Nogo-A, but longer than the Nogo-A short form and brain my043. Sequence analysis showed that Rtn-T protein has two hydrophobic regions that may be membrane-spanning domains. Expression profiles showed that Rtn-T is specifically and strongly expressed in testis. The results of the present study indicate that the Rtn-T gene is differentially expressed in adult and fetal testes and encodes a membrane protein that may have a function in testis development.

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