RGD Reference Report - The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome.

Authors: Nelson, VL  Qin, KN  Rosenfield, RL  Wood, JR  Penning, TM  Legro, RS  Strauss JF, 3RD  McAllister, JM 
Citation: Nelson VL, etal., J Clin Endocrinol Metab. 2001 Dec;86(12):5925-33.
RGD ID: 4888511
Pubmed: PMID:11739466   (View Abstract at PubMed)
DOI: DOI:10.1210/jcem.86.12.8088   (Journal Full-text)

Ovarian theca cells propagated from patients with polycystic ovary syndrome (PCOS) convert steroid precursors into T more efficiently than normal theca cells. To identify the basis for increased T production by PCOS theca cells, we examined type I-V 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) isoform expression in long-term cultures of theca and granulosa cells isolated from normal and PCOS ovaries. RT-PCR analysis demonstrated that theca cells express type V 17 beta HSD a member of the aldo-keto reductase (AKR) superfamily (17 beta HSDV, AKR1C3), whereas expression of type I, II, and IV 17 beta HSD, which are members of the short-chain dehydrogenase/reductase superfamily, was limited to granulosa cells. Type III 17 beta HSD, the testicular isoform, was not detected in either granulosa or theca cells. Northern and real-time PCR analyses demonstrated that 17 beta HSDV transcripts were not significantly increased in PCOS theca cells compared with normal theca cells. RT-PCR analysis revealed that theca cells also express another AKR, 20 alpha HSD (AKR1C1). Both basal and forskolin-stimulated 20 alpha HSD mRNA levels were increased in PCOS theca cells compared with normal theca cells. However, 17 beta HSD enzyme activity per theca cell was not significantly increased in PCOS, suggesting that neither AKR1C3 nor AKR1C1 contributes to the formation of T in this condition. In contrast, 17 alpha-hydroxylase/C17,20 lyase and 3 beta HSD enzyme activities were elevated in PCOS theca cells, driving increased production of T precursors. These findings indicate that 1) increased T production in PCOS theca cells does not result from dysregulation of "androgenic" 17 beta HSD activity or altered expression of AKRs that may express 17 beta HSD activity; and 2) increased synthesis of T precursors is the primary factor driving enhanced T secretion in PCOS.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
polycystic ovary syndrome  IEP 4888511; 4888511protein:increased activity:ovary follicle and theca cell (human)RGD 
polycystic ovary syndrome  ISOCYP17A1 (Homo sapiens)4888511; 4888511protein:increased activity:ovary follicle and theca cell (human)RGD 
polycystic ovary syndrome  ISOHSD3B2 (Homo sapiens)4888511; 4888511protein:increased activity:ovary follicle and theca cell (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp17a1  (cytochrome P450, family 17, subfamily a, polypeptide 1)
Hsd3b1  (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1)

Genes (Mus musculus)
Cyp17a1  (cytochrome P450, family 17, subfamily a, polypeptide 1)
Hsd3b2  (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2)

Genes (Homo sapiens)
CYP17A1  (cytochrome P450 family 17 subfamily A member 1)
HSD3B2  (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2)


Additional Information