Sertoli Cell Androgen Receptor Expression Regulates Temporal Fetal and Adult Leydig Cell Differentiation, Function, and Population Size
| Autor: | David J. Handelsman, Rasmani Hazra, Mark Jimenez, Charles M. Allan, Reena Desai |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Patched Receptors endocrine system medicine.medical_specialty Receptor Platelet-Derived Growth Factor alpha Receptors Peptide medicine.drug_class Cellular differentiation Cell Count Mice Transgenic Receptors Cell Surface Biology Ligands Mice Endocrinology Internal medicine Testis medicine Animals Testosterone Congeners Hemizygote Sertoli Cells Sexual Development Cholesterol side-chain cleavage enzyme Leydig Cells Cell Differentiation Leydig cell differentiation Sertoli cell Androgen Up-Regulation Isoenzymes Patched-1 Receptor Androgen receptor medicine.anatomical_structure SRD5A1 Animals Newborn Receptors Androgen Dihydrotestosterone Receptors Transforming Growth Factor beta Biomarkers medicine.drug |
| Zdroj: | Endocrinology. 154:3410-3422 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2012-2273 |
| Popis: | We recently created a mouse model displaying precocious Sertoli cell (SC) and spermatogenic development induced by SC-specific transgenic androgen receptor expression (TgSCAR). Here we reveal that TgSCAR regulates the development, function, and absolute number of Leydig cells (LCs). Total fetal and adult type LC numbers were reduced in postnatal and adult TgSCAR vs control testes, despite normal circulating LH levels. Normal LC to SC ratios found in TgSCAR testes indicate that SC androgen receptor (SCAR)-mediated activity confers a quorum-dependent relationship between total SC and LC numbers. TgSCAR enhanced LC differentiation, shown by elevated ratios of advanced to immature LC types, and reduced LC proliferation in postnatal TgSCAR vs control testes. Postnatal TgSCAR testes displayed up-regulated expression of coupled ligand-receptor transcripts (Amh-Amhr2, Dhh-Ptch1, Pdgfa-Pdgfra) for potential SCAR-stimulated paracrine pathways, which may coordinate LC differentiation. Neonatal TgSCAR testes displayed normal T and dihydrotestosterone levels despite differential changes to steroidogenic gene expression, with down-regulated Star, Cyp11a1, and Cyp17a1 expression contrasting with up-regulated Hsd3b1, Hsd17b3, and Srd5a1 expression. TgSCAR males also displayed elevated postnatal and normal adult serum testosterone levels, despite reduced LC numbers. Enhanced adult-type LC steroidogenic output was revealed by increased pubertal testicular T, dihydrotestosterone, 3α-diol and 3β-diol levels per LC and up-regulated steroidogenic gene (Nr5a1, Lhr, Cyp11a1, Cyp17a1, Hsd3b6, Srd5a1) expression in pubertal or adult TgSCAR vs control males, suggesting regulatory mechanisms maintain androgen levels independently of absolute LC numbers. Our unique gain-of-function TgSCAR model has revealed that SCAR activity controls temporal LC differentiation, steroidogenic function, and population size. |
| Databáze: | OpenAIRE |
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