title: NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration.
abstract: Nerve growth factor (NGF) has been reported to be involved in male reproductive physiology. However, few reports have described the activity of NGF during Leydig cell development. The objective of the present study was to examine the role of NGF during stem-Leydig-cell (SLC) regeneration. We investigated the effects of NGF on Leydig-cell (LC) regeneration by measuring mRNA levels in the adult rat testis after ethane dimethanesulfonate (EDS) treatment. Furthermore, we used the established organ culture model of rat seminiferous tubules to examine the regulation of NGF during SLC proliferation and differentiation using EdU staining, real-time PCR and western blotting. Progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs) were also used to investigate the effects of NGF on LCs at different developmental stages. NGF mRNA levels changed significantly during Leydig-cell regeneration in vivo. In vitro, NGF significantly promoted the proliferation of stem Leydig cells and also induced steroidogenic enzyme gene expression and 3β-HSD protein expression. The data from PLCs and ILCs showed that NGF could increase Cyclin D1 and Hsd 17b3 mRNA levels in PLCs and Cyclin D1 mRNA levels in ILCs. These results indicate that NGF may play an important role during LC regeneration by regulating the proliferation and differentiation of LCs at different developmental stages, from SLCs to PLCs and from PLCs to ILCs. The discovery of this effect of NGF on Leydig cells will provide useful information for developing new potential therapies for PADAM (Partial Androgen Deficiency in the Aging Male).
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, 510632 Guangzhou, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Huaxi
authors.initials: H
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Qihao
authors.initials: Q
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiang
authors.forename: Renshan
authors.initials: R
authors.lastname: Ge
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008698:Mesylates / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D020932:Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D009924:Organ Culture Techniques; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012671:Seminiferous Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013251:Steroid Isomerases / Q000235:genetics / Q000378:metabolism; D013738:Testolactone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D008698:Mesylates; D009097:Multienzyme Complexes; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D019938:Cyclin D1; C018155:testololactone; D013738:Testolactone; D020932:Nerve Growth Factor; D011375:Progesterone Reductase; D013251:Steroid Isomerases; C002994:ethylene dimethanesulfonate