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Brain-derived neurotrophic factor: A steroidogenic regulator of Leydig cells.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2019 Aug; Vol. 234 (8), pp. 14058-14067. Date of Electronic Publication: 2019 Jan 09. - Publication Year :
- 2019
-
Abstract
- The brain-derived neurotrophic factor (BDNF) was first recognized for its roles in the peripheral and central nervous systems, and its complex functions on mammalian organs have been extended constantly. However, to date, little is known about its effects on the male reproductive system, including the steroidogenesis of mammals. The purpose of this study was to elucidate the effects of BDNF on testosterone generation of Leydig cells and the underlying mechanisms. We found that BDNF-induced proliferation of TM3 Leydig cells via upregulation of proliferating cell nuclear antigen ( Pcna) and promoted testosterone generation as a result of upregulation of steroidogenic acute regulatory protein ( Star), 3b-hydroxysteroid dehydrogenase ( Hsd3b1), and cytochrome P450 side-chain cleavage enzyme ( Cyp11a1) both in primary Leydig cells and TM3 Leydig cells, which were all attenuated in Bdnf knockdown TM3 Leydig cells. Furthermore, the possible mechanism of testosterone synthesis was explored in TM3 Leydig cells. The results showed that BDNF enhanced extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation, and the effect was disrupted by Bdnf deletion. Moreover, PD98059, a potent selective inhibitor of ERK1/2 activation, compromised BDNF-induced testosterone generation and upregulation of Star, Hsd3b1, and Cyp11a1. The Bdnf knockdown assay, on the other hand, indicated the autocrine effect of BDNF on steroidogenesis in TM3 Leydig cells. On the basis of these results, we concluded that BDNF, acting as an autocrine factor, induced testosterone generation as a result of the upregulation of Star, Hsd3b1, and Cyp11a1 via stimulation of the ERK1/2 pathway.<br /> (© 2019 Wiley Periodicals, Inc.)
- Subjects :
- Animals
Autocrine Communication genetics
Brain-Derived Neurotrophic Factor pharmacology
Cell Proliferation drug effects
Cholesterol Side-Chain Cleavage Enzyme genetics
Gene Expression Regulation, Developmental genetics
Gene Knockdown Techniques
Leydig Cells drug effects
Leydig Cells metabolism
MAP Kinase Signaling System genetics
Male
Mice
Multienzyme Complexes genetics
Progesterone Reductase genetics
Steroid Isomerases genetics
Testosterone genetics
Brain-Derived Neurotrophic Factor genetics
Phosphoproteins genetics
Proliferating Cell Nuclear Antigen genetics
Reproduction genetics
Testosterone biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 234
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 30628054
- Full Text :
- https://doi.org/10.1002/jcp.28095