Venlafaxine-induced adrenergic signaling stimulates Leydig cells steroidogenesis via Nur77 overexpression: a possible role of EGF

Abstract Background Leydig cells reflect the activation of inflammation, decrease of androgen production, inhibition of cell growth and promotion of cell apoptosis under orchitis. Maternally expressed gene 3 (MEG3) exerts a crucial role in various human diseases, but under orchitis, the role and underlying molecular mechanism of MEG3 in Leydig cells remain unclear. Methods Lipofectamine 2000 was used for the cell transfections. qPCR and western blots assay were applied to assess the gene expression. ELISA assay was used to measure the TNFα, IL6 and testosterone secretion. CCK8 and EdU assay was employ to test the cell viability and proliferation respectively. Luciferase reporter and RIP assay were introduced to detect the binding of miR-93-5p with MEG3 and PTEN. Results Lipopolysaccharides (LPS) induced TNFα and IL6 secretion, lowered testosterone production, inhibited cell viability and proliferation, and induced cell apoptosis in Leydig cells. MEG3 was upregulated in Leydig cells treated with LPS and that knockdown of MEG3 inhibited the role of LPS in Leydig cells. MEG3 absorbed miR-93-5p and that suppression of miR-93-5p restored the role of silenced MEG3 in Leydig cells under LPS treatment. miR-93-5p inhibited PTEN expression and that over-expressed PTEN alleviated the effect of miR-93-5p in Leydig cells treated with LPS. LPS activated the MEG3/miR-93-5p/PTEN signalling pathway in Leydig cells. Conclusions This study revealed that MEG3 serves as a molecular sponge to absorb miR-93-5p, thus leading to elevation of PTEN expression in Leydig cells under LPS treatment, offering a theoretical basis on which to establish potential new treatment strategies for orchitis.

Download Full-text

Sustained in vivo blockade of α1-adrenergic receptors prevented some of stress-triggered effects on steroidogenic machinery in Leydig cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00100.2013 ◽

2013 ◽

Vol 305 (2) ◽

pp. E194-E204 ◽

Cited By ~ 12

Author(s):

Natasa J. Stojkov ◽

Marija M. Janjic ◽

Aleksandar Z. Baburski ◽

Aleksandar I. Mihajlovic ◽

Dragana M. Drljaca ◽

...

Keyword(s):

Adrenergic Receptors ◽

Leydig Cells ◽

High Affinity ◽

Testosterone Production ◽

Transcription Profiles ◽

Steroidogenic Cells ◽

Main Regulator ◽

Stimulatory Factor

This study was designed to systematically analyze and evaluate the effects of in vivo blockade of α1-adrenergic receptors (α1-ADRs) on the stress-induced disturbance of steroidogenic machinery in Leydig cells. Parameters followed 1) steroidogenic enzymes/proteins, transcription factors, and cAMP/testosterone production; 2) the main hallmarks of stress (epinephrine, glucocorticoids); and 3) transcription profiles of ADRs and oxidases with high affinity to inactivate glucocorticoids. Results showed that sustained blockade of α1-ADRs prevented stress-induced 1) decrease of the transcripts/proteins for main steroidogenic CYPs (CYP11A1, CYP17A1); 2) decrease of Scarb1 and Hsd3b1 transcripts; 3) decrease of transcript for Nur77, one of the main activator of the steroidogenic expression; and 4) increase of Dax1 and Arr19, the main steroidogenic repressors in Leydig cells. In the same cells, the expression of steroidogenic stimulatory factor Creb1, StAR, and androgen receptor increased. In this signaling scenario, stress-induced stimulation of Adra1a/Adra1b/Adrbk1 and Hsd11b2 (the unidirectional oxidase with high affinity to inactivate glucocorticoids) was not changed. Blockade additionally stimulated stress-increased transcription of the most abundantly expressed ADRs Adra1d/Adrb1/Adrb2 in Leydig cells. In the same cells, stress-decreased testosterone production, the main marker of Leydig cells functionality, was completely prevented, while reduction of cAMP, the main regulator of androgenesis, was partially prevented. Accordingly, the presented data provide a new molecular/transcriptional base for “fight/adaptation” of steroidogenic cells and new molecular insights into the role of α1-ADRs in stress-impaired Leydig cell steroidogenesis. The results are important in term of wide use of α1-ADR selective antagonists, alone/in combination, to treat high blood pressure, nightmares associated with posttraumatic stress disorder, and disrupted sexual health.

Download Full-text

Role of β-Adrenergic Signaling in Exercise Conditioning in Mice

Pediatric Research ◽

10.1203/00006450-199904020-00184 ◽

1999 ◽

Vol 45 (4, Part 2 of 2) ◽

pp. 30A-30A

Author(s):

Lucy Ruwitch ◽

Eric Schauble ◽

Kavin Desai ◽

Brian Kobilka ◽

Daniel Bernstein

Keyword(s):

Adrenergic Signaling

Download Full-text

SOMATOMEDIN-C (Sm-C) RECEPTORS IN CULTURED PIG LEYDIG CELLS (LC): CHARACTERIZATION AND REGULATION. ROLE OF Sm-C ON LC FUNCTIONS

Pediatric Research ◽

10.1203/00006450-198611000-00111 ◽

1986 ◽

Vol 20 (11) ◽

pp. 1192-1192

Author(s):

M H Perrard-Sapori ◽

P G Chatelain ◽

A Ruitton ◽

J Bertrand ◽

J M Saez

Keyword(s):

Leydig Cells ◽

Somatomedin C

Download Full-text

Carcinoma of the Horn in a Cryptorchid Bull

Pathologia veterinaria ◽

10.1177/030098587000700304 ◽

1970 ◽

Vol 7 (3) ◽

pp. 265-269 ◽

Cited By ~ 1

Author(s):

S.N. Naik ◽

H.P. Randelia ◽

R.D Dabholkar

Keyword(s):

Leydig Cells ◽

Epidemiological Survey ◽

Seminiferous Tubules ◽

Coagulative Necrosis ◽

Significant Difference

The first histologically confirmed case of carcinoma of the horn in a bilaterally cryptorchid Malvi bull, detected during an epidemiological survey, is reported. Examinations of 78,024 bullocks and 1,468 bulls, belonging to 7 different Zebu breeds revealed horn cancer in 793 bullocks and 1 cryptorchid bull but not in a normal bull. Histologically cryptorchid testes were devoid of spermatogenesis and had hyperplasia of Leydig cells. The remnant of castrated testes had only seminiferous tubules with coagulative necrosis and were devoid of spermatogenesis and Leydig cells. The significant difference in the incidence of HC in bullocks and cows and its absence in bulls is discussed in the light of the role of hormone in the causation of HC.

Download Full-text

Gonadal expression of c-kit encoded at the W locus of the mouse

Development ◽

10.1242/dev.110.4.1057 ◽

1990 ◽

Vol 110 (4) ◽

pp. 1057-1069 ◽

Cited By ~ 26

Author(s):

K. Manova ◽

K. Nocka ◽

P. Besmer ◽

R.F. Bachvarova

Keyword(s):

In Situ Hybridization ◽

Germ Cells ◽

Leydig Cells ◽

Interstitial Tissue ◽

Type B ◽

Age Dependence ◽

Oocyte Growth ◽

Adult Mice

Recently, it has been shown that the c-kit proto-oncogene is encoded at the white spotting (W) locus in mice. Mutations of this gene cause depletion of germ cells, some hematopoietic cells and melanocytes. In order to define further the role of c-kit in gametogenesis, we have examined its expression in late fetal and postnatal ovaries and in postnatal testis. By RNA blot analysis, c-kit transcripts were not detected in late fetal ovaries but appeared at birth. The relative amount reached a maximum in ovaries of juvenile mice, and decreased in adult ovaries. c-kit transcripts were present in increasing amounts in isolated primordial, growing and full-grown oocytes, as well as in ovulated eggs. Little was detected in early 2-cell embryos and none in blastocysts. In situ hybridization revealed c-kit transcripts in a few oocytes of late fetal ovaries and in all oocytes (from primordial to full-grown) in ovaries from juvenile and adult mice. Expression was also observed in ovarian interstitial tissue from 14 days of age onward. Using indirect immunofluorescence, the c-kit protein was detected on the surface of primordial, growing and full-grown oocytes, as well as on embryos at the 1- and 2-cell stages; little remained in blastocysts. In situ hybridization analysis of testes from mice of different ages demonstrated expression in spermatogonia from 6 days of age onward. Using information provided by determining the stage of the cycle of the seminiferous epithelium for a given tubule and by following the age dependence of labeling, it was concluded that the period of expression of c-kit extends from at least as early as type A2 spermatogonia through type B spermatogonia and into preleptotene spermatocytes. Leydig cells were labelled at all ages examined. The expression pattern in oocytes correlates most strongly with oocyte growth and in male germ cells with gonial proliferation.

Download Full-text