Statin drugs markedly inhibit testosterone production by rat Leydig cells in vitro: Implications for men

2014 ◽  
Vol 45 ◽  
pp. 52-58 ◽  
Author(s):  
G.R. Klinefelter ◽  
J.W. Laskey ◽  
R.P. Amann
2003 ◽  
Vol 77 (5) ◽  
pp. 3297-3300 ◽  
Author(s):  
Ronan Le Goffic ◽  
Thomas Mouchel ◽  
Annick Ruffault ◽  
Jean-Jacques Patard ◽  
Bernard Jégou ◽  
...  

ABSTRACT Mumps virus is responsible for sterility. Here, we show that the mumps virus infects Leydig cells in vitro and totally inhibits testosterone secretion and that ribavirin in mumps virus-infected Leydig cell cultures completely restores testosterone production. Moreover, we show that gamma interferon-induced protein 10 (IP-10) is highly expressed by mumps virus-infected Leydig cells and that ribavirin does not block IP-10 production.


1984 ◽  
Vol 62 (9) ◽  
pp. 1166-1169 ◽  
Author(s):  
M. Bernier ◽  
W. Gibb ◽  
R. Collu ◽  
J. R. Ducharme

For this study, purified immature porcine Leydig cells in primary culture were used. After 2 days of culture, the cells were incubated with dexamethasone (5 × 10−9, 1 × 10−7 M) for various periods of time (3–45 h). The media were discarded and treatment was repeated with or without the addition of human chorionic gonadotropin (HCG, 10 mIU/mL) for 3 h. Dexamethasone (10−7 M) decreased testosterone production of HCG-treated cells (up to 40%) in a time-dependent fashion while the lower dose was ineffective. The effect of varying doses (10−8 and 10−6 M) of natural glucocorticoids (corticosterone, cortisol) or synthetic glucocorticoids (triamcinolone, triamcinolone acetonide, betamethasone, dexamethasone) and that of a synthetic progestin (R-5020) on cultured Leydig cells was also studied. After 18 h of preincubation, the various synthetic but not the natural steroids nor R-5020, were able to decrease testosterone production of control and HCG-treated cells by 20–40%. Of a number of other hormonal and nonhormonal substances studied at concentrations of 10−9 – 10−5 M, only lysine8-vasopressin at a concentration of 10−6 M was able to inhibit testosterone production by these cells. These results indicate that dexamethasone and other synthetic glucocorticoids, and to a lesser degree lysine8-vasopressin, may exert a direct inhibitory effect on testosterone production by purified porcine immature Leydig cells in vitro.


2002 ◽  
Vol 61 (4) ◽  
pp. 493-503 ◽  
Author(s):  
Emilce S. Diaz ◽  
Eliana Pellizzari ◽  
Silvina Meroni ◽  
Selva Cigorraga ◽  
Livia Lustig ◽  
...  

1984 ◽  
Vol 102 (3) ◽  
pp. 319-327 ◽  
Author(s):  
R. M. Sharpe ◽  
I. Cooper ◽  
D. G. Doogan

ABSTRACT Adult rats were made unilaterally cryptorchid (UCD) and 6–7 weeks later Leydig cells were isolated from the scrotal and abdominal testes and their capacity to secrete testosterone in vitro was compared. Basal testosterone production by Leydig cells from the abdominal testes of UCD rats was lowered, compared with cells from the contralateral scrotal testes, whilst their responsiveness to both human chorionic gonadotrophin and an LH releasing hormone agonist was enhanced two- to threefold (P< 0·001) compared both with cells from the contralateral scrotal testes and with cells isolated from untreated rats of the same age. In the UCD rats, concentrations of testosterone in testicular interstitial fluid (IF) were reduced (P< 0·001) by 70–90% in abdominal, compared with scrotal, testes. A similar reduction was evident in the levels of testosterone in spermatic venous blood, and both this decrease and that in IF levels of testosterone varied according to the degree of testicular involution. The ontogeny of the above changes was investigated. After induction of unilateral cryptorchidism, the weight of the abdominal compared with the scrotal testis declined slowly, such that by day 5 there was only a 25% reduction in weight compared with a 70% reduction by day 40. In contrast, the levels of testosterone in IF from abdominal testes declined rapidly, such that by day 5 an 80% reduction was attained, compared with scrotal testes, with little further change by day 40. Hormone-stimulated testosterone production by Leydig cells isolated from the abdominal testes was unchanged or marginally reduced over the first 3 days compared with cells from the scrotal testes, but by day 5 there was a significant increase in responsiveness; this increase was of smaller magnitude than that evident at day 40. These results suggest a possible association between the fall in intratesticular levels of testosterone induced by unilateral cryptorchidism and the Leydig cell hypertrophy and hyper-responsiveness that occurs in the same testes. The implications with respect to altered Sertoli–Leydig cell interaction are discussed. J. Endocr. (1984) 102, 319–327


1989 ◽  
Vol 121 (3) ◽  
pp. 327-333 ◽  
Author(s):  
Hannu Nikula ◽  
Ilpo Huhtaniemi

Abstract. The role of protein kinase C in modulation of the endocrine function of rat Leydig cells was studied. Percoll-purified rat Leydig cells were stimulated with hCG, forskolin, cholera toxin, pertussis toxin and 8-bromo-cAMP in the presence and absence of two activators of protein kinase C, 12-0-tetradecanoylphorbol 13-acetate (TPA) or 1-oleoyl-2-acetyl-sn-glycerol (OAG). The two activators had no effect on basal cAMP, but decreased hCG-stimulated, and increased cholera toxinand forskolin-stimulated cAMP production. Cells pre-incubated with pertussis toxin showed enhanced rate of cAMP production in response to forskolin, but were no more responsive to TPA and OAG stimulation. These findings suggest that protein kinase C activation may on one hand inhibit the LH-receptor and Gs-protein coupling and on the other hand inhibit the Gi-protein mediated suppression of adenylyl cyclase activity. TPA and OAG effects on testosterone production were measured in the absence and presence of 8-bromo-cAMP stimulation. TPA enhanced basal testosterone production, but this effect was shifted to inhibition when steroidogenesis was stimulated by 8-bromo-cAMP. The OAG effect on testosterone production was inhibitory throughout the dose-response curve of 8-bromo-cAMP. The basal stimulation of testosterone production by TPA was probably due to a marginal increase of cAMP caused by inhibition of the Gi-protein, since a similar effect was observed by pertussis toxin, and therafter TPA was without effect on testosterone. The inhibition of stimulated testosterone production by TPA and OAG indicates that protein kinase C activity also affects steroidogenesis at a step(s) beyound cAMP formation.


1997 ◽  
Vol 155 (1) ◽  
pp. 87-92 ◽  
Author(s):  
DE Brigham ◽  
G Little ◽  
YO Lukyanenko ◽  
JC Hutson

We undertook the present studies to determine if clodronate-containing liposomes have direct effects on Leydig cells. Macrophages and Leydig cells were isolated and maintained separately in culture. Following treatment with clodronate-containing liposomes, macrophages were killed in a dose-response fashion over a range of 5-200 microliters liposomes. By comparison, a 500 microliters dose was required to kill Leydig cells, but this was not dependent upon clodronate since liposomes containing buffer elicited an identical response. The concentration of testosterone in medium from Leydig cells treated with clodronate-containing liposomes was significantly reduced compared with untreated cells. However, we subsequently found that liposomes can adsorb testosterone. Therefore, testosterone production was determined at various times following removal of liposomes from Leydig cells, thereby circumventing this complication. It was found that testosterone production was not altered by liposomes under these conditions. Finally, free clodronate had no effect on testosterone production, even at doses representing the amount present within the 500 microliters dose of liposomes. In summary, clodronate-containing liposomes killed testicular macrophages at a far smaller dose than required to kill Leydig cells. Most importantly, neither liposomes no free clodronate had a direct effect on testosterone production. Thus, clodronate-containing liposomes represent a valuable tool to study Leydig cell-macrophage interactions.


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