scholarly journals Characterization of Endozepines in the Human Testicular Tissue: Effect of Triakontatetraneuropeptide on Testosterone Secretion

2003 ◽  
Vol 88 (11) ◽  
pp. 5521-5528 ◽  
Author(s):  
Celine Duparc ◽  
Herve Lefebvre ◽  
Marie-Christine Tonon ◽  
Hubert Vaudry ◽  
Jean-Marc Kuhn

Abstract Previous studies have shown that endozepines, i.e. endogenous ligands of benzodiazepine (BZD) receptors, stimulate steroidogenesis in adrenocortical and Leydig cells. In the present report, we have investigated the presence and action of endozepines in the human testis. Immunohistochemical labeling revealed the occurrence of endozepine-like immunoreactivity in Leydig, Sertoli, and germ cells. HPLC analysis combined with a specific RIA resolved two immunoreactive peaks that coeluted with synthetic octadecaneuropeptide (ODN) and triakontatetraneuropeptide (TTN). RT-PCR amplification showed that the mRNA encoding the endozepine precursor diazepam-binding inhibitor is expressed in the human testis. The action of endozepines on testosterone production was studied in vitro using perifused human testicular fragments. Administration of TTN provoked a dose-dependent increase in testosterone secretion, whereas ODN had no effect. The stimulatory action of TTN on testosterone production was totally blocked by flunitrazepam, a peripheral-type BZD receptor antagonist/central-type BZD receptor (CBR) agonist. Conversely, the CBR agonist clonazepam and the CBR antagonist flumazenil did not affect testosterone secretion. Collectively, these results suggest that, in the human testicular tissue, TTN may exert an intracrine and/or paracrine control of steroidogenesis through activation of a peripheral-type BZD receptor.

1976 ◽  
Vol 71 (2) ◽  
pp. 231-238 ◽  
Author(s):  
RÉGINE PICON

SUMMARY Testosterone secretion by foetal rat testes (13½–21½ days of gestation) explanted for 3 days in a synthetic medium was measured every 24 h by radioimmunoassay. During the first day of explantation, the foetal testis produced, respectively, 1013 ± 132, 8734 ± 1118, 9179 ± 2185 and 3886 ± 309 (s.e.m.) pg/testis when explanted at 14½, 16½, 18½ and 21½ days respectively. Testosterone production by 13½-day-old testes was not detectable on the first day of culture, but appeared on subsequent days. Daily testosterone secretion increased on the 2nd and 3rd days of culture in 14½-day-old testes and decreased in older stages. These results suggest that the functional differentiation of the testis is independent of stimulatory factors like gonadotrophins. Dibutyryl cyclic AMP was found to stimulate testosterone production significantly from 14½ days of gestation onwards.


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.


1998 ◽  
Vol 20 (1) ◽  
pp. 45-53 ◽  
Author(s):  
O Lesouhaitier ◽  
M Feuilloley ◽  
H Vaudry

Diazepam-binding inhibitor (DBI) was initially isolated from the rat brain as a result of its ability to compete with benzodiazepines for their receptors. Immunohistochemical studies have recently shown the presence of peripheral-type benzodiazepine receptor (PBR)- and DBI-like immunoreactivity in the frog adrenal gland. The aim of the present study was to investigate the effect of two biologically active DBI-derived peptides, the triakontatetraneuropeptide [TTN; DBI(17-50)] and the octadecaneuropeptide [ODN; DBI(33-50)], on corticosteroid secretion by frog adrenocortical cells. Exposure of frog adrenal explants to graded concentrations of TTN (3.16 x 10(-8) to 3.16 x 10(-6) M) induced a dose-related increase in corticosterone and aldosterone secretion. In contrast, ODN did not modify corticosteroid output. When repeated pulses of TTN (10(-6) M) were administered at 2-h intervals, the response of the adrenal explants to the second dose of TTN was markedly reduced, suggesting the existence of a desensitization phenomenon. Exposure of dispersed adrenal cells to TTN also induced a marked stimulation of corticosteroid secretion, indicating that TTN acts directly on adrenocortical cells. The central-type benzodiazepine receptor (CBR) agonist, clonazepam, did not stimulate corticosteroid secretion and the CBR antagonist, flumazenil, did not block the stimulatory action of TTN. Similarly, the PBR agonist, Ro5-4864, did not mimic the stimulatory effect of TTN and the PBR antagonist, flunitrazepam, did not affect the stimulatory action of TTN. The present study provides the first evidence for a stimulatory effect of TTN on intact adrenocortical cells. The receptor mediating the corticotropic action of TTN is not related to central- or peripheral-type benzodiazepine receptors. Our data suggest that TTN, released by chromaffin cells, may act as a paracrine factor regulating the activity of adrenocortical cells.


1989 ◽  
Vol 121 (1) ◽  
pp. 43-48 ◽  
Author(s):  
A. I. Frankel ◽  
J. C. Chapman ◽  
B. Cook

ABSTRACT The testicular response to hemicastration (in which testicular vein testosterone from the remaining testis doubles in concentration) was studied in vitro in order to establish whether the response is maintained after testicular tissue is removed from the animal. Decapsulated testes and collagenase-dispersed cells from decapsulated testes of rats were incubated for 24 h after hemicastration and testosterone production was compared with that in tissue collected at the time of surgery. Testosterone concentration in the remaining testis 24 h after hemicastration was significantly (P <0·05) higher than in the testis removed at the time of hemicastration, but testosterone production in vitro was similar in both tissues. Apparently the single testis remaining in a hemicastrated rat requires extratesticular support in order to maintain its stimulated state. Journal of Endocrinology (1989) 121, 43–48


Andrologia ◽  
2009 ◽  
Vol 18 (2) ◽  
pp. 196-200 ◽  
Author(s):  
M. HAMMAR ◽  
F. PETERSSON

2012 ◽  
pp. 221-225 ◽  
Author(s):  
L. ZAMRAZILOVÁ ◽  
L. SOSVOROVÁ ◽  
J. HERÁČEK ◽  
V. SOBOTKA ◽  
R. HAMPL

In order to assess whether intratesticular hormone content may be helpful for prediction of successful conception in men with fertility problems, five sex steroids, testosterone, dihydrotestosterone, androstenedione, estradiol and, for the first time epitestosterone, were measured in testicular tissue obtained by surgical retrieval from total 84 men. The group consisted of non-obstructive azoospermic men, aged 21-67 years who attended the centre for in vitro fertilization. Steroids after ether extraction and solvent partition were separated by high performance liquid chromatography and then measured by specific radioimmunoassays. The values varied considerably with means ± S.D. 2.43±2.47, 0.27±0.24, 0.080±0.13, 0.071±0.089 and 0.31±0.27 for testosterone, dihydrotestosterone, androstenedione, estradiol and epitestosterone, respectively.


1999 ◽  
Vol 161 (2) ◽  
pp. 211-218 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
C Dieguez ◽  
FF Casanueva ◽  
...  

Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed adult rats. In addition, 10(-9) M leptin inhibited LH and FSH secretion by incubated hemi-pituitaries from fasted adult males, whereas, at all doses tested, it was ineffective in modulating PRL release. Our results show that leptin, depending on the state of sexual maturation, is able to inhibit testosterone secretion acting at the testicular level. Furthermore, the present data suggest that the actions of leptin on the reproductive system are complex and are probably carried out at different levels of the hypothalamic-pituitary-gonadal axis.


1992 ◽  
Vol 127 (6) ◽  
pp. 526-530 ◽  
Author(s):  
A Mayerhofer ◽  
RW Steger ◽  
G Gow ◽  
A Bartke

Several lines of evidence suggest that catecholamines are involved in the regulation of the development of the testis. We have therefore investigated the ability of testicular parenchyma (decapsulated pieces of testes) from 18 to 20-day-old golden hamsters to respond to catecholaminergic stimuli in vitro. Norepinephrine and epinephrine, as well as the beta-receptor agonist isoproterenol and the alpha-adrenoreceptor agonist phenylephrine were able to significantly stimulate testicular testosterone production. Dopamine and serotonin were not effective. The stimulatory action of norepinephrine on testosterone production was dependent on the concentration. In incubations of testes with human chorionic gonadotropin (hCG) and norepinephrine, no synergistic effects on testosterone release were observed. The stimulatory effect of norepinephrine could be partially blocked by incubation with beta-receptor antagonist propranolol, or with alpha-receptor antagonist prazosin, while a combination of propranolol and prazosin completely inhibited the norepinephrine-induced testosterone production. Moreover, isoproterenol and phenylephrine in combination stimulated testosterone more than either drug did alone. Measurements of concentrations of norepinephrine and epinephrine in testicular homogenates revealed higher values for these catecholamines than in the plasma, implying that catecholamine levels in the interstitial spaces of the testis might be in the range of concentrations effectively stimulating testosterone production in vitro. This suggests that in the immature testis of the golden hamster, catecholamines acting through both alpha- and beta-adrenergic receptors may be potent physiological stimulators of testosterone production.


2021 ◽  
Vol 22 (5) ◽  
pp. 2325
Author(s):  
Alaa Sawaied ◽  
Eden Arazi ◽  
Ahmad AbuElhija ◽  
Eitan Lunenfeld ◽  
Mahmoud Huleihel

Spermatogenesis is a complex process, in which spermatogonial cells proliferate and differentiate in the seminiferous tubules of the testis to generate sperm. This process is under the regulation of endocrine and testicular paracrine/autocrine factors. In the present study, we demonstrated that colony stimulating factor-1 (CSF-1) is produced by mouse testicular macrophages, Leydig, Sertoli, peritubular cells and spermatogonial cells (such as CDH1-positively stained cells; a marker of spermatogonial cells). In addition, we demonstrated the presence of CSF-1 and its receptor (CSF-1R) in testicular macrophages, Leydig, Sertoli, peritubular cells and spermatogonial cells of human testis. We also show that the protein levels of CSF-1 were the highest in testis of 1-week-old mice and significantly decreased with age (2–12-week-old). However, the transcriptome levels of CSF-1 significantly increased in 2–3-week-old compared to 1-week-old, and thereafter significantly decreased with age. On the other hand, the transcriptome levels of CSF-1R was significantly higher in mouse testicular tissue of all examined ages (2–12-week-old) compared to 1-week-old. Our results demonstrate the involvement of CSF-1 in the induction the proliferation and differentiation of spermatogonial cells to meiotic and postmeiotic stages (BOULE- and ACROSIN-positive cells) under in vitro culture conditions, using methylcellulose culture system (MCS). Thus, it is possible to suggest that CSF-1 system, as a testicular paracrine/autocrine system, is involved in the development of different stages of spermatogenesis and may be used in the development of future therapeutic strategies for treatment of male infertility.


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