scholarly journals Urocortin 1 Inhibits Rat Leydig Cell Function

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6425-6432 ◽  
Author(s):  
Catherine L. Rivier

Corticotropin-releasing factor (CRF) has previously been reported in rat testes in which it inhibits Leydig cells activity. However, recent studies in our laboratory have suggested that some of the effects originally attributed to CRF were instead due to the related peptide Urocortin 1 (Ucn 1) and that this latter hormone, not CRF, was detectable in Leydig cells. We show here that Ucn 1 [a mixed CRF receptor (CRFR) type 1 and CRFR2 agonist] and the CRFR1-selective peptide Stressin 1, but not Ucn 2 or Ucn 3 (both considered selective CRFR2 ligands), significantly blunt the testosterone response to human chorionic gonadotropin. The effect of Ucn 1 is observed regardless of whether this peptide is injected iv or directly into the testes, and it is reversed by the mixed CRFR1/R2 antagonist Astressin B. Blockade of GnRH receptors with the antagonist Azalin B does not interfere with the influence of Ucn 1, thereby demonstrating that pituitary luteinizing hormone does not appear to be involved in this model. Collectively these results suggest that Ucn 1, not CRF, is present in the rat testes and interferes with Leydig cell activity. However, whereas we previously reported that alcohol up-regulated gonadal Ucn 1 gene expression, CRF receptor antagonists were unable to reverse the inhibitory effect exerted by alcohol on human chorionic gonadotropin-induced testosterone release. The functional role played by testicular Ucn 1 in stress models characterized by blunted androgen levels therefore needs to be further investigated.

Author(s):  
Г.В. Брюхин ◽  
С.Д. Антонов

Цель исследования - анализ содержания и субпопуляционного состава клеток Лейдига у потомства самок крыс «Вистар» экспериментальным сахарным диабетом 1 типа в период новорождённости. Методика. Исследования выполнены на белых крысах - самках «Вистар» и их потомстве в возрасте 1 сут. У взрослых половозрелых самок моделировали стрептозотоциновый сахарный диабет 1 типа. Изучены морфофункциональные особенности эндокринных клеток семенников у потомства самок крыс с экспериментальным диабетом 1 типа в ранний неонатальный период. Определяли площадь интерстициальной соединительной ткани семенников, число активных и неактивных эндокриноцитов, вычисляли индекс активности клеток Лейдига, расчитывали коэффициент, отражающий отношение числа клеток Лейдига к суммарному содержанию сперматогенных клеток, а также коэффициент, отражающий отношение суммарного количества интерстициальных гландулоцитов к содержанию сустентоцитов. Результаты. Показано, что у подопытных крысят снижена абсолютная масса семенника и его весовой индекс, увеличена площадь стромы, изменено количество клеток Лейдига и их субпопуляционный состав и, как следствие, изменен индекс активности этих клеток. Выявлено существенное снижение у подопытных животных отношения числа клеток Лейдига к содержанию клеток Сертоли, между которыми существуют определенные паракринные взаимоотношения. Заключение. Выявленные изменения могут являться одной из возможных причин нарушения сперматогенного цикла у потомства самок крыс с экспериментальным сахарным диабетом 1 типа. Numerous clinical observations have shown that maternal diabetes adversely affects pregnancy and childbirth as well as the development and condition of the fetus. These women often give birth to children with signs of diabetic fetopathy. However, the effect of type 1 diabetes mellitus on morphology and function of the male offspring reproductive system is still understudied. The aim of the study was evaluating morpho-functional characteristics of Leydig cells in newborn offspring of female rats with experimental type 1 diabetes. Methods. Experiments were performed on Wistar female rats and their one-day offspring. Type 1 diabetes mellitus was modelled in adult, sexually mature females using streptozotocin. Morpho-functional features of testicular endocrine cells were studied in the offspring of female rats with experimental type 1 diabetes in the early neonatal period. The following indexes were determined: area of testicular interstitial tissue; number of active and inactive endocrinocytes; Leydig cell activity index; the ratio of Leydig cells number to the total number of spermatogenic cells; and the ratio of total number of interstitial glandulocytes to the number of sustentocytes. Results. The offspring of experimental rats had a decreased absolute testis weight and testis weight index; an increased area of interstitial tissue; changes in the count of Leydig cells and their subpopulation composition and resultant changes in the Leydig cell activity index. The ratio of Leydig cell number to Sertoli cell number, which are characterized with paracrine interrelations, was decreased. Conclusion. The found changes may underlie disorders of the spermatogenic cycle in the offspring of female rats with experimental type 1 diabetes.


Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4266-4274 ◽  
Author(s):  
Luca De Toni ◽  
Vincenzo De Filippis ◽  
Simone Tescari ◽  
Marco Ferigo ◽  
Alberto Ferlin ◽  
...  

Abstract Recent studies disclosed a cross talk between testis and bone. By the action of LH, Leydig cells are able to modulate bone metabolism through testosterone and insulin-like factor 3. Moreover, LH modulates the Leydig expression of CYP2R1, the key enzyme involved in vitamin D (Vit D) 25-hydroxylation. However, pathways regulating CYP2R1 expression have been poorly investigated. The cross talk from the bone to the testis of the vitamin D 25-hydroxylase CYP2R1 involves osteocalcin (OC), which is produced by the osteoblasts and stimulates the production of testosterone by the Leydig cells through its putative receptor GPRC6A, a cation-sensing G-protein-coupled receptor. The aim of this study was to investigate the possible action of OC on CYP2R1 expression and 25-hydroxy Vit D (25-OH Vit D) production in a mouse Leydig cell line (MA-10). After confirmation of the expression of GPRC6A by MA-10, we found that stimulation with either human chorionic gonadotropin or uncarboxylated-OC (ucOC) increases CYP2R1 protein expression in a dose-dependent manner and, in turn, increases the release of 25-OH Vit D in culture medium. This effect was abolished by receptor blockade with, respectively, anti-LH receptor and anti-GPRC6A antibodies. Moreover, both agonists converged to phosphorylation of Erk1/2 by a likely differential action on second messengers. Human chorionic gonadotropin induced slow “tonic” increase of intercellular calcium and accumulation of cAMP, whereas ucOC mainly induced phasic increase of cell calcium. Supporting these findings, we found that serum ucOC positively correlated with 25-OH Vit D levels in 40 overweight male patients and 21 controls. Altogether, our results suggest that OC contributes with LH to 25-OH Vit D production by Leydig cells.


Endocrinology ◽  
1982 ◽  
Vol 110 (1) ◽  
pp. 138-145 ◽  
Author(s):  
G. P. RISBRIDGER ◽  
D. M. ROBERTSON ◽  
D. M. DE KRETSER

1985 ◽  
Vol 248 (2) ◽  
pp. E176-E181
Author(s):  
M. Benahmed ◽  
J. Reventos ◽  
E. Tabone ◽  
J. M. Saez

To determine the precise role of Sertoli cells in the stimulating effects of follicle stimulating hormone (FSH) on Leydig cell activity, porcine purified Leydig and Sertoli cells were cultured separately or together in a chemically defined medium in the absence or presence of porcine, FSH 50 ng/ml. Leydig cell activity was evaluated using two parameters: human chorionic gonadotropin (hCG) binding sites; and hCG-stimulated cAMP production and testosterone secretion. First, it was found that FSH increases Leydig cell activity in crude Leydig cell preparations (40–60% of Leydig cells), whereas it exerts no effect on purified Leydig cells (greater than 90% of Leydig cells). Second, FSH stimulates the activity of Leydig cells cocultured with Sertoli cells, whereas it remains without effect on purified Leydig cells cultured alone. This stimulating effect of FSH on Leydig cell activity is dependent on the Sertoli cell number in the coculture. These data 1) show that the stimulating effect of FSH on Leydig cell function is mediated by Sertoli cells and 2) support the concept of local control of Leydig cell function originating from Sertoli cells.


1994 ◽  
Vol 266 (6) ◽  
pp. E975-E979 ◽  
Author(s):  
G. P. Risbridger ◽  
A. Davies

The cytotoxic drug ethane dimethane sulfonate (EDS) has been extensively used as a means of studying the regeneration of Leydig cells in the adult rat testis. This study used the EDS-treated rat testis as a source of material for the isolation of regenerating Leydig cells and their precursors and describes the procedures required for the isolation of these cell preparations. As early as 13-15 days after EDS, cells in the precursor fraction can bind low, but detectable, levels of iodinated purified human chorionic gonadotropin. However, no luteinizing hormone (LH) response was detected in terms of steroid production. The precursor fraction of cells isolated from the EDS-treated rat testis 17-19 days after the administration of EDS was heterogeneous in light-microscopic appearance, but identifiable Leydig-like cells were present. The cells in this fraction were the first to exhibit the ability to respond to LH with the production of detectable levels of the reduced androgen, 5 alpha-androstane-3 alpha,17 beta-diol. The amount of androgen produced by both the Leydig cell and precursor fractions had increased by 21 days after EDS and reached the levels produced by immature adultlike Leydig cells, which can be isolated from the 20-day-old rat testes. These studies demonstrate that steroidogenically responsive precursor forms of Leydig cells can be isolated from the EDS-treated testes 17-19 days after depletion of the adult Leydig cell population.


Sign in / Sign up

Export Citation Format

Share Document