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O Avallet

Publications and source records attributed to O Avallet.

26 records · Page 2Linked to original sources

Cell-cell communication in the testis.

In addition to the well-established endocrine regulation of testicular functions by gonadotropins, many data accumulated in the last few years indicate that a local control is required for a normal production of androgens and spermatogenesis. In the present paper we review the cell-cell interactions between somatic and germ cells in the testis and their role on the function of each cell type. Also, we will present evidences indicating that some of these interactions are mediated by several growth factors produced and acting within the testis. Moreover, very often the production of these factors are under control of gonadotropins, and in turn the growth factors regulate the sensitivity of testicular cells to these hormones.

Animals↗

Regulation of c-fos, c-jun, jun-B, and c-myc messenger ribonucleic acids by gonadotropin and growth factors in cultured pig Leydig cell.

The nuclear protooncogenes have been implicated in the coordinate regulation of gene expression during cell proliferation and differentiation. Previous work has shown that LH and human h CG as well as several growth factors including epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta, and insulin-like growth factor-I play a role in Leydig cell differentiated functions. To evaluate the possibility that protooncogenes mediate long term effects of these factors, their action on the levels of c-fos, c-jun, jun-B, and c-myc messenger (m) RNAs was studied. hCG (10(-9) M) produced a time-dependent increase in c-fos (9-fold), jun-B (18-fold) and c-myc (5-fold) mRNA levels but did not affect c-jun. The concentration of hCG required for half-maximal stimulation (ED50 = 7 +/- 4 x 10(-12) M) was similar to that required to induce half-maximal testosterone production. At optimal concentrations, the effects of EGF and bFGF on c-fos and jun-B mRNAs were lower than those induced by hCG, but their effects on c-myc mRNA were higher. In addition, they stimulated c-jun. Moreover, EGF and bFGF potentiated the effects of hCG on c-fos and jun-B, whereas hCG potentiated the action of growth factors on c-jun. Transforming growth factor-beta increased only jun-B mRNA, whereas insulin-like growth factor I increased c-fos, jun-B, and c-myc but less effectively than hCG. Lastly, the phorbol ester phorbol 12-myristate 13-acetate increased the level of the four protooncogene mRNAs, and its effects on c-fos and c-myc were significantly higher than those produced by hCG. These data indicate that the regulation of protooncogene mRNAs in normal Leydig cells is multifactorial. They also show differential responsiveness of the members of the Jun family to several factors. Our results are consistent with the hypothesis that the Fos and Jun families of regulatory proteins could play a role in mediating long term responses to the complex array of hormones and growth factors to which Leydig cells are exposed in vivo.

Animals↗

Control of production of insulin-like growth factor I by pig Leydig and Sertoli cells cultured alone or together. Cell-cell interactions.

The production of insulin-like growth factor I (IGF-I) by pig Leydig cells and pig Sertoli cells cultured alone or together was investigated. Human chorionic gonadotropin (hCG) and basic fibroblast growth factor (FGF) stimulate in a dose-dependent manner IGF-I production by Leydig cells. At maximal concentrations the effects of both factors were almost additive. Insulin at micromolar concentrations enhanced IGF-I production and potentiated the effects of hCG and FGF. The secretion of IGF-I by Sertoli cells was stimulated by FSH and FGF. Under basal conditions, the production of IGF-I by the coculture was similar to the addition of the production by each cell cultured alone. In contrast, in the presence of hCG, FSH or FGF, the production of IGF-I by the coculture largely exceeded that expected from the monocultures. Moreover, stimulation of the coculture with both hCG and FSH resulted in a further increase in IGF-I production. These results indicate that Leydig as well as Sertoli cells secrete IGF-I and that the secretion of both cell types is stimulated by the corresponding gonadotropin. In addition, they indicate that Leydig-Sertoli interactions play a role in the control of IGF-I production, supporting the contention that this growth factor plays an important role in the paracrine and autocrine control of testicular functions.

Animals↗

Regulation of pig Leydig cell aromatase activity by gonadotropins and Sertoli cells.

The present work was done to investigate the cell localization of testicular aromatase activity and its regulation in immature pig testis using an in vitro model. Leydig cells and Sertoli cells were isolated from immature pig testes and cultured alone or together in the absence or presence of human chorionic gonadotropin (hCG) or porcine follicle-stimulating hormone (pFSH) for 2 days. At the end of incubation, the amounts of testosterone (T), estrone sulfate (E1S) and estradiol (E2) were measured. Then the cells were incubated for 4 h in the presence of saturating concentrations of delta 4-androstenedione (3 microM) and the amounts of E1S and E2 were measured again (aromatase activity). The ability of Sertoli cells to produce estrogens was very low and neither hCG nor pFSH had any significant effect. hCG stimulated, in a dose-dependent manner, the secretion of T and E1S by Leydig cells cultured alone as well as the aromatase activity of these cells. The main estrogen produced by Leydig cells was E1S. pFSH also stimulated the above parameters of Leydig cell function; this may have been due to the contamination of this hormone with luteinizing hormone (LH). Coculture of Leydig cells with Sertoli cells without gonadotropins had very small effects on T and E1S production and on aromatase activity. However, treatment of coculture with increasing concentrations of hCG had a dramatic effect on Leydig cell functions. For each hCG concentration, the amounts of T and E1S secreted, as well as the aromatase activity of the coculture, were 2- to 3-fold higher than those of Leydig cells cultured alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗

Transforming growth factor beta inhibits Leydig cell functions.

The role of transforming growth factor beta (TGF-beta) on the functions of pig Leydig cells cultured in a chemically defined medium was investigated. TGF-beta reduced the number of hCG receptors, without modification of the binding affinity, and reduced the cAMP and testosterone response to this hormone. These effects were dose-dependent. The minimal effective dose was 10 pg/ml (4 X 10(-13) M) and half-maximal inhibition for the three effects was observed at about 100 pg/ml. At maximal effective concentration (1 ng/ml), the inhibitory effect was time-dependent, the first effects were observed after a lag period of 12 h and the maximal effect after 72 h. At maximal concentrations TGF-beta reduced by 70% the number of hCG receptors and the steroidogenic response to this hormone and reduced by 50% the cAMP response to hCG. Moreover, TGF-beta also reduced the cAMP response to forskolin and the steroidogenic effects of this diterpene and 8-Bromo-cAMP. In contrast, the conversion of exogenous pregnenolone to testosterone was increased in TGF-beta-treated cells. The inhibition of Leydig cell steroidogenesis can be dissociated from any effect on cell proliferation and is related to modifications located at the membrane level and beyond cAMP formation, but before pregnenolone formation. The results suggest that in the testis, as in other steroidogenic tissues, TGF-beta may play a role in the development and maintenance of differentiated function.

8-Bromo Cyclic Adenosine Monophosphate↗

Oestrone sulphate metabolism in normal human endometrium grown in organ culture.

Samples of human endometrium were maintained in organ culture for 6 days on growth medium. On Day 6, ultrastructural studies were performed on endometrial explants, demonstrating that human endometrium grown in organ culture preserved its normal structure. The effect of oestrone sulphate was studied on the endometrium explants. The endometrium was cultured on harvest medium for 4 days to ensure the complete removal of endogenous steroids, the tissues were then incubated with 10(-7) M oestrone sulphate for 24 h. The oestrone sulphatase known to interfere with oestrone sulphate metabolism was present in endometrial organ culture. By incubation with estrone sulphate for 24 h it was demonstrated that oestrone sulphate is hydrolysed to active oestrogens.

Endometrium↗