Genes upregulated during castration-induced rat prostatic apoptosis: cloning and characterization of new cDNAs.
; ; et al
in BJU International (2000), 85(9), 1134-42
OBJECTIVE: To isolate new cDNAs corresponding to genes whose expression is increased during castration-induced rat prostate apoptosis. MATERIALS AND METHODS: Differential display of mRNAs from 3-day ... [more ▼]
OBJECTIVE: To isolate new cDNAs corresponding to genes whose expression is increased during castration-induced rat prostate apoptosis. MATERIALS AND METHODS: Differential display of mRNAs from 3-day castrated and normal rat ventral prostates was used to identify differentially expressed clones. Northern blots were hybridized to confirm the positive regulation of the candidates and to follow the change in their expression in the involuting rat prostate, and in thymocytes of dexamethazone-treated rats. RESULTS: Five cDNAs were cloned: one encoding ribosomal protein L7, one coding for the insulin-like growth factor binding protein-3 (IGFBP-3), and three whose products are unknown. After castration, all five genes had expression kinetics that closely paralleled the proportion of prostatic epithelial cells undergoing apoptosis. The gene encoding L7 and two of the unknown genes were also upregulated in glucocorticoid-induced programmed death in thymocytes. In addition to the IGFBP-3 gene, those coding for proteins IGFBP-4, -5 and -6 were also overexpressed in the involuting prostate of androgen-deprived rats. CONCLUSION: Five new genes were identified that are up-regulated during castration-induced rat prostate apoptosis, three of which are potentially involved in the common intracellular pathway leading to programmed cell death. [less ▲]Detailed reference viewed: 6 (1 ULg)
A novel messenger ribonucleic acid homologous to human MAGE-D is strongly expressed in rat Sertoli cells and weakly in Leydig cells and is regulated by follitropin, lutropin, and prolactin.
Hennuy, Benoît ; ; Cornet, Anne et al
in Endocrinology (2000), 141(10), 3821-31
We have cloned a novel complementary DNA whose expression was decreased in rat Sertoli cell cultures after treatment with FSH. This complementary DNA encodes a protein of 570 amino acids and shares 92 ... [more ▼]
We have cloned a novel complementary DNA whose expression was decreased in rat Sertoli cell cultures after treatment with FSH. This complementary DNA encodes a protein of 570 amino acids and shares 92% homology with the human MAGE-D protein. In contrast to other MAGE genes (A, B, or C), we have shown that MAGE-D expression was ubiquitous in healthy rat tissues. In the seminiferous tubules, the MAGE-D was expressed in Sertoli cells but not in germ cells as demonstrated by RT-PCR and in situ hybridization, whereas for the other MAGE genes, expression has been shown to be restricted to germ cells. Interestingly, MAGE-D was also detected for the first time in the female gonad by Northern blotting. In MLTC-1 cells (mouse Leydig tumor cell line-1), LH and PRL stimulated MAGE-D expression. Using hypophysectomized rats, it was confirmed that FSH decreased MAGE-D expression, whereas LH and PRL increased MAGE-D messenger RNA level in the whole testis most probably through a direct action on Leydig cells. As MAGE-D is present in both the seminiferous compartment and interstitium and hormonally regulated in each, it is possible that it has specific functions in each compartment during the development and the maintenance of the testis. [less ▲]Detailed reference viewed: 33 (6 ULg)
Effects of pituitary hormones on the prostate.
; Hennuy, Benoît ; et al
in Prostate (1999), 38(2), 159-65
BACKGROUND: Although essential, androgens alone are not sufficient to induce normal growth and functionality of the prostate. Nonandrogenic hormones must also be involved in the proliferation of the ... [more ▼]
BACKGROUND: Although essential, androgens alone are not sufficient to induce normal growth and functionality of the prostate. Nonandrogenic hormones must also be involved in the proliferation of the prostate cancer cells which do not respond to antiandrogenic therapy and which thus become androgen-independent. Prolactin, but also growth hormone and luteinizing hormone, are potentially able to act on both normal and abnormal prostatic cells. METHODS: In this review we summarize data from the literature concerning the physiological and pathological implications of prolactin, growth hormone, and luteinizing hormone on the prostate. RESULTS: In rodent prostates, prolactin and growth hormone can induce a variety of effects independently of androgens (e.g., transactivation of certain genes, or synthesis of the major secretion products). Moreover, hyperprolactinemia is responsible for inflammation and dysplasia of the gland, while growth hormone promotes the development of prostate tumors in vivo in the mouse and rat. Growth hormone acts on the gland directly, through prostatic growth hormone receptors, and/or indirectly via the stimulation of insulin-like growth factor-I (IGF-I) synthesis in the liver. Luteinizing hormone receptor is expressed in rat and human prostates. Luteinizing hormone increases the amount of various transcripts in the rat prostate through an androgen-independent pathway. CONCLUSIONS: Prolactin, growth hormone, and luteinizing hormone, alone or synergistically with androgens, play physiologically significant roles in the normal prostate. The involvement of these hormones in the development of benign prostatic hyperplasia and prostatic carcinoma is an issue that needs to be addressed. [less ▲]Detailed reference viewed: 11 (0 ULg)
A novel gene overexpressed in the prostate of castrated rats: hormonal regulation, relationship to apoptosis and to acquired prostatic cell androgen independence.
; Hennuy, Benoît ; Cornet, Anne et al
in Endocrinology (1999), 140(10), 4789-99
We have identified a novel complementary DNA (cDNA) corresponding to a gene overexpressed in the rat ventral prostate after castration. This cDNA displays 89.4% identity with 453 bp of a mouse EST and 81 ... [more ▼]
We have identified a novel complementary DNA (cDNA) corresponding to a gene overexpressed in the rat ventral prostate after castration. This cDNA displays 89.4% identity with 453 bp of a mouse EST and 81.5% identity with 157 bp of a human EST and was named PARM-1 for prostatic androgen-repressed message-1. The complete cDNA is 1187 bp long and codes for a protein of 298 amino acids that contains four potential glycosylation sites and three half cystinyl residues. The PARM-1 gene was found to be expressed at quite low levels in most rat tissues including those of the urogenital tract. The kinetic of induction of PARM-1 gene in the prostate was highly correlated to the development of apoptosis in the whole organ. Supplementation of castrated animals with androgens reversed both the process of apoptosis and the overexpression of PARM-1 gene. Supplementation with estrogens did not result in an increase in the PARM-1 messenger RNA levels when compared with the castration alone. However, the treatment resulted in a more rapid return to intact levels in the castrated plus estrogen group. When apoptosis of testis and prostate was induced in vivo by hypophysectomy, it was found that PARM-1 was only overexpressed in the prostate. Therefore, PARM-1 seems to be regulated by androgens only in the prostate. Using in situ hybridization and immunohistological techniques, we have shown that PARM-1 gene product is found exclusively in the epithelial cells of involuting prostate. Analysis by flow cytometry of MAT LyLu epithelial cells transiently expressing PARM-1 protein did not allow us to demonstrate a direct effect of PARM-1 gene overexpression on the programmed death of the transfected cells. Treatment of MAT LyLu cells by transforming growth factor-beta induced apoptosis but had no effect on PARM-1 production. However PARM-1 protein has been detected by Western blotting in various cell lines such as MAT LyLu, MAT Lu, and PIF, which are androgen independent. This would suggest that PARM-1 gene product would be a marker for acquired androgen-independence of these tumor cells. [less ▲]Detailed reference viewed: 13 (1 ULg)
Luteinizing hormone increases the abundance of various transcripts, independently of the androgens, in the rat prostate.
; Poncin, Joseph ; Hennuy, Benoît et al
in Biochemical and Biophysical Research Communications (1997), 233(1), 108-12
Differential display analysis was carried out to find, in the rat prostate, genes that could be regulated by Luteinizing Hormone (LH), independently of the androgens. Hypophysectomized and castrated adult ... [more ▼]
Differential display analysis was carried out to find, in the rat prostate, genes that could be regulated by Luteinizing Hormone (LH), independently of the androgens. Hypophysectomized and castrated adult rats were treated with either LH, testosterone or saline. Regulated discrete bands have been eluted and reamplified. After Northern blotting, the levels of mRNA corresponding to 8 PCR fragments were significantly increased by LH treatment. None of these inserts were found to be induced by testosterone. One insert was subcloned, sequenced and identified as the ribosomial protein S 23. A competitive RT-PCR assay was carried out on the full length S 23 cDNA and confirmed that its mRNA levels were stimulated by LH but not by testosterone. These results strongly suggest that the LH membrane receptor, previously shown to be expressed in the rat prostate, has a physiological significance in this organ. Moreover, it appears that the effect of LH on the rat prostate are independent of the androgens. [less ▲]Detailed reference viewed: 15 (4 ULg)
Benign Prostatic Hyperplasia and Normal Prostate Aging: Differences in Types I and Ii 5 Alpha-Reductase and Steroid Hormone Receptor Messenger Ribonucleic Acid (Mrna) Levels, but Not in Insulin-Like Growth Factor Mrna Levels
Bonnet, Pierre ; ; et al
in Journal of Clinical Endocrinology and Metabolism (The) (1993), 77(5), 1203-8
Benign prostatic hyperplasia (BPH) is so common in elderly men that the development of adenomatous nodules in this organ can be seen as a normal age-dependent process. In this work, we used Northern ... [more ▼]
Benign prostatic hyperplasia (BPH) is so common in elderly men that the development of adenomatous nodules in this organ can be seen as a normal age-dependent process. In this work, we used Northern blotting to compare the levels of androgen, estrogen, and insulin-like growth factor-I (IGF-I) receptor in young (age range, 23-33; n = 3), old normal (age range, 52-80; n = 3), and BPH-affected subjects (age range, 66-87; n = 15). We have also investigated in these groups the expression of genes coding for the two 5 alpha-reductases (types I and II), aromatase, IGF-I, and IGF-II. Our results show significantly increased levels of IGF mRNA in old healthy and BPH-affected subjects; the respective rises for IGF-I, IGF-II, and IGF-I receptor mRNAs were 3.0-, 2.9-, and 1.5-fold (BPH) and 2.7-, 2.4-, and 1.8-fold (old normal controls). For estrogen receptor, androgen receptor, and type I and II 5 alpha-reductase mRNAs, a marked but opposite effect was observed in adenomatous tissues only; the respective levels were 2.2-, 1.8-, 3.9-, and 1.7-fold lower than those in young adult subjects, whereas no significant differences were recorded between the two normal groups. Morphometric analysis of each tissue specimen confirmed the significantly lower epithelium/stroma ratio in adenomas compared to young or old healthy tissues. Together, these observations suggest that prostatic adenomas may result from at least two conjugate processes: one characterized by a drop in the mRNA levels of steroid hormone receptors, which might be associated with a lower epithelium/stroma ratio, and another characterized by normal aging phenomena, of which the increased production of IGFs and IGF-I receptor transcripts could be biochemical markers. [less ▲]Detailed reference viewed: 10 (0 ULg)