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ABSTRACT: Iodine uptake and production of iodine-aminoacids are evolutionarily very old phenomena. Seaweed are the first eukaryotic organism presenting these functions; they are rich in iodine and are at basis of the food chain. The monoiodotirosines, precursors of thyroxine, have been identified in a wide variety of invertebrates, such as Gorgonians and Tunicates. The structure of the thyroid appears for the first time in Cyclostomes adults (Lamprey), while in Tunicates (Ciona intestinalis) and Amphioxus is present a similar structure, the endostyle, which is an invagination of the ventral wall of the pharynx containing glandular cells that are able to concentrate iodine. This is not a true endocrine gland because the secretion is poured into the alimentary canal. In the larva of Lamprey (Ammocoetes) during the metamorphosis some of the epithelial cells persist and transform in the follicles. The cyclostomes, therefore, represent a link between the endostyle of protochordates and the thyroid gland of higher chordates. This hypothesis is confirmed by molecular genetic studies which have demonstrated the expression of Thyroid Transcription Factor (TTF-1) in the endostyle of Ciona, Lamprey and Amphioxus. The TTF-1 is an ancestral transcription factor which controls the survival of thyroid follicular cells at the beginning of organogenesis and regulates the expression of thyroid-specific genes in adult life.
La Clinica terapeutica 03/2012; 163(2):e73-6. · 0.27 Impact Factor
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ABSTRACT: The Aurora kinases regulate chromosome segregation and cytokinesis, and alterations in their expression associate with cell malignant transformation. In this study, we demonstrated by qRT-PCR analysis of 14 seminomas that Aurora-A mRNA was, with respect to control tissues, augmented in five of 14 tumour tissues by 2.17 +/- 0.30 fold (P < 0.05) and reduced in 9 to 0.38 +/- 0.10 (P < 0.01). Aurora-B mRNA was increased in 11 tumour tissues by 4.33 +/- 0.82 fold (P < 0.01) and reduced in 3 to 0.41 +/- 0.11 fold. Aurora-C mRNA was reduced to 0.20 +/- 0.32 fold (P < 0.01) in 13 seminomas and up-regulated in one case. Western blot experiments, performed on protein extracts of nine seminomas and six normal testes, showed an up-regulation of Aurora-B protein by 10.14 +/- 3.51 fold (P < 0.05), while Aurora-A protein was found increased in four seminomas by 2.16 +/- 0.43 (P < 0.05), unchanged in three and reduced in two tumour tissues. Aurora-C protein was increased by 9.2 +/- 2.90 fold (P < 0.05), suggesting that post-transcriptional mechanisms modulate its expression. In conclusion, we demonstrated that expression of Aurora kinases is deregulated in seminomas, suggesting that they may play a role in the progression of testicular cancers.
Andrologia 08/2010; 42(4):260-7. · 1.55 Impact Factor
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M Ruggieri,
A Fumarola,
A Straniero,
A Maiuolo,
I Coletta,
A Veltri,
A Di Fiore,
P Trimboli,
P Gargiulo,
M Genderini, M D'Armiento
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ABSTRACT: Actually, thyroid volume >25 ml, obtained by preoperative ultrasound evaluation, is a very important exclusion criteria for minimally invasive thyroidectomy. So far, among different imaging techniques, two-dimensional ultrasonography has become the more accepted method for the assessment of thyroid volume (US-TV). The aims of this study were: (1) to estimate the preoperative thyroid volume in patients undergoing minimally invasive total thyroidectomy using a mathematical formula and (2) to verify its validity by comparing it with the postsurgical TV (PS-TV).
In 53 patients who underwent minimally invasive total thyroidectomy (from January 2003 to December 2007), US-TV, obtained by ellipsoid volume formula, was compared to PS-TV determined by the Archimedes' principle. A mathematical formula able to predict the TV from the US-TV was applied in 34 cases in the last 2 years.
Mean US-TV (14.4 +/- 5.9 ml) was significantly lower than mean PS-TV (21.7 +/- 10.3 ml). This underestimation was related to gland multinodularity and/or nodular involvement of the isthmus. A mathematical formula to reduce US-TV underestimation and predict the real TV was developed using a linear model. Mean predicted TV (16.8 +/- 3.7 ml) perfectly matched mean PS-TV, underestimating PS-TV in 19% of cases. We verified the accuracy of this mathematical model in patients' eligibility for minimally invasive total thyroidectomy, and we demonstrated that a predicted TV <25 ml was confirmed post-surgery in 94% of cases.
We demonstrated that using a linear model, it is possible to predict from US the PS-TV with high accuracy. In fact, the mean predicted TV perfectly matched the mean PS-TV in all cases. In particular, the percentage of cases in which the predicted TV perfectly matched the PS-TV increases from 23%, estimated by US, to 43%. Moreover, the percentage of TV underestimation was reduced from 77% to 19%, as well as the range of the disagreement from up to 200% to 80%. This study shows that two-dimensional US can provide the accurate estimation of thyroid volume but that it can be improved by a mathematical model. This may contribute to a more appropriate surgical management of thyroid diseases.
Langenbeck s Archives of Surgery 09/2008; 393(5):721-4. · 1.81 Impact Factor
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ABSTRACT: The targets of minimally invasive thyroidectomy could be summarised by: achievement of the same results as those obtained with traditional surgery, better postoperative course and improved cosmetic
In minimally invasive surgical approach the skin incision should not exceed 30 mm in length. In our experience this limit may be extended of 5 mm for thyroid between 25 and 50 mL in volume. This way allows more patients, excluded before, to take the advantages of minimally invasive approach. The aim of this work has been to demonstrate that the central neck minimally invasive approach is safe, less painful, better for cosmetic results and easily reproducible in surgical practice.
From January 2003 to June 2007, 75 patients have been selected for minimally invasive thyroidectomy. The procedure was carried out through a central skin incision performed ''high'' between the cricoid and jugular notch. Our ''modified Miccoli-procedure'' consists in five-easily repeatable steps. In the postoperative stay, all patients were asked to evaluate the pain that feel and the cosmetic result by means of a numeric scale.
The skin incision performed was from 25 to 30 mm (mean 27.39 +/- 2.6 mm). We obtained in all cases excellent results about patients cure rate and comfort, few postoperative pain and attractive cosmetic
In this study we demonstrate that the central neck minimally invasive approach is safe, less painful, better for cosmetic results, with less paresthetic consequences and easily reproducible in surgical practice. In our opinion a longer incision (up to 35 mm), does not affect negatively the advantages of minimally invasive procedure. This way allows more patients to take the advantages of minimally invasive approach.
Minerva chirurgica 11/2007; 62(5):309-14. · 0.77 Impact Factor
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E Baldini,
S Ulisse,
E Marchioni,
A Di Benedetto,
G Giovannetti,
E Petrangeli,
S Sentinelli,
R P Donnorso,
M G Reale,
M Mottolese,
L Gandini,
A Lenzi, M D'Armiento
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ABSTRACT: In the present study, we analysed the expression of Fas ligand (FasL) and its cognate receptor Fas in 14 seminomatous testicular germ cell tumours (TGCT) and six normal testicular tissues obtained following orchiectomy. Tissue samples have been processed to prepare either total RNA or protein extracts or fixed and embedded in paraffin for immunohistochemistry (IHC) experiments. Quantitative RT-PCR experiments demonstrated in TGCT a significant (p < 0.01) increase of the FasL mRNA expression of 21.1 +/- 5.4 fold, with respect to normal tissues. On the contrary, in the same cancer tissues, the levels of Fas mRNA were significantly (p < 0.01) reduced to 0.27 +/- 0.06 fold. These observations were confirmed in western blot experiments showing a significant increase of FasL and a concomitant decrease of Fas proteins in testicular cancer tissues, with respect to normal testis. Moreover, IHC experiments showed a strong FasL immuno-reactivity in six out of eight TGCT samples analysed, while Fas immuno-positivity was found in cancer cells of only two TGCT tissues. In addition, in all tumour samples, infiltrating lymphocytes were Fas positive. However, no correlation could be observed between Fas or FasL mRNA variations and clinical parameters such as patient's age, TNM stage or tumour size. We also compared the serum levels of soluble FasL (sFasL) of 15 patients affected by seminomatous TGCT, of four patients with non-seminomatous TGCT and six age-matched healthy males. No significant differences in sFasL serum level could be identified. In conclusion, our data demonstrated that the majority of seminomas are characterized by an increased expression of FasL and a concomitant reduction of Fas, with respect to human normal testis, and that sFasL serum level is not a tumour marker for patients affected by TGCT.
International Journal of Andrology 10/2007; 32(2):123-30. · 3.59 Impact Factor
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ABSTRACT: Recently, the Italian Network of Cancer Registries analyzed 5101 cases of thyroid carcinoma showing a reduction of mortality rate of 4%/year. This prompts us to evaluate the temporal trend in tumor size, age at diagnosis, and histology in a retrospective analysis of 500 thyroid cancers diagnosed over 20 years. Thyroid cancers were divided in two groups. The first included 193 cases diagnosed from 1985 to 1994, and the second 307 from 1995 to 2004. The size of all tumors was significantly reduced from 30 +/- 1.4mm in the first group to 15 +/- 0.8mm in the second group. In particular, papillary thyroid carcinoma (PTC) size decreased from 28 +/- 1.2mm to 14 +/- 0.8mm and follicular carcinoma from 40 +/- 6.3mm to 17 +/- 4.5 mm. Age at diagnosis of all carcinomas increased significantly from 40 +/- 1.3 years in the first group to 48 +/- 0.9 years in the second group. Analysis of the histological types revealed a significant increase of PTC rate in the second decade from 82% to 92% and a concomitant reduction of anaplastic thyroid carcinoma (ATC) from 3.7% to 1.0%. Moreover, a significant increase of micro-PTC rate, from 7.3% to 36.4%, was observed. In conclusion, it may be speculated that the above mentioned decreased mortality rate for thyroid carcinoma could be related to the significant reduction with time of cancer size, to the progressive increase of PTC rate and to the reduction of ATC rate. These data, if confirmed in other series, underscore the importance of evaluating thyroid nodules smaller than 10mm and corroborate recent findings suggesting that age be reconsidered as an independent prognostic factor for differentiated thyroid cancers.
Thyroid 12/2006; 16(11):1151-5. · 4.79 Impact Factor
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S Ulisse,
E Baldini,
M Toller,
E Marchioni,
L Giacomelli,
E De Antoni,
E Ferretti,
A Marzullo,
F M Graziano,
P Trimboli,
L Biordi,
F Curcio,
A Gulino,
F S Ambesi-Impiombato, M D'Armiento
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ABSTRACT: We characterised the expression of the plasminogen activators (uPA and tPA), the uPA receptor (uPAR) and the PAs inhibitors (PAI-1 and PAI-2) in human thyroid cell lines derived from normal thyroid, follicular adenoma, follicular, papillary and anaplastic carcinomas. Urokinase PA activity was detected in the supernatant of normal thyrocytes and augmented in those of all tumour cells. Quantitative RT-PCR analysis showed that uPA, uPAR and PAI-1 mRNAs increased in all carcinoma cells. Similar results were found in 13 papillary thyroid carcinoma (PTC) tissues which were mirrored in Western blot experiments. A correlation was found between tumour size and uPA mRNA increase, and higher levels of uPA and uPAR mRNAs were found in metastatic PTC. In conclusion, thyroid carcinoma cell lines and PTC overexpress uPA, uPAR and PAI-1 and the correlation of uPA and its cognate receptor with tumour size and metastasis may suggest their potential prognostic relevance in thyroid cancer.
European Journal of Cancer 11/2006; 42(15):2631-8. · 5.54 Impact Factor
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E Baldini,
M Toller,
F M Graziano,
F P Russo,
M Pepe,
L Biordi,
E Marchioni,
F Curcio,
S Ulisse,
F S Ambesi-Impiombato, M D'Armiento
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ABSTRACT: In the present study we investigated, by means of zymography and reverse transcription-polymerase chain reaction (RT-PCR), the expression of different matrix metalloproteinases (MMPs) and of the specific tissue inhibitor of metalloproteinases [TIMPs] in human cell lines derived from normal thyrocytes (HTU5), follicular adenoma (HTU42), and follicular (FTC-133), papillary (B-CPAP), and anaplastic (CAL-62, 8305C) thyroid carcinomas. We demonstrated that normal thyrocytes constitutively express MMP-1, MMP-2, MMP-10, MMP-14, and TIMP-1, TIMP-2, TIMP-3, and TIMP-4, and this pattern of expression is profoundly modified in all thyroid tumor-derived cell lines. Analysis of the gelatinolytic activity in the different cell supernatants showed that the expressions of MMP-2 and MMP-9 are, respectively, increased or induced in all the neoplastic cell lines, except in CAL-62. Caseinolytic activity was found only in the supernatants of the 8305C and B-CPAP cells. Using RTPCR analysis we detected an increased expression of MMP-1 in cell lines derived from papillary and from one (8305C) of the two anaplastic carcinomas. MMP-13 mRNA was expressed only in the 8305C, FTC-133, and BCPAP cells. Among stromelysins, MMP-3 mRNA could not be detected in any cell line, while MMP-10 mRNA was expressed in all of them, although at variable levels. MMP-11 mRNA was absent in normal and follicular adenoma derived thyrocytes and induced in all carcinoma cell types. The expression of MMP-14 (MT1-MMP) mRNA was found significantly increased in all thyroid tumor cell lines with respect to HTU5 and HTU42 cells. The expression of TIMP-1 and TIMP-2 mRNAs was maintained in all cell lines tested, while that of TIMP-3 was lost in both anaplastic carcinoma cell lines and that of TIMP-4 was absent in the CAL-62. In conclusion, our data demonstrated a differential expression of MMPs and TIMPs in different thyroid tumor cell types with respect to normal thyrocytes. In particular, the induction of MMP-11 in all thyroid-derived carcinoma cell lines studied and of MMP-13 in all but one may represent, if confirmed in other thyroid tumor-derived cell lines and in thyroid tumor tissues, a new marker of thyrocyte transformation.
Thyroid 12/2004; 14(11):881-8. · 4.79 Impact Factor
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N Ferri,
S Ulisse,
F Aghini-Lombardi,
F M Graziano,
T Di Mattia,
F P Russo,
M Arizzi,
E Baldini,
P Trimboli,
D Attanasio,
A Fumarola,
A Pinchera, M D'Armiento
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ABSTRACT: The aims of the study were to monitor sheep iodine intake in different sheep breeding farms in Abruzzo and to evaluate the effects of iodine supplementation on ovine fertility. The urinary iodine concentrations (UIC) in animals of 8 out of the 11 breeding farms analyzed were borderline (UIC 100-150 microg/l) or very low (UIC < or = 50 microg/l). Only animals bred in 3 farms showed an adequate iodine intake with a mean UIC > or = 300 microg/l. Animals with very low iodine intake had lower T4 and T3 (p < 0.01) serum levels, compared to those with adequate iodine intake. To investigate the effects of iodine supplementation on ovine fertility, 32 ewes and 20 rams, characterized by low UIC, were randomly divided into 2 groups. One group (16 ewes and 10 rams) received a sc injection of 1 ml of Lipiodol, containing 480 mg of iodine, while the remaining animals were employed as control. This treatment was able to maintain UIC above 300 microg/l for 3 months and to increase T4 and T3 serum levels (p < 0.01). After 9 months, the fertility of control and treated animals was assessed by monitoring the rate of successful matings by ultrasonography. The results showed that 100% of treated ewes mated with treated rams were pregnant vs 37% of the control ewes mated with control rams (p = 0.007). The iodine content was 4-fold higher in milk from treated ewes (2393 +/- 453 microg/l), compared to controls (675 +/- 154 microg/l). The results demonstrated that iodine supplementation restores fertility of sheep living in iodine deficient areas and may represent a means to achieve a silent iodine prophylaxis of local populations.
Journal of endocrinological investigation 11/2003; 26(11):1081-7. · 1.57 Impact Factor
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ABSTRACT: The aim of this study was to investigate the regional expression of thyroid hormone nuclear receptor forms (TR(alpha) and TR(beta)) and isoform (TR(alpha1) and TR(beta2)) mRNAs in normal and neoplastic (benignant and malignant) human thyroid tissue. Tumor specimens from patients with thyroid carcinomas (papillary: 5 cases; follicular: 5 cases; anaplastic: 2 cases), thyroid follicular adenomas (7 cases) and tissue from normal thyroid glands (12 cases) were analyzed by in situ hybridization and semiquantitative RT-PCR for the expression of TR(alpha1) and beta, as well as for the isoform alpha2 that does not bind the hormone. In normal tissues, TR(alpha2) was expressed at lower levels compared to TR(alpha1) (alpha1/alpha2 = 4.3). In papillary and follicular carcinomas, the expression of TR(alpha1) and TR(beta) did not change as compared with normal thyroid tissue and adenomas (0.87 +/- 0.15 SD vs 0.89 +/- 0.17 densitometric units, DU, and 0.15 +/- 0.02 vs 0.14 +/- 0.03 DU, respectively). However, the expression of TR(alpha2) was significantly higher in differentiated carcinomas compared to normal thyroid tissue and adenomas (0.47 +/- 0.05 vs 0.20 +/- 0.05 DU, p < 0.05) with alpha1/alpha2 = 1.4. In anaplastic carcinoma all TRs were absent. We concluded that both normal and pathological thyroid tissues, with the exception of anaplastic carcinoma, express all TRs in thyreocites and that differentiated thyroid carcinomas are associated in enhancing the expression of TR(alpha2) mRNA.
Journal of endocrinological investigation 10/2003; 26(10):1008-12. · 1.57 Impact Factor
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ABSTRACT: In the present study we demonstrated that CD95L cross-linking generated reverse signalling in the mouse derived Sertoli cell line TM4. Treatment of TM4 cells with mAb anti-CD95L induced activation of the cytosolic phospholipase A2 (cPLA2). Cytosolic PLA2 activation was controlled by the MAPK pathway as indicated by the ability of the specific MEK inhibitor, PD098059, to abolish cPLA2 activation. In addition, Western blot experiments showed a rapid increase in phosphorylated Erk1/2 following CD95L cross-linking, while no effect on the phosphorylation of other MAPK, p38 or JNK, was observed. CD95L cross-linking by mAb increased the levels of soluble CD95L and apoptotic activity of TM4 cell supernatants, which was blocked by co-incubation with the PLA2 inhibitor, AACOCF3 or PD098059. Finally, pre-treatment of TM4 cells with AACOCF3 or PD098059 completely abolished TM4-induced apoptosis of Jurkat T cells, thus indicating that the Erk/cPLA2 pathway is required for CD95L-induced apoptosis.
Cell Death and Differentiation 11/2000; 7(10):916-24. · 8.85 Impact Factor
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ABSTRACT: We studied the spatiotemporal distribution of thyroid hormone nuclear receptors (TRs) alpha1 and alpha2 and beta messenger RNA (mRNA) levels in normal human testicular tissue during development and in adulthood. Nonpathological specimens from five aborted fetuses (17 and 23 weeks of gestation, three and two cases, respectively) and from four patients undergoing orchiectomy (18 months old and 38-, 42-, and 52-yr-old, respectively) were analyzed by Northern blot, semiquantitative RT-PCR amplification using DNA sequences or specifically designed primers for the TR isoforms, and in situ hybridization. By using PCR amplification, we found that TRalpha1 and TRalpha2 are both expressed at different levels in fetal and adult testis. At all ages TRalpha2 is found at higher levels. Northern analysis showed hybridization signals corresponding to the expression of TRalpha2 and TRalpha in a ratio that increased from 2.6 at 17 weeks of gestation to 12.0 in adulthood. In fact, the expression of TRalpha1 dramatically decreased throughout development, being faintly detectable in the adult testis. Expression of TRbeta was not detected at any age studied. This finding was further confirmed by PCR, which did not amplify TRbeta either in fetal or in adult testis mRNAs. In situ hybridization studies showed the absence of TRbeta and that TRalpha1 and TRalpha2 colocalized in Sertoli cells of prepubertal testis, whereas germ and interstitial cells appeared devoid of TR mRNA signals. From these results it can be concluded that the human testis exclusively expresses TRalpha, which is localized in Sertoli cells, TRbeta being always undetectable. Fetal and prepubertal ages represent the period of maximal expression of TRalpha1 and TRalpha2. The alpha2/alpha1 ratio rises dramatically after development. These results confirm a critical window for the action of thyroid hormone in human testis, in the period of maximal expression of T3 binding isoform TRalpha1, and may account for the macroorchidism without virilization occurring when hyposecretion of thyroid hormones occurs before puberty.
Journal of Clinical Endocrinology & Metabolism 10/2000; 85(9):3453-7. · 6.50 Impact Factor
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ABSTRACT: High affinity-low capacity nuclear triiodothyronine (T3) receptors (TRs), identified as a product of c-erbAalpha proto-oncogene, are expressed in prepubertal rat Sertoli cell. At this age, exogenous T3 treatment as well as hypothyroidism affects Sertoli cell functions. We examined the ontogenetic expression pattern of TRs in the rat testis. Northern analysis confirms that TRs are expressed at high level from fetal development until prepubertal period. RNase protection analysis demonstrates that TRalpha2, the variant isoform of TRalpha1, is constitutively expressed at all ages, while TRalpha3 is absent in the adult gonad. While TRalpha1 and TRalpha2 expression declines during development, Rev-erbAalpha (Rev), the antisense mRNA encoded by the same c-erbAalpha genomic locus, increases beginning 5 days after birth and maximizing in adulthood. TRalpha1, TRalpha2, and Rev mRNAs do not appear to be directly regulated by thyroid hormone in testis; however, short-term neonatal hypothyroidism leads to the expression of TRalpha1 and its variant in adult testis, which is absent in control coeval animals. Thus, during development of rat testis, the levels of messages of genes encoded in the c-erbAalpha. genomic locus have different ontogenetic control. The ontogenetic profile of TRalpha1 and its variant isoforms within the seminiferous epithelium suggests that these receptors are involved in the differentiation of the male gonad.
Journal of endocrinological investigation 01/2000; 22(11):843-8. · 1.57 Impact Factor
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ABSTRACT: In the present study we evaluated the role of T3 on the in vitro processes of mouse cumulus cell-oocyte complex expansion, oocyte meiotic maturation, and granulosa cell aromatase activity. Results obtained from cumuli oophori isolated from immature and adult mice ovaries demonstrated that T3 at all concentrations tested (0.1-100 nM) did not affect basal or FSH-induced cumulus expansion or interfere with oocyte meiotic maturation up to metaphase II stage. On the contrary, T3 inhibited in a time- and dose-dependent manner FSH-induced aromatase activity in cultured granulosa cells obtained from either adult or immature female mice. The half-maximal dose (ED50) of T3 inhibition was 0.87 +/- 0.21 nM, which is in agreement with the reported dissociation constant of T3 nuclear receptor (Kd = 0.4-5 nM) in mammalian granulosa cells. Time-course experiments demonstrated higher sensitivity to T3 of adult granulosa cells with respect to immature granulosa cells in culture. Indeed, in immature granulosa cells T3 inhibition became significantly evident only after 6 days of hormonal treatment, whereas in adult granulosa cells the inhibitory effect was present after only 2 days of treatment. (Bu)2cAMP- or 3-isobutyl-1-methyl-xanthine-stimulated aromatase activity was also significantly decreased by T3, thus suggesting that the inhibition was downstream from cAMP formation. Lastly, analysis of aromatase messenger RNA (mRNA) levels by semiquantitative RT-PCR demonstrated the ability of FSH to increase aromatase mRNA level in cultured granulosa cells by 2.4 +/- 0.5-fold. In agreement with the effect on enzyme activity, the stimulatory effect of FSH on aromatase mRNA level was greatly reduced after T3 cotreatment. In conclusion, T3 inhibition of aromatase activity may be of physiological relevance in the complex multihormonal regulation of mammalian follicle development and may contribute to explaining the alteration in female reproductive functions after thyroid hormone hypo- or hypersecretion.
Endocrinology 05/1999; 140(4):1783-8. · 4.46 Impact Factor
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S Ulisse,
N Rucci,
D Piersanti,
E Carosa,
F M Graziano,
A Pavan,
P Ceddia,
M Arizzi,
P Muzi,
L Cironi,
L Gnessi, M D'Armiento,
E A Jannini
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ABSTRACT: The present study reports the modulation of basement membrane (BM) components, laminin, entactin, and type IV collagen, expression in prepubertal rat Sertoli cell by the thyroid hormone T3. Immunocytochemical studies of permeabilized Sertoli cells in culture showed that T3 treatment (10[-7] M for 24 h) increased the number of cells staining positive for laminin and/or entactin (from 58 +/- 5.3% to 86.4 +/- 6.5%, P < 0.01). In contrast, a strong inhibition of type IV collagen immunopositivity was observed. Western blot analysis of Sertoli cell-conditioned media indicated that T3 treatment significantly (P < 0.01) increased the level of secreted entactin by 60-65% without affecting the levels of laminin A and B1/B2 chains. Moreover, thyroid hormone treatment of Sertoli cells significantly reduced type IV collagen secretion by 62% (P < 0.05). Slot blot analysis of poly-A RNA demonstrated a significant (P < 0.01) increase in the level of entactin messenger RNA (mRNA) by 140% (P < 0.01) and a 50% reduction of type IV collagen alpha1 chain mRNA after thyroid hormone treatment. No effect of the hormone was observed on the accumulation of the laminin B1 and B2 chain mRNAs in Sertoli cell cultures. These effects cannot be ascribed to changes in the degradation of BM components, because no effect of thyroid hormone was observed on plasminogen activators or metalloproteinase secretion by Sertoli cells. These observations indicate the Sertoli cell as a source of entactin within the testis, demonstrate the ability of T3 to differentially regulate the expression of BM components, and can be regarded as a part of the integrated mechanism by which thyroid hormone affects testicular development and differentiation.
Endocrinology 02/1998; 139(2):741-7. · 4.46 Impact Factor
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ABSTRACT: Cryptorchidism is a pathological condition which affects up to 6% of newborns. Main etiopathogenetic hypotheses are the hormonal and the dysgenetic one. Ultrasonography is useful in locating testis in the inguinal canal, while in the management of intraabdominal testis, laparoscopy is considered the best diagnostic technique and, in many cases, can be coupled with surgical management. Medical treatment with LH-RH or with hCG or, better, combined (LH-RH+hCG) is recommended before the second year. Impairment of fertility is a complication mainly in subjects with a history of bilateral cryptorchidism. Undescended testis has a risk of malignant degeneration ranging from 3% to 18% and for this reason some authors suggest a gonadal biopsy after puberty.
Minerva endocrinologica 01/1996; 20(4):201-10. · 0.98 Impact Factor
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Endocrine Reviews 09/1995; 16(4):443-59. · 19.93 Impact Factor
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Journal of Clinical Endocrinology & Metabolism 09/1995; 80(8):2543-4. · 6.50 Impact Factor
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ABSTRACT: Primary cultures of prepubertal rat Sertoli cells secrete two major tissue inhibitors of metalloproteinases: TIMP-1 (M(r) 28K) and TIMP-2 (M(r) 21 K). FSH stimulated Sertoli cell TIMP-1 and TIMP-2 activity in a time- and dose-dependent manner and also stimulated TIMP-1 and TIMP-2 protein and messenger RNA levels. These effects were mimicked by the cAMP analog, 8-bromo-cAMP, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The protein kinase C activating phorbol ester phorbol myristate acetate (TPA) stimulated TIMP-1 but not TIMP-2 activity and messenger RNA levels. Cycloheximide and actinomycin-D inhibited basal TIMP-1 and TIMP-2 activity and inhibited the ability of FSH, 8-bromo-cAMP, and TPA to stimulate TIMP activity. The protein kinase A (PKA) inhibitor AMP Rp isomer did not affect basal TIMP-1 and TIMP-2 activity or TPA-stimulated TIMP-1 activity. However, the PKA inhibitor markedly reduced FSH and 3-isobutyl-1-methylxanthine stimulation of TIMP-1 and TIMP-2 activity. FSH, 8-bromo-cAMP, and TPA stimuli induced DNA binding complexes capable of binding to a TIMP-1 AP-1 site consensus sequence oligonucleotide. The AP-1 site binding complex(es) induced by all three treatments reacted with antibodies directed broadly against fos and jun protooncogene families and against the specific family members c-fos, junB, and junD but not c-jun proteins. Constitutive cAMP response element binding activity capable of binding an artificial cAMP response element binding site oligonucleotide was demonstrated in Sertoli cell nuclear extracts. This activity was minimally modulated by FSH, 8-bromo-cAMP, or TPA treatment. In summary, Sertoli cells secrete TIMP-1 and TIMP-2 that can be coordinately up-regulated by FSH through a cAMP, PKA-dependent pathway. a convergence of TPA, FSH, and cAMP mediated signals in prepubertal Sertoli cells may occur with the induction of specific AP-1 site binding complex(es) containing jun and fos proteins. Our data suggest that FSH stimulation of TIMP-2 expression may be regulated independently to that of TIMP-1. We propose that the ability of FSH to stimulate Sertoli cell TIMP activity suggests a central role for this hormone in the control of extracellular matrix turnover during testicular development at the level of metalloproteinase inhibition.
Endocrinology 01/1995; 135(6):2479-87. · 4.46 Impact Factor
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ABSTRACT: Iodine is a fundamental element of diet since it is important in thyroid hormone biosynthesis. Dietary iodine deficiency can provoke not only thyroid enlargement, but also symptoms and signs of hypothyroidism of various degree, known as "iodine deficiency disorders" (IDD). Thus, the iodine supplementation is mandatory. It can be obtained, in our regions, where subendemic deficiency is frequent, by adding iodine to salt. This is the only way to avoid anatomo-functional lesions, that are dramatic in pregnancy and childhood.
Minerva endocrinologica 10/1994; 19(3):149-54. · 0.98 Impact Factor
