Assuntos
Tumor de Células de Leydig , Orquiectomia/métodos , Neoplasias Testiculares , Testículo , Adulto , Preservação da Fertilidade , Humanos , Tumor de Células de Leydig/patologia , Tumor de Células de Leydig/fisiopatologia , Tumor de Células de Leydig/cirurgia , Imageamento por Ressonância Magnética/métodos , Masculino , Neoplasias Testiculares/patologia , Neoplasias Testiculares/fisiopatologia , Neoplasias Testiculares/cirurgia , Testículo/diagnóstico por imagem , Testículo/patologia , Testículo/cirurgia , Resultado do Tratamento , Ultrassonografia/métodosRESUMO
Testicular tumor of adrenogenital syndrome is a rare and benign anomaly usually presenting as bilateral testicular masses. It is the most important cause of infertility in adult male congenital adrenal hyperplasia. Distinction between testicular tumors of adrenogenital syndrome and Leydig cell tumors can be problematic; it is based on clinical, histopathologic, immunohistochemical and endocrine features. Biopsy is advised in cases of longstanding tumors in infertile patients and when surgery is indicated. Fertility preservation is a key management goal in testicular tumor of adrenogenital syndrome. In stages 2 and 3, intensified glucocorticoid treatment is recommended as a first step treatment. Sparing surgical approach is preferred for tumors of stage 4 and steroid unresponsive masses. Magnetic resonance imaging is recommended before surgery. The only indication of surgery in stage 5 is testicular pain.
Assuntos
Síndrome Adrenogenital/fisiopatologia , Síndrome Adrenogenital/terapia , Neoplasias Testiculares/fisiopatologia , Neoplasias Testiculares/terapia , Tumor de Resto Suprarrenal/diagnóstico , Tumor de Resto Suprarrenal/patologia , Tumor de Resto Suprarrenal/fisiopatologia , Tumor de Resto Suprarrenal/terapia , Hormônio Adrenocorticotrópico/sangue , Síndrome Adrenogenital/diagnóstico , Síndrome Adrenogenital/patologia , Adulto , Diagnóstico Diferencial , Glucocorticoides/uso terapêutico , Humanos , Tumor de Células de Leydig/diagnóstico , Tumor de Células de Leydig/patologia , Tumor de Células de Leydig/fisiopatologia , Tumor de Células de Leydig/terapia , Imageamento por Ressonância Magnética , Masculino , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia , Testículo/patologia , Testículo/fisiopatologiaRESUMO
The luteinizing hormone receptor (LHCGR) is necessary for fertility, and genetic mutations cause defects in reproductive development and function. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP). We have previously characterized a mouse model (KiLHRD582G) for FMPP that exhibits the same phenotype of precocious puberty, Leydig cell hyperplasia, and elevated testosterone as boys with the disorder. We observed that KiLHRD582G male mice became infertile by 6 months of age, although sperm count and motility were normal. In this study, we sought to determine the reason for the progressive infertility and the long-term consequences of constant LHCGR signaling. Mating with superovulated females showed that infertile KiLHRD582G mice had functional sperm and normal accessory gland function. Sexual behavior studies revealed that KiLHRD582G mice mounted females, but intromission was brief and ejaculation was not achieved. Histological analysis of the reproductive tract showed unique metaplastic changes resulting in pseudostratified columnar epithelial cells with cilia in the ampulla and chondrocytes in the penile body of the KiLHRD582G mice. The infertile KiLHRD582G exhibited enlarged sinusoids and a decrease in smooth muscle content in the corpora cavernosa of the penile body. However, collagen content was unchanged. Leydig cell adenomas and degenerating seminiferous tubules were seen in 1-year-old KiLHRD582G mice. We conclude that progressive infertility in KiLHRD582G mice is due to sexual dysfunction likely due to functional defects in the penis.
Assuntos
Adenoma/fisiopatologia , Infertilidade Masculina/genética , Infertilidade Masculina/fisiopatologia , Tumor de Células de Leydig/fisiopatologia , Receptores do LH/genética , Transdução de Sinais/genética , Neoplasias Testiculares/fisiopatologia , Animais , Ejaculação , Estradiol/metabolismo , Genitália Masculina/patologia , Genitália Masculina/fisiopatologia , Infertilidade Masculina/patologia , Tumor de Células de Leydig/patologia , Masculino , Camundongos , Pênis/patologia , Puberdade Precoce/genética , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Neoplasias Testiculares/patologiaRESUMO
Leydig cell hyperplasia and Leydig cell tumours of the ovary are rare. We present two cases in which patients had increased blood levels of testosterone and frank hirsutism. Imaging showed minimal abnormalities. After adrenal disease had been ruled out, they underwent a bilateral oophorectomy. One case showed a Leydig cell hyperplasia, the other a Leydig cell tumour. An androgen producing tumour should be excluded in every woman with evidence of hirsutism or frank virilization and markedly elevated testosterone levels. Adrenal disease with androgen hypersecretion can be suspected by detailed clinical, laboratory and radiologic imaging. Although DHEAS has a good sensitivity in the detection of adrenal origin of hyperandrogenism (and hence a good negative predictive value) it is not specific (specificity ranging from 85 to 98%). Imaging of the ovaries can be helpful but does not rule out ovarian disease if normal. Indeed, diffuse stromal Leydig cell hyperplasia and Leydig cell tumours (usually small) may escape imaging and in some cases diagnosis can only be made on pathology. As these clinical entities represent a diagnostic and therapeutic challenge, oophorectomy should be considered in postmenopausal women with hirsutism and elevated testosterone levels, after the exclusion of adrenal causes. The procedure is relatively safe and effective. Follow-up remains indicated.
Assuntos
Células Epiteliais/patologia , Tumor de Células de Leydig/diagnóstico , Neoplasias Ovarianas/diagnóstico , Ovário/patologia , Idoso , Diagnóstico Diferencial , Feminino , Hirsutismo/etiologia , Humanos , Hiperplasia , Tumor de Células de Leydig/patologia , Tumor de Células de Leydig/fisiopatologia , Tumor de Células de Leydig/cirurgia , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/cirurgia , Ovariectomia , Ovário/cirurgia , Testosterona/sangue , Resultado do TratamentoRESUMO
Androgen-producing ovarian tumours can lead to assessment difficulties because of their small size. We present a case of virilising steroid cell ovarian tumour in a 41-year-old woman localised with Fluorine-18-Deoxyglucose Positron Emission Tomography/Computed Tomography ((18)FDG-PET/CT). Although the biochemical evaluation pointed to an ovarian source of androgen, diagnostic attempts to localise the source of hyperandrogenism with transvaginal ultrasound (US), and magnetic resonance imaging (MRI) of pelvis failed. Additional evaluation with (18)FDG-PET/CT showed an increased uptake in the right ovary. A laparoscopic right oophorectomy was performed and histopathology examination revealed a 1.2-cm Leydig cell tumour. The patient showed regression of clinical signs.
Assuntos
Tumor de Células de Leydig/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Adulto , Feminino , Fluordesoxiglucose F18 , Humanos , Tumor de Células de Leydig/patologia , Tumor de Células de Leydig/fisiopatologia , Tumor de Células de Leydig/cirurgia , Imagem Multimodal , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/cirurgia , Ovariectomia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral , Virilismo/etiologiaRESUMO
We report the F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) findings of a patient with a testicular Leydig cell tumor. A 43-year-old man was referred for whole body FDG PET/CT imaging for health care screening. FDG PET/CT imaging demonstrated the presence of a focal hypermetabolic lesion in the right testicle and no specific findings in other areas. Based on the preoperative impression, right testis-sparing surgery was attempted. The tumor was pathologically confirmed as a Leydig cell tumor.
Assuntos
Fluordesoxiglucose F18 , Tumor de Células de Leydig/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Neoplasias Testiculares/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Humanos , Tumor de Células de Leydig/patologia , Tumor de Células de Leydig/fisiopatologia , Masculino , Neoplasias Testiculares/patologia , Neoplasias Testiculares/fisiopatologiaRESUMO
OBJECTIVE: To report a case of hyperandrogenism attributable to the presence of an adrenal adenoma secreting dehydroepiandrosterone sulfate (DHEA-S) and an ovarian Sertoli-Leydig cell tumor secreting testosterone in a postmenopausal woman. METHODS: The laboratory, radiologic, and pathologic findings in our case are described. In addition, the pertinent literature is reviewed. RESULTS: A 56-year-old woman presented with a history of gradual increase in facial and body hair, scalp hair loss, male pattern baldness, and deepening of her voice, beginning a few years after spontaneous menopause at age 49 years. She had hypertension, obesity, and type 2 diabetes mellitus. Laboratory tests showed elevated levels of total testosterone (348 ng/dL) and DHEA-S (2,058 microg/dL), and a left adrenal tumor (3 by 4 cm) was detected on abdominal computed tomographic scan. Laparoscopic left adrenalectomy was performed, and the pathologic diagnosis was adrenal adenoma. The DHEA-S returned to normal levels, but the serum testosterone concentration remained elevated. Transvaginal ultrasonography disclosed an ovarian tumor. Bilateral oophorectomy was performed, and an ovarian Sertoli-Leydig cell tumor was diagnosed. The hormonal and clinical picture normalized after this surgical intervention. CONCLUSION: After extensive review of the literature, we believe that this is the first reported case of a coincidental DHEA-S-secreting adrenal adenoma and a testosterone- secreting ovarian Leydig cell tumor causing signs of virilization.
Assuntos
Adenoma Adrenocortical/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Hiperandrogenismo/diagnóstico , Hiperandrogenismo/etiologia , Tumor de Células de Leydig/metabolismo , Testosterona/metabolismo , Adenoma Adrenocortical/patologia , Adenoma Adrenocortical/fisiopatologia , Alopecia , Feminino , Humanos , Hiperandrogenismo/patologia , Tumor de Células de Leydig/patologia , Tumor de Células de Leydig/fisiopatologia , Pessoa de Meia-Idade , Pós-MenopausaRESUMO
AIM: We describe the clinical features of a 6-year-old boy with sexual precocity caused by a somatic activating mutation of the luteinizing hormone (LH) receptor gene preceding gonadotropin-releasing hormone (GnRH)-dependent sexual precocity. STUDY DESIGN: Genomic DNA was extracted from the right testis and from the peripheral leukocytes followed by DNA amplification and sequencing of the LH receptor gene. We described the clinical characteristics including anthropometric parameters, bone age, and endocrine evaluation when the boy presented with sexual precocity. These data were compared with the clinical and hormonal evaluation after orchiectomy preceding GnRH-dependent sexual precocity and after subsequent treatment with GnRH agonist. RESULTS: No mutation was found in the sequence of the LH receptor gene extracted from peripheral leukocytes. Interestingly, sequencing of the tumor LH receptor gene revealed a heterozygous mutation in exon 11 encoding a replacement of Asp(578)His. Despite normalization of plasma testosterone, true precocious puberty was triggered within a year. CONCLUSIONS: Inmales with GnRH-independent sexual precocity the presence of small testicular Leydig cell tumorous lesions harboring a somatic mutation of the LH receptor gene should be considered. A close follow-up of affected patients should be instigated in order to monitor recurrence or subsequent true precocity.
Assuntos
Tumor de Células de Leydig/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Puberdade Precoce/genética , Receptores do LH/genética , Neoplasias Testiculares/genética , Substituição de Aminoácidos , Criança , Éxons/genética , Hormônio Liberador de Gonadotropina/sangue , Heterozigoto , Humanos , Tumor de Células de Leydig/sangue , Tumor de Células de Leydig/fisiopatologia , Masculino , Proteínas de Neoplasias/metabolismo , Puberdade Precoce/sangue , Puberdade Precoce/fisiopatologia , Receptores do LH/metabolismo , Neoplasias Testiculares/sangue , Neoplasias Testiculares/fisiopatologiaRESUMO
Little is known about the pathogenesis of Leydig cell tumours (LCTs) of the testis. The observation of several associated dysgenetic features in the non-tumoural parenchyma and in the contralateral testes of men with testicular germ cell neoplasms has served as the basis to propose that there may be a common mechanism for different male reproductive disorders. However, the possible relationship between LCTs and other testicular lesions has not been explored. Here we describe the presence of primary lesions in the non-tumoural parenchyma of testes with LCT, from which we try to establish possible pathogenetic associations. We studied the non-tumoural parenchyma adjacent to 16 LCT specimens. Parameters as Leydig cell hyperplasia (LCHY), qualitative evaluation of the germinal epithelium and spermatogenesis, the presence of Sertoli cell-only tubules (SCOT), and the Sertoli cell nuclear morphology were consistently assessed in all cases. SCOT associated with Sertoli cell dysgenetic morphology was the most frequent finding, present in 50% of the cases. Another interesting finding was the presence of LCHY in four cases (25%). Abnormal spermatogenesis was found in 81.25% of the cases, and it consisted of lesions of the adluminal or basal compartments of seminiferous tubules. The occurrence of either dysgenetic Sertoli cells or LCHY adjacent to LCTs could represent primary anomalies, resulting from a common insult also involved in tumourigenesis. The abnormalities in spermatogenesis observed here are likely to represent consequences of either tumour compression or abnormal hormonal production. The significance of these associations merits further investigation regarding a common pathogenesis.
Assuntos
Tumor de Células de Leydig/patologia , Neoplasias Testiculares/patologia , Testículo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Forma do Núcleo Celular , Humanos , Hiperplasia , Tumor de Células de Leydig/fisiopatologia , Células Intersticiais do Testículo/patologia , Masculino , Pessoa de Meia-Idade , Células de Sertoli/patologia , Espermatogênese , Neoplasias Testiculares/fisiopatologia , Testículo/fisiopatologiaAssuntos
Composição Corporal , Hiperandrogenismo/fisiopatologia , Resistência à Insulina , Testosterona/sangue , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/fisiopatologia , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Hiperandrogenismo/etiologia , Hiperandrogenismo/cirurgia , Tumor de Células de Leydig/complicações , Tumor de Células de Leydig/fisiopatologia , Tumor de Células de Leydig/cirurgia , Pessoa de Meia-IdadeRESUMO
Among the various causes of gynaecomastia, testicular malignancies are an uncommon, life-threatening condition, which require prompt treatment. The case of a 26-year-old healthy man is described, who reported a 6-month painful bilateral gynaecomastia associated with secondary hypogonadism. Normal circulating 17beta-oestradiol (E2) levels showed an enhanced response to human chorionic gonadotrophin (hCG) testing, which led to a reduced testosterone (T)/E2 ratio. Both clinical and hormonal findings normalized following surgical exeresis of a left testicular mass, which proved to be a Leydig cell tumour (LCT) at histology. This report underlines the importance of ultrasonographic evaluation of the testes, whenever breast enlargement occurs in a healthy man, despite unremarkable findings on testicular examination. In addition, our case demonstrates that normal unstimulated circulating E2 levels do not allow the presence of a stromal testicular tumour to be ruled out and that the response of restored T levels to hCG testing can remain blunted up to 1 year after surgery. Finally, we claim that T/E2 ratio may be a useful tool in evaluating derangement of the endocrine milieu secondary to LCT.
Assuntos
Ginecomastia/etiologia , Tumor de Células de Leydig/complicações , Neoplasias Testiculares/complicações , Adulto , Gonadotropina Coriônica/sangue , Estradiol/sangue , Ginecomastia/fisiopatologia , Humanos , Tumor de Células de Leydig/fisiopatologia , Masculino , Neoplasias Testiculares/fisiopatologiaRESUMO
Pituitary tumor transforming gene (PTTG), the human ortholog of securin, is an oncogene. Few normal tissues express PTTG, although in the testis, it is more abundantly expressed. In cancer, however, its wide expression has been directly correlated with the proliferation and angiogenesis, although very little is known about the overall regulation of the PTTG gene. In this study, we investigate the role of the calcium-sensing receptor (CaR), a G protein-coupled receptor (GPCR), in regulating PTTG in a widely used model of humoral hypercalcemia of malignancy, the rat H-500 Leydig cell testicular cancer. We show that extracellular calcium (Ca2+o) up-regulates PTTG mRNA. This up-regulation has a rapid onset, starting at 0.5 h, and remains up-regulated until 40 h. The up-regulation was also Ca2+o concentration dependent, with increases (mean +/- se) of 4.22 +/- 1.61-fold, 5.11 +/- 1.11-fold, and 5.64 +/- 1.92-fold at 5, 7.5, and 10 mm calcium, respectively, compared with 0.5 mm Ca2+o. This effect was abolished by overexpression of a dominant-negative CaR (R185Q), thereby confirming that the effect of high Ca2+o is CaR mediated. Another GPCR agonist, ADP, had no effect on PTTG expression. Because PTTG has been reported to induce angiogenesis, we investigated the effect of elevated Ca2+o on vascular endothelial growth factor (VEGF) expression. Indeed high calcium up-regulated VEGF mRNA by 1.59 +/- 0.22-fold. In conclusion, we show for the first time that a GPCR, the CaR, stimulates the synthesis of PTTG mRNA in a nonmetastasizing model for humoral hypercalcemia of malignancy and, in the process, might induce angiogenesis via VEGF.
Assuntos
Tumor de Células de Leydig/fisiopatologia , Células Intersticiais do Testículo/fisiologia , Proteínas de Neoplasias/genética , Receptores de Detecção de Cálcio/metabolismo , Neoplasias Testiculares/fisiopatologia , Animais , Cálcio/farmacologia , Linhagem Celular Tumoral/transplante , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Tumor de Células de Leydig/metabolismo , Células Intersticiais do Testículo/citologia , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos F344 , Securina , Neoplasias Testiculares/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
A 33-year-old male was referred to our hospital for male infertility with painless swelling of the left scrotal content. Left high orchiectomy was performed under the diagnosis of left testicular tumor. Histologically, this testicular mass was a Leydig cell tumor. We reviewed 55 cases of Leydig cell tumor of the testis previously reported in Japan, and reported the hormonal profile in our case before and after surgery.
Assuntos
Infertilidade Masculina/etiologia , Tumor de Células de Leydig/complicações , Neoplasias Testiculares/complicações , Adulto , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Tumor de Células de Leydig/fisiopatologia , Tumor de Células de Leydig/cirurgia , Hormônio Luteinizante/sangue , Masculino , Contagem de Espermatozoides , Neoplasias Testiculares/fisiopatologia , Neoplasias Testiculares/cirurgia , Testosterona/sangue , Resultado do TratamentoRESUMO
Widely varied chemicals--including certain herbicides, plasticizers, drugs, and natural products--induce peroxisome proliferation in rodent liver and other tissues. This phenomenon is characterized by increases in the volume density and fatty acid oxidation of these organelles, which contain hydrogen peroxide and fatty acid oxidation systems important in lipid metabolism. Research showing that some peroxisome proliferating chemicals are nongenotoxic animal carcinogens stimulated interest in developing mode of action (MOA) information to understand and explain the human relevance of animal tumors associated with these chemicals. Studies have demonstrated that a nuclear hormone receptor implicated in energy homeostasis, designated peroxisome proliferator-activated receptor alpha (PPARalpha), is an obligatory factor in peroxisome proliferation in rodent hepatocytes. This report provides an in-depth analysis of the state of the science on several topics critical to evaluating the relationship between the MOA for PPARalpha agonists and the human relevance of related animal tumors. Topics include a review of existing tumor bioassay data, data from animal and human sources relating to the MOA for PPARalpha agonists in several different tissues, and case studies on the potential human relevance of the animal MOA data. The summary of existing bioassay data discloses substantial species differences in response to peroxisome proliferators in vivo, with rodents more responsive than primates. Among the rat and mouse strains tested, both males and females develop tumors in response to exposure to a wide range of chemicals including DEHP and other phthalates, chlorinated paraffins, chlorinated solvents such as trichloroethylene and perchloroethylene, and certain pesticides and hypolipidemic pharmaceuticals. MOA data from three different rodent tissues--rat and mouse liver, rat pancreas, and rat testis--lead to several different postulated MOAs, some beginning with PPARalpha activation as a causal first step. For example, studies in rodent liver identified seven "key events," including three "causal events"--activation of PPARalpha, perturbation of cell proliferation and apoptosis, and selective clonal expansion--and a series of associative events involving peroxisome proliferation, hepatocyte oxidative stress, and Kupffer-cell-mediated events. Similar in-depth analysis for rat Leydig-cell tumors (LCTs) posits one MOA that begins with PPARalpha activation in the liver, but two possible pathways, one secondary to liver induction and the other direct inhibition of testicular testosterone biosynthesis. For this tumor, both proposed pathways involve changes in the metabolism and quantity of related hormones and hormone precursors. Key events in the postulated MOA for the third tumor type, pancreatic acinar-cell tumors (PACTs) in rats, also begin with PPARalpha activation in the liver, followed by changes in bile synthesis and composition. Using the new human relevance framework (HRF) (see companion article), case studies involving PPARalpha-related tumors in each of these three tissues produced a range of outcomes, depending partly on the quality and quantity of MOA data available from laboratory animals and related information from human data sources.
Assuntos
Carcinógenos/toxicidade , Transformação Celular Neoplásica , Modelos Animais de Doenças , Receptores Citoplasmáticos e Nucleares/fisiologia , Fatores de Transcrição/fisiologia , Animais , Bioensaio/métodos , Proteínas de Ligação a DNA , Ácidos Graxos/metabolismo , Humanos , Tumor de Células de Leydig/etiologia , Tumor de Células de Leydig/fisiopatologia , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Fígado/fisiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Camundongos , Microcorpos , Proteínas Nucleares , Oxirredução , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/fisiopatologia , Primatas , Ratos , Proteínas Repressoras , Medição de Risco , Neoplasias Testiculares/etiologia , Neoplasias Testiculares/fisiopatologia , Testículo/efeitos dos fármacos , Testículo/patologia , Dedos de ZincoRESUMO
We investigated in this study the effects of ovine PRL on endocrine functions of cultured murine Leydig tumor cells (mLTC-1). The parameters studied were the activation of signal transduction systems involving cAMP and intracellular free Ca(2+), the expression of Janus kinase 2 (JAK2), expression and function of LH and PRL receptors (R), expression of the steroidogenic acute regulatory (StAR) protein, and stimulation of steroidogenesis. Very similar biphasic dose- and time-dependent responses of all the parameters studied were found upon PRL stimulation, comprising a fast inhibition within 24 h in response to high PRL doses (>/=30 microgram/liter), and a slow stimulation, between 48-72 h, in response to lower PRL doses (1-10 microgram/liter). In addition, extracellular Ca(2+) (1.5 mmol/liter) increased the effect of PRL on human CG (hCG)-stimulated StAR messenger RNA expression and progesterone (P) production. Importantly, the biphasic effects of PRL on LHR gene expression and hCG-mediated P production were abolished in the presence of anti-PRL antiserum, demonstrating specificity of PRL action. The PRL effects on StAR expression, and steroid and cAMP production, apparently reflect its effects on LHR function. The relevance of the PRL effects observed in mLTC-1 cells was supported by demonstration of similar PRL responses in hCG-stimulated testosterone production of isolated mouse Leydig cells. Collectively, these findings clearly demonstrate the biphasic regulatory actions of PRL, and clarify some facets of the controversial role of this hormone in Leydig cell function.
Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Tumor de Células de Leydig/fisiopatologia , Prolactina/farmacologia , Proteínas Proto-Oncogênicas , Neoplasias Testiculares/fisiopatologia , Animais , Cálcio/metabolismo , Gonadotropina Coriônica/metabolismo , Humanos , Janus Quinase 2 , Cinética , Masculino , Camundongos , Fosfoproteínas/genética , Proteínas Tirosina Quinases/genética , Receptores do LH/efeitos dos fármacos , Receptores do LH/genética , Receptores do LH/fisiologia , Receptores da Prolactina/genética , Ovinos , Células Tumorais CultivadasRESUMO
The aims of this investigation were to quantify the changes in canine spermatogenesis that occur during ageing and to study the prevalence of testicular tumours and their effects on spermatogenesis in dogs. Testes from 74 dogs of various breeds without clinically detected testicular disease and from 28 dogs with clinically palpable tumours were examined. Testicular tumours were classified histologically according to the criteria of Nielsen and Kennedy (1990). Spermatogenesis was evaluated using a modified Johnsen score adapted for use in dogs. The diameter of the seminiferous tubules was measured in dogs without testicular disease to examine the possible effects of ageing. The different lifespans of small and large breeds were compensated for by expression as a percentage of the age at which dogs with various body weights are considered to be geriatric. Of the dogs without clinically detected disease, 21 of 74 had small testicular tumours. As in the 28 dogs with clinically detected tumours, multiple types of tumour and bilateral occurrence of tumours were common findings. The prevalence of tumours increased during ageing. Eighty-six per cent of the clinically detected tumours and 57% of the non-clinically detected tumours were found in geriatric dogs. The diameter of the seminiferous tubules did not change with age. Impairment of spermatogenesis was found only in dogs with bilateral tumours and in the affected testis of dogs with clinically detected tumours. In conclusion, it appears that spermatogenesis per se does not decrease during ageing in dogs. However, the occurrence of testicular tumours increases with age and this may affect spermatogenesis significantly.
Assuntos
Envelhecimento , Doenças do Cão/fisiopatologia , Espermatogênese , Neoplasias Testiculares/fisiopatologia , Neoplasias Testiculares/veterinária , Animais , Cães , Tumor de Células de Leydig/fisiopatologia , Masculino , Seminoma/fisiopatologia , Tumor de Células de Sertoli/fisiopatologiaRESUMO
This study was conducted to determine if osteoporosis in male leprosy patients is caused by testicular atrophy. Bone volume (BV/TV), trabecular number (TbN), trabecular thickness (TbTh), and trabecular separation (TbSp) were measured in two areas in decalcified paraffin sections of lumbar bones from 29 male leprosy and 6 male nonleprosy autopsy cases. We found significant differences in the average BV/TV measurements among the 7 patients with nodular Leydig cell hyperplasia (BV/TV 12.24%) and the 22 patients without hyperplasia (BV/TV 7.35%) and 6 patients without leprosy (BV/TV 12.98%). Bone volume was maintained in patients with nodular Leydig cell hyperplasia, and we determined no clinical factor other than the Leydig cell hyperplasia that reflected the bone volume. The osteoporosis of male leprosy patients was attributed to secondary gonadal dysfunction due to testicular atrophy, and Leydig cell hyperplasia appears to preserve bone volume.
Assuntos
Humanos , Células Intersticiais do Testículo/citologia , Células Intersticiais do Testículo/fisiologia , Hanseníase/complicações , Tumor de Células de Leydig/fisiopatologiaRESUMO
Seven patients (aged 25-38 years) were admitted because of mono- or bilateral gynaecomastia. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone, 17-beta-estradiol, delta4-androstenedione, dehydropiandrosterone sulphate (DHEA-S) and 17-OH-progesterone were determined and semen analysis was carried out. FSH and LH levels were also measured after acute LH-RH administration (100 microg intravenously), and testosterone and 17-beta-estradiol were also evaluated after acute human chorionic gonadotrophin (hCG) administration (5000 IU intramuscularly). Testicular echography demonstrated the presence of a solid hypoechoic tumour. Therefore all patients were submitted to hemicastration by orchidofuniculotomy and a benign Leydig cell tumour was diagnosed in the removed testes. Hormonal and semen evaluations were repeated 3, 6, 9 and 12 months after surgery. The data before and after surgery were compared with a control group of 10 age-matched males. Before surgery, patients showed low FSH basal plasma levels; high levels of 17-beta-estradiol and low testosterone levels similar to those after hCG administration. A dyspermia was observed. Unilateral orchidectomy eliminated the autonomous secretion of oestrogen(s) so an increase of LH, FSH and testosterone levels, together with an improvement of spermatogenesis, were obtained.
Assuntos
Hormônios Esteroides Gonadais/sangue , Tumor de Células de Leydig/cirurgia , Orquiectomia , Neoplasias Testiculares/cirurgia , 17-alfa-Hidroxiprogesterona/sangue , Adulto , Androstenodiona/sangue , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Tumor de Células de Leydig/sangue , Tumor de Células de Leydig/fisiopatologia , Hormônio Luteinizante/sangue , Masculino , Prolactina/sangue , Sêmen/fisiologia , Neoplasias Testiculares/sangue , Neoplasias Testiculares/fisiopatologia , Testosterona/sangueRESUMO
OBJECTIVES: To define the clinical and laboratory characteristics and natural history of Leydig cell tumours in order to define a general management plan. MATERIAL AND METHODS: The files of 10 patients operated for Leydig cell testicular tumour between 1982 and 1996 were studied retrospectively. RESULTS: In nine out of ten cases, the presenting complaint was gynaecomastia, erectile dysfunction or infertility. In every case, serum testosterone was normal or low and oestradiol was normal or elevated. Eight patients were treated by radical orchidectomy, and two by subcapsular orchidectomy. The course was favourable in 9 out of 10 cases in the absence of any other treatment. Only one patient had an immediately malignant form with a fatal outcome. CONCLUSION: Although many teams prefer total orchidectomy because of the diagnostic difficulty associated with malignant forms, simple subcapsular orchidectomy should become the first-line treatment, provided it is subsequently followed by close surveillance, as it preserves maximum fertility, and these tumours usually have a favourable prognosis.