RESUMEN
PURPOSE: Liquid-chromatography tandem mass-spectrometry (LC-MS/MS) was developed in parallel to Immunoassays (IAs) and today is proposed as the "gold standard" for steroid assays. Leydig cells of men with Klinefelter syndrome (KS) are able to respond to human chorionic gonadotropin (hCG) stimulation, even if testosterone (T) production was impaired. The aim was to evaluate how results obtained by IAs and LC-MS/MS can differently impact on the outcome of a clinical research on gonadal steroidogenesis after hCG stimulation. METHODS: A longitudinal, prospective, case-control clinical trial. (clinicaltrial.gov NCT02788136) was carried out, enrolling KS men and healthy age-matched controls, stimulated by hCG administration. Serum steroids were evaluated at baseline and for 5 days after intramuscular injection of 5000 IU hCG using both IAs and LC-MS/MS. RESULTS: 13 KS patients (36 ± 9 years) not receiving T replacement therapy and 14 controls (32 ± 8 years) were enrolled. T, progesterone, cortisol, 17-hydroxy-progesterone (17OHP) and androstenedione, were significantly higher using IAs than LC-MS/MS. IAs and LC-MS/MS showed direct correlation for all five steroids, although the constant overestimation detected by IAs. Either methodology found the same 17OHP and T increasing profile after hCG stimulation, with equal areas under the curves (AUCs). CONCLUSIONS: Although a linearity between IA and LC-MS/MS is demonstrated, LC-MS/MS is more sensitive and accurate, whereas IA shows a constant overestimation of sex steroid levels. This result suggests the need of reference intervals built on the specific assay. This fundamental difference between these two methodologies opens a deep reconsideration of what is needed to improve the accuracy of steroid hormone assays.
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Gonadotropina Coriónica/uso terapéutico , Hormonas Esteroides Gonadales/sangre , Inmunoensayo/métodos , Síndrome de Klinefelter/sangre , Espectrometría de Masas en Tándem/métodos , 17-alfa-Hidroxiprogesterona/sangre , Adolescente , Adulto , Estudios de Casos y Controles , Humanos , Hidrocortisona/sangre , Síndrome de Klinefelter/tratamiento farmacológico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Progesterona/sangre , Estudios Prospectivos , Testosterona/sangre , Adulto JovenRESUMEN
BACKGROUND: Italy is characterized by high prevalence of goiter. To date, only limited data about the prevalence of goiter in the Italian adult population are available. AIM: To investigate the prevalence of thyroid ultrasound abnormalities in adults unaware of any thyroid disease and evaluate the rate of differentiated thyroid cancer (DTC) obtained by this intervention. METHODS: Ultrasound (US) thyroid scan was performed in adult volunteers recruited by advertisement in Modena, Italy. One hundred and thirty-five women and 66 men (no.= 201), unaware of any thyroid disease (mean age of 46 ± 10.7 yr) underwent their first thyroid US scan. RESULTS: US thyroid abnormalities were found in 101 subjects (50.3%): 91 nodular goiters (45.2%) and 13 US-thyroiditis (6.5%) associated with positive auto-antibodies in 11 of them. Seventeen subjects (18%) with nodules underwent US-fine needle aspiration biopsy with the following cytological class (C) outcome: 14 patients C2 (82%), 1 patient C3 (6%), 2 patients had C4 (12%), the latter received histological confirmation. CONCLUSIONS: The prevalence of thyroid abnormalities is very high in subjects unaware of any thyroid disease. DTC was found in 1% of subjects and in 2% of those affected by nodular goiter. Compared to the detection rate of the well-established screening programs for breast (0.45%) and colorectal (0.27%) cancer, the prevalence of DTC seems to be much higher. Thyroid US screening could allow the detection of DTC in asymptomatic subjects and this diagnosis often includes DTC at an advanced stage. Thus, US screening not necessarily results in the over-diagnosis of clinically not relevant thyroid diseases.
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Enfermedades de la Tiroides/epidemiología , Glándula Tiroides/diagnóstico por imagen , Adulto , Anciano , Autoanticuerpos/análisis , Biopsia con Aguja Fina , Femenino , Bocio Nodular/diagnóstico por imagen , Bocio Nodular/epidemiología , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedades de la Tiroides/diagnóstico por imagen , Glándula Tiroides/inmunología , Glándula Tiroides/patología , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/epidemiología , Tiroiditis/patología , UltrasonografíaAsunto(s)
Anabolizantes/efectos adversos , Andrógenos/efectos adversos , Tumor de Células de Leydig/inducido químicamente , Trastornos Relacionados con Sustancias/complicaciones , Neoplasias Testiculares/inducido químicamente , Adulto , Humanos , Tumor de Células de Leydig/patología , Masculino , Pronóstico , Neoplasias Testiculares/patologíaRESUMEN
Male age-related bone loss is caused, at least in part, by hypogonadism that occurs with advancing age. The study of the effects of sex steroids on bone physiology in men has recently highlighted the central role of estrogens on bone pathophysiology. This review focuses on particular aspects of bone physiology and pathophysiology in aging men, noting both the similarities to and the differences from female counterparts. In particular, the role of sex steroids on bone sexual dimorphism in health and disease has been analyzed.
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Huesos/fisiopatología , Hipogonadismo/fisiopatología , Osteoporosis/fisiopatología , Factores de Edad , Anciano , Densidad Ósea/fisiología , Estradiol/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Testosterona/fisiologíaRESUMEN
OBJECTIVE: Aromatase, the key enzyme involved in estrogen synthesis, is expressed in a variety of cells and tissues including human peripheral blood leukocytes (PBLs). The present study was designed to evaluate PBL aromatase gene expression in male and female subjects of different age groups. In addition, differences in gene expression during the follicular and luteal phase of the menstrual cycle in women, and before and after testosterone administration in men, were estimated. DESIGN: Aromatase mRNA and protein were measured in PBLs obtained from young (n = 10) and postmenopausal women (n = 10), men (n = 15), and prepubertal children (n = 10). Aromatase mRNA and protein were also measured during the follicular and luteal phases of the menstrual cycle in women, and before and after the intramuscular administration of 250 mg testosterone enanthate in men. METHODS AND RESULTS: Aromatase mRNA measured by real-time PCR in PBLs from women during the follicular phase was significantly higher than during the luteal phase of the menstrual cycle (P < 0.05). In men, PBL aromatase mRNA values increased significantly following testosterone administration (P < 0.05). PBL mRNA aromatase levels in women during the follicular phase and men after testosterone administration were significantly higher (one-way ANOVA; P < 0.05) than in any other group. Children, postmenopausal women, and women during the luteal phase showed the lowest aromatase mRNA expression. The results of the immunoblot analysis confirmed the data obtained by real-time PCR. A positive correlation between PBL aromatase mRNA values and plasma estradiol and estrone levels during the follicular phase of the menstrual cycle was observed in the group of adult women. No other correlations were found. CONCLUSIONS: The aromatase gene is differentially expressed in PBLs from women, men, and prepubertal children, indicating a sexual dimorphism in the enzyme expression and an important role of sex steroids in the modulation of aromatase gene expression.
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Envejecimiento/metabolismo , Aromatasa/sangre , Leucocitos/enzimología , Adulto , Aromatasa/biosíntesis , Western Blotting , Separación Celular , Niño , ADN/biosíntesis , ADN/genética , Estradiol/sangre , Estrona/sangre , Femenino , Fase Folicular/metabolismo , Humanos , Fase Luteínica/metabolismo , Masculino , Ciclo Menstrual/metabolismo , Progesterona/sangre , ARN/biosíntesis , ARN/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Caracteres Sexuales , Testosterona/sangreRESUMEN
Sarcoidosis is a systemic disease characterized by non-caseating granulomas that rarely involve the thyroid gland. Thyroid sarcoidosis has seldom been documented, and few cases have so far been described in association with hyperthyroidism. Here, we review the literature on this association, report two patients presenting with hyperthyroidism and histologically-proven sarcoidosis, and discuss related clinical, biochemical, pathological and genetic findings.
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Hipertiroidismo/complicaciones , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Enfermedades de la Tiroides/complicaciones , Enfermedades de la Tiroides/diagnóstico , Adulto , Femenino , Humanos , Hipertiroidismo/diagnóstico , Hipertiroidismo/patología , Masculino , Persona de Mediana Edad , Sarcoidosis/patología , Enfermedades de la Tiroides/patología , Glándula Tiroides/patologíaRESUMEN
Using Northern blotting, the expression levels of the genes for polyamine metabolism regulatory proteins and clusterin have been measured in a series of 23 human prostate cancers (CaPs) dissected from radical prostatectomy specimens. Patient matched, nontumor tissue was dissected from benign areas of the gland. The results indicate that transcripts encoding ornithine decarboxylase (ODC), ODC antizyme, adenosylmethionine decarboxylase, and spermidine/spermine N1-acetyltransferase (SSAT) were significantly higher, whereas clusterin (sulfated glycoprotein 2) mRNA was significantly lower in tumors compared with the benign tissue. All mRNA levels were compared with those of histone H3 and growth arrest-specific gene 1, markers of cell proliferation and cell quiescence, respectively, and glyceraldehyde 3-phosphate dehydrogenase, a housekeeping gene. In poorly differentiated and locally invasive CaPs and in tumors with unfavorable prognosis or total prostate-specific antigen (PSA) levels > 10.0 ng/ml at diagnosis, an overall increase in the levels of H3 mRNA and a decrease in growth arrest-specific gene 1 mRNA was detected, indicative of higher proliferation activity, whereas the differences in expression levels for the polyamine metabolism and clusterin genes were higher. ODC and SSAT changes were positively correlated in normal tissue but not in high-grade cancer, whereas ODC antizyme and SSAT changes were positively correlated in more malignant CaPs but not in normal tissue. Tumor classification based on the changes in expression levels of all of the genes studied could be correlated to differentiation grade and local invasiveness classification systems in 72.2 and 83.3% of the cases, respectively. In a 1-year follow-up period, three patients whose CaPs ranked as less aggressive according to clinical staging, but classified as advanced cancers with the proposed molecular classification, showed increases in total PSA levels, indicative of tumor relapse. Thus, molecular classification, based on gene expression, may enhance the available prognostic tools for prostate tumors.
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Genes Reguladores/fisiología , Glicoproteínas/metabolismo , Chaperonas Moleculares , Proteínas de Neoplasias/metabolismo , Poliaminas/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteínas de Saccharomyces cerevisiae , Acetiltransferasas/metabolismo , Adenosilmetionina Descarboxilasa/metabolismo , Proteínas de Ciclo Celular , División Celular , Clusterina , Progresión de la Enfermedad , Proteínas Ligadas a GPI , Regulación Neoplásica de la Expresión Génica , Histonas/metabolismo , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas de la Membrana , Ornitina Descarboxilasa/metabolismo , Pronóstico , Neoplasias de la Próstata/patología , Proteínas/metabolismo , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Men with Klinefelter syndrome (KS) show hypergonadotropic hypogonadism, but the pathogenesis of hypotestosteronemia remains unclear. Testicular steroidogenesis in KS men was evaluated over three decades ago after human chorionic gonadotropin (hCG) stimulation, but inconclusive results were obtained. Intriguingly, some recent studies show increased intratesticular testosterone concentrations in men with KS. OBJECTIVE: To analyze serum steroid profile, as a proxy of testicular steroidogenesis, after hCG stimulation in KS compared with control men. DESIGN: A prospective, longitudinal, case-control, clinical trial. METHODS: Thirteen KS patients (36±9 years) not receiving testosterone (TS) replacement therapy and 12 eugonadic controls (32±8 years) were enrolled. Serum steroids were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline and for five consecutive days after intramuscular injection of 5000IU hCG. RESULTS: Progesterone (P), 17-hydroxyprogesterone (17OHP), TS, and estradiol (E2) showed a significant increase (P<0.001) after hCG stimulation in both groups. On the contrary, androstenedione (AS) and dehydroepiandrosterone did not increase after hCG stimulation. The 17OHP/P ratio increased in both groups (P<0.001), the TS/AS ratio (17ß-hydroxysteroid dehydrogenase type 3 (17ßHSD3) activity) did not increase after hCG in any group, and the E2/TS ratio (aromatase activity) increased significantly in both groups (P=0.009 in KS and P<0.001 in controls). Luteinizing hormone decreased after hCG in both groups (P=0.014 in KS and P<0.001 in controls), whereas follicle-stimulating hormone decreased only in control men (P<0.001). CONCLUSION: This study demonstrates for the first time using LC-MS/MS that Leydig cells of KS men are able to respond to hCG stimulation and that the first steps of steroidogenesis are fully functional. However, the TS production in KS men is impaired, possibly related to reduced hydroxysteroid deydrogenase activity due to an unfavorable intratesticular metabolic state.
Asunto(s)
Gonadotropina Coriónica/uso terapéutico , Síndrome de Klinefelter/tratamiento farmacológico , Testículo/efectos de los fármacos , Testosterona/sangre , 17-Hidroxiesteroide Deshidrogenasas/sangre , Adulto , Gonadotropina Coriónica/farmacología , Cromatografía Liquida , Estradiol/sangre , Humanos , Síndrome de Klinefelter/sangre , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Progesterona/sangre , Estudios Prospectivos , Espectrometría de Masas en Tándem , Resultado del TratamientoRESUMEN
The first International Workshop on estrogen and male reproduction was held in Isola Capo Rizzuto, Italy and was organized by the University of Calabria (COSENZA), the University of Naples and the University of Modena and Reggio Emilia. The workshop, which was attended by general scientists, endocrinologists and andrologists, addressed the impressive recent progress in this area of male reproduction. Owing to space limitations, this report focuses on only a few of the recent advances related to the role of estrogen in the male genital tract.
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Estrógenos/fisiología , Genitales Masculinos/fisiología , Reproducción/fisiología , Animales , Humanos , Masculino , RatonesRESUMEN
Urinary norepinephrine (NE) and epinephrine (E) excretion was measured at 4-h intervals for 2 consecutive days in nine type I diabetic patients with no signs of autonomic neuropathy before and after 3 weeks of glycemic control with continuous insulin infusion (CSII). Twenty-four-hour urinary E excretion was significantly higher in the diabetic patients than in normal subjects both before and after the period of CSII treatment [mean, 198.9 +/- 20.6 +/- SE and 127.8 +/- 24.4 vs, 46.6 +/- 9.8 nmol/day; P less than 0.05 for both]. The values in each of the 4-h periods before and in two of three of the periods after the 3-week period of CSII were significantly higher than those in normal subjects. Total urinary NE excretion was similar to that in the normal subjects at both times. The 24-h urinary NE/E ratio was significantly lower in diabetic patients even after they had achieved good metabolic control, compared with that in normal subjects (1.4 +/- 0.2 vs, 11.6 +/- 3.7; P less than 0.03). These data demonstrate hyperactivity of the adrenal medulla in type I diabetic patients, which is only partially reversed by a short period of glycemic control.
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Médula Suprarrenal/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Insulina/farmacología , Adulto , Epinefrina/orina , Humanos , Hiperglucemia/metabolismo , Sistemas de Infusión de Insulina , Masculino , Norepinefrina/orinaRESUMEN
The effects of different doses of transdermal estradiol (TE) on bone mineral density (BMD) in a man with aromatase deficiency were evaluated. The study protocol was divided in the following four phases: phase 1, before estradiol treatment; phase 2, 50 microg TE twice weekly for 6 months; phase 3, 25 microg TE twice weekly for 9 months; and phase 4, 12.5 microg TE twice weekly for 9 months. X-rays of hands, legs, and pelvis were performed, and BMD of the lumbar spine, hormonal parameters (LH, FSH, testosterone, and estradiol), and markers of bone turnover were determined during each phase. BMD in phase 1 was 0.933 g/cm2 and increased to 1.051 and 1.173 g/cm2 after 4 and 7 months of TE, respectively. In phase 3, BMD reached the maximum value (1.275 g/cm2). In phase 4, BMD decreased to 1.180 g/cm2 and was 1.029 g/cm2 at the end of the study protocol. A bilateral necrosis of femoral heads was also detected by x-ray films. In phase 1 serum testosterone was in the normal range, whereas serum estradiol was undetectable. During the 24-month period of treatment with TE (phases 2-4), estradiol was directly related to the amount of TE, whereas LH was inversely related to estradiol serum levels. Estradiol and gonadotropins reached optimal values only in phase 3, when FSH also was near normal; serum testosterone concentrations were normal in phases 3 and 4. This study confirms the role of estrogens in achieving and maintaining bone mineral content in the human male, providing further clinical tools useful in the management of bone loss in aromatase deficiency in the male. We suggest that the adequate substitutive dose of TE for maintaining both bone mass and normal estradiol serum levels in adult men with aromatase deficiency may be 25 microg twice weekly (0.47 microg/kg weekly).
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Aromatasa/deficiencia , Densidad Ósea/efectos de los fármacos , Estradiol/uso terapéutico , Terapia de Reemplazo de Estrógeno , Testosterona/sangre , Administración Cutánea , Adulto , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Calcio/sangre , Estradiol/administración & dosificación , Estradiol/sangre , Hormona Folículo Estimulante/sangre , Estudios de Seguimiento , Humanos , Hormona Luteinizante/sangre , Masculino , Osteocalcina/sangre , Fosfatos/sangre , Factores de TiempoRESUMEN
Experimental data support a role for GH and IGF-I in the reproductive process in humans, but the effect of chronic GH excess on gonadal and reproductive function in men has been never investigated. To understand the effects of short-term GH and IGF-I suppression on the gonadal axis and seminal fluid characteristics in men with acromegaly, we evaluated 35 patients (age 27-59 yr) with active disease and 35 age-matched healthy controls. Gonadal hormones and seminal fluid analysis were evaluated before and 6 months after surgery or lanreotide (LAN) (60 mg/month). At study entry, FSH, testosterone (T), and dihydrotestosterone (DHT) (P < 0.0001) levels, seminal volume, sperm count, total motility and forward progression, normal morphology, and vitality were significantly lower in patients with acromegaly than in controls. After 6 months, 22 patients achieved disease control after surgery (n = 11) or LAN (n = 11), whereas 13 had uncontrolled disease. Serum T and DHT levels and sperm number significantly increased in all groups. FSH and LH levels and total motility increased only in patients achieving disease control. Posttreatment IGF-I levels significantly correlated with total motility (r = -0.45; P = 0.006). In conclusion, short-term GH and IGF-I suppression after surgery or LAN significantly increased T and DHT levels and improved sperm number and motility in acromegalic men.
Asunto(s)
Acromegalia/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Hormona de Crecimiento Humana/antagonistas & inhibidores , Factor I del Crecimiento Similar a la Insulina/antagonistas & inhibidores , Péptidos Cíclicos/uso terapéutico , Somatostatina/uso terapéutico , Recuento de Espermatozoides , Acromegalia/etiología , Acromegalia/fisiopatología , Adenoma/complicaciones , Adulto , Dihidrotestosterona/sangre , Progresión de la Enfermedad , Estradiol/sangre , Hormona Folículo Estimulante/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/complicaciones , Análisis de Regresión , Somatostatina/análogos & derivados , Motilidad Espermática/efectos de los fármacos , Testosterona/sangreRESUMEN
Increased glucocorticoid secretion is frequent in mood disorders and is normalized by long-term antidepressant therapy. Many antidepressants act by increasing central serotonin transmission. We investigated the effects of a serotonin precursor, indole-pyruvic acid (IPA), in an animal model of depression based on repeated exposure to unpredictable stress. Rats were divided in groups, and IPA (20 mg/kg), the tricyclic antidepressant imipramine (IMI) (5 mg/kg), or vehicle was administered daily during 3 weeks of repeated exposure to various stressors according to the procedure described by Katz et al [Katz RJ, Roth KA, Carroll BJ (1981): Neurosci Biobehav Rev 5:247-251]. After treatment, rats were evaluated for stress-induced exploratory behavior and killed 24 hr later. Serum corticosterone levels and glucocorticoid receptor (GR) immunoreactivity (IR) in the nuclei of neurons located in the hippocampal subregion CA1 were also measured. Rats exposed to repeated stress showed a lower exploratory behavior score (p < 0.01), higher basal corticosterone levels (p < 0.01), and stronger GR IR in the hippocampus (p < 0.05) than control rats. All of these effects were antagonized by IMI treatment. IPA administration did not affect the behavioral response induced by repeated stress (p < 0.01) but normalized serum corticosterone levels. In addition, IPA treatment produced a decrease in GR IR (p < 0.05 versus control group) that was not modified by exposure to repeated stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Anticonvulsivantes/farmacología , Antidepresivos/farmacología , Nivel de Alerta/efectos de los fármacos , Corticosterona/sangre , Trastorno Depresivo/fisiopatología , Hipocampo/efectos de los fármacos , Indoles/farmacología , Serotonina/fisiología , Estrés Psicológico/complicaciones , Estimulación Acústica , Animales , Nivel de Alerta/fisiología , Trastorno Depresivo/psicología , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Hipocampo/fisiología , Imipramina/farmacología , Técnicas para Inmunoenzimas , Ratas , Ratas Sprague-Dawley , Receptores de Glucocorticoides/efectos de los fármacos , Receptores de Glucocorticoides/fisiología , Estrés Psicológico/fisiopatologíaRESUMEN
The reports of congenital estrogen deficiency - notably, estrogen resistance and aromatase deficiency - have completely changed our knowledge on the role of estrogen on bone in males. Particularly, the bone changes at puberty, which were classically considered androgen-dependent, are now considered to be induced at least in part by estrogen action. Clinical cases of congenital estrogen deficiency have clearly demonstrated that the role of estrogens in epiphyseal closure, skeletal proportions and bone mineralization is crucial not only in women but also in men. In addition progress have been made in the treatment of such a rare disease even though further studies are needed to a definitive understanding of this issue.
Asunto(s)
Huesos/fisiología , Estrógenos/deficiencia , Estrógenos/fisiología , Aromatasa/deficiencia , Aromatasa/genética , Densidad Ósea/fisiología , Desarrollo Óseo/fisiología , Epífisis/crecimiento & desarrollo , Terapia de Reemplazo de Estrógeno , Femenino , Humanos , Masculino , Modelos Biológicos , Pubertad/fisiologíaRESUMEN
Recently, a remarkable progress has been made in our understanding about the role of sex steroids in male physiology. In this paper, we consider the clinical aspects of congenital estrogen deficiency - notably, estrogen resistance and aromatase deficiency - in men and we discuss both well-established and supposed estrogen roles in the human male reproductive function. These topics include the role of estrogens in the control of gonadotropin secretion, in male fertility determination and psychosexual behavior. Briefly, estrogens play a pivotal role in the control of serum gonadotropin concentrations in the human male. Furthermore, a possible role of estrogens on both human male fertility and sexuality has also been suggested by recent studies, even though the available data are far from being conclusive. Conversely, for what concern fertility and sexual behavior, a well-established effect of estrogens has been provided by recent studies on male rodents, which show impaired sexual behavior and fertility as a consequence of estrogen defect.
Asunto(s)
Estrógenos/deficiencia , Estrógenos/fisiología , Reproducción/fisiología , Animales , Aromatasa/deficiencia , Aromatasa/genética , Receptor alfa de Estrógeno , Femenino , Fertilidad/fisiología , Identidad de Género , Gonadotropinas Hipofisarias/metabolismo , Humanos , Infertilidad Masculina/genética , Infertilidad Masculina/fisiopatología , Masculino , Mutación , Fenotipo , Receptores de Estrógenos/deficiencia , Receptores de Estrógenos/genética , Caracteres Sexuales , Conducta Sexual/fisiologíaRESUMEN
Eleven adult males, previously submitted to neurosurgery because of a pituitary lesion (three with craniopharyngioma, three with clinically non-functioning adenoma and five with macroprolactinoma) were treated with recombinant GH for 12 months after the diagnosis of GH deficiency was made. Circulating FSH, LH, prolactin, testosterone, 17 beta-estradiol (E2), dehyroepiandrosterone (DHEA-S), androstenedione. 17-OH-progesterone (17OHP), IFG-I, and steroid hormone-binding protein (SHBG) levels were assayed before and after CG test at study entry and 6 and 12 months after GH treatment. A significant increase in plasma IGF-I levels was obtained after 6 and 12 months of GH treatment. In addition, CG-stimulated, but not baseline, testosterone levels showed a significant increase after 6 and 12 months of GH treatment when compared with study entry (9.6 +/- 0.5 and 9.9 +/- 0.5 vs 7.9 +/- 0.5 ng/ml; P < 0.05). Baseline, but not CG-stimulated, serum 17OHP levels were significantly increased only after 12 months of GH treatment (1.7 +/- 0.1 vs 1.4 +/- 0.1 ng/ml; P < 0.05). No significant difference was found as far as both basal and CG-stimulated E2, androstenedione, DHEA-S and SHBG were concerned. With regards to the semen analysis, only seminal plasma volume was significantly increased after 12 months of GH treatment (2.9 +/- 0.3 vs 1.7 +/- 0.3 ml; P < 0.05). No significant change in sperm count, motility and abnormal forms was observed. These data show that GH treatment displays a clear-cut effect upon Leydig cell function and increases the production of seminal plasma volume in fertile adult males with isolated GH deficiency.
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Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/deficiencia , Espermatogénesis/efectos de los fármacos , 17-alfa-Hidroxiprogesterona/sangre , Adulto , Androstenodiona/sangre , Gonadotropina Coriónica/fisiología , Deshidroepiandrosterona/sangre , Estradiol/sangre , Fluoroinmunoensayo , Hormona Folículo Estimulante/sangre , Hormona del Crecimiento/farmacología , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Prolactina/sangre , Estudios Prospectivos , Radioinmunoensayo , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangreRESUMEN
Further evidence that nocturnal erections are androgen-dependent and erectile responses to visual erotic stimuli are androgen-independent is presented from six men with secondary hypogonadism and six eugonadal controls. Erections during sleep were substantially less in the hypogonadal men, in terms of both tumescence and rigidity. In response to visual erotic stimuli, the percentage increase in circumference over baseline and the increase in rigidity were similar for the two groups.
Asunto(s)
Ritmo Circadiano/fisiología , Hipogonadismo/fisiopatología , Libido/fisiología , Erección Peniana/fisiología , Fases del Sueño/fisiología , Testosterona/sangre , Adulto , Hormona Folículo Estimulante/sangre , Hormona Liberadora de Gonadotropina , Humanos , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Prolactina/sangreRESUMEN
Nocturnal penile tumescence (NPT) and erectile response to visual erotic stimuli (VES) were measured, by means of a Rigiscan device, in nine hypogonadal men, and repeated after 3 months of androgen replacement. The same assessments were carried out once in 12 eugonadal controls. The number of satisfactory NPT responses, in terms of both circumference increase and rigidity, were less in the hypogonadal men than the controls and were significantly increased by androgen replacement, confirming the results of earlier studies. In terms of circumference increase, erectile response to VES did not differ between the hypogonadal men and the controls, and did not increase with androgen replacement. In terms of rigidity, the erectile response to VES did not differ between hypogonadal men and controls. However, in terms of both duration and maximum level of rigidity, there was a significant increase following androgen replacement in the hypogonadal men. These new findings, in relation to rigidity, require a modification of the earlier formulation, which saw NPT as androgen dependent and erectile response to VES as androgen independent. NPT, and possibly spontaneous erections at other times, clearly involve an androgen sensitive system. Erectile response to VES predominantly involves an androgen independent system but may also be influenced by androgen sensitive mechanisms.
Asunto(s)
Hipogonadismo/tratamiento farmacológico , Erección Peniana/efectos de los fármacos , Testosterona/uso terapéutico , Adulto , Literatura Erótica , Fantasía , Humanos , Hipogonadismo/sangre , Hipogonadismo/fisiopatología , Masculino , Sueño/efectos de los fármacos , Sueño/fisiología , Sueño REM/efectos de los fármacos , Testosterona/sangreRESUMEN
Endocrine responses to erotic stimulation in the laboratory were assessed in eight normal subjects. Each subject was tested on two occasions. On one occasion only neutral stimuli were involved. After 15 min baseline, 30 min of films were shown. For the erotic condition on the other occasion, two 10-min erotic films were interspersed with 10 min of neutral film. Fifteen-minute blood samples were taken from the start of each test and continued for 5 hr after the films. Plasma was assayed for testosterone, LH, prolactin, cortisol, ACTH and beta-endorphin. Urine was collected for 4 hr before and 4 hr after the films; this was assayed for adrenaline, noradrenaline and dopamine. Sexual arousal occurred in response to the erotic films in all subjects, as shown by erectile and subjective responses. There were no significant changes in hormone or catecholamine levels following either the erotic or the neutral stimuli, except for a rise in cortisol during the neutral but not the erotic film. These results indicate that in the laboratory, substantial sexual response can occur without accompanying endocrine or biochemical changes.
Asunto(s)
Hormonas/metabolismo , Conducta Sexual/fisiología , Hormona Adrenocorticotrópica/sangre , Adulto , Catecolaminas/sangre , Catecolaminas/orina , Hormonas/sangre , Hormonas/orina , Humanos , Hidrocortisona/sangre , Hormona Luteinizante/sangre , Masculino , Erección Peniana/fisiología , Prolactina/sangre , Testosterona/sangre , betaendorfina/sangreRESUMEN
Evidence has been presented that behavioral actions of NT, inducing its neuroleptic-like action, can be explained on the basis of NT-D2 intramembrane receptor-receptor interactions in the basal ganglia, unrelated to the coexistence phenomenon, leading to reduced affinity and transduction of the D2 agonist binding site. By reducing selectively D2 receptor transduction at the pre- and postsynaptic level, the NT receptor appears capable of switching the DA synapses towards a D1 receptor-mediated transduction, illustrating how receptor-receptor interactions can increase the functional plasticity of central synapses (FIG. 12).