Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency.

Androgens are considered to have immunomodulatory effects but their cellular mechanisms of action remain largely unknown. In the present study we prospectively analyzed the serial effects of androgen-replacement therapy on both the distribution of peripheral blood lymphocytes, monocytes and dendritic cells as well as on the production of interleukin (IL)-1beta, IL-6 and tumor necrosis factor alpha (TNFalpha) inflammatory cytokines by circulating monocytes and CD33 myeloid, CD16 and plasmacytoid dendritic cell subsets, the most potent antigen-presenting cells (APCs) in type-2 diabetic men with partial androgen deficiency. Analyses were performed before therapy and at 1, 3, 6 and 12 months after treatment with 150 mg testosterone enanthate every 2 weeks in a group of 13 type-2 diabetic men. Our results show for the first time that testosterone-replacement therapy is associated with a reduction or complete abrogation of spontaneous ex vivo production of IL-1beta, IL-6 and TNFalpha by APCs. Meanwhile, the in vitro production of inflammatory cytokines by these cells after stimulation with lipopolysaccharide plus recombinant human interferon-gamma remained unchanged, suggesting that APCs preserve their constitutive machinery to produce inflammatory cytokines under androgen treatment. These results confirm and extend previous observations about the anti-inflammatory effects of androgen therapy on APCs in a new, previously unexplored model of androgen deficiency; namely, aging type-2 diabetic men. A decreased production of inflammatory cytokines by APCs might have important consequences for sex differences in susceptibility to autoimmune diseases, inflammatory response to injury and atheromatosis.

Partial androgen deficiency in aging type 2 diabetic men and its relationship to glycemic control.

Aging in the male is associated with both a higher incidence of type 2 diabetes and hypogonadism. However, little information is available about the complex of symptoms and hormonal changes related to partial androgen deficiency in aging (called andropause) in type 2 diabetic men. Here, for the first time, we used a combination of clinical and hormonal criteria to define andropause and to analyze the relationships between the androgen environment and glucose metabolism in 55 type 2 diabetic men (63.6 +/- 7.9 years, mean +/- SD). Low plasma levels of total testosterone (< or =3.4 ng/mL) and free testosterone (< or =11 pg/mL) were found in 20% and 54.5%, respectively, of the diabetic men. The fraction of diabetic men with subnormal levels of total testosterone increased with aging: 14.2% (50 to 59 years), 17.4% (60 to 69 years) and 36% (> 70 years). The corresponding figures for subnormal values of free testosterone were 38%, 69.6%, and 54.5%, respectively. In the whole group of type 2 diabetic men, no significant linear correlations between total or free testosterone with fasting plasma glucose, insulin, C-peptide, or fructosamine values could be established. Total testosterone was positively correlated with glycosylated haemoglobin (HbA(1c)) levels (r =.322, P =.01). Although fasting plasma glucose was marginally higher in aging type 2 diabetic patients with andropause than in those without andropause (162 +/- 6.9 v 139 +/- 8.9, mean +/- SEM, P =.05), there were no differences between both subgroups for plasma fasting insulin, C-peptide, fructosamine, or HbA(1c) levels. Replacement therapy (150 mg intramuscular [IM] of enanthate of testosterone every 14 days for 6 months) was applied in 10 type 2 diabetic men with clinical features of andropause associated with subnormal concentrations of serum testosterone. The treatment induced significant increases in total plasma testosterone (baseline: 3.9 +/- 0.3; at 6 months: 7.1 +/- 0.9 ng/mL, mean +/- SEM, P =.003) and free testosterone (baseline: 9.3 +/- 0.6; at 6 months 17.6 +/- 2.4 pg/mL, P =.003), but had a neutral effect on overall glycemic control. These data show a high prevalence of andropause in aging type 2 diabetic men and suggest that the endogenous androgen environment, as well as correction of the partial androgen deficiency, do not have a meaningful effect on glycemic control.

Adenoma ovárico de células de Leydig: una rara causa devirilización asociada a factores de riesgo cardiovascular / Leydig cell ovarian adenoma: a rare cause of virilization associated with cardiovascular risk factors

La masculinización de la mujer adulta ovirilismo es un trastorno endocrino infrecuente debido a un exceso de secreción androgénica causado por tumores adrenales u ováricos 1. Dentro de estos últimos, los más comunes son los de células de Sertoli-Leydig (androblastomas), si bien otros tipos patológicos, como los tumores de la granulosa-teca, de células hiliares, de células lipoideas y de restos adrenales, también pueden generar el cuadro1. Presentamos un caso clínico de virilización debido a un adenoma de células de Leydig, un tumor ovárico raro que sólo representa un 0,1% de los tumores ováricos. Describimos su asociación con factores de riesgo cardiovascular y el efecto de la corrección permanente del hiperandrogenismo sobre los mismos (AU)

Abnormal expression of acid glycosidases in seminal plasma and spermatozoa from infertile men with varicocele.

The activities of acid beta-glucuronidase, alpha-mannosidase, alpha-glucosidase, alpha-galactosidase, beta-galactosidase and beta-N-acetylglucosaminidase were analysed in seminal plasma and spermatozoa from 26 infertile men with varicocele and from 36 men of normal fertility. Semen samples from ten men with non-obstructive azoospermia were used as control specimens that contained the other components of semen. Spermatozoa were solubilized by both physical (homogenization) and chemical (Triton-X100) methods to obtain the soluble and non-soluble fractions. The activities of several glycosidases measured both in seminal plasma and spermatozoa were directly correlated with the numbers of spermatozoa and sperm motility, confirming previous studies. As some infertile patients with varicocele have normal semen parameters, whereas others have low numbers of spermatozoa and low sperm motility, the varicocele patients were prospectively divided into two groups: one (n = 15) with normal spermiograms and the other (n = 11) with abnormal spermiograms. The activities (expressed in mU ml(-1)) of alpha-mannosidase, beta-galactosidase and beta-N-acetylglucosaminidase in seminal plasma of normozoospermic infertile patients with varicocele were significantly higher than those of fertile controls, but not when expressed in U per 10(8) spermatozoa. The activities of beta-glucuronidase, alpha-mannosidase, beta-galactosidase and beta-N-acetylglucosaminidase in seminal plasma when expressed in U per 10(8) spermatozoa in varicocele patients with abnormal spermiograms were significantly higher than in those of men of normal fertility. The activity of alpha-mannosidase in the soluble fraction of sperm homogenates, expressed as U per 10(8) spermatozoa, was significantly higher in infertile patients with varicocele and abnormal spermiograms than in controls. In the non-soluble fraction of spermatozoa from infertile patients with varicocele, there was an increase in the expression of beta-galactosidase and beta-N-acetylglucosaminidase activities compared with the fraction of spermatozoa from fertile subjects. In summary, infertile patients with varicocele displayed an overexpression of acid alpha-mannosidase, beta-galactosidase and beta-N-acetylglucosaminidase activities in seminal plasma and spermatozoa that may be associated with functional defects in spermatozoa as these glycosidases play an important role in mammalian fertilization.

Edema agudo de pulmón en una mujer joven con masa suprarrenal / Acute pulmonary edema in a young woman with an adrenal mass

El feocromocitoma es un tumor neuroendocrino responsable del 0,05-0,1 por ciento de las hipertensiones secundarias, asociándose en ocasiones con normotensión. La miocardiopatía es una complicación rara, inducida por el exceso de catecolaminas. Presentamos el caso de una mujer joven que inició con cuadro de edema agudo de pulmón no cardiogénico sin hipertensión arterial asociada, debido a una miocardiopatía hipertrófica obstructiva grave. La paciente presentaba niveles elevados de catecolaminas y un tumor localizado en la glándula suprarrenal derecha. Después del comienzo del tratamiento alfa-beta bloqueante, se observó mejoría clínica y ecocardiográfica de la miocardiopatía, y la normalización posterior de los diámetros ventriculares tras la extirpación del feocromocitoma (AU)

Abnormalities in sperm acid glycosidases from infertile men with idiopathic oligoasthenoteratozoospermia.

OBJECTIVE: To analyze and compare acid beta-glucuronidase, alpha-mannosidase, alpha-glycosidase, alpha-galactosidase, beta-galactosidase, and beta-N-acetylglucosaminidase activities in fertile and infertile patients. DESIGN: An observational, controlled, clinical study. SETTING: A university tertiary hospital. PATIENT(S): Thirty-six fertile controls, 24 infertile oligoasthenoteratozoospermic (OAT) patients, and 10 azoospermic patients, who served as negative controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Analysis of the six glycosidase activities in seminal plasma and in solubilized spermatozoa. RESULT(S): alpha-galactosidase and beta-galactosidase activities in spermatozoa were significantly correlated with the serum levels of gonadotropins both in fertile controls and in OAT patients. The relative contribution of alpha-galactosidase and beta-galactosidase from the soluble fraction of spermatozoa to the total activity measured in the ejaculate of OAT patients was significantly lower than in fertile controls. The activities of beta-galactosidase and beta-N-acetylglucosaminidase in the soluble fraction of spermatozoa from OAT patients were significantly lower than in fertile controls. In seminal plasma, the activity of alpha-mannosidase from OAT patients was significantly higher than in fertile controls. The activity of beta-N-acetylglucosaminidase in the nonsoluble fraction of spermatozoa from OAT patients was three times higher than in fertile controls. CONCLUSION(S): The abnormalities in the distributions and contents of alpha-galactosidase, beta-galactosidase, and beta-N-acetylglucosaminidase in sperm suggest possible functional defects in spermatozoa from OAT infertile patients.

Enzyme and hormonal markers in the differential diagnosis of human azoospermia.

The serum concentrations of FSH, LH, prolactin, testosterone, and estradiol and the enzymatic activities of hyaluronidase, glucosidases (alpha-glucosidase, beta-glucosidase, alpha-mannosidase, N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, and beta-galactosidase), lactate dehydrogenase and its isoenzymes (LDH1, LDH2, LDH3, LDH-X, LDH4), and total proteins were measured in the semen of 69 subjects (8 normozoospermic controls, 7 secretory, and 54 excretory azoospermic subjects). FSH levels rose with the deterioration in spermatogenesis and served to differentiate the secretory from the excretory azoospermias. The only source of hyaluronidase and LDH-X in the ejaculate is the spermatozoa. alpha-Glucosidase activity essentially originates in the epididymis. The seminal determination of alpha-glucosidase and, to a lesser extent, alpha-mannosidase and N-acetyl-beta-D-glucosaminidase helps rapidly, sensitivity, reliably, and noninvasively to differentiate secretory azoospermias (with higher enzymatic activity) from the excretory type (less enzymatic activity) and may be of use in identifying with a certain degree of reliability the site of obstruction in the male genital tract.