DAX-1 and DAX-1A expression in human testicular tissues with primary spermatogenic failure.

DAX-1 [dosage-sensitive sex reversal-adrenal hypoplasia congenital (AHC) critical region on the X chromosome gene 1; NR0B1] is an orphan nuclear receptor that acts as a transcriptional repressor in adrenal/gonadal development, steroidogenesis and probably spermatogenesis. An alternatively spliced form called DAX-1A (NR0B1A) has been described in several tissues including the testis, and in vitro studies have shown an inhibitory effect on DAX-1 transcriptional function. We aimed to study the mRNA and protein expression of DAX-1 in testicular tissues of 65 men with primary spermatogenic failure [complete Sertoli cell only syndrome (SCOS), focal SCOS, maturation arrest and mixed atrophy] compared with 33 controls with normal spermatogenesis. As a novel finding, we observed intense immunostaining, not only in the nucleus of Sertoli cells, but also in pachytene spermatocytes and round spermatids. The quantitative mRNA expression of DAX-1 and DAX-1A was similar between cases and controls and was not associated with the levels of gonadotrophins and steroids. Moreover, DAX-I transcript expression level was ∼750-fold higher than DAX-1A, and there was a strong positive correlation between them (r = 0.52; P< 0.001). We conclude that, in addition to Sertoli cells, DAX-1/DAX-1A is expressed in germ cells from spermatogonia to round spermatids. Besides, the similar mRNA expression of DAX-I and DAX-IA in testicular tissues from cases and controls does not support the involvement of DAX-1 in the etiology of primary spermatogenic failure. Finally, the low level of expression of the alternative transcriptional variant DAX-1A would not support its putative inhibitory function in vivo.

Alteraciones genéticas en la producción, secreción y acción de las gonadotrofinas / Genetic disorders of gonadotropin synthesis, release and function

Pulsatile secretion of Gonadotropin-Releasing Hormone (GnRH) by the hipothalamus and its action on the pituitary gland is a complex process involving many pre and post natal events. For example, migration of GnRH neurons from the olfactory placode, GnRH release and signalling, normal anterior pituitary development and function are all needed to allow GnRH to stimulate pulsaltile pituitary secretion of follicle-stimulating hormone (FSH) and liteinizing hormone (LH). Hypogonadotropic hypogonadism can be the result of absent or inadequate GnRH secretion or action. Abnormalities in gonadotropin hormone release and function can arise from mutations in a variety of genes implicated in hypogonadotropic hypogonadism is continually growing. A given genotype at a single locus cannot reliably predict the phenotypic manifestations in any given member of affected families. Thus, the identification and characterization of these mutations are providing important information about the reproductive axis in humans and may result in improved treatment and counselling for patients with infertility.

Hypothalamic-pituitary-testicular function in prepubertal children with chronic liver disease.

Adult patients with chronic liver disease (CLD) show clinical and biochemical signs of hypogonadism and estrogenization. However, no information is available on hypothalamo-pituitary-testicular function in prepubertal or early pubertal children with CLD. Eighteen prepubertal children with CLD, aged 5.8+/-5.5 years (mean +/- SD; range 0.32-12.8), were studied. Most of them had moderate liver function abnormality. Height was slightly decreased (SDS: -1.44-/+1.88) but weight for height was adequate. Serum gonadotropins were evaluated as a function of age. In the age group younger than 1 year (n = 7), serum LH was elevated (4.88+/-6.22 IU/l) when compared with a group of 39 control children (1.2+/-1.65), while serum FSH was normal. In this young group, serum testosterone was normal, but serum estradiol was significantly increased (24.1+/-19.7 pg/ml) when compared with the control group (6.5+/-3.54). In contrast, in the age group older than 2 years, no difference between patients with CLD and controls was observed, either in serum gonadotropins or in serum sex hormones. Taking the 18 patients with CLD together, serum SHBG (113.7+/-51 nmol/l; mean +/- SD) was significantly higher than in normal controls (76+/-38 nmol/l, n = 91, p <0.001). Moreover, and different from normal controls, no change with age was observed in serum SHBG, total testosterone or bioavailable testosterone (non-SHBG-bound). Normal testosterone response to hCG stimulation (>1 ng/ml) was found in a subgroup of 11 children with CLD. By contrast, eight of 11 patients with CLD had an inadequate decrease in SHBG after androgen stimulation. In conclusion, we observed that during the first year of life, a period which includes the postnatal activation of the hypothalamo-pituitary-testicular axis, there is an elevation of serum LH and serum estradiol that suggests the existence of a moderate deficiency of Leydig cell function. This disorder is no longer observed in older prepubertal children. Similar to reports in adults, children with CLD have elevation of serum SHBG levels. Furthermore, the lack of SHBG decrease and bioavailable testosterone increase with age, probably modulated by GH, suggests some degree of hepatic GH resistance in prepubertal patients with CLD.

Fisiología ovárica postparto: gonadotropinas hipofisarias, estradiol y prolactina durante 12 meses a la resolución del embarazo / Post-partum ovarian physiology. Hypophysial gonadotropins, estradiol and prolactin during 12 months at pregnancy resolution

Se realizó un seguimiento por doce meses en una cohorte de 17 mujeres, a partir de la resolución del embarazo para tratar de valorar la asociación hiperprolactinemia lactacional/hormonas estimulante de folículo (FSH)/hormona luteinizante (LH) y reinicio de la actividad ovárica. El estudio se dividió en dos fases: Lactancia (Lac) y post-lactancia (post-Lac). En ambas etapas se tomaron muestras de sangre venosa periférica cada semana hasta la semana 52, para cuantificar: FSH, LH, prolactina (PRL) y estradiol (E-2). Durante Lac, las concentraciones periféricas del PRL, fueron significativamente mayores a Post-Lac; observándose una relación inversamente proporcional E-2/PRL a lo largo del seguimiento. No existieron cambios significativos para LH y FSH en ambas fases y las cifras se mantuvieron dentro de niveles fisiológicos. Al compararlas con un sujeto control no mostraron diferencias. Los coeficientes de correlación revelaron una asociación negativa entre PRL y los días que transcurrieron al postparto y positiva para E-2. Los hallazgos indican una función folicular, aparentemente independiente del estímulo gonadotrópico hipofisario

Cambios en el contenido cerebral de la hormona liberadora de las gonadotrofinas (GnRH) en el caribe colorado, Pygocentrus notatus, durante el ciclo reproductivo / Changes in brain content of gonadotrophin releasing hormone (GnRH) of caribe colorado, pygocentrus notatus, during the reproductive cycle

Usando radioinmunoensayo detectamos inmunoreactividad positiva para la hormona liberadora de las gonadotrofinas (GnRH-ir) en extratos de techo áptico (TO), cerebelo (CER) y tallo cerebral (TC) del caribe colorado, Pygocentrus notatus.P. notatus, al igual que la mayoría de los peces de la zona posee un ciclo reproductivo estrechamente ligado a los cambios en las condiciones medioambientales. Nuestros resultados muestran una correlación entre la maduración gonadal expresada como Indice Gonosomático (IG) y el comienzo de las lluvias (abril-mayo) en hembras y machos de esta especie. Asimismo, en las hembras se observaron flutuaciones en los niveles de GnRH-ir en extractos de TO y CER, dependientes del estadío reproductivo y de las condiciones medioambientales. Por el contrario, en los machos no se observaron cambios excepto en TO, donde se observó un aumento durante mayo